Transcript Electrolytes

Sodium and Water:
What Laboratory Scientists Need to
Know
Graham Jones
Staff Specialist in Chemical Pathology
St Vincent’s Hospital, Sydney
Presented RCPA/AACB Chemical Pathology
training Course, February 2004, Adelaide
Objectives
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Measurement
Physiology
Pathology
Lab-based knowledge
Sodium Measurement
• Most Australian Laboratories use Ion
Sensitive Electrodes (ISE)
• May be direct or indirect
• Indirect
– Dilution of the sample
– Most automated analysers
– Affected by lipid and protein concentrations
• Direct
– No dilution of the sample
– Blood gas machines
– Vitros analysers
What we measure
• Analyte: Sodium
• Measurand:
– activity of sodium ions per volume of sample
(indirect)
– Activity of sodium ions per mass of water*
(concentration)
* expressed per volume of plasma
Sodium Measurement: Interferences
• Analytical
– Electrodes are very specific
– In the presence of increased amounts of nonaqueous components we get reduced values with
indirect methods (pseudohyponatraemia)
• Pre-analytical
– Drip-arm
– Wrong patient
– Gross haemolysis (dilution with intracellular
fluid)
Drip arm contamination
• Common diluents:
– Normal saline: 154 mmol/L Na and Cl
– 5% dextrose: 278 mmol/L glucose
– 4% & 1/5th saline: 222 mmol/L gluc, 31 Na & Cl
• Results tend to values in diluent
– eg Na of 170 unlikely to be drip-arm
• Osmolality tends to be normal
• Measuring glucose, albumin and protein helpful
Artefacts: examples
Sodium
133-145 mmol/L
Potassium
3.5-5.0 mmol/L
Chloride
99-108 mmol/L
Bicarbonate 24-34 mmol/L
Urea
2.0-7.0 mmol/L
Creatinine 0.05-0.08 mmol/L
Glucose
3.5-8.0 mmol/L
Protein
60-80 g/L
Albumin
40-55 g/L
S1
140
4.5
105
28
4
0.08
5
70
45
S2
S3
145
165*
3.2*
4.5
120*
130*
20
28
2.8
20*
0.06
0.15*
3.5
5
49 *
85*
32 *
55*
Questions: Could it be pathology? Could it be artefact?
How good are we
• Average analytical CV about 1%
• Gives SD of about 1.4 mmol/L for normal
result
• 95% of results in a 5.6 mmol/L range
(+/- 2SD)
• Biological variation
– Within person 0.6 %
– Between person variation 0.6%
• Acceptable CV is <0.75 x within person CV
– Not acceptable!!
Water Measurement
• Clinical
– Weight (change in weight)
– Physical examination: pulse, blood pressure,
JVP, lung auscultation, oedema
• Concentration of blood components
– High albumin#, high sodium may mean low
water content of samples.
• # or prolonged tourniquet for albumin
– Low albumin or low sodium may mean high
water concentration of samples
– 5% dehydration highly significant
Water and electrolytes: Other Tests
• Serum
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Urea, Creatinine
Glucose
Osmolality (and osmolar gap)
Albumin, Total Protein
Lipids
• Urea
– Sodium
– Osmolality
– Creatinine
Physiology
Body Sodium
• Sodium: major extracellular cation
– Approx 10 mmol/L intracellularly
– 140 mmol/L extracellularly
• Intake: 100 - 200 mmol/day
• Excretion:
– Faecal: 10 mmol/d
– Sweat: 10-20 mmol/d
– Renal: the rest (ie matches intake)
• Equally distributed in extracellular fluid
– ie drain fluid
– except urine and gastro-intestinal fluid!
Sodium and Water
• Sodium and Water homeostasis are
inextricably linked
• “where sodium goes, water follows”
• Measure sodium concentration
– Affected by changes in water and sodium
• Clinical effects due to movement of water
in and out of cells
Salt and Water regulation
• Water
– Thirst (regulates input)
– Vasopressin (ADH) (regulates output)
• Sodium
– Renin-Angiotensin-Aldosterone (RAA)
– Natriuretic peptides
– Both regulate output
Vasopressin (ADH)
• Hormone from Posterior pituitary
• Released in response to high osmolality
• Released in response to low volume
– Low volume over-rides low osmolality
• Increases permeability of kidney distal tubule
• Controls renal WATER excretion
– Low ADH -> high urine volume, low urine osmo
– High ADH -> low urine volume, high urine osmo
• Also potent vasocontrictor
Vasopressin (ADH)
Dehydration
Hypernatraemia
(Increased osmolality)
Reduced BP
ADH Release
Reduced renal water loss
Vasocontriction
Concentrated
Urine
Euvolaemia
Renin-angiotensin-aldosterone (RAA)
• Low renal perfusion -> renin release
– eg hypovolaemia, heart failure, shock.
• Renin converts Angiotensinogen to
Angiotensin I
• ACE converts AI to AII
• AII releases Aldosterone from adrenal gland
• Aldosterone acts in proximal tubule
– resorbs sodium, excretes potassium
• Controls urine SODIUM excretion
RAA Response to Dehydration
Dehydration
Vasocontriction
Reduced Renal Perfusion
Renin release
Angiotensin I Production
Aldosterone release
Angiotensin II Production
Renal Sodium resorption
Incr Plasma osmolality, ADH, thirst
ACEI
Low urine sodium
Euvolaemia
Renal Water & Sodium Handling
Sodium: 25 mol/d
Water: 150 L/d
Active sodium
Passive water
Sodium only (no water)
Makes dilute urine
Sodium:
Aldosterone-sensitive
Water:
ADH-sensitive
Sodium: 100-200 mmol/d
Water: 1-2 L/d
Additional Mechanisms
• Thirst
– Responds to high osmolality and low volume
– Powerful but slow regulator
• Natrurietic Peptides
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Atrial (ANP, atrium); Brain (BNP, ventricle)
Respond to stretch (over filling)
Causes renal sodium and water loss
Blocks RAA, causes vasodilation
Markers of heart failure, HT
Pathology
Sodium and Water balance
• In normals:
– Sodium in = sodium out
– Water in = water out
• With changes:
– Systems try to correct changes
– eg dehydration -> water retention
• With defects in systems:
– other mechanisms try and correct defect
– eg DI, thirst can correct body interior
Clinical Derangements
• Water
– Too much, too little, just right
• Sodium
– Too much, too little just right
• Combination leads to sodium concentration
Sodium\Water Too little Just right Too much
Too little
N
L
L
Just right
H
N
L
Too much
H
H
N
Sodium - Clinical Effects
• Hypernatraemia - draws water out of cells
• Hyponatraemia - water drawn into cells
– Main effects on brain!!
>160
>150
<130
<120
<110
twitching, siezures, coma
weakness, lethargy
nausea, drowsiness
vomiting, confusion
convulsions, coma
Depends on rate of change and other factors
Hyponatraemia
Hyponatraemia: Important Diagnoses
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Diuretics
Renal Failure
Addison’s disease
Hypothyroidism
Liver failure
Heart Failure
SIADH
• Artefacts
Hyponatraemia diagnosis
Hyponatraemia
Exclude common
drugs, eg diuretics
Measure plasma osmolality
Normal
Drip-arm
Pseudohyponatraemia:
- Hyperlipidaemia
- Hyperproteinaemia
Decreased
True Hyponatraemia
Increased
Hypertonic Hyponatraemia:
- Hyperglycaemia
- Hyperglycinaemia (post TURP)
Measure Urine Sodium and osmolality,
state of hydration
Urine sodium >20 mmol/L
Urine sodium <20 mmol/L
Hyponatraemia diagnosis
Hyponatraemia
Exclude common
drugs, eg diuretics
Measure plasma osmolality
Normal
Drip-arm
Pseudohyponatraemia:
- Hyperlipidaemia
- Hyperproteinaemia
Decreased
True Hyponatraemia
Increased
Hypertonic Hyponatraemia:
- Hyperglycaemia
- Hyperglycinaemia (post TURP)
Measure Urine Sodium and osmolality,
state of hydration
Urine sodium >20 mmol/L
Urine sodium <20 mmol/L
Drugs and Hyponatraemia
• Diuretics (sodium loss)
– Eg thiazides, frusemide, indapamide
• Potentiate ADH secretion (water retention)
– barbiturates; narcotics; oral hypoglycaemics;
antineoplastics; anticonvulsants, antidepressants
– miscellaneous (clofibrate, isoprenaline, nicotine
derivatives)
• Potentiate ADH action (water retention)
– Chlorpropamide, paracetamol, indomethacin
Hyponatraemia diagnosis
Hyponatraemia
Exclude common
drugs, eg diuretics
Measure plasma osmolality
Normal
Decreased
Increased
Drip-arm
Pseudohyponatraemia:
- Hyperlipidaemia
- Hyperproteinaemia
True Hyponatraemia
Hypertonic Hyponatraemia:
- Hyperglycaemia
- Hyperglycinaemia (post TURP)
Measure Urine Sodium and osmolality,
state of hydration
Urine sodium >20 mmol/L
Urine sodium <20 mmol/L
Low Sodium and Normal Osmolality
• Normal Osmolar gap
– Drip Arm
– Glucose high, included in osmolar gap
calculation
• High Osmolar Gap
– Pseudohyponatraemia
– High total protein (>100 g/L)
– High Lipids
• Triglycerides
• Lipoprotein X
Pseudohyponatraemia
• Reduced measured sodium (and other analytes)
in indirect measurements
• Caused by increase in non-aqueous components
– Triglycerides > 30 mmol/L
– Protein > 100 g/L
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Sodium molality is normal
Sodium molarity is low
Normal measured osmolality (high osmolar gap)
Normal result in blood gas analyser
BODY THINKS SODIUM IS NORMAL
Hyperosmolar Hyponatraemia
(dilutional hyponatraemia)
• High extracellular osmolality
– Glucose (normal osmolar gap)
– Glycine (raised osmolar gap)
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• Occurs after TURP
• Draws water out of cells
• With treatment glucose returns into cells
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Water follows glucose into cells
Sodium level increases
Sodium rise = glucose(mmol/L)/4
Eg Sodium 125 mmol/L Glucose 40 mmol/L
True Hyponatraemia
• Low osmolality
• Normal osmolar gap
• Further investigation indicated
– Clinical evaluation of state of hydration
– Spot urine sample
• sodium
• Osmolality
Hyponatraemia: further investigation
Measure Urine sodium and
osmolality,
determine state of hydration
Urine sodium > 20 mmol/L
Urine sodium < 20 mmol/L
Patient Hypovolaemic
Patient Euvolaemic
Patient Overloaded
Renal losses (UPO>1)
- Diuretic therapy
- Addisons Disease
- Salt-losing nephritis
- Proximal RTA
Osmotic diuresis
(UPO1)
- glucose, urea
Chronic water overload
- SIADH (U osmo>200)
- Hypothyroidism
- Cortisol deficiency
(UPO>1)
Acute Water Overload
- Stress, post surgery
- Psychogenic polydipsia
(UPO<1)
Renal failure
- acute, chronic
Hyponatremia: low Urine sodium
Measure Urine sodium and
osmolality,
determine state of hydration
Urine sodium > 20 mmol/L
Urine sodium < 20 mmol/L
Patient Hypovolaemic
Patient Euvolaemic
Patient Oedematous
Extra-renal losses (UPO>1)
- vomiting, diarrhoea
- skin loss, pancreatitis
Fluid depletion and
hypotonic replacement
SIADH with fluid
restriction
Renal sodium retent’n
- cirrhosis, CCF
- nephrotic synd.
Sodium in urine
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Vital investigation for sodium abnormalities
Spot urine most useful
Normal range: NOT USEFUL
Decision point: 20 mmol/L
– Only when patient has true hyponatraemia
• Consider effects of salt (RAA) and water (ADH)
• 24 hour urine
– In normals reflects daily intake
– Can be useful for assessing replacement
Hyponatraemia: Important Diagnoses
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Diuretics - History
Renal Failure - creatinine
Addison’s disease - Cortisol, Synacthen test
Hypothyroidism - TFTs
Liver failure - LFTs
Heart Failure – History, BNP
SIADH
SIADH
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True Hyponatramia
Euvolaemic (slight overload)
Urine sodium > 20 mmol/L (RAAS not on)
Urine osmolality > 200 (ADH present)
• No renal, cardiac, liver or adrenal problems
• Response to water restriction
• CNS lesions, lung lesions, cancer
SIADH
Increased ADH
Water retention in
Kidney
Hypervolaemia
(not dehydrated)
Inhibition of RAAS
Urine osmolality high
(>200 mosm/kg)
Hyponatraemia
Urine sodium
> 20 mmol/L
Hypernatraemia
Hypernatraemia diagnosis
“Dehydration until proven otherwise”
1. Exclude artefact (drip arm)
2. Not enough water
– Not enough in
• too sick, old, young, restrained; thirst center lesion
– Too much out
• DI, GIT, renal
3. Too much salt
– Iatrogenic, sea water drowning, Conn’s
Hypernatraemia
Determine state of hydration and
measure urine sodium and osmolality.
Patient Dehydrated
U Na < 10 mmol/L
Inadequate intake (U osmo > 800)
- too young, too old, too sick,
prevented,
oesophageal stricture, thirst centre
damage
Non-renal water loss (Uosmo > 800)
- GI loss, skin loss
Diabetes insipidus with inadequate
fluid
intake (U osmo < 300)
U Na > 20 mmol/L
Renal Sodium loss
- osmotic diuresis (UPO  1)
- diuretics with decreased water intake
- renal disease
Patient Euvolaemic
U osmo < 800
Diabetes insipidus
- central
- nephrogenic
U osmo > 800
Insensible water losses
- lung
- skin
Patient Hypervolaemic
U Na > 20 mmol/L
Salt ingestion (tablets,
sea water, iv
hypertonic saline or
Na Bicarbonate)
Mineralocorticoid
excess syndromes
(only with inadequate
fluid intake)
Polyuria
Polyuria
1. Distinguish from urinary frequency
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Timed collection can be useful
High Urine osmo makes polyuria unlikely
2. Consider causes
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Diabetes mellitus (osmotic)
Drugs: Diuretics, lithium
Diabetes insipidus (insufficient ADH)
Psychogenic polydipsia (depressed ADH)
Renal failure (polyuria)
Polyuria investigation
• Urine osmolality
• >400: not present at time of testing
• Approx 300: osmotic, eg diabetes, renal
• <200: Diabetes Insipidus, Psychogenic polydipsia
• Biochemically indistinguishable
• Needs water deprivation test
Laboratory Knowledge
• Laboratory
– Type of assay
– Alternatives (blood gas, osmolality)
– What drip-arm sample look like
• Hyponatraemia
– Interpretation of serum osmolality
– Pseudohyponatraemia, dilutional hyponatraemia
– Importance of drugs
– Requires spot urine Na and osmo
– “Reference intervals” are not required for urine
sodium
• Hypernatraemia usually dehydration
• Polyuria
– Spot urine
– Cannot separate DI and polydipsia
Closing thoughts
• Sodium measurements very common
• Sodium and water must be considered
together
• Diagnosis of disorders requires both clinical
and laboratory investigation
• Drug history and urine samples are vital
• www.sydpath.com.au