Transcript RENAL FUNCTION

Water distribution
Intracellular 28L
(66%)
Extracellular 14L
(33%)
Interstitial
10.5 L
(25%)
Cell membrane
Osmotic pressure
Osmi (K+) = Osmo (Na+)
Plasma
3.5 L
(8%)
Capillary wall
Colloid osmotic pressure
(albumin)
vs.
Hydrostatic pressure
Water Balance
INTAKE
OUTPUT
Unregulated: food & social drink
Insensible and obligate loss
Regulated:
AVP modulated water output
thirst
Thirst

Hyperosmolar stimulus



Hypovolaemic stimulus




hypothalamic osmoreceptors
threshold 1 to 4% above basal
baroreceptors
threshold 10 - 15%
? absent in man (inconvenient with postural change!)
Normally inactive as unregulated input is in excess
AVP secretion

Synthesized in hypothalamic supraoptic and paraventricular nuclei

Stored and released from posterior pituitary (> 1 week store!)

Interacts via V2 receptors to insert aquaporin-2 water channels
AVP secretion - stimulation

Osmolar threshold within ‘normal range’

High ‘gain’ (i.e steep curve and high renal sensitivity)
100
Plasma AVP (pmol/L)
8
Subjective thirst (analogue scale)
10
BASAL
6
4
2
0
270
280
290
300
Plasm a osm olality (m Osm /Kg)
0
310
AVP secretion - stimulation

Osmotic stimulus
high sensitivity

Hypovolaemic stimulus
high threshold (>10% depletion)
AVP secretion - stimulation

Osmotic stimulus
high sensitivity

Hypovolaemic stimulus
high threshold (>10%)

Nausea
most powerful known stimulus

Stress
e.g. post-operative

Drugs
‘SIADH’
Integration of thirst and AVP

Unregulated water intake supplies water in excess of need

Excess water is excreted

AVP secretion regulates free water clearance

AVP maintains osmolality within narrow limits

This avoids ‘inconvenient’ thirst and water-seeking behaviour

Thirst kicks-in when deficiency reaches harmful levels
Renin-aldosterone system
Renin - aldosterone system
Low arterial
pressure
Low sodium
intake
Carotid sinus
Low renal
Blood flow
Renin
KIDNEY
Juxtaglomerular
apparatus
Renin substrate
Angiotensin I
(inactive)
Vasoconstriction
Angiotensin II
Thirst
Increased perfusion pressure
Renal sodium &
water retention
Aldosterone
High K+
Causes of hyponatraemia
HYPONATRAEMIA
Pseudohyponatraemia
YES
Lipaemia / hyperproteinaemia ?
NO
Compensatory
hyponatraemia
YES
Hyperglycaemia ?
NO
Volume
depleted
UNa
Rx
Volume
expanded
Total body water
Renal
loss
Extra-renal
loss
No oedema
Oedema
Diuretics
Addison’s
Vomiting
Diarrhoea
SIADH
Hypothyroid
>20
<10
>20
Nephrotic
Cirrhosis
CCF
<10
Normal saline
Fluid restriction
Pseudohyponatraemia
ADH
Aldosterone
Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+ Na+Na+
K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+
Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- ClHCO3- HCO3- HCO3- HCO3- HCO3- HCO3- HCO3- HCO3Measured sodium concentration 140 mmol/L
Pseudohyponatraemia
ADH
Aldosterone
Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+ Na+Na+
K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+
Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- ClHCO3- HCO3- HCO3- HCO3- HCO3- HCO3- HCO3- HCO3Measured sodium concentration 120 mmol/L
Osmolality (solute concentration in water) normal
Case
A 17-year old woman was seen in outpatients with a two
month history of increasing lethargy and giddiness. She was
found to be hyperpigmented and had postural hypotension
Serum
Sodium
Potassium
Urea
Creatinine
132
5.4
8.5
101
mmol/L
mmol/L
mmol/L
umol/L
Ref range
133 – 143
3.6 – 4.6
3.0 – 7.0
55 - 110
Case

A 66-year old man was admitted for investigation of possible
bronchogenic carcinoma
Serum
Sodium
Potassium
Urea
121
4.1
4.4
mmol/L
mmol/L
mmol/L
Ref range
133 – 143
3.6 – 4.6
3.0 – 7.0
SIADH - pathogenesis

Inappropriately high AVP levels

Ongoing (unregulated) water intake

Blood volume rises

>10% expansion inhibits aldosterone and triggers natriuresis
Syndrome of Inappropriate ADH
Bartter and Schwartz criteria (1967)

hyponatraemia with hypotonicity of plasma

urine osmolality inappropriately high

ongoing renal sodium excretion

absence of oedema or volume depletion

normal renal and adrenal function
i.e. Clinically normovolaemic hyponatraemia
Syndrome of Inappropriate ADH
Symptoms relate to rate of fall as well as severity
Sodium <120 mmol/L
 Lethargy
 Anorexia
 Nausea and vomiting
 Irritability
 Headache
 Muscle weaknes
 Cramps
Sodium <110 mmol/L

Drowsiness

Confusion

Depressed reflexes
 Extensor plantar responses

Seizures

Coma

Death
No oedema because water distributed in both compartments
Causes of SIADH
Neoplasia

Carcinoma of
lung, pancreas,
bladder

Leukaemia

Thymoma

Lymphoma

Sarcoma

Mesothelioma
Lung disease

Pneumonia

TB

Pneumothorax

Asthma

IPPV
Neurological disorders

Meningitis

Encephalitis

Brain tumour

Subarachnoid haemorrhage

Cerebral and cerebellar
atrophy

Guillain-Barré syndrome

Acute intermittent porphyria

Shy-Drager syndrome

Head injury
Causes of SIADH
Drugs

Vasopressin

Oxytocin

Vinca alkaloids

Cisplatin

Chlorpropamide

Carbamazepine

Phenothiazines

Thiazides

MAOI’s
 SSRI’s

Tricyclics

Nicotine

Ecstacy
Miscellaneous

Acute psychosis

Post-operative state

AIDS

Glucocorticoid deficiency

Severe hypothyroidism

Idiopathic
Patterns of AVP release in SIADH
Diagnosis of SIADH


Essential criteria

True plasma hypo-osmolality (<275 mOsm/Kg)

Inappropriate urine osmolality (>~100 mOsm/Kg)

Euvolaemia; no oedema, ascites or intravascular hypovolaemia

Urine sodium not low (>30 mmol/L during normal intake)

Normal renal, adrenal, and thyroid function
Supplemental criteria



Low serum urea and urate
Unable to excrete >80% of water load (20mL/Kg) in 4h and/or failure
to achieve urine osmolality <100 mOsm/Kg
No significant rise in serum [Na] after volume expansion but
improvement with fluid restriction
Treatment of SIADH

Identification and treatment of underlying cause

Clearance of excess water

not necessary in asymptomatic chronic hyponatraemia

fluid restriction to 500 - 1000 mL/24h

Demeclocycline


600 to 1,200 mg daily

may take three weeks to reach maximal effect

caution in renal or hepatic insufficiency
Specific V2 receptor antagonists (OPC-31260)
Treatment of SIADH

Hypertonic saline

Only if significantly symptomatic

Calculate sodium required
Na+ req. (mmol) = (125 – [Na+]) x 0.6 x body weight (kg)

Also measure and re-infuse urinary sodium output

Rate of increase not usually >0.5 mmol/L/h

? combine with i.v. furosemide

Stop saline when sodium reaches 120 - 125 mmol/L
Other causes of euvolameic
hyponatraemia

Psychogenic hyponatraemia



Beer-drinker’s potomania


High volume low solute drinks impair ability to excrete water
Hypothyroidism


Massive water intake (20 - 30 L/day)
Urine osmolality <100 mOsm/kg
Reset osmostat
Pure glucocorticoid deficiency

Cortisol is required for renal free water excretion
Cerebral salt wasting
SIADH

1º increase in AVP
 Inappropriate urine hyperosm.

Volume-expansion

Suppressed aldosterone

Appropriate natriuresis

Decreased urea and urate
CSW

Cerebral damage

Reduced SNS efferents +/- BNP

Inappropriate natriuresis

Volume-depletion
 Volume mediated AVP release

Appropriate urine hyperosm.
Treatment: fluid restriction
Treatment: Normal saline infusion
Case 4

A 53-year old bachelor was brought to the A&E department having
been found semi-comatose. He was known to be a heavy drinker of
alcohol. On examination he was jaundiced. His abdomen was
distended; there was hepatomegaly and evidence of ascites. He
had ankle oedema.
Serum
Creatinine
Urea
Sodium
Potassium
Bilirubin
Alk phos
ALT
Albumin
Total protein
Globulin
84
10.0
111
4.9
µmol/L
mmol/L
mmol/L
mmol/L
Ref range
75 – 120
3.0 – 7.0
133 – 143
3.6 – 4.6
166
175
450
24
72
48
µmol/L
U/L
U/L
g/L
g/L
g/L
< 17
21 - 92
5 – 40
35 – 55
62 – 80
22 - 36