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Disorders of the Thirst Axis

Dr Shamila De SilvaDepartment of Medicine

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Vasopressin (ADH)

aka anti-diuretichormone (ADH)

Controls thirst &water regulation

Acts mainly onkidneys

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Actions of Vasopressin

Stimulate V2 receptors in collecting ductsmakes them permeable to water

Cause re-absoption of hypotonic luminal fluid

Reduce diuresis - retain water

(at high concs vasoconstriction)

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Actions of Vasopressin

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Vasopressin Response toSerum Osmolality

Changes in plasma osmolality sensed byosmoreceptors in hypothalamus

< 280 mOsm/kg (dilute plasma) vasopressinsecretion suppressed maximum waterdiuresis (dilute urine)

At 295 mOsm/kg (concentrated plasma)maximum antidiuresis (concentrated urine)

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Vasopressin Response

to Increasing Serum Osmolality

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Disorders of Vasopressin

Deficiency -

a) cranial diabetes insipidushypothalamic

diseaseb) nephrogenic diabetes insipidusrenal

tubular insensitivity

Excess

Syndrome of Inappropriate Anti-DiureticHormone (SIADH)

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Diabetes Insipidus (DI)

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Symptoms

polyuria (>3L urine/day)

nocturia

compensatory polydipsia

dehydration

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D/D

Diabetes mellitus

Primary (hysterical) polydipsia

Hypokalaemia

Hypercalcaemia

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Causes of Cranial DI

Familial - DIDMOAD

Idiopathicautoimmune

Tumours - hypothalamic InfectionsTB, meningitis, abscess

Infiltrations

Post-surgical

Post-radiotherapy

Vascularhaemorrhage, thrombosis

Trauma

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Causes of Nephrogenic DI

Familial

Idiopathic

Renal disease -RTA

Hypokalaemia

Hypercalcaemia

DrugsLithium, Glibenclamide

Sickle cell disease

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Biochemistry

High / high-normal plasma osmolality

High / high-normal plasma sodium

Low urine osmolality

High 24 hour urine volume

Failure of urine concentration with fluiddeprivation

Restoration of urine concentration withvasopressin / analogue cranial DI

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Water Deprivation Test I

Fasting with no fluids

Monitor serum & urine osmolality, urine volume& weight hourly for 8 hours

Normal serum osmolality normal

urine osmolality high

(primary polydipsia)

DI serum osmolality high / high normal

urine osmolality low

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Water Deprivation Test II

Give Desmopressin (Vasopressin analogue)

Allow fluid intake

Re-check serum & urine osmolality

Cranial DI serum osmolality normal

urine osmolality high (normal response)

Nephrogenic DI -

serum osmolality high / high normal

urine osmolality low (no response)

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Treatment

Cranial DIDesmopressinThiazides

CarbamazepineChlorpropamide

Nephrogenic DI

reverse cause ifpossibleeg correct serum potassium/calcium

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Remember ..

Cortisol deficiency may mask DI

When cortisol is replaced massive water

diuresis if that is due to DI

Mild temporary nephrogenic DI can occurwith prolonged polyuria due to any cause

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Primary Polydipsia

aka hysterical over-drinking

Relatively common psychiatric disturbance

Thirst & polyuria

Plasma osmolality & sodium low, urine dilute

If prolonged reduced renal concentrating ability(renal medullary washout)

Diagnosis - Water Deprivation Test

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Syndrome of Inappropriate

Anti Diuretic Hormone(SIADH)

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Increased ADH

water retention Dilute plasma hyponatraemia

Mild symptoms when s.sodium

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Clinical Features

Confusion

Nausea

Irritability

Fits

Coma NO oedema

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Causes

Tumours smal cell lung CA

Pulmonary lesions pneumoniaTBlung abscess

CNS meningitis SDHtumours cerebral abscesshead injury

Metabolic alcohol withdrawal

Drugs CarbamazepinePhenothiazines

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Diagnostic Criteria

Low serum sodium

dilutional - due to excess water retention

Low plasma osmolality

Inappropriately high urine osmolality

Urinary sodium excretion > 30 mmol/l

NO hypokalaemia or hypotension

Normal renal, adrenal & thyroid function

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D/D

Excess infusion of water/dextrose

Diuretic usethiazide, amiloride

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Treatment

Correct underlying cause

Restrict fluid intake to 500 1000 ml/day

Check weight daily

Measure serum sodium & plasma osmolalityregularly

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Treatment

Demeclocycline

inhibits Vasopressin action on kidney

In severe SIADH hypertonic saline (caution!!)

Correct serum sodium SLOWLY

Vasopressin V2 antagonists (tolvaptan)

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Remember

Hyponatraemia very common during illness infrail elderly patients

May be clinically difficult to distinguish SIADHfrom salt and water depletion

Trial infusion of 1-2 L 0.9% saline- SIADH will not respond

- sodium depletion will respond

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