Vasopressin Physiology
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Direct answer
Vasopressin, synthesised in the supraoptic (chiefly) and paraventricular nuclei and released from the posterior pituitary, is governed by two inputs of different sensitivity: osmoreceptors trigger release above a plasma osmolality of about 280-285 mOsm/kg (a 1 per cent rise suffices), while baroreceptor unloading requires a larger 5-10 per cent volume fall but drives a far more vigorous response. V2 receptors in collecting duct principal cells raise cAMP and insert aquaporin-2 water channels, permitting urine concentration up to 1200 mOsm/kg; V1a receptors constrict vascular smooth muscle when concentrations climb, as in haemorrhage or shock. Its half-life is 15-20 minutes; deficiency produces central diabetes insipidus, renal unresponsiveness nephrogenic diabetes insipidus, and excess the hyponatraemia of SIADH.
What you must remember
- Anatomy: supraoptic and paraventricular neurons with axons to the posterior pituitary — hence suprasellar surgery and head injury cause central DI.
- Thresholds worth quoting: osmotic release from 280-285 mOsm/kg; thirst from about 290-295; the osmostat is the sensitive controller, the baroreflex the powerful one.
- V2 mechanism: Gs-coupled receptor, adenylate cyclase, protein kinase A, aquaporin-2 vesicle trafficking into the apical membrane — and with chronic stimulation, more aquaporin-2 gene expression; basolateral aquaporin-3 and -4 provide the exit route.
- Medullary partner: vasopressin also increases urea transporters (UT-A) in the inner medulla, maintaining the 1200 mOsm gradient that makes concentration possible.
- Central DI: polyuria over 3 L/day, urine osmolality under 300 (often under 100) mOsm/kg, dilute urine despite dehydration; causes include craniopharyngioma, pituitary surgery, trauma; responds to desmopressin.
- Nephrogenic DI: the kidney is deaf — lithium (the commonest acquired cause) and V2 receptor mutations (X-linked); desmopressin does not work; thiazides paradoxically help by volume contraction.
- SIADH: plasma sodium under 135 with hypo-osmolality, inappropriately concentrated urine (over 100 mOsm/kg) and urine sodium over 40 mmol/L in a euvolaemic patient; small-cell lung cancer, CNS disease, carbamazepine and SSRIs lead the lists; treat with fluid restriction, with hypertonic saline for seizures.
- Non-osmotic supremacy: in severe hypovolaemia, vasopressin defends volume even at the cost of osmolality — the reason hypovolaemic hyponatraemia exists at all.
A worked case: sodium 118 in a smoker
A 68-year-old smoker with a cough is brought in confused; sodium is 118 mmol/L, plasma osmolality 240, urine osmolality 420 mOsm/kg, urine sodium 55 mmol/L, and examination shows euvolaemia with normal urea and creatinine. The logic tightens like a vice: hypo-osmolal hyponatraemia with an inappropriately concentrated urine and high urinary sodium means vasopressin is acting on a kidney that should be diluting — SIADH, and the chest X-ray small-cell carcinoma makes the cause. Fluid restriction and, if seizures demand it, cautious hypertonic saline follow; correcting sodium no faster than 8-10 mmol/L per day protects the pons from osmotic demyelination. The contrast case is the same sodium after a marathon with vomitting and volume loss: vasopressin is high there too, but appropriately — the kidney conserving volume for a depleted body — and the treatment is saline, not restriction. Same hormone, same low sodium, opposite logic.
High-yield viva angles
The water deprivation test with a desmopressin phase is the classic differentiator of polyuria: urine osmolality rising above 50 per cent after desmopressin means central DI; no rise means nephrogenic; a flat dilute curve throughout with low baseline vasopressin suggests primary polydipsia. Expect the sensitivity comparison next: a 1 per cent osmolality change moves vasopressin, but 7-10 per cent volume loss is needed for the baroreflex arm — though the latter reaches far higher plasma concentrations. Finally, copeptin (the C-terminal fragment released equimolarly) is supplanting immunoassay vasopressin in modern practice as the stable measurable surrogate.
Frequently asked questions
Where is vasopressin synthesised and stored?
In the supraoptic and paraventricular nuclei of the hypothalamus, transported down axons and stored in posterior pituitary terminals for release.
What plasma osmolality triggers vasopressin release and thirst?
Release begins near 280-285 mOsm/kg (a rise of about 1 per cent), and thirst is engaged around 290-295 mOsm/kg.
How does vasopressin concentrate urine?
V2 receptors raise cAMP in collecting duct principal cells, inserting aquaporin-2 channels apically so water re-enters the medullary interstitium; urea transporter recruitment sustains the gradient.
Why does lithium cause polyuria?
It enters principal cells through epithelial sodium channels and downregulates aquaporin-2, producing nephrogenic diabetes insipidus in which desmopressin is ineffective.
What four features define SIADH?
Hypo-osmolal hyponatraemia, inappropriately concentrated urine (osmolality above 100 mOsm/kg), urine sodium above 40 mmol/L, and clinical euvolaemia with normal renal, adrenal and thyroid function.