# Vasopressin Physiology > Vasopressin (ADH) physiology in MBBS Physiology: osmotic thresholds, V1 and V2 receptors, aquaporin-2, diabetes insipidus and SIADH with case reasoning. - Canonical URL: https://prepelephant.com/topics/mbbs/physiology/vasopressin-physiology - Exam / course: MBBS · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Vasopressin Physiology", PrepElephant, https://prepelephant.com/topics/mbbs/physiology/vasopressin-physiology ## 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.