Physiology · Renal, fluids and acid–base

ADH, thirst and water balance !

Regulation
Exam priority: high

The brain senses how concentrated the blood is. If it rises, you get thirsty and ADH tells the kidney to keep water. Blood sodium mirrors that balance.

Updated 2026-11-01

Also called: Vasopressin, Antidiuretic hormone, Osmoregulation

See it in 3D: Hypothalamus · Pituitary gland · Kidneys

What it is

Body water is regulated through plasma osmolality, which depends mostly on sodium. Osmoreceptors in the anterior hypothalamus detect ≈ 1% changes and adjust two outputs: ADH (vasopressin), which makes the kidney reabsorb water, and thirst, which drives drinking. That is why serum sodium is a marker of water, not of total sodium.

How it works, step by step

Water is lost (sweat, breathing, low intake) and plasma osmolality rises.
Osmoreceptor neurons in the anterior hypothalamus (circumventricular organs) shrink and fire.
They drive the supraoptic and paraventricular nuclei: the posterior pituitary releases ADH and thirst appears.
ADH binds the V2 receptor in the collecting duct, cAMP rises and AQP2 channels are inserted into the luminal membrane.
Water leaves the collecting duct toward the hypertonic medulla; urine concentrates and its volume falls.
With what is drunk and what is retained, osmolality returns to normal and ADH falls (negative feedback).

The nephron: segments, transporters and diuretics

Na⁺ reabsorbed ≈ 2–5%Water reabsorbed variable (ADH)

Collecting tubule and duct

What it does: Fine tuning: reabsorbs ≈ 2–5% of Na⁺, secretes K⁺ and H⁺ and reabsorbs water as ADH allows (urine from ≈ 50 to ≈ 1200 mOsm/kg). Principal cells handle Na⁺, K⁺ and water; intercalated cells handle acid–base.
Transporters: Principal: ENaC, ROMK and BK (K⁺ secretion; BK is flow-driven), apical AQP2 (ADH) and basolateral AQP3/4. α-intercalated: H⁺-ATPase and H⁺/K⁺-ATPase (secrete acid). β-intercalated: pendrin (secrete HCO₃⁻). Inner medulla: urea transporters (ADH).
Hormones: Aldosterone (more ENaC, ROMK, Na⁺/K⁺-ATPase and H⁺-ATPase); ADH via the V2 receptor → cAMP → AQP2 insertion; atrial natriuretic peptide curbs Na⁺ reabsorption.
Drugs: ENaC blockers (6) and mineralocorticoid receptor antagonists (7): K⁺-sparing (risk of hyperkalemia). V2 receptor antagonists (8, vaptans): aquaretics.
Disorders: Liddle syndrome (overactive ENaC: hypertension, hypokalemia, low renin and aldosterone); nephrogenic diabetes insipidus (V2 or AQP2, lithium); type 1 distal renal tubular acidosis (H⁺ secretion fails: urine pH > 5.5, hypokalemia, stones) and type 4 (hypoaldosteronism: hyperkalemia); SIADH (excess ADH).

Glomerulus and arterioles
Proximal tubule
Thin descending limb
Thin ascending limb
Thick ascending limb
Distal convoluted tubule
Collecting tubule and duct
Juxtaglomerular apparatus (macula densa)
Cortex
Medulla
Interstitial osmolality (≈ 300 → 1200 mOsm/kg)

Illustrative schematic drawn by Durgical (a long-loop juxtamedullary nephron); proportions and percentages are approximate and not for clinical decisions.

Equations

Calculated plasma osmolalityOsm ≈ 2 × Na⁺ + glucose/18 + BUN/2.8

Na⁺: in mEq/L
glucose, BUN: in mg/dL

Sodium and its anions supply almost all osmolality; urea does not change tonicity because it crosses membranes.

Regulation

+High plasma osmolality: The most sensitive stimulus: releases ADH and causes thirst.
+Hypovolemia or hypotension (baroreceptors): Releases ADH even with low osmolality if the drop is large.
+Angiotensin II: Stimulates thirst and ADH release.
+Nausea, pain, stress, nicotine: Release ADH without an osmotic stimulus.
−Low osmolality or volume expansion: Suppresses ADH: dilute urine (down to ≈ 50 mOsm/kg).
−Alcohol: Inhibits ADH release: water diuresis.

ADH: too little or too much

Situation	ADH	Urine	Plasma sodium
Dehydration	↑ (appropriate)	Concentrated, scant	Normal or ↑
Central diabetes insipidus	↓	Dilute, copious	↑ if not drinking
Nephrogenic diabetes insipidus	↑ (no effect)	Dilute, copious	↑ if not drinking
SIADH	↑ (inappropriate)	Concentrated	↓ with normal volume
Primary polydipsia	↓ (appropriate)	Very dilute	Normal or ↓

Clinical notes

SIADH: hyponatremia with inappropriately concentrated urine (> 100 mOsm/kg), high urine sodium and clinically normal volume.
Diabetes insipidus after pituitary surgery or trauma; the nephrogenic form is linked to lithium, hypercalcemia and hypokalemia.
Correcting chronic hyponatremia too fast can cause osmotic demyelination, because neurons had already adapted.

Test yourself

Think of the answer, then tap the question to see it.

Why can a patient with severe hypovolemia have hyponatremia even when osmolality is already low?

A large fall in circulating volume releases ADH through baroreceptors, overriding the osmotic signal: the kidney retains free water and sodium is diluted.

What physiologically separates central from nephrogenic diabetes insipidus?

In central DI ADH is missing; in nephrogenic DI ADH is high but the collecting duct does not respond (V2 receptor or AQP2). Urine stays dilute in both.

Why does SIADH cause hyponatremia without edema?

Retained water spreads into all compartments and the mild expansion triggers natriuresis (natriuretic peptides, less aldosterone): Na⁺ is lost and extracellular volume stays near normal.

Why doesn't a high urea cause thirst even though measured osmolality rises?

Urea crosses cell membranes, so it does not pull water out of cells or stimulate osmoreceptors: osmolality rises but tonicity does not.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

Serum osmolality and osmolar gap

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 26.2 Water Balance (OpenStax (Rice University), 2022); Syndrome of inappropriate antidiuretic hormone secretion: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Antidiuretic hormone blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 29). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.