A patient with syndrome of inappropriate antidiuretic hormone secretion (SIADH) has: serum Na+ 118 mEq/L, serum osmolality 245 mOsm/kg, urine osmolality 620 mOsm/kg, urine Na+ 55 mEq/L. The mechanism by which excess ADH causes hyponatremia despite relatively high urine sodium excretion is:

• A ADH (via V2 receptors and aquaporin-2 insertion) causes free water retention; expanded ECF volume suppresses aldosterone and stimulates ANP, causing natriuresis that further dilutes serum sodium without correcting the water excess ✓
• B ADH stimulates proximal tubular sodium reabsorption, causing dilutional water retention
• C ADH directly inhibits Na-K-ATPase in the collecting duct, causing sodium loss into urine
• D Inappropriately concentrated urine traps sodium in the tubular lumen, preventing reabsorption

Explanation

SIADH: ADH acts via V2 receptors on collecting duct principal cells, activating adenylyl cyclase → cAMP → PKA → AQP2 phosphorylation and insertion into apical membrane → free water reabsorption. Water retention expands ECF volume. Volume expansion (1) suppresses the RAAS (reduced aldosterone → reduced Na reabsorption in collecting duct); (2) stretches atrial walls releasing ANP, which promotes sodium excretion; (3) increases GFR (volume expansion → increased filtered sodium load). The net result is a euvolemic or mildly hypervolemic patient with appropriately high urine sodium excretion and diluted serum — the urine sodium is high not due to ADH but due to these secondary volume-responsive mechanisms. This is why SIADH urine Na+ >20-40 mEq/L despite hyponatremia.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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