A patient with syndrome of inappropriate ADH secretion (SIADH) has serum Na⁺ 118 mEq/L, serum osmolality 245 mOsm/kg, urine Na⁺ 65 mEq/L, and urine osmolality 520 mOsm/kg. Which statement correctly identifies the key physiological defect?

• A Persistent ADH activity maintains aquaporin-2 in collecting duct apical membranes, enabling continued water reabsorption despite hypoosmolality; the kidney appropriately reabsorbs Na⁺ (high urine Na⁺ reflects normovolaemia-mediated ANP/suppression of aldosterone, not Na⁺ wasting) ✓
• B ADH excess causes primary renal Na⁺ reabsorption in the thick ascending limb, increasing urine Na⁺ concentration as a direct mineralocorticoid-like effect
• C The high urine Na⁺ indicates that the collecting duct is impermeable to Na⁺ in the presence of ADH, so Na⁺ is excreted instead of reabsorbed
• D SIADH involves reset osmostat where osmoreceptors are reset to a lower threshold; the patient's kidneys appropriately respond to the lower set-point, maintaining hyponatraemia at a new equilibrium without continued ADH secretion

Explanation

In SIADH, non-suppressible ADH continuously inserts AQP2 into collecting duct apical membranes, allowing excessive free water reabsorption despite low plasma osmolality (which should suppress ADH). The resulting water retention expands ECF volume; this volume expansion suppresses aldosterone (via ANP-mediated and stretch-mediated mechanisms) and stimulates natriuresis—hence the high urine Na⁺ (>40 mEq/L). The patient is euvolaemic or mildly expanded, not Na⁺-deplete. ADH itself has no direct mineralocorticoid effect on the TAL. Option D describes reset osmostat (a separate variant of SIADH), which would not show an inappropriately concentrated urine at this degree of hypo-osmolality.

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

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