An 82-year-old woman started on chlorthalidone three weeks ago presents with confusion. Serum sodium is 118 mEq/L, urine osmolality is high, and urine sodium is elevated. Her euvolemic state and the timing suggest drug-induced hyponatremia. The primary mechanism is:

• A Inhibition of sodium chloride reabsorption in the medullary thick ascending limb with loss of the corticomedullary gradient
• B Osmotic diuresis obligating water excretion greater than sodium excretion
• C Primary stimulation of thirst centers causing compulsive water drinking
• D Impaired diluting capacity of the distal nephron combined with persistent vasopressin action, producing retention of free water disproportionate to solute loss ✓

Explanation

Thiazides act on the cortical diluting segment, so the kidney cannot generate maximally dilute urine even when water intake is high. Natriuresis causes mild hypovolemia that stimulates vasopressin release, adding water retention on top of impaired water excretion. Elderly women are the classic demographic. Loop diuretics spare the diluting defect partly because they preserve some diluting capacity relative to their strong natriuresis, which is why they rarely cause severe hyponatremia by comparison.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.