A 58-year-old woman on lithium carbonate for bipolar disorder for 9 years reports polyuria of 6 litres daily and polydipsia. Serum sodium 146 mEq/L, urine osmolality 110 mOsm/kg which does not rise after desmopressin administration. The mechanism responsible is:

• A Autoimmune destruction of ADH-secreting neurons
• B Downregulation of aquaporin-2 water channels in collecting ducts ✓
• C Impaired medullary concentration gradient from protein wasting
• D Activation of V2 receptors with rebound tachyphylaxis

Explanation

Lithium enters principal cells through ENaC and inhibits glycogen synthase kinase-3 beta signalling, reducing expression and apical trafficking of aquaporin-2 channels so the collecting duct cannot respond to ADH, producing nephrogenic diabetes insipidus. Failure to concentrate urine after desmopressin confirms the renal defect. Central DI would respond briskly to desmopressin, and impaired medullary gradient describes sickle cell or analgesic nephropathy rather than lithium injury.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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