A 55-year-old man on long-term lithium therapy develops polyuria of 7 litres per day with serum sodium of 148 mEq/L. Urine osmolality is 110 mOsm/kg and does not respond to desmopressin. What is the underlying mechanism?
- A Destruction of the hypothalamic cells that synthesize vasopressin
- B Downregulation of aquaporin-2 channels in the collecting duct ✓
- C Impaired sodium chloride reabsorption in the thick ascending limb
- D Resistance of the collecting duct to aldosterone
Correct answer: B. Downregulation of aquaporin-2 channels in the collecting duct
Explanation
Lithium enters principal cells through ENaC and reduces expression and apical trafficking of aquaporin-2 water channels in the collecting duct, producing nephrogenic diabetes insipidus that does not respond to vasopressin. Desmopressin fails because the defect is downstream of the vasopressin receptor. Amiloride works by blocking ENaC entry of lithium into principal cells and is the preferred agent.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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