A 46-year-old man with bipolar disorder on lithium carbonate for eight years reports polyuria of 7 litres/day and polydipsia. Serum sodium is 149 mEq/L, urine osmolality is 110 mOsm/kg, and urine osmolality rises by less than 10% after subcutaneous desmopressin. Which mechanism underlies his condition?
- A Autoimmune destruction of hypothalamic vasopressin neurons
- B Mutated V2 receptor preventing cyclic AMP generation
- C Downregulation of aquaporin-2 water channels in the collecting duct ✓
- D Osmotic diuresis from glycosuria induced by lithium
Correct answer: C. Downregulation of aquaporin-2 water channels in the collecting duct
Explanation
Lithium enters principal cells through ENaC and impairs vasopressin signalling, reducing aquaporin-2 expression and apical membrane targeting, producing acquired nephrogenic diabetes insipidus. Failure of urine osmolality to rise after desmopressin proves renal resistance rather than central deficiency. Central diabetes insipidus responds briskly to desmopressin, and congenital V2 receptor mutation presents in childhood, not after years of lithium therapy.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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