A 60-year-old woman on lithium for bipolar disorder presents with polyuria, serum Na+ 150 mEq/L, and urine osmolality of 180 mOsm/kg that fails to increase after desmopressin. The collecting duct principal cells are unresponsive to ADH. Which signaling component is most likely disrupted by lithium?
- A V2 receptor binding of ADH
- B Na+/K+-ATPase activity in the basolateral membrane
- C Glycogen synthase kinase-3beta (GSK-3beta) inhibition and AQP2 transcription ✓
- D Urea transporter UT-A1 in the inner medullary collecting duct
Correct answer: C. Glycogen synthase kinase-3beta (GSK-3beta) inhibition and AQP2 transcription
Explanation
Lithium enters principal cells via ENaC, accumulates, and inhibits GSK-3beta and adenylyl cyclase, impairing AQP2 synthesis and trafficking. This causes nephrogenic diabetes insipidus unresponsive to exogenous ADH. Lithium does not block V2 receptor binding directly, nor does it primarily impair UT-A1 or Na+/K+-ATPase.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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