A 28-year-old woman on long-term lithium for bipolar disorder presents with polyuria producing 5 litres of urine per day, polydipsia, and a urine specific gravity of 1.001. Serum sodium is 148 mEq/L. Which mechanism explains this presentation?

• A Lithium causes central diabetes insipidus by suppressing ADH secretion from the hypothalamus
• B Lithium causes nephrogenic diabetes insipidus by impairing ADH-mediated aquaporin-2 expression in the collecting duct ✓
• C Lithium causes osmotic diuresis by increasing the glomerular filtration rate
• D Lithium blocks the renal Na-K-ATPase, leading to sodium loss and compensatory water diuresis

Explanation

Chronic lithium therapy causes nephrogenic diabetes insipidus by downregulating aquaporin-2 water channels in the renal collecting duct. Lithium enters principal cells via epithelial sodium channels (ENaC) and inhibits adenylyl cyclase, reducing cAMP formation in response to ADH at V2 receptors, thereby impairing water reabsorption. ADH levels are normal or elevated, differentiating it from central DI. Amiloride, by blocking ENaC, reduces lithium entry into tubular cells and is the preferred management for lithium-induced nephrogenic DI.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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