A 32-year-old woman on lithium for bipolar disorder presents with coarse tremor, polyuria, and vomiting. Serum lithium is 1.9 mEq/L. The mechanism of lithium toxicity is best explained by:
- A Lithium competes with sodium for reabsorption in the proximal tubule; sodium depletion triggers lithium retention and toxicity ✓
- B Lithium competes with potassium at Na+/K+-ATPase, causing intracellular K+ depletion
- C Lithium directly inhibits thyroid peroxidase, causing hypothyroid-induced retention
- D Lithium accumulates by binding to plasma proteins in a saturable manner
Correct answer: A. Lithium competes with sodium for reabsorption in the proximal tubule; sodium depletion triggers lithium retention and toxicity
Explanation
Lithium is handled by the kidney similarly to sodium — it is filtered and partially reabsorbed in the proximal tubule. When sodium is depleted (from diuretics, sweating, vomiting, or salt restriction), the proximal tubule compensates by increasing both sodium and lithium reabsorption, elevating lithium levels dangerously. This is why sodium-depleting states and thiazide diuretics are major causes of lithium toxicity. Lithium is not protein-bound and is renally cleared unchanged.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.