A patient with SIADH has serum Na 118 mEq/L, serum osmolality 248 mOsm/kg, urine osmolality 620 mOsm/kg, urine sodium 68 mEq/L, and is euvolemic. Which renal mechanism best explains why these patients retain free water despite low plasma osmolality?
- A Excessive aldosterone increases distal sodium reabsorption, expanding ECF
- B Constitutively active V2 receptors maintain high collecting duct water permeability (AQP2 insertion) independent of plasma osmolality ✓
- C GFR falls due to hyponatremia, reducing water delivery to the collecting duct
- D Baroreceptor-stimulated ADH secretion overrides osmotic suppression
Correct answer: B. Constitutively active V2 receptors maintain high collecting duct water permeability (AQP2 insertion) independent of plasma osmolality
Explanation
In SIADH, ADH (arginine vasopressin) is secreted in excess of what plasma osmolality would normally dictate. ADH binds V2 receptors in the collecting duct principal cells, activating cAMP, which inserts AQP2 water channels into the luminal membrane. This allows continued free water reabsorption despite already-low plasma osmolality. The result is dilutional hyponatremia with inappropriately concentrated urine. Urine Na >40 mEq/L reflects normal natriuresis in response to volume expansion, not sodium wasting.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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