The countercurrent multiplier system in the loop of Henle generates the renal medullary osmotic gradient. Which of the following mechanisms is MOST important for maintaining the papillary tip interstitial osmolality of approximately 1200 mOsm/kg?

• A Active NaCl reabsorption in the thick ascending limb without water permeability, progressively concentrating the medullary interstitium in a countercurrent fashion; urea recycling from collecting duct amplifies the gradient in the inner medulla ✓
• B Active water secretion by thin descending limb into the medullary interstitium driven by aquaporin-1
• C Active transport of urea from medullary interstitium into thin ascending limb maintains urea concentration gradient
• D Vasa recta actively pump NaCl from blood into the interstitium to build the gradient

Explanation

The countercurrent multiplier operates through active transport of NaCl by NKCC2 cotransporters in the thick ascending limb (TAL) of Henle, which is water-impermeable. NaCl exits into the medullary interstitium while water cannot follow, progressively raising medullary osmolality. Urea recycling is critical for the inner medulla: ADH-stimulated urea transporters (UT-A1/UT-A3) in the inner medullary collecting duct allow urea to enter the interstitium; urea then enters the thin descending limb of Henle via UT-A2, recycling back to the TAL, amplifying the papillary gradient. Together, NaCl (outer medulla) and urea (inner medulla) account for the ~1200 mOsm/kg papillary osmolality. Water follows the osmotic gradient passively from the thin descending limb; the vasa recta are passive countercurrent exchangers, not active pumps.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.