Which segment of the nephron is responsible for the generation of 'free water' (electrolyte-free water) for urinary dilution, and what is the transport mechanism?
- A The medullary and cortical thick ascending limb of Henle (TAL), which actively reabsorbs Na⁺, K⁺, and Cl⁻ via NKCC2 but is impermeable to water, diluting tubular fluid to <100 mOsm/kg — generating solute-free (free) water in the tubular lumen ✓
- B The proximal convoluted tubule, which reabsorbs glucose, amino acids, and Na⁺ in excess of water, generating dilute filtrate
- C The collecting duct in the absence of ADH, which actively secretes Na⁺ while retaining water, generating free water in the collecting duct lumen
- D The descending thin limb of Henle, which is highly permeable to NaCl but impermeable to water, concentrating tubular fluid and generating a diluting gradient
Explanation
Free water clearance requires generating hypo-osmotic tubular fluid. The TAL actively transports NaCl (via apical NKCC2 cotransporter, furosemide-sensitive) but is water-impermeable because it lacks constitutive aquaporins. This solute reabsorption without water progressively dilutes tubular fluid from ~300 mOsm/kg at the TAL entry to ~100 mOsm/kg at the macula densa. This segment is therefore the 'diluting segment' — the source of free water. In the absence of ADH, the collecting duct remains impermeable to water and the dilute fluid is excreted (maximum dilution ~50 mOsm/kg). Furosemide inhibits NKCC2 and thereby impairs free water generation, causing isosthenuria.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.