loop of Henle

The loop of Henle consists of a thin descending limb, thin ascending limb, and thick ascending limb (TAL). The descending limb is highly permeable to water (via aquaporin-1) but impermeable to solutes (Na+, Cl-, urea), allowing water reabsorption as filtrate descends into the hyperosmotic medulla, concentrating tubular fluid. The thin and thick ascending limbs are impermeable to water but actively reabsorb Na+, K+, and Cl- (via the Na-K-2Cl cotransporter, NKCC2, in the TAL), diluting the tubular fluid while contributing solute to the medullary interstitium — this is the basis of the countercurrent multiplier that generates the corticomedullary osmotic gradient (up to ~1200 mOsm/kg at the papilla). This gradient is essential for the countercurrent exchange system in the vasa recta and for ADH-mediated water reabsorption in the collecting duct, allowing production of concentrated urine when needed. The TAL also reabsorbs Ca2+ and Mg2+ paracellularly, driven by the lumen-positive potential generated by K+ backleak through ROMK channels. Clinically, loop diuretics (furosemide, bumetanide, torsemide) inhibit NKCC2 in the TAL, causing natriuresis, loss of the medullary concentration gradient (impairing urine concentrating ability), and increased Ca2+ and Mg2+ excretion (unlike thiazides, which increase Ca2+ reabsorption). Bartter syndrome is a genetic disorder mimicking chronic loop diuretic use due to mutations affecting NKCC2, ROMK, or ClC-Kb channels, presenting with hypokalemic metabolic alkalosis, hypercalciuria, and salt wasting. The loop of Henle also plays a role in tubuloglomerular feedback via the macula densa (located at the junction of the TAL and distal convoluted tubule), which senses NaCl delivery and regulates afferent arteriolar tone and renin release.