Loop of Henle - Renal Tubule Transport Mechanisms

LOOP OF HENLE

At the boundary between the inner and outer stripes of the outer medulla, the proximal tubule empties into the thin descending limb of Henle’s loop. Water is extracted from the descending limb of this loop by osmotic forces found in the hypertonic medullary interstitium. As in the proximal tubule, impermeant luminal sol-utes such as mannitol oppose this water extraction and thus have aquaretic activity. The thin ascending limb is relatively water-im-permeable but is permeable to some solutes.

The thick ascending limb (TAL), which follows the thin limb of Henle’s loop, actively reabsorbs NaCl from the lumen (about 25% of the filtered sodium), but unlike the proximal tubule and the thin descending limb of Henle’s loop, it is nearly impermeable to water.

Salt reabsorption in the TAL therefore dilutes the tubular fluid, and it is called a diluting segment. Medullary portions of the TAL contrib-ute to medullary hypertonicity and thereby also play an important role in concentration of urine by the collecting duct.

The NaCl transport system in the luminal membrane of the TAL is a Na⁺/K⁺/2Cl⁻ cotransporter (called NKCC2 or NK2CL) (Figure 15–3). This transporter is selectively blocked by diuretic agents known as “loop” diuretics. Although the Na⁺/K⁺/2Cl⁻ transporter is itself electrically neutral (two cations and two anions are cotransported), the action of the transporter contrib-utes to excess K⁺ accumulation within the cell. Back diffusion of this K⁺ into the tubular lumen causes a lumen-positive electrical poten-tial that provides the driving force for reabsorption of cations— including magnesium and calcium—via the paracellular pathway. Thus, inhibition of salt transport in the TAL by loop diuretics, which reduces the lumen-positive potential, causes an increase in urinary excretion of divalent cations in addition to NaCl.