Key Points

• The nephron beyond the proximal tubule is specialized to produce urine of variable composition that can be quite different from the plasma. Urine osmolality can vary from 50-1200 mOsm/kg H2O, and the Na+ excreted can vary from nearly zero to 2% of the amount filtered at the glomerulus.

• The thin descending limb of the loop of Henle is surrounded by medullary interstitial fluid, the osmolality of which can be as high as 1200 mOsm/kg H2O in the papilla. Urea contributes approximately one-half of this osmolality, and NaCl contributes approximately one half.

• Due to the presence of aquaporin-1, the thin descending limb of the loop of Henle is very water permeable regardless of the final urine osmolality, but it is less permeable to solutes.

• In contrast to the descending limb, the water permeability of the ascending limb of the loop of Henle is nearly zero regardless of the final urine osmolality. In the thin segment of the ascending limb, NaCl reabsorption is due to passive diffusion from a higher concentration in the tubular fluid to the interstitium. Active reabsorption of NaCl in the thick segment is produced by a cotransporter carrying one Na+, one K+, and two Cl~ ions. The most potent diuretics, such as furosemide, directly block this transporter.

• NaCl reabsorption in the medullary thick ascending limb produces the hypertonicity of the interstitium, but in the cortex the continued active reabsorption of NaCl dilutes the tubular fluid to less than one-half the osmolality of the plasma.

Essential Medical Physiology, Third Edition

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