The balance of water and solute reabsorption rates determines urine osmolarity. Water reabsorption is driven by an osmotic gradient, particularly evident as filtrate passes through tubule segments of the hypertonic renal medulla. Reabsorption and secretion characteristics are specific for each solute and can result from both passive (diffusion) and active transport.

Renal cortex interstitial fluid is isotonic with plasma, around 300 mOsm. Renal medullary interstitial fluid is hypertonic to plasma, up to 1600 mOsm. The accumulation of solute particles in the renal medulla is due to (1) solute reabsorption in the ascending loop of Henle and (2) reabsorption of urea in the inner medullary collecting duct under the influence of ADH. In addition, renal medullary blood flow does not disrupt gradient. This is because the vasa recta allow countercurrent exchange of osmotic particles as blood passes into the medulla and because only 5% of renal blood flow goes to the medulla.

Glomerular ultrafiltrate is isosmotic with plasma. The ultrafiltrate, however, lacks large plasma proteins and blood cells. Proximal tubule filtrate also is isosmotic with plasma. This is because the “leaky” tight junctions allow osmotic movement of water to match the reabsorption of solute (NaHCO3) in this tubule segment. An increase in the number of osmotic particles in proximal tubular filtrate can decrease water reabsorption. Consequently, blockade of HCO3 reabsorption by carbonic anhydrase inhibitors also causes an osmotic diuresis.

The descending limb of the loop of Henle conducts filtrate to the hypertonic renal medulla. The leaky “tight” junctions allow movement of both solute and water. Consequently, filtrate osmolarity is increased as tubular fluid comes into equilibrium with the hypertonic medullary interstitial fluid. In addition, urea enters tubular fluid from the medullary interstitial fluid.

In the thick ascending limb of the loop of Henle, the tight “tight” junctions are impermeable to water. The active Na+, K+, 2 Cl transport. decreases osmolarity to below plasma osmolarity by end of thick limb. Urea becomes the major remaining osmotic particle.

The “tight” tight junctions of the distal tubule and connecting segment allow tubular fluid osmolarity to differ from interstitial fluid osmolarity. Distal tubular fluid osmolarity can fall as low as 100 mOsm owing to selective Na/Cl reabsorption and the absence of water reabsorption.

In the collecting duct, tight junctions remain tight, preventing the paracellular movement of water and solutes. The collecting duct carries fluid through the renal medulla. Transcellular water permeability of the collecting duct is under the control of ADH and determines the final urine osmolarity.ADH stimulates the insertion of water channels— aquaporins—on the collecting duct apical membrane. Consequently, ADH increases water permeability and therefore enhances water reabsorption. ADH also increases urea permeability and reabsorption in the medullary collecting duct.

Medullary interstitial fluid osmolarity sets the upper limit on urine osmolarity around 1600 mOsm. Additional Na/Cl reabsorption from the hypotonic distal tubule filtrate sets the lower limit on urine osmolarity. In the absence of ADH, there is little water reabsorption, so distal tubular filtrate osmolarity (150 mOsm) is further reduced to 100 mOsm by active Na/Cl transport. Excessive ADH stimulates water reabsorption along the entire length of the collecting duct, so urine osmolarity equilibrates with medullary interstitial fluid osmolarity, around 1600 mOsm.