The fluid that reaches the collecting duct is hypoosmotic compared to the surrounding interstitial fluid because of NaCl reabsorption by the ascending limb of the loop of Henle. This establishes an osmotic gradient across the collecting duct. With the presence of AVP, water permeability increases in the latter portion of the distal tubule and the collecting duct due to the insertion of AQP2 into the luminal membrane of the cells. As a result, water diffuses out of the tubule lumen and the tubule fluid osmolality increases. This diffusion of water initiates the process of urine concentration. The maximum osmolality that the fluid in the distal tubule and cortical portion of the collecting duct can achieve is approximately 290 mOsm/kg H2O, which is the same as the osmolality of the interstitial fluid and plasma within the cortex of the kidney.

As the tubular fluid travels deeper into the medulla, water continues to be reabsorbed from the collecting duct, increasing the tubular fluid osmolality to 1200 mOsm/kg H2O at the tip of the papilla.

When AVP levels are elevated, the urine produced has an osmolality of 1200 mOsm/kg H2O and contains high concentrations of urea and other nonreabsorbed solutes. Under this condition, urine volume can be as low as 0.5 L/day.

Comparing the two described conditions, it is evident that a relatively constant volume of dilute tubular fluid is delivered to the AVP-sensitive parts of the nephron (latter portion of the distal tubule and collecting duct). The amount of water reabsorbed by these segments is determined by plasma AVP levels. When AVP levels are low, these segments reabsorb a relatively small volume of water, resulting in the excretion of a large volume of hypoosmotic urine (up to 10% of the filtered water). Conversely, when AVP levels are high, these segments reabsorb a large volume of water, leading to the excretion of a small volume of hyperosmotic urine (<1% of filtered water). During antidiuresis, most of the water is reabsorbed in the distal tubule and cortical and outer medullary parts of the collecting duct. This allows for a minimal volume of fluid to reach the inner medullary collecting duct, where it is subsequently reabsorbed. By distributing water reabsorption along the length of the collecting duct (i.e., cortex > outer medulla > inner medulla), a hyperosmotic interstitial environment is maintained in the inner medulla, as it minimizes the amount of water entering this compartment.

The medullary interstitial gradient primarily consists of NaCl and urea. The concentrations of NaCl and urea shown in the figure reflect those found in the antidiuretic state (i.e., excretion of hyperosmotic urine). Please refer to the text for further details. The renal medulla's interstitial fluid plays a crucial role in urine concentration. It provides the osmotic pressure necessary for reabsorbing water from both the descending thin limb of the loop of Henle and the collecting duct. The primary solutes in the medullary interstitial fluid are NaCl and urea, although their concentrations are not uniform throughout the medulla (i.e., there is a gradient from cortex to papilla). Other solutes, such as NH4+ and K+, also accumulate in the medullary interstitium, but NaCl and urea are the most abundant solutes. For the sake of simplicity, this discussion focuses on NaCl and urea as the only solutes.
Because of NaCl reabsorption by the ascending limb of the loop of Henle, the fluid reaching the collecting duct is hypoosmotic with respect to the surrounding interstitial fluid. Thus an osmotic gradient is established across the collecting duct. In the presence of AVP, which increases the water permeability of the latter portion of the distal tubule and the collecting duct by causing insertion of AQP2 into the luminal membrane of the cells, water diffuses out of the tubule lumen and the tubule fluid osmolality increases. This diffusion of water out of the lumen of the collecting duct begins the process of urine concentration. The maximum osmolality the fluid in the distal tubule and cortical portion of the collecting duct can attain is approximately 290 mOsm/kg H2O (i.e., the same as plasma), which is the osmolality of the interstitial fluid and plasma within the cortex of the kidney.
6.
As the tubular fluid descends deeper into the medulla, water continues to be reabsorbed from the collecting duct, increasing the tubular fluid osmolality to 1200 mOsm/ kg H2O at the tip of the papilla.
7.
The urine produced when AVP levels are elevated has an osmolality of 1200 mOsm/kg H2O and contains high concentrations of urea and other nonreabsorbed solutes. Urine volume under this condition can be as low as 0.5 L/day.
In comparing the two conditions just described, it should be apparent that a relatively constant volume of dilute tubular fluid is delivered to the AVP-sensitive portions of the nephron (latter portion of the distal tubule and collecting duct). Plasma AVP levels then determine the amount of water reabsorbed by these segments. When AVP levels are low, a relatively small volume of water is reabsorbed by these segments and a large volume of hypoosmotic urine is excreted (up to 10% of the filtered water). When AVP levels are high, a large volume of water is reabsorbed by these same segments and a small volume of hyperosmotic urine is excreted (<1% of filtered water). During antidiuresis, most of the water is reabsorbed in the distal tubule and cortical and outer medullary portions of the collecting duct. Thus a relatively small volume of fluid reaches the inner medullary collecting duct where it is then reabsorbed. This distribution of water reabsorption along the length of the collecting duct (i.e., cortex > outer medulla > inner medulla) allows for maintenance of a hyperosmotic interstitial environment in the inner medulla by minimizing the amount of water entering this compartment.
• Fig. 35.8 The medullary interstitial gradient comprises primarily NaCl and urea. The concentrations for NaCl and urea depicted reflect those found in the antidiuretic state (i.e., excretion of hyperosmotic urine). See text for details. (Adapted from Sands JM et al. Urine concentration and dilution. In: Brenner and Rector’s The Kidney. 9th ed. Philadelphia: Elsevier; 2012.) 100200300400500600Concentration(mmol/L)CortexO termed llaInnerMed llaUreaNacl
As noted earlier, the interstitial fluid of the renal medulla is critically important in concentrating urine. The osmotic pressure of the interstitial fluid provides the driving force for reabsorbing water from both the descending thin limb of the loop of Henle and the collecting duct. The principal solutes of the medullary interstitial fluid are NaCl and urea, but the concentration of these solutes is not uniform throughout the medulla (i.e., a gradient exists from cortex to papilla). Other solutes also accumulate in the medullary interstitium (e.g., NH4 + and K+), but the most abundant solutes are NaCl and urea. For simplicity, this discussion assumes that NaCl and urea are the only solutes.