Fluid leaving the proximal tubule is isosmotic to plasma. However, the excretion of an isosmotic urine is usually not adequate to meet the homeostatic requirements of the body. After a water load, for example, water must be excreted in excess of solute. This requires the excretion of urine that is hypoosmotic to plasma. Conversely, water must be retained and a hyperosmotic urine excreted after a period of water restriction. The formation of a dilute (hypoosmotic to plasma) or concentrated (hyperosmotic to plasma) urine is achieved via the countercurrent mechanism, which includes the loops of Henle, the cortical and medullary collecting tubules, and the blood supply to these segments.
Before discussing these processes in detail, it is useful to summarize their basic aspects. The excretion of a concentrated urine involves two major steps:
●The medullary interstitium is made hyperosmotic by the reabsorption of NaCl without water in the medullary ascending limb of the loop of Henle. Urea entry into the interstitium from the medullary collecting tubule also contributes to this process.
●As the urine enters the medullary collecting tubule, it equilibrates osmotically with the interstitium, resulting in the formation of a concentrated urine. Antidiuretic hormone (ADH), released from the posterior pituitary, plays an essential role in this process by increasing collecting tubule permeability to water, which is very low in the basal state. ADH appears to act by inserting aquaporin-2 water channels into the luminal membrane, thereby allowing transcellular water reabsorption to occur down an osmotic gradient. (See "Chapter 6B: Antidiuretic hormone and water balance".)
In addition, two modifying factors are important for the maintenance of medullary hyperosmolality: