Because water cannot leave the thin ascending limb, the interstitium becomes hyperosmotic relative to the luminal contents. Although some of the Cl and Na of the interstitium diffuses back into the nephron at the thin descending limb, the ions are transported out again in the thin ascending limb and distal straight tubule (thick ascending limb). This produces the countercurrent multiplier effect. Thus, the concentration of NaCl in the interstitium gradually increases down the length of the loop of Henle and, consequently, through the thickness of the medulla from the corticomedullary junction to the papilla.
Vasa recta containing descending arterioles and ascending venules act as countercurrent exchangers.
For an understanding of the countercurrent exchange mechanism, it is necessary to resume the description of the renal circulation at the point at which the efferent arteriole leaves the renal corpuscle.
The efferent arterioles of the renal corpuscles of most of the cortex branch to form the capillary network that surrounds the tubular portions of the nephron in the cortex, the peritubular capillary network. The efferent arterioles of the juxtamedullary renal corpuscles form several unbranched arterioles that descend into the medullary pyramid. These arteriolae rectae make a hairpin turn deep in the medullary regulated by antidiuretic hormone (ADH, vasopressin), a hormone produced in the hypothalamus and released from the posterior lobe of the pituitary gland. ADH increases the permeability of the collecting duct to water, thereby producing more-concentrated urine. At the molecu-lar level, ADH acts on ADH-regulated water channels, aqua-porin 2 (AQP-2), located in the epithelium of the terminal portion of the distal convoluted tubule and in the epithelium of the collecting tubules and ducts. However, the action of ADH is more significant in the collecting tubules and collect-ing ducts. ADH binds to receptors on the cells of these tubules and triggers the following actions:  Translocation of the AQP-2–containing intracyto-plasmic vesicles into the apical cell surface—a short-term effect. This results in an increased number of available AQP-2 channels at the cell surface, thus increas-ing water permeability of the epithelium.  Synthesis of AQPs-2 and their insertion into the apical cell membrane—a long-term effect volume stimulates release of ADH, as does nicotine. In the absence of ADH, copious, dilute urine is produced. This condition is called central diabetes insipidus (CDI). Recent studies indicate that mutation of two genes encoding AQP-2 and ADH receptors is responsible for a form of CDI called nephrogenic diabetes insipidus. In this disease, the kidney does not respond to ADH because of defective AQP-2 and ADH receptor proteins synthesized by the col-lecting tubule and duct epithelial cells. Excess water con-sumption can also inhibit ADH release, thereby promoting the production of a large volume of hyposmotic urine. Increased secretion of ADH can produce an extremely hyperosmotic urine, thereby conserving water in the body. Inadequate consumption of water or loss of water because of sweating, vomiting, or diarrhea stimulates release of ADH. This leads to an increase in the permeability of the epithelium of the distal and collecting tubules and pro-motes the production of a small volume of hyperosmotic urine.
 FOLDER 20.6 Functional Considerations: Hormonal Regulation of Collecting Duct Function