Porth's Essentials of Pathophysiology, 4e

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Structure and Function of the Kidney

C h a p t e r 2 4

Concentrates Urine

Action of ADH. Antidiuretic hor- mone, also known as vasopressin, acts at the level of the collecting tubule to increase water absorp- tion. It exerts its action by bind- ing to vasopressin receptors on the basolateral membrane of the tubu- lar cell. Binding of ADH to the vasopressin receptors causes water channels ( aquaporin-2 channels ) to move into the luminal side of the cell membrane, which is normally impermeable to water. Insertion of the channels allows water from the tubular fluids to move into the tubu- lar cell and then out into the sur- rounding hyperosmotic interstitial fluid on the basolateral side of the cell. From there it moves into the peritubular capillaries for return to the circulatory system. Thus, when ADH is present, the water that moved from the blood into the urine filtrate in the glomeruli is returned to the circulatory system, and when ADH is absent, the water is excreted in the urine. 3

Basolateral membrane

Luminal membrane

Peritubular capillary

Collecting duct epithelium

Blood

Tubular urine

Vasopressin receptor

Cyclic AMP

Aquaporin-2 channels

ADH

ATP

H 2 O

H 2 O

H 2 O

H 2 O

Interstitial fluid

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constriction of the afferent and efferent arterioles and thus a decrease in renal blood flow. Intense sympathetic stimulation such as occurs in shock and trauma can pro- duce marked decreases in renal blood flow and GFR, even causing blood flow to cease altogether. Several humoral substances, including angiotensin II, ADH, and the endothelins, produce vasoconstriction of renal vessels. The endothelins are a group of peptides released from damaged endothelial cells in the kid- ney and other tissues. Although not thought to be an important regulator of renal blood flow during everyday activities, endothelin I may play a role in the reduction of blood flow in conditions such as postischemic renal failure (see Chapter 26). Other substances such as dopamine, nitric oxide, and prostaglandins (i.e., E 2 and I 2 ) produce vasodi- lation. Nitric oxide, a vasodilator produced by the vascular endothelium, appears to be important in pre- venting excessive vasoconstriction of renal blood vessels and allowing normal excretion of sodium and water. Prostaglandins are a group of mediators of cell func- tion that are produced locally and exert their effects

locally. Prostaglandins do not appear to play a major role in regulating renal blood flow and GFR under normal conditions, but may protect the kidneys against the vasoconstricting effects of sympathetic stimulation and angiotensin II. This effect is important because it prevents severe and potentially harmful vasoconstric- tion and ischemia during conditions such as hemorrhage and shock. Aspirin and other nonsteroidal anti-inflam- matory drugs (NSAIDs) that inhibit prostaglandin syn- thesis may decrease renal blood flow and GFR under certain conditions. Autoregulatory Mechanisms The constancy of blood flow through body tissues is maintained by a process called autoregulation. In most tissues other than the kidneys, autoregulation functions to maintain blood flow at a level consistent with the metabolic needs of the tissues. In the kidney, autoregula- tion of blood flow also functions to maintain a relatively constant GFR and to allow for the precise regulation of solute and water excretion.