[excerpt starts]

AVP secretion and thirst are stimulated by the body. NaCl reabsorption is enhanced in several segments of the nephron, with the proximal tubule experiencing the greatest effect. Aldosterone, a hormone produced by the glomerulosa cells of the adrenal cortex, is primarily stimulated by angiotensin II secretion and an increase in plasma K+ concentration. It acts on the kidneys to reduce NaCl excretion by promoting reabsorption in various nephron segments. The aldosterone-sensitive distal nephron (ASDN), which consists of the latter portion of the distal tubule and the collecting duct, is the most affected segment. The thick ascending limb of Henle’s loop and the early portion of the distal tubule also experience some stimulation. Aldosterone sensitivity is determined by the presence of mineralocorticoid receptors and the enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). The mineralocorticoid receptor, which also binds glucocorticoids, requires 11β-HSD2 for aldosterone specificity. This enzyme metabolizes glucocorticoids, preventing them from binding to the mineralocorticoid receptor. The aldosterone-sensitive distal nephron expresses both the mineralocorticoid receptor and 11β-HSD2. In the ASDN, aldosterone increases the abundance and activity of ENaC in the apical membrane of principal cells, facilitating Na+ entry. Na+ extrusion from cells across the basolateral membrane is facilitated by Na+,K+-ATPase, whose abundance is also increased by aldosterone. Consequently, aldosterone promotes the reabsorption of NaCl in distal nephron segments, and reduced levels of aldosterone decrease NaCl reabsorption. Although the ASDN is the primary site of aldosterone action, aldosterone also increases the abundance of the Na+/Cl− symporter in the distal tubule and the Na+/K+/2Cl− symporter in the thick ascending limb of Henle’s loop. Activation of the RAAS, particularly with ECFV depletion, decreases NaCl excretion. Diseases of the adrenal cortex can disrupt aldosterone levels, affecting the ability of the kidneys to maintain Na+ balance and euvolemia. Decreased aldosterone secretion (hypoaldosteronism) reduces NaCl reabsorption, resulting in urinary NaCl loss and negative Na+ balance, leading to decreased ECFV. This prompts increased sympathetic tone and elevated levels of renin, angiotensin II, and AVP. On the other hand, increased aldosterone secretion (hyperaldosteronism) enhances NaCl reabsorption, decreasing NaCl excretion. As a result, ECFV increases, sympathetic tone decreases, and levels of renin, angiotensin II, and AVP decrease. ANP and BNP levels also elevate in this scenario. The RAAS is suppressed during ECFV expansion, leading to enhanced renal NaCl excretion.

[excerpt ends]
stimulation of AVP secretion and thirst 4.
enhancement of NaCl reabsorption by the proximal tubule, thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct (Of these segments the effect on the proximal tubule is quantitatively the largest.) Angiotensin II is an important secretagogue for aldoste rone. An increase in plasma K+ concentration is the other important stimulus for aldosterone secretion (see ). Aldosterone is a steroid hormone produced by the glomerulosa cells of the adrenal cortex and acts in a number of ways on the kidneys (see also
Chapters 34, 36, and ). With regard to regulation of the ECFV, aldosterone reduces NaCl excretion by stimulating its reabsorption by several nephron segments. Most importantly it stimulates NaCl reabsorption in the aldosterone-sensitive distal nephron (ASDN), which consists of the latter portion of the distal tubule and the collecting duct. To a lesser extent it also stimulates NaCl reabsorption by the thick ascending limb of Henle’s loop and the early portion of the distal tubule.
Aldosterone sensitivity is conferred by the presence of mineralocorticoid receptors as well as the enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Because the mineralocorticoid receptor also binds glucocorticoids, 11β-HSD2 is required for aldosterone specificity because it metabolizes glucocorticoids and thus prevents them from binding to the mineralocorticoid receptor. The aldosterone-sensitive distal nephron expresses both the mineralocorticoid receptor and 11β-HSD2.
). In the ASDN it increases the abundance and activity of ENaC in the apical membrane of principal cells. This increases Na+ entry into cells across the apical membrane. Extrusion of Na+ from cells across the basolateral membrane occurs by Na+,K+-ATPase, the abundance of which is also increased by aldosterone. Thus aldosterone increases reabsorption of NaCl from the tubular fluid by distal nephron segments, whereas reduced levels of aldosterone decreases the amount of NaCl reabsorbed by these segments. Although the principal site of action of aldosterone is the ASDN, aldosterone also increases the abundance of the Na+/Cl− symporter in the distal tubule and the Na+/K+/2Cl− symporter in the thick ascending limb of Henle’s loop.
Box 35.1 , activation of the RAAS, as occurs with ECFV depletion, decreases excretion of NaCl
Diseases of the adrenal cortex can alter aldosterone levels and thereby impair the ability of the kidneys to maintain Na+ balance and euvolemia. With decreased secretion of aldosterone (hypoaldosteronism), the reabsorption of NaCl, mainly by the aldosterone-sensitive distal nephron, is reduced and NaCl is lost in the urine. Because urinary NaCl loss can exceed the amount of NaCl ingested in the diet, negative Na+ balance ensues and ECFV decreases. In response to ECFV contraction, sympathetic tone is increased and levels of renin, angiotensin II, and AVP are elevated. With increased aldosterone secretion (hyperaldosteronism) the effects are the opposite; NaCl reabsorption by the aldosterone-sensitive distal nephron is enhanced and excretion of NaCl is reduced. Consequently, ECFV is increased, sympathetic tone is decreased, and levels of renin, angiotensin II, and AVP are decreased. As described later, ANP and BNP levels are also elevated in this setting.
by the kidneys. The RAAS is suppressed with ECFV expansion, and renal NaCl excretion is therefore enhanced.