Sodium reabsorption Aldosterone

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Mineralocorticoids are involved in controlling electtolyte and fluid levels.9,44 The primary mineralo-corticoid produced by the adrenal cortex is aldosterone. Aldosterone increases the reabsorption of sodium from the renal tubules. By increasing sodium reabsorption, aldosterone facilitates the reabsorption of water. Aldosterone also inhibits the renal reabsorption of potassium, thus increasing potassium excretion. Mineralocorticoid release is regulated by fluid and electrolyte levels in the body and by other hormones, such as the renin-angiotensin system. 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure. 

Recall that the reabsorption of Na+ ions is accompanied by reabsorption of Cl- ions, which diffuse down their electrical gradient, and by reabsorption of water, which diffuses down its osmotic gradient. The net result is an expansion of plasma volume and consequently an increase in blood pressure. Therefore, the regulation of sodium reabsorption is important in the long-term regulation of blood pressure. As such, aldosterone and ANP, as well as the factors involved in their release, are discussed further in subsequent sections. 

Sodium is freely filtered at the glomerulus. Therefore, any factor that affects GFR will also affect sodium filtration. As discussed previously, GFR is directly related to RBF. In turn, RBF is determined by blood pressure and the resistance of the afferent arteriole (RBF = AP/R). For example, an increase in blood pressure or a decrease in resistance of the afferent arteriole will increase RBF, GFR, and, consequently, filtration of sodium. The amount of sodium reabsorbed from the tubules is physiologically regulated, primarily by aldosterone and, to a lesser extent, by ANP. Aldosterone promotes reabsorption and ANP inhibits it. The alterations in sodium filtration and sodium reabsorption in response to decreased plasma volume are illustrated in Figure 19.6. 

Widespread vasoconstriction supplements the increase in TPR induced by the sympathetic nervous system. Angiotensin II also causes vasoconstriction of the afferent arteriole in particular, which enhances the decrease in RBF and sodium filtration. Finally, angiotensin II promotes secretion of aldosterone from the adrenal cortex. Aldosterone then acts on the distal tubule and collecting duct to increase sodium reabsorption. 

Therefore, inhibition of ANP release leads to vasoconstriction and increased MAP. Furthermore, less ANP promotes the release of renin and secretion of aldosterone, which further enhance sodium reabsorption. 

Spironolactone and eplerenone block the mineralocorticoid receptor, the target site for aldosterone. In the kidney, aldosterone antagonists inhibit sodium reabsorption and potassium excretion. However, diuretic effects are minimal, suggesting that their therapeutic benefits result from other... 

Sodium reabsorption Much less than 10% of the filtered load of NaCl reaches the distal nephron. Regulation of Na uptake, occurring mainly in the principal cells of the cortical collecting tubule, is controlled by the steroid hormone aldosterone (see Section 4.4). The net effect of aldosterone is the reclamation of NaCl and potassium excretion in to the luminal fluid. 

Amiloride and triamterene-Am or 6e and triamterene not only inhibit sodium reabsorption induced by aldosterone, but they also inhibit basal sodium reabsorption. They are not aldosterone antagonists, but act directly on the renal distal tubule, cortical collecting tubule and collecting duct. They induce a reversal of polarity of the transtubular electrical-potential difference and inhibit active transport of sodium and potassium. Amiloride may inhibit sodium, potassium-ATPase. 

Another major function of the adrenal cortex is the regulation of water and electrolyte metabolism. The principal mineralocorticoid, aldosterone, can increase the rate of sodium reabsorption and potassium excretion severalfold. This will occur physiologically in response to sodium or volume depletion or both. The primary site of... 

Mechanism of Action A potassium-sparing diuretic that interferes with sodium reabsorption by competitively inhibiting the action of aldosterone in the distal tubule, thus promoting sodium and water excretion and increasing potassium retention. Therapeutic Effect Produces diuresis lowers BP diagnostic aid for primary aldosteronism. 

Aldosterone It is a mineralocorticoid. Its actions are retention of sodium and reduction of serum potassium. It acts on distal tubules of kidney to increase sodium reabsorption (details are discussed in chapter Diuretics ... 

Administration of ANP produces prompt and marked increases in sodium excretion and urine flow. Glomerular filtration rate increases, with little or no change in renal blood flow, so that the filtration fraction increases. The ANP-induced natriuresis is due to both the increase in glomerular filtration rate and a decrease in proximal tubular sodium reabsorption. ANP also inhibits the secretion of renin, aldosterone, and vasopressin these changes may also increase sodium and water excretion. Finally, ANP causes vasodilation and decreases arterial blood pressure. Suppression of ANP production or blockade of its action impairs the natriuretic response to volume expansion, and increases blood pressure. 

Aldosterone and other steroids with mineralocorticoid properties promote the reabsorption of sodium from the distal part of the distal convoluted tubule and from the cortical collecting renal tubules, loosely coupled to the excretion of potassium and hydrogen ion. Sodium reabsorption in the sweat and salivary glands, gastrointestinal mucosa, and across cell membranes in general is also increased. Excessive levels of aldosterone produced by tumors or overdosage with synthetic mineralocorticoids lead to hypokalemia, metabolic alkalosis, increased plasma volume, and hypertension. 

Thiazide diuretics such as chlorothiazide (Diuril) and hydrochlorothiazide (HCTZ) work by blocking the action of aldosterone, a hormone that promotes sodium reabsorption by the kidneys. They are potassium-deplet-... 

The adrenal glands are located anatomically above the kidneys. They comprise a three-layer cortex and a medulla. The medulla is the source of catecholamines such as epinephrine, the fight-or-flight hormone. The cortex is the source of aldosterone, the primary mineralocorticoid that is involved in the regulation of sodium reabsorption in the kidneys. In addition, the cortex is also the source of steroids known as glucocorticoids, of which cortisol is the principal endogenous representative. Synthesis and release of cortisol is under the control of adrenocorticotropic hormone (ACTH). 

Spironolactone competes for the mineralocorticoid receptor and thus inhibits sodium reabsorption in the kidney (see p. 232). It can also antagonize aldosterone and testosterone synthesis. It is effective against hyperaldosteronism. The drug is also useful in the treatment of hirsutism in women, probably due to interference at the androgen receptor of the hair follicle. 

Body sodium content is primarily regulated by aldosterone, which stimulates renal reabsorption of sodium. Atrial natriuretic peptide decreases sodium reabsorption by the nephron and increases its excretion in urine. 

The reduced intravasal volume leads to a stimulation of volume receptors. In addition, the renin-angiotensin-aldosterone system as well as the sympathoadrenergic system are activated the ADH level rises. This leads to a reduction in the glomerular filtration rate (GFR). The result is increased tubular sodium reabsorption,... 

Insulin edema is a rare complication, more often seen in the earlier years of insulin therapy (SEDA-11, 364). It is mostly seen when dysregulated patients with progressive weight loss are treated with relatively high amounts of insulin. Reduced sodium excretion (88), sodium reabsorption, and water retention by a possible direct action of insulin on the kidney may be involved (89). The role of aldosterone or of inhibition of the renin-angiotensin-aldosterone system in insulin edema is unclear. Insulin edema is a specific adverse effect, but it can aggravate pulmonary edema, congestive heart failure, and hypertension. Treatment consists of reduction of the insulin dose, after which the edema resolves within 3 days. 

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