Aldosterone homeostasis

The renin-angiotensin-aldosterone system (RAAS) generates the peptide hormone angiotensin II and subsequently the mineralocorticoid aldosterone, which both exert considerable impact on blood pressure ( blood pressure control) and fluid homeostasis, and... 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

L3. Laragh, J. H., Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure-electrolyte homeostasis. N. Engl. J. Med. 313, 1330-1340 (1985). 

The incidence of classic CAH-P450c21 in the United States ranges from 1 10,000 to 1 18,000, with approximately 75% of patients with CAH-P450c21 exhibiting classic salt wasting (White and Speiser, 2000). Aldosterone is essential for normal sodium homeostasis and acts to enhance sodium absorption and potassium excretion (Fig. 33-3). In the relative absence of aldosterone, there is an increase in sodium loss... 

In addition to vasodilatory responses, PGs have a number of other effects in the kidney. For example, PGs stimulate adenylate cyclase in juxtaglomerular cells, resulting in an increase in cAMP production this, in turn, increases renin release. Renin stimulates the release of aldosterone, which increases renal tubular secretion of potassium (Stillman Schlesinger 1990). PGs also enhance tubular excretion of sodium and water (Patrono Dunn 1987). By causing these effects in the kidneys, PGs can alter electrolyte homeostasis. Therefore, other renal side-effects of NSAID therapy can include hyperkalemia, hypernatremia and edema. Often these metabolic changes are not observed in individuals with normal renal function, but in the presence of pre-existing disease they can become clinically significant. 

Mineralocorticoid refers to those steroids that regulate salt homeostasis (sodium conservation and potassium loss) and extracellular fluid volume.Aldosterone is the most potent naturally occurring mineralocorticoid and is synthesized exclusively in the zona glomerulosa region of the adrenal cortex. This zone uniquely contains the enzyme aldosterone synthase, an obligatory enzyme in the synthetic pathway to aldosterone. Other adrenocortical steroids that have mineralocorticoid properties with varying degrees of potency include DOC, 18-hydroxy-DOC, corticosterone,... 

Mineralocorticoid excess also plays a significant role in the maintenance of metabolic alkalosis. In patients with volume-responsive metabolic alkalosis, intravascular volume depletion stimulates aldosterone secretion. As discussed earlier, excess mineralocorticoid activity may also underlie the generation of metabolic alkalosis. In either situation, the increased mineralocorticoid effect stimulates collecting duct H+ secretion. Metabolic alkalosis may also be maintained by persistent hypokalemia. Hypokalemia has a multitude of effects on renal acid-base homeostasis, enhancing proximal tubular bicarbonate reabsorption, stimulating ammoniagenesis and increasing distal tubular H secretion. ... 

Apart from catecholamine secretion, it is not obvious what role increased endocrine activity would have in homeostasis after injury. In adrenalectomized dogs subjected to hemorrhagic injury, cortisol and aldosterone will each cause an expansion of extracellular fluid volume by mobilization of cell water within 6 hours of administration. Cortisol, but not aldosterone, also will cause an expansion of plasma volume which can be attributed to its effects on the peripheral vasculature. Spironolactone will prevent the shift of water from the body cell mass to the interstitial fluid (M3). The above experimental evidence clearly im-... 

As with other K+-sparing diuretics, spironolactone often is coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. Such combinations result in increased mobilization of edema fluid while causing lesser perturbations of K+ homeostasis. Spironolactone is particularly useful in the treatment of primary hyperaldosteronism (adrenal adenomas or bilateral adrenal hyperplasia) and of refractory edema associated with secondary aldosteronism (cardiac failure, hepatic cirrhosis, nephrotic syndrome, and severe ascites). Spironolactone is considered the diuretic of choice in patients with hepatic cirrhosis. Added to standard therapy, spironolactone substantially reduces morbidity and mortality and ventricular arrhythmias in patients with heart failure. 

The major disease clearly linked with disordered sodium homeostasis, among other diseases, is hypertension, and this is observed in very small populations with genetic defects including glucocorticoid-responsive aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess (AME) (Anke 2002). Cystic fibrosis is another genetically determined defect in the chloride channels. This leads to the secretion of sweat with high NaCl concen-... 

The attenuation of aldosterone production by ACE inhibitors also influences K+ homeostasis. There is only a very small and chnicaUy unimportant rise in serum K+ when these agents are used alone in patients with normal renal function. However, substantial K+ retention can occur in patients... 

Fig. 4.10. Body fluid homeostasis (constant body water balance). Intake is influenced by availability of fluids and food, thirst, hunger, and the ability to swallow. The rates of breathing and evaporation and urinary volume influence water loss. The body adjusts the volume of urinary excretion to compensate for variations in other types of water loss and for variations in intake. The hormones aldosterone and antidiuretic hormone (ADH) help to monitor blood volume and osmolality through mechanisms regulating thirst and sodium and water balance.

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