Plasma aldosterone

Labs lytes, blood urea nitrogen (BUN)/creatinine, urine albumin, plasma aldosterone/plasma renin ratio to screen for excess aldosterone or mineralocorticoid production, or renin for renal artery stenosis (RAS) or renin-secreting tumor. 

In primary aldosteronism, low renin activity and high aldosterone concentration are expected. Many other factors, however, influence the secretion of renin and aldosterone, and these factors must be recognized and understood before testing. Because drugs such as ACE inhibitors, beta blockers, and spironolactone alter renin release, patients should be withdrawn from these medications for several weeks before determining the plasma aldosterone/plasma renin activity... 

The determination of plasma renin responsiveness, however, is not sufficient to diagnose primary aldosteronism because suppressed PRA also occurs in about 25% of patients with essential hypertension. Primary aldosteronism can be differentiated from other hypermineralocorticoid states on the basis of inappropriate secretion of aldosterone. The demonstration of an elevated concentration of aldosterone in blood or urine in a patient with an unequivocally suppressed PRA concentration (a plasma aldosterone/ plasma PRA ratio >50) is presumptive evidence of primary aldosteronism. Because hypokalemia has a suppressive effect on aldosterone secretion, the potassium deficit should be replaced before aldosterone measurements are done. To establish aldosterone autonomy, the clinician may attempt to suppress aldosterone production with rapid volume expansion (see Box 51-10), with a potent mineralocorticoid (see Box 51-11), or as mentioned with captopril. Failure... 

The volume of extracellular fluid is direcdy related to the Na" concentration which is closely controlled by the kidneys. Homeostatic control of Na" concentration depends on the hormone aldosterone. The kidney secretes a proteolytic enzyme, rennin, which is essential in the first of a series of reactions leading to aldosterone. In response to a decrease in plasma volume and Na" concentration, the secretion of rennin stimulates the production of aldosterone resulting in increased sodium retention and increased volume of extracellular fluid (51,55). 

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). 

In an attempt to conserve sodium, the kidney secretes renin increased plasma renin activity increases the release of aldosterone, which regulates the absorption of potassium and leads to kafluresis and hypokalemia. Hypokalemia is responsible in part for decreased glucose intolerance (82). Hyponatremia, postural hypotension, and pre-renal azotemia are considered of tittle consequence. Hypemricemia and hypercalcemia are not unusual, but are not considered harmful. However, hypokalemia, progressive decreased glucose tolerance, and increased semm cholesterol [57-88-5] levels are considered... 

In the tongue, ENaC is expressed in taste bud epithelial cells. The expression of a, (3 and y subunits at the apical membrane of taste buds is observed under low salt diet, known to greatly increase plasma aldosterone. This observation suggests that ENaC could play a significant role in the transduction of salt sensation. 

MR has a high affinity for mineralocorticoids such as aldosterone and DOC. In addition, MR also binds glucocorticoids although in mineralocorticoid target tissues this is prevented by the enzyme 11 (3-HSDII (see above). Since mineralocorticoids are no substrate for 11 (3-HSD II due to their cyclic 11,18-hemiacetyl-group, they are able to bind to MR despite the 1,000-fold lower concentration in plasma as compared with cortisol. 

Liddle s syndrome is an autosomal dominant disorder that is caused by persistent hyperactivity of the epithelial Na channel. Its symptoms mimic aldosterone excess, but plasma aldosterone levels are actually reduced (pseudoaldosteronism). The disease is characterized by early onset arterial hypertension, hypokalemia, and metabolic alkalosis. 

As previously discussed, increased portal pressure triggers the release of nitric oxide to directly vasodilate the splanchnic arterial bed and decrease portal pressure. Unfortunately, nitric oxide also dilates the systemic arterial system, causing a decrease in blood pressure and a decrease in renal perfusion by lowering the effective intravascular volume. The kidney reacts by activating the renin-angiotensin-aldosterone system, which increases plasma renin activity, aldosterone production, and sodium retention. This increase in intravascular volume furthers the imbalance of intravascular oncotic pressure, allowing even more fluid to escape to the extravascular spaces. 

Plasma Measure plasma Primary adrenal insufficiency low plasma aldosterone level. ... 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

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. 

More specific laboratory tests are used to diagnose secondary hypertension. These include plasma norepinephrine and urinary metanephrine levels for pheochromocytoma, plasma and urinary aldosterone levels for primary aldosteronism, and plasma renin activity, captopril stimulation test, renal vein renins, and renal artery angiography for renovascular disease. 

I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. ACE inhibitors also block the degradation of bradykinin and stimulate the synthesis of other vasodilating substances including prostaglandin E2 and prostacyclin. The fact that ACE inhibitors lower BP in patients with normal plasma renin activity suggests that bradykinin and perhaps tissue production of ACE are important in hypertension. 

Aliskiren blocks the renin-angiotensin-aldosterone system at its point of a activation, which results in reduced plasma renin activity and BP. It provides BP reductions comparable to an ACE inhibitor, ARB, or CCB. It also has additive antihypertensive effects when used in combination with thiazides, ACE inhibitors, ARBs, or CCBs. It is approved for monotherapy or in combination with other agents. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Mobilization of edemas (A) In edema there is swelling of tissues due to accumulation of fluid, chiefly in the extracellular (interstitial) space. When a diuretic is given, increased renal excretion of Na and H2O causes a reduction in plasma volume with hemoconcentra-tion. As a result, plasma protein concentration rises along with oncotic pressure. As the latter operates to attract water, fluid will shift from interstitium into the capillary bed. The fluid content of tissues thus falls and the edemas recede. The decrease in plasma volume and interstitial volume means a diminution of the extracellular fluid volume (EFV). Depending on the condition, use is made of thiazides, loop diuretics, aldosterone antagonists, and osmotic diuretics. 

The smallest functional unit of the kidney is the nephron. In the glomerular capillary loops, ultrafiltration of plasma fluid into Bowman s capsule (BC) yields primary urine. In the proximal tubules (pT), approx. 70% of the ultrafiltrate is retrieved by isoosmotic reabsorption of NaCl and water. In the thick portion of the ascending limb of Henle s loop (HL), NaCl is absorbed unaccompanied by water. This is the prerequisite for the hairpin countercurrent mechanism that allows build-up of a very high NaQ concentration in the renal medulla In the distal tubules (dT), NaCl and water are again jointly reabsorbed. At the end of the nephron, this process involves an aldosterone-controlled exchange of Na+ against 1C or H. In the collecting tubule (C), vasopressin (antidiuretic hormone, ADH) increases the epithelial permeability for water, which is drawn into the hyperosmolar milieu of the renal medulla and thus retained in the body. As a result, a concentrated urine enters the renal pelvis. 

Secondary hypotension is a sign of an underlying disease that should be treated first. If stroke volume is too low, as in heart failure, a cardiac glycoside can be given to increase myocardial contractility and stroke volume. When stroke volume is decreased due to insufficient blood volume, plasma substitutes will be helpful in treating blood loss, whereas aldosterone deficiency requires administration of a mineralocor-ticoid (e.g., fludrocortisone). The latter is the drug of choice for orthostatic hypotension due to autonomic failure. A parasympatholytic (or electrical pacemaker) can restore cardiac rate in bradycardia. 

Reduction in plasma volume secondary to the enhanced excretion of sodium ions and water and the regression of edema, if present. These effects are accompanied by a reduction in cardiac preload. During long-term treatment most of these effects are counteracted by various regulatory mechanisms, such as a persistent rise in plasma renin and aldosterone. 

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