Hyperkalemia aldosterone secretion

As nephron mass decreases, both the distal tubular secretion and GI excretion are increased because of aldosterone stimulation. Functioning nephrons increase FEK up to 100% and GI excretion increases as much as 30% to 70% in CKD,30 as a result of aldosterone secretion in response to increased potassium levels.30 This maintains serum potassium concentrations within the normal range through stages 1 to 4 CKD. Hyperkalemia begins to develop when GFR falls below 20% of normal, when nephron mass and renal potassium secretion is so low that the capacity of the GI tract to excrete potassium has been exceeded.30... 

Hyperkalemia due to a decrease in aldosterone secretion is rarely found in patients with normal renal function, but it is relatively common in those with CHF and in the elderly. Hyperkalemia is more frequent in patients with renal impairment, diabetes, and in those receiving either K+ or potassium K+-sparing diuretics, heparin or non-steroidal anti-inflammatory drugs (NSAIDs). 

Treatment with angiotensin-converting enzyme inhibitors is also more likely to be associated with hyperkalemia in older individuals (69). Impaired angiotensin II formation limits this potent stimulus for aldosterone secretion, and this is superimposed on the already age-related decrease in activity of the renin-angiotensin-aldosterone axis. The same drug-induced hyporeninemic hypoaldosteronism is predicted for the angiotensin receptor blockers. However, to date this has not been documented clincally. 

Drug-Drug Interaction Lithium. Telmisartan 40 mg per day was added into the antihypertensive regimen of a 52-year-old schizophrenic woman who had been on lithium 900 mg and haloperidol 20 mg per day. Her lithium level increased to 2.6 meq/L from a range of between 0.83 meq/L and 1.02 meq/L prior to the introduction of telmisartan urea and creatinine increased from normal baseline values to 76 mg/dL and 4.6 mg/dL, respectively, and potassium level was 7.0 mmol/L. Following haemodialysis, her laboratory results retiuned to normal, symptoms abated and lithium was replaced with valproic acid [18 ]. The exact mechanism of this interaction is not known however, it is thought that activation of ATI results in increasing sodium reabsorption at the proximal convoluted tubules which subsequently results in reduction in aldosterone secretion. This ultimately causes hyperkalemia and hyponatraemia. Sodium depletion may cause increase in lithium reabsorption from the proximal convoluted tubules. 

Aldosterone secretion is also stimulated directly by hyperkalemia (elevated plasma K+) and promotes potassium excretion. 

Concurrent acidosis in patients with trimethoprim-induced hyperkalemia is uncommon, which could be explained if the action of trimethoprim, like that of amiloride, is hmited to the cortical collecting tubule but does not affect the medullary collecting tubule, which has a large capacity to secrete hydrogen ions and may therefore prevent the development of acidosis. Predisposing factors for the rare adverse effect of renal tubular acidosis in this case may have been aldosterone deficiency or resistance, medullary dysfunction of sickle cell anemia, and renal insufficiency. All these factors could contribute to impaired renal handling of secretion of hydrogen ions (72). 

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. 

Selective Aldosterone Deficiency (Type IV RTA). In type IV RTA, there is failure of distal potassium and hydrogen ion secretion because of aldosterone deficiency or resistance. This may occur because of a range of steroid or steroid receptor synthetic defects or because of hyporeninemic hypoaldosteronism (e.g., due to diabetic nephropathy, tubulointerstitial disease, urinary obstruction, renal transplantation, or SLE). Hyperkalemia, although mild, is a usual manifestation. 

Failure of the kidneys to synthesize renin, failure of the adrenal cortex to secrete aldosterone, and renal tubular resistance to aldosterone are the most common causes of this type of acidosis (often called type IV RTA). This inhibits Na" reabsorption, and both and are thus abnormally retained. The result is decreased renal ammonia formation and therefore decreased elimination of H. If associated with increased ECF volume, HCO3 reclamation in the tubules may be depressed. There is usually an associated mild renal msuf-ficiency (elevated serum creatinine), but urine may stiU be acidified to a pH <5.5. Hyperkalemia is also usually present. 

Release of Aldosterone from the Adrenal Cortex Angll stimulates the zona glomerulosa of the adrenal cortex to increase the synthesis and secretion of aldosterone and also exerts permissive effects that augment responses to ACTH and K+. Increased output of aldosterone is elicited by concentrations of Angll that have little or no acute effect on blood pressure. Aldosterone acts on the distal and collecting tubules to cause retention of Na+ and excretion of K+ and H+. Angll-induced stimulation of aldosterone synthesis is enhanced by hyponatremia or hyperkalemia. 

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