Pathophysiology of metabolic alkalosis in primary high mineralocorticoid activity

Pathophysiology of metabolic alkalosis in primary high mineralocorticoid activity

What is the pathophysiology of metabolic alkalosis in patients with primary high mineralocorticoid activity?

In patients with primary hyperaldosteronism, caused by either benign adrenal adenomas or bilateral adrenal hyperplasia, metabolic alkalosis and hypertension are expected. H + -ATPase activity is directly stimulated.

There is an initial positive balance of NaCl as a result of actions of mineralocorticoids. Distal tubular and collecting duct epithelial sodium channel (ENaC) activity are increased and hypertension results. Renin and angiotensin II secretion are suppressed.

Secondly, there is excretion of K + . Mineralocorticoids facilitate kaliuresis through several mechanisms. Stimulation of ENaC activity makes the luminal potential difference more negative, facilitating K + secretion by the renal outer medullary K + channel, ROMK.

ROMK channel open activity also is increased. In addition, this negative luminal potential difference facilitates the activity of H + -ATPase, further stimulating distal proton secretion.

The resulting deficit of K + and hypokalemia acidifies proximal convoluted tubular cells, stimulates proximal NaHCO 3 reabsorption, and stimulates sodium/citrate reabsorption, causing retention of dietary alkali and lowering excretion of citrate.

However, this process is opposed by suppression of renin and angiotensin II by the volume-expanding effect of aldosterone, suppressing NHE3 activity. An increased rate of excretion of NH 4 + due to hypokalemia also follows.

In total body terms, there is net gain of NaHCO 3 . When plasma bicarbonate rises sufficiently to return the ICF pH toward normal, these patients can achieve acid-base balance by excreting appropriate amounts of NH 4 + and organic anions in the urine, as dictated by their dietary intake but at a higher [HCO 3  ]. Note that these patients are not Cl  depleted and urine Cl  is not low. As H + -ATPase activity is stimulated, urine pH is generally 6.0 or less.

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