What causes chloride-responsive metabolic alkalosis?

Updated: Dec 10, 2020
  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

The principal causes of chloride-responsive alkalosis are the loss of gastric secretions, ingestion of large doses of nonabsorbable antacids, and use of thiazide or loop diuretics. [2] Miscellaneous causes account for the remainder of cases. [3]

Gastric secretions are rich in hydrochloric acid (HCl). The secretion of HCl by the stomach usually stimulates bicarbonate secretion by the pancreas once the HCl reaches the duodenum. Ordinarily, these pancreatic secretions neutralize the gastric secretions, and no net gain or loss of hydrogen ions or bicarbonate occurs.

When HCl is lost through vomiting (including purging, in persons with eating disorders [4] ) or nasogastric suction, pancreatic secretions are not stimulated and a net gain of bicarbonate into the systemic circulation occurs, generating a metabolic alkalosis. Volume depletion maintains alkalosis. In this case, the hypokalemia is secondary to the alkalosis itself and to renal loss of potassium ions from the stimulation of aldosterone secretion.

Ingestion of large doses of nonabsorbable antacids (eg, magnesium hydroxide) may generate metabolic alkalosis by a rather complicated mechanism. Upon ingestion of magnesium hydroxide, calcium, or aluminum with base hydroxide or carbonate, the hydroxide anion buffers hydrogen ions in the stomach. The cation binds to bicarbonate secreted by the pancreas, leading to loss of bicarbonate with stools. In this process, both hydrogen ions and bicarbonate are lost, and, usually, no acid-base disturbance occurs. Sometimes, however, not all the bicarbonate binds to the ingested cation, which means that some bicarbonate is reabsorbed in excess of the lost hydrogen ions. This occurs primarily when antacids are administered with a cation-exchange resin (eg, sodium polystyrene sulfonate [Kayexalate]); the resin binds the cation, leaving bicarbonate unbound.

Thiazides and loop diuretics enhance sodium chloride excretion in the distal convoluted tubule and the thick ascending loop, respectively. These agents cause metabolic alkalosis by chloride depletion and by increased delivery of sodium ions to the collecting duct, which enhances potassium ion and hydrogen ion secretion.

Volume depletion also stimulates aldosterone secretion, which enhances sodium ion reabsorption in the collecting duct and increases hydrogen ion and potassium secretion in this segment. Urine chloride is low after discontinuation of diuretic therapy, while it is high during active diuretic use.

Miscellaneous causes of metabolic alkalosis include villous adenomas, which are a rare cause of diarrhea. Villous adenomas usually lead to metabolic acidosis from loss of colonic secretions that are rich in bicarbonate, but occasionally these tumors cause metabolic alkalosis. The mechanism is not well understood. Some authors opine that hypokalemia from these tumors is the etiology of the metabolic alkalosis.

Congenital chloridorrhea (see Chloride Diarrhea, Familial. Online Mendelian Inheritance in Man [OMIM]) is a rare form of severe secretory diarrhea that is inherited as an autosomal recessive trait. Mutations in the down-regulated adenoma gene result in defective function of the chloride/bicarbonate exchange in the colon and ileum, leading to increased secretion of chloride and reabsorption of bicarbonate.

During respiratory acidosis, the kidneys reabsorb bicarbonate and secrete chloride to compensate for the acidosis. In the posthypercapnic state, urine chloride is high and can lead to chloride depletion. Once the respiratory acidosis is corrected, the kidneys cannot excrete the excess bicarbonate because of the low luminal chloride.

Infants with cystic fibrosis may develop metabolic alkalosis because of loss of chloride in sweat. These infants are also prone to volume depletion.


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