What are the pathogenic mechanisms of 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

Metabolic alkalosis may be generated by one of the following mechanisms:

  • Loss of hydrogen ions
  • Shift of hydrogen ions into the intracellular space
  • Alkali administration
  • Contraction alkalosis

Hydrogen ions may be lost through the kidneys or the GI tract. Vomiting or nasogastric (NG) suction generates metabolic alkalosis by the loss of gastric secretions, which are rich in hydrochloric acid (HCl). Whenever a hydrogen ion is excreted, a bicarbonate ion is gained in the extracellular space.

Renal losses of hydrogen ions occur whenever the distal delivery of sodium increases in the presence of excess aldosterone, which stimulates the electrogenic epithelial sodium channel (ENaC) in the collecting duct. As this channel reabsorbs sodium ions, the tubular lumen becomes more negative, leading to the secretion of hydrogen ions and potassium ions into the lumen.

Shift of hydrogen ions into the intracellular space mainly develops with hypokalemia. As the extracellular potassium concentration decreases, potassium ions move out of the cells. To maintain neutrality, hydrogen ions move into the intracellular space.

Administration of sodium bicarbonate in amounts that exceed the capacity of the kidneys to excrete this excess bicarbonate may cause metabolic alkalosis. This capacity is reduced when a reduction in filtered bicarbonate occurs, as observed in renal failure, or when enhanced tubular reabsorption of bicarbonate occurs, as observed in volume depletion (see Maintenance of metabolic alkalosis).

Loss of bicarbonate-poor, chloride-rich extracellular fluid, as observed with thiazide diuretic or loop diuretic therapy or chloride diarrhea, leads to contraction of extracellular fluid volume. Because the original bicarbonate mass is now dissolved in a smaller volume of fluid, an increase in bicarbonate concentration occurs. This increase in bicarbonate causes, at most, a 2- to 4-mEq/L rise in bicarbonate concentration.


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