What are the causes of metabolic alkalosis?

From the Guidelines

Metabolic alkalosis is primarily caused by excessive loss of hydrogen ions or gain of bicarbonate in the body, with the main causes including vomiting, diuretic use, excessive alkali administration, severe potassium depletion, and certain endocrine disorders. The underlying mechanisms involve the removal of stomach acid, increased renal bicarbonate reabsorption, and contraction alkalosis due to volume depletion 1. Key causes of metabolic alkalosis can be broken down into:

• Vomiting or nasogastric suction, which directly removes stomach acid
• Diuretic use, particularly loop and thiazide diuretics like furosemide and hydrochlorothiazole, which increase renal bicarbonate reabsorption
• Excessive alkali administration such as sodium bicarbonate or antacids
• Severe potassium depletion, often defined as K<3.5 mEq/L 1
• Certain endocrine disorders like hyperaldosteronism and Cushing's syndrome
• Contraction alkalosis, which can occur with volume depletion as the kidneys retain sodium and bicarbonate

For treatment to be effective, the underlying cause must be addressed, typically involving fluid replacement with normal saline to correct volume depletion, potassium and chloride repletion, and discontinuation of offending medications. In severe cases with pH > 7.60, dilute hydrochloric acid may be administered intravenously under careful monitoring. The body normally maintains acid-base balance through respiratory and renal mechanisms, but when these compensatory mechanisms are overwhelmed, metabolic alkalosis develops and can lead to symptoms like confusion, muscle cramps, and cardiac arrhythmias if left untreated, as seen in conditions like Bartter syndrome, characterized by hypokalemic metabolic alkalosis 1.

From the FDA Drug Label

Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially myocardial effects hypochloremic alkalosis, hypokalemia,

Causes of metabolic alkalosis include:

• Hypokalemia: Furosemide therapy may cause hypokalemia, which can lead to metabolic alkalosis.
• Hypochloremic alkalosis: Excessive diuresis may cause dehydration and blood volume reduction, leading to hypochloremic alkalosis. Furosemide tablets therapy may precipitate metabolic alkalosis, especially in patients with cirrhosis or those receiving high doses 2, 2.

From the Research

Causes of Metabolic Alkalosis

• Metabolic alkalosis is characterized by the primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco2 consequent to adaptive hypoventilation 3.
• The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid 3, 4.
• The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake 3, 4.
• Factors that interfere with the kidney's mechanisms to eliminate excess bicarbonate include:
  • Volume contraction
  • Low glomerular filtration rate
  • Potassium deficiency
  • Hypochloremia
  • Aldosterone excess
  • Elevated arterial carbon dioxide 3
• Major clinical states associated with metabolic alkalosis include:
  • Vomiting
  • Aldosterone or cortisol excess
  • Licorice ingestion
  • Chloruretic diuretics
  • Excess calcium alkali ingestion
  • Genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis 3, 4
• Metabolic alkalosis can also be caused by:
  • Chloride depletion alkalosis
  • Mineralocorticoid excess syndromes
  • Apparent mineralocorticoid excess syndromes
  • Excess alkali administration 5