What are the causes of metabolic alkalosis?

From the Guidelines

Metabolic alkalosis is primarily caused by hypokalemic and hypochloremic conditions, often resulting from salt-wasting disorders, such as Bartter syndrome, or other rare tubulopathies.

Causes of Metabolic Alkalosis

• Genetic disorders: Bartter syndrome, a rare genetic disorder, is characterized by hypokalemic metabolic alkalosis, polyhydramnios, and other distinct features, as outlined in the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders consensus statement 1.
• Salt-wasting disorders: Conditions like congenital chloride diarrhea can cause pronounced hypokalemic and hypochloremic metabolic alkalosis due to excessive salt loss in the gut 1.
• Renal tubular acidosis: Certain types of renal tubular acidosis, such as distal renal tubular acidosis, can present with hypokalemic alkalosis and hypomagnesemia 1.
• Hormonal imbalances: Primary hyperaldosteronism can lead to hypokalemic metabolic alkalosis due to excessive aldosterone production 1.
• Gastrointestinal losses: Prolonged vomiting or nasogastric suction can cause hypochloremic metabolic alkalosis due to loss of hydrogen and chloride ions 1.
• Medications: Certain medications, such as diuretics (e.g., loop diuretics, thiazides) and laxatives, can induce hypokalemic metabolic alkalosis by promoting salt and water loss in the urine or gut 1. It is essential to distinguish between renal and extrarenal causes of salt loss, as well as to consider the potential role of genetic testing and other diagnostic tools in evaluating patients with suspected metabolic alkalosis 1.

From the Research

Causes of Metabolic Alkalosis

The causes of metabolic alkalosis can be categorized into two main groups: generation and maintenance of alkalosis.

• Generation of metabolic alkalosis may be due to:
  • Excessive hydrogen ion loss by the gastrointestinal tract (e.g. vomiting) 2, 3, 4, 5
  • Excessive hydrogen ion loss by the kidney (e.g. use of loop diuretics) 2, 3, 4, 5
  • Exogenous base gain (e.g. oral or parenteral alkali intake) 3, 4, 5
• Maintenance of metabolic alkalosis reflects the inability of the kidney to excrete the excess of bicarbonate due to:
  • Hypovolemia 2, 3, 4, 5
  • Chloride depletion 2, 3, 4, 5
  • Hypokalemia 2, 3, 4, 5
  • Hyperaldosteronism 2, 3, 4, 5
  • Renal failure 2, 3, 4, 5
  • A combination of these factors 2, 3, 4, 5

Clinical States Associated with Metabolic Alkalosis

Metabolic alkalosis is associated with various clinical states, including:

• Vomiting 2, 3, 4, 5
• Mineralocorticoid excess 3, 4, 5
• Licorice ingestion 3, 4, 5
• Diuretic administration 2, 3, 4, 5
• Bartter's and Gitelman's syndromes 3, 4, 5
• Genetic diseases such as cystic fibrosis 3

Pathophysiology of Metabolic Alkalosis

The pathophysiology of metabolic alkalosis involves the gain of bicarbonate or the loss of nonvolatile acid from extracellular fluid 4, 5. The kidney preserves normal acid-base balance by two mechanisms: bicarbonate reclamation and bicarbonate generation 4, 5. Factors that affect these mechanisms, such as effective arterial blood volume, glomerular filtration rate, chloride, and potassium, can contribute to the development of metabolic alkalosis 4, 5. A new classification of the causes of metabolic alkalosis has been proposed based on the centrality of stimulated collecting duct ion transport 6.