What are the causes of metabolic alkalosis?

Causes of Metabolic Alkalosis

Metabolic alkalosis is primarily caused by either excessive loss of acid or gain of bicarbonate, and is maintained by factors that prevent the kidney from excreting excess bicarbonate. 1, 2

Classification of Causes

1. Chloride Depletion Alkalosis

• Gastrointestinal losses

  • Vomiting (loss of gastric HCl) 1, 2
  • Nasogastric suction 2
  • Congenital chloridorrhea 3

• Renal losses

  • Diuretic therapy (especially loop and thiazide diuretics) 1, 4
  • Post-hypercapnic state 3
  • Bartter syndrome 2, 5
  • Gitelman syndrome 2, 5

2. Mineralocorticoid Excess Syndromes

• Primary hyperaldosteronism 2, 5
• Secondary hyperaldosteronism 2
• Cushing syndrome 3
• Adrenogenital syndrome 5
• Exogenous corticosteroid administration 2

3. Apparent Mineralocorticoid Excess Syndromes

• Licorice ingestion (glycyrrhizic acid inhibits 11β-hydroxysteroid dehydrogenase) 2, 5
• Liddle syndrome 2
• 11β-hydroxysteroid dehydrogenase deficiency 2

4. Excess Alkali Administration

• Oral or parenteral sodium bicarbonate administration 3
• Massive blood transfusions (citrate metabolism) 3
• Milk-alkali syndrome (calcium carbonate ingestion) 2, 4
• Administration of lactate, acetate, or citrate (metabolized to bicarbonate) 3

Maintenance Factors

Metabolic alkalosis persists when the kidney fails to excrete excess bicarbonate due to:

• Volume depletion/hypovolemia 1, 3
• Chloride depletion (hypochloremia) 1, 3
• Potassium depletion (hypokalemia) 1, 3
• Decreased glomerular filtration rate 3, 5
• Hyperaldosteronism 1, 5

Pathophysiological Mechanisms

• Generation phase: Initial loss of acid or gain of bicarbonate 2

  • Acid loss: Through vomiting, nasogastric suction, or diuretic-induced renal excretion
  • Base gain: Through exogenous bicarbonate administration or metabolism of organic anions

• Maintenance phase: Factors that prevent renal correction of alkalosis 2, 3

  • Hypovolemia activates renin-angiotensin-aldosterone system, promoting H+ secretion
  • Hypochloremia limits bicarbonate excretion due to lack of chloride for reabsorption
  • Hypokalemia enhances proximal bicarbonate reabsorption and distal H+ secretion

Clinical Approach to Diagnosis

The evaluation of metabolic alkalosis should include:

• Assessment of volume status (hypovolemic vs. euvolemic) 1
• Measurement of urinary chloride concentration 1
  • Low urinary chloride (<10 mEq/L): Suggests chloride-responsive alkalosis
  • High urinary chloride (>20 mEq/L): Suggests chloride-resistant alkalosis
• Evaluation of plasma renin and aldosterone levels to identify mineralocorticoid excess 1
• Serum electrolytes to assess for associated hypokalemia and hypochloremia 2

Understanding these causes and mechanisms is essential for appropriate treatment, which focuses on addressing the underlying cause and correcting the factors maintaining the alkalosis 1, 4.