Causes of Metabolic Alkalosis
Metabolic alkalosis is primarily caused by excessive hydrogen ion loss or bicarbonate gain, and is characterized by elevated plasma bicarbonate (>26 mmol/L) and blood pH (>7.43). 1 The causes can be categorized into four main groups based on their pathophysiological mechanisms.
Chloride Depletion Alkalosis
- Gastrointestinal losses:
- Renal losses:
Mineralocorticoid Excess Syndromes
- Primary hyperaldosteronism 2, 5
- Secondary hyperaldosteronism (renovascular hypertension, renin-secreting tumors) 2
- Cushing syndrome 2
- Bartter syndrome 2, 5
- Gitelman syndrome 2, 5
Apparent Mineralocorticoid Excess Syndromes
- Licorice ingestion (glycyrrhizic acid inhibits 11β-hydroxysteroid dehydrogenase) 2, 5
- Congenital adrenal hyperplasia 5
- Liddle syndrome 2
Exogenous Alkali Administration
- Excessive oral or parenteral bicarbonate administration 2, 5
- Administration of bicarbonate precursors (lactate, acetate, citrate) 5
- Massive blood transfusions 2
- Milk-alkali syndrome (excessive calcium carbonate intake) 2
Pathophysiological Mechanisms
Generation of Metabolic Alkalosis
- Loss of hydrogen ions through the gastrointestinal tract or kidneys 1
- Gain of bicarbonate through exogenous administration 5
- Contraction alkalosis due to loss of chloride-rich, bicarbonate-poor fluid 2
Maintenance Factors
For metabolic alkalosis to persist, certain factors must impair the kidney's ability to excrete excess bicarbonate:
- Volume depletion (reduces glomerular filtration rate) 1, 5
- Chloride depletion (impairs bicarbonate excretion) 4
- Hypokalemia (enhances bicarbonate reabsorption) 1, 5
- Reduced GFR (decreases filtered bicarbonate load) 5
- Hyperaldosteronism (increases hydrogen ion secretion) 2
Diagnostic Approach
- Assess arterial blood gases showing elevated pH and bicarbonate 4
- Evaluate compensatory increase in PaCO₂ 2
- Determine volume status (supine and standing blood pressure) 4
- Measure urinary chloride concentration:
- Assess renin-angiotensin-aldosterone axis 4
- Check serum potassium and chloride levels 1
Treatment Principles
- Address the underlying cause 3
- Correct volume depletion with sodium chloride in chloride-responsive alkalosis 4
- Replace potassium chloride in cases with hypokalemia 1
- In severe cases, consider hydrochloric acid infusion (0.1 N HCl), though this carries risk of hemolysis 4
- For emergency situations with severe alkalosis, dialysis with higher K⁺, Cl⁻, and low HCO₃⁻ bath may be appropriate 4
- Carbonic anhydrase inhibitors may be used in selected cases 5
Clinical Impact
Severe metabolic alkalosis (arterial pH ≥7.55) is associated with significantly increased mortality in critically ill patients and can affect multiple organ systems including the central nervous system, myocardium, and skeletal muscle 2, 5.