What are the causes of metabolic alkalosis?

Causes of Metabolic Alkalosis

Metabolic alkalosis is characterized by increased plasma bicarbonate (>26 mmol/L) and elevated arterial pH (>7.43), and is caused by either excessive hydrogen ion loss or exogenous base gain, combined with factors that maintain the alkalotic state.

Primary Mechanisms of Metabolic Alkalosis

Generation Factors

• Gastrointestinal causes: Vomiting leads to loss of hydrogen ions and chloride from gastric secretions 1
• Renal causes: Loop diuretics promote chloride and potassium excretion, leading to alkalosis 1, 2
• Exogenous base gain: Administration of bicarbonate, lactate, acetate, or citrate can directly increase serum bicarbonate 2, 3

Maintenance Factors

• Volume depletion: Hypovolemia stimulates bicarbonate reabsorption 1, 2
• Chloride depletion: Low chloride levels impair the kidney's ability to excrete bicarbonate 1, 3
• Hypokalemia: Potassium deficiency enhances bicarbonate reabsorption and hydrogen ion secretion 1, 2
• Hyperaldosteronism: Excess aldosterone promotes hydrogen ion secretion 1, 3
• Renal failure: Impaired kidney function limits bicarbonate excretion 1

Classification of Metabolic Alkalosis

Chloride-Responsive (Volume-Depleted) Alkalosis

• Vomiting and nasogastric suction: Direct loss of hydrochloric acid from stomach 2, 4
• Diuretic therapy: Particularly loop and thiazide diuretics causing chloride and potassium wasting 2, 5
• Posthypercapnic alkalosis: Occurs after rapid correction of chronic respiratory acidosis 2
• Chloride-wasting diarrhea: Some forms of diarrhea can paradoxically cause alkalosis 6

Chloride-Resistant (Volume-Expanded) Alkalosis

• Primary hyperaldosteronism: Conn's syndrome with autonomous aldosterone production 2, 3
• Secondary hyperaldosteronism: Renovascular hypertension, renin-secreting tumors 2
• Cushing's syndrome: Excess cortisol has mineralocorticoid effects 2
• Bartter syndrome: Genetic disorder mimicking chronic loop diuretic use 2, 3
• Gitelman syndrome: Genetic disorder mimicking chronic thiazide diuretic use 2, 3
• Licorice ingestion: Contains glycyrrhizic acid which inhibits 11β-hydroxysteroid dehydrogenase 2, 3

Exogenous Alkali Administration

• Bicarbonate therapy: Excessive administration during cardiac arrest or metabolic acidosis 3
• Milk-alkali syndrome: Excessive intake of calcium and absorbable alkali 2
• Massive blood transfusion: Citrate in blood products metabolizes to bicarbonate 2
• Parenteral nutrition: Solutions containing acetate or lactate 3

Clinical Presentation and Diagnosis

Laboratory Findings

• Elevated serum bicarbonate: >26 mmol/L 1, 2
• Elevated arterial pH: >7.43 1, 2
• Compensatory increase in PaCO2: Due to hypoventilation 2
• Associated electrolyte abnormalities: Hypokalemia, hypochloremia 1, 4

Diagnostic Approach

• Urinary chloride measurement: <10 mEq/L in chloride-responsive alkalosis, >20 mEq/L in chloride-resistant forms 4, 5
• Assessment of volume status: Physical examination for signs of volume depletion or excess 1, 5
• Measurement of renin and aldosterone levels: To identify mineralocorticoid excess 1, 5

Complications of Metabolic Alkalosis

• Decreased cardiac output: Alkalemia causes decreased cardiac contractility 6
• Hypoventilation: Compensatory mechanism can lead to hypoxemia 2
• Neuromuscular irritability: Can cause tetany, seizures, and arrhythmias 3
• Decreased tissue oxygen delivery: Alkalemia shifts the oxyhemoglobin dissociation curve to the left 2
• Increased protein catabolism: Alkalemia increases protein degradation and decreases albumin synthesis 6

Treatment Principles

• Chloride-responsive alkalosis: Sodium chloride and potassium chloride repletion 1, 4
• Chloride-resistant alkalosis: Treatment of underlying cause (e.g., primary hyperaldosteronism) 5
• Severe cases: May require hydrochloric acid infusion or dialysis with low bicarbonate bath 4
• Addressing underlying causes: Discontinuation of diuretics, treatment of vomiting 1, 5