What are the causes of metabolic alkalosis and how should it be corrected?

Causes and Correction of Metabolic Alkalosis

Understanding Metabolic Alkalosis

Metabolic alkalosis is characterized by elevated serum bicarbonate (>26 mmol/L) and arterial pH (>7.45), with compensatory hypoventilation raising PaCO₂. 1 The disorder arises from either net bicarbonate gain or fixed acid loss, and its persistence requires impaired renal bicarbonate excretion. 1, 2

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Major Causes of Metabolic Alkalosis

Gastrointestinal Acid Loss

• Vomiting or nasogastric suction causes loss of hydrochloric acid, generating bicarbonate and producing volume contraction that maintains the alkalosis. 1, 2
• Villous adenomas and congenital chloride diarrhea can cause chloride-rich fluid loss leading to metabolic alkalosis. 1

Renal Acid Loss

• Loop and thiazide diuretics are the most common cause of metabolic alkalosis in hospitalized patients, producing volume contraction, chloride depletion, and secondary hyperaldosteronism. 3, 1
• Mineralocorticoid excess (primary hyperaldosteronism, Cushing syndrome, exogenous steroids) increases distal sodium reabsorption and hydrogen ion secretion. 1, 2
• Bartter and Gitelman syndromes are genetic tubulopathies causing renal salt wasting, hypokalemia, and metabolic alkalosis with elevated renin and aldosterone despite normal blood pressure. 3, 1

Alkali Administration

• Excessive sodium bicarbonate administration (oral or intravenous) or metabolism of citrate, lactate, or acetate in parenteral nutrition can generate metabolic alkalosis. 1, 2
• Milk-alkali syndrome from excessive calcium carbonate ingestion produces metabolic alkalosis with hypercalcemia. 1

Maintenance Factors

• Volume contraction, hypochloremia, hypokalemia, decreased GFR, and aldosterone excess all impair renal bicarbonate excretion and perpetuate metabolic alkalosis even after the initiating cause resolves. 1, 2, 4

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Diagnostic Approach

Initial Assessment

• Measure arterial blood gas to confirm pH >7.45, elevated bicarbonate, and compensatory PaCO₂ elevation (expected PaCO₂ = 40 + 0.7 × [HCO₃⁻ − 24]). 1
• Check serum electrolytes for hypokalemia (<3.5 mEq/L), hypochloremia (<99 mEq/L), and calculate the anion gap to exclude mixed disorders. 3, 1

Urinary Chloride Classification

• Urinary chloride <20 mEq/L indicates chloride-responsive (volume-depleted) alkalosis from vomiting, nasogastric suction, diuretics (remote use), or post-hypercapnic state. 3, 1
• Urinary chloride >20 mEq/L indicates chloride-resistant alkalosis from mineralocorticoid excess, ongoing diuretic use, Bartter/Gitelman syndrome, or severe hypokalemia. 3, 1

Additional Testing for Chloride-Resistant Cases

• Measure plasma renin and aldosterone to identify primary hyperaldosteronism (low renin, high aldosterone) versus secondary hyperaldosteronism (both elevated in Bartter/Gitelman). 3
• Assess fractional chloride excretion (>0.5% suggests renal salt wasting in Bartter/Gitelman syndrome). 3
• Check urinary calcium (high in Bartter syndrome, low in Gitelman syndrome) to differentiate genetic tubulopathies. 3

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Treatment Strategies

Chloride-Responsive Alkalosis (Urinary Cl⁻ <20 mEq/L)

Volume and Electrolyte Repletion

• Administer isotonic saline (0.9% NaCl) to restore extracellular volume and provide chloride, which allows the kidney to excrete excess bicarbonate. 3, 5
• Potassium chloride supplementation (20-60 mEq/day) is essential to correct hypokalemia and provide additional chloride; target serum potassium 4.5-5.0 mEq/L. 3
• Avoid potassium citrate or potassium bicarbonate, as these worsen the alkalosis; use only potassium chloride. 3

Chloride-Resistant Alkalosis (Urinary Cl⁻ >20 mEq/L)

First-Line Pharmacologic Therapy

• Potassium-sparing diuretics are first-line treatment: amiloride 2.5 mg daily (titrate to 5 mg) or spironolactone 25 mg daily (titrate to 50-100 mg) block distal sodium reabsorption and reduce hydrogen ion secretion. 3
• Monitor serum potassium closely when using potassium-sparing diuretics, especially in patients on ACE inhibitors or with renal dysfunction. 3

Bartter and Gitelman Syndromes

• Sodium chloride supplementation (5-10 mmol/kg/day) replaces renal salt losses. 3
• Potassium chloride for hypokalemia correction. 3
• NSAIDs (indomethacin or ibuprofen) reduce prostaglandin-mediated salt wasting in symptomatic patients. 3
• Co-administer gastric acid suppression (proton-pump inhibitor) when prescribing NSAIDs to prevent gastrointestinal complications. 3

Severe Metabolic Alkalosis (pH >7.55)

Acetazolamide Therapy

• Acetazolamide 500 mg IV as a single dose rapidly lowers serum bicarbonate by inhibiting proximal tubular bicarbonate reabsorption. 3, 5
• Use only when renal function is adequate (contraindicated in significant renal impairment). 3
• Particularly effective in heart failure patients with diuretic-induced alkalosis who require continued diuresis. 3
• Monitor for hypokalemia, which can worsen with carbonic anhydrase inhibition. 3

Acid Infusion (Rarely Needed)

• Dilute hydrochloric acid (0.1-0.2 N) via central venous catheter is reserved for life-threatening alkalosis (pH >7.60) when other measures fail or cannot be used. 5
• Ammonium chloride is an alternative but contraindicated in hepatic or severe renal dysfunction. 5

Renal Replacement Therapy

• Hemodialysis with low-bicarbonate/high-chloride dialysate is the treatment of choice for refractory metabolic alkalosis with concurrent renal failure. 3

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Special Clinical Scenarios

Diuretic-Induced Contraction Alkalosis

• Reduce or temporarily hold diuretics if bicarbonate rises significantly above 30 mmol/L and volume depletion is present. 3
• Replete volume with normal saline and provide chloride to restore volume and allow bicarbonate excretion. 3
• Consider acetazolamide in heart failure patients who require continued diuresis but have developed severe alkalosis. 3

Post-Hypercapnic Alkalosis

• Occurs when chronic respiratory acidosis is rapidly corrected (e.g., mechanical ventilation initiation), leaving compensatory elevated bicarbonate without the elevated PaCO₂. 1
• Treatment is usually supportive with volume repletion and chloride administration; the alkalosis typically resolves spontaneously as the kidneys excrete excess bicarbonate. 1

Compensated Chronic Respiratory Acidosis

• Do NOT treat the elevated bicarbonate when pH is normal and PaCO₂ is chronically elevated (>45 mmHg), as the bicarbonate is protective compensation. 6
• Focus on managing the underlying respiratory disorder and maintaining oxygen saturation 88-92% in chronic hypercapnic patients. 6

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Critical Monitoring Parameters

• Serial arterial or venous blood gases to assess pH and bicarbonate response to treatment. 1
• Serum electrolytes (sodium, potassium, chloride, bicarbonate) every 2-4 hours during acute treatment. 1
• Urinary chloride to guide ongoing therapy and assess response. 3, 1
• Blood pressure and volume status to avoid over-resuscitation or worsening hypertension. 3

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Common Pitfalls to Avoid

• Administering sodium bicarbonate or alkalinizing agents in metabolic alkalosis is contraindicated and will worsen the disorder. 3
• Using furosemide to treat alkalosis perpetuates the problem unless hypervolemia, hyperkalemia, or renal acidosis are present. 3
• Overlooking Bartter or Gitelman syndrome in euvolemic patients with unexplained hypokalemic metabolic alkalosis and no diuretic use. 3
• Failing to provide adequate chloride when correcting hypokalemia; potassium citrate or bicarbonate will worsen alkalosis. 3
• Attempting to correct compensatory bicarbonate elevation in chronic respiratory acidosis, which removes protective buffering. 6