What are the causes of metabolic alkalosis in adults and the elderly with a history of gastrointestinal disorders, kidney disease, or those taking medications such as diuretics, corticosteroids, or laxatives?

Causes of Metabolic Alkalosis

Metabolic alkalosis results from either loss of hydrogen ions (via gastrointestinal or renal routes) or gain of bicarbonate, with maintenance factors preventing renal bicarbonate excretion. 1, 2

Generation Mechanisms

Gastrointestinal Hydrogen Loss

• Vomiting is a primary cause, leading to direct loss of gastric hydrochloric acid and generating metabolic alkalosis 1, 2
• Nasogastric suction produces the same effect as vomiting through continuous gastric acid removal 2

Renal Hydrogen Loss

• Loop and thiazide diuretics are the most common medication-related causes, promoting urinary hydrogen and chloride loss 3, 4
• Diuretic therapy increases distal sodium delivery, enhancing hydrogen ion secretion in the collecting duct despite systemic alkalosis 4
• Mineralocorticoid excess (primary hyperaldosteronism, Cushing's syndrome) drives renal hydrogen secretion 2, 5
• Corticosteroid medications mimic aldosterone effects, promoting hydrogen ion excretion 2

Bicarbonate Gain

• Excessive oral or parenteral bicarbonate administration directly increases extracellular bicarbonate 5, 6
• Metabolism of lactate, acetate, or citrate (found in blood products and parenteral nutrition) generates bicarbonate 5, 6
• Milk-alkali syndrome from excessive calcium carbonate intake (often from antacids or calcium supplements) 2

Genetic Tubulopathies

• Bartter syndrome causes salt wasting in the thick ascending limb, leading to hypokalemic metabolic alkalosis with elevated urinary chloride (>20 mEq/L) and secondary hyperaldosteronism 3, 2
• Gitelman syndrome presents similarly but with hypocalciuria distinguishing it from Bartter syndrome 3
• Both conditions show normal to low blood pressure despite severe electrolyte derangements 3

Maintenance Factors

The kidney normally excretes excess bicarbonate rapidly, so metabolic alkalosis persists only when maintenance factors impair renal bicarbonate excretion. 1, 2

Volume Depletion

• Hypovolemia is the most critical maintenance factor, stimulating proximal tubule sodium and bicarbonate reabsorption to preserve intravascular volume 1, 2
• Volume contraction activates the renin-angiotensin-aldosterone system, further promoting bicarbonate retention 4

Electrolyte Abnormalities

• Hypochloremia prevents bicarbonate excretion by limiting chloride availability for bicarbonate exchange in the collecting duct 4, 1
• Hypokalemia (typically <3.5 mmol/L) maintains alkalosis by shifting hydrogen ions intracellularly and increasing renal hydrogen secretion 3, 1
• Potassium depletion enhances proximal tubule bicarbonate reabsorption 2, 5

Reduced Glomerular Filtration

• Decreased GFR reduces filtered bicarbonate load, impairing the kidney's ability to excrete excess bicarbonate 1, 5
• Chronic kidney disease progressively limits bicarbonate excretion capacity 2

Aldosterone Excess

• Elevated aldosterone (primary or secondary) increases distal sodium reabsorption and hydrogen secretion 1, 5
• Licorice ingestion inhibits 11β-hydroxysteroid dehydrogenase, causing apparent mineralocorticoid excess 2, 5

Clinical Context Classification

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

• Vomiting or nasogastric suction 2
• Remote diuretic use (after discontinuation) 2
• Post-hypercapnic state 2
• Characterized by volume depletion and responds to saline administration 1

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

• Active diuretic therapy 3, 2
• Primary hyperaldosteronism 2
• Bartter or Gitelman syndrome (fractional chloride excretion >0.5% despite volume depletion) 3, 7
• Cushing's syndrome 2
• Requires specific treatment of underlying cause rather than saline 2

Common Pitfalls

• Overlooking Bartter syndrome in patients with unexplained metabolic alkalosis, especially with history of polyhydramnios and premature birth—always consider genetic tubulopathies when urinary chloride remains elevated despite apparent volume depletion 3
• Using potassium citrate or potassium bicarbonate for potassium repletion worsens the alkalosis—always use potassium chloride exclusively 3
• Continuing loop diuretics perpetuates the alkalosis unless hypervolemia, hyperkalemia, or renal acidosis are present 3
• Paradoxical aciduria (acid urine despite alkalemia) occurs with volume depletion and hypokalemia, reflecting enhanced distal hydrogen secretion driven by aldosterone—this is not a treatment target but rather confirms the diagnosis 4