What are the causes of metabolic alkalosis in patients, particularly in geriatric individuals with a history of gastrointestinal disorders or renal conditions, such as gastroesophageal reflux disease (GERD), peptic ulcer disease, nephrotic syndrome, or impaired renal function?

Causes of Metabolic Alkalosis

Metabolic alkalosis results from either loss of fixed acid (primarily via gastrointestinal or renal routes) or net accumulation of bicarbonate, with maintenance of the alkalosis requiring impaired renal bicarbonate excretion due to volume depletion, hypochloremia, hypokalemia, or aldosterone excess. 1, 2

Primary Mechanisms of Generation

Gastrointestinal Acid Loss

• Vomiting or nasogastric suction causes loss of hydrochloric acid from gastric secretions, representing one of the most common causes of metabolic alkalosis 1, 2
• Intestinal fistulas or drainage can lead to significant chloride and acid losses 3
• In geriatric patients with GERD or peptic ulcer disease, protracted vomiting can cause severe metabolic alkalosis with secondary renal impairment 4

Renal Acid Loss

• Diuretic therapy (loop diuretics like furosemide and thiazides) causes increased urinary chloride and potassium excretion, leading to hypochloremic, hypokalemic metabolic alkalosis 5, 1, 3
• Contraction alkalosis develops when diuretics cause volume and chloride losses, concentrating existing bicarbonate in the extracellular fluid 5
• Hyperaldosteronism (primary aldosterone-producing adenoma) increases distal tubular hydrogen ion secretion and potassium loss 1, 3
• Cushing syndrome produces excess cortisol with mineralocorticoid effects 1

Genetic Tubulopathies

• Bartter syndrome involves defective chloride transport in the thick ascending limb of Henle, causing salt wasting, hypokalemia, and metabolic alkalosis with elevated urinary chloride (fractional excretion >0.5%) 5, 1, 3
• Gitelman syndrome results from defective sodium-chloride cotransporter in the distal tubule 1, 2

Exogenous Base Administration

• Excessive oral or parenteral bicarbonate administration 1, 3
• Administration of bicarbonate precursors (lactate, acetate, citrate) 2, 6
• Milk-alkali syndrome from excessive calcium and alkali ingestion 2

Post-Hypercapnic Alkalosis

• Occurs after rapid correction of chronic respiratory acidosis (chronic CO₂ retention) 1
• The kidneys retain bicarbonate to compensate for chronic hypercapnia; when CO₂ normalizes rapidly, the elevated bicarbonate persists, causing metabolic alkalosis 1
• Particularly relevant in patients with chronic lung disease or those on mechanical ventilation 3

Maintenance Factors (Why the Kidney Cannot Correct It)

The kidney normally prevents metabolic alkalosis by excreting excess bicarbonate, but several factors impair this protective mechanism:

• Volume depletion activates sodium reabsorption, which obligates increased hydrogen ion secretion to maintain electrical neutrality 5, 1
• Hypochloremia limits the kidney's ability to excrete bicarbonate by reducing the chloride gradient needed for bicarbonate excretion 5, 1
• Hypokalemia (typically <3.5 mmol/L) promotes bicarbonate reabsorption and paradoxical hydrogen ion secretion despite systemic alkalosis 5, 1
• Aldosterone excess increases distal tubular hydrogen ion secretion 1
• Reduced glomerular filtration rate decreases bicarbonate filtration 2, 6

Special Considerations in Geriatric and Renal Populations

Nephrotic Syndrome Context

• Volume contraction from urinary protein losses and diuretic use can precipitate metabolic alkalosis 5
• Hypoalbuminemia may mask the severity of alkalosis on routine laboratory assessment 2

Impaired Renal Function

• In patients with chronic kidney disease, even mild vomiting can cause severe, recurrent metabolic alkalosis due to reduced baseline bicarbonate excretion capacity 4
• Hemodialysis patients are particularly vulnerable when vomiting occurs between dialysis sessions, as they lack the ability to excrete bicarbonate renally 7
• Latent renal insufficiency combined with dehydration from vomiting can cause rapid deterioration of renal function 4

Diagnostic Approach

Measure urinary chloride to distinguish between causes:

• Urinary chloride <20 mEq/L (chloride-responsive): Indicates volume depletion from vomiting, nasogastric suction, or remote diuretic use 2, 8
• Urinary chloride >20 mEq/L (chloride-resistant): Suggests ongoing diuretic therapy, mineralocorticoid excess, Bartter/Gitelman syndrome, or severe hypokalemia 2, 8

Assess volume status clinically to determine if the patient has volume depletion (most common) or volume expansion (mineralocorticoid excess) 8

Measure plasma renin and aldosterone when urinary chloride is elevated to identify primary versus secondary hyperaldosteronism 8

Clinical Pitfalls

• Paradoxical aciduria: In severe hypokalemic metabolic alkalosis, urine pH may be acidic (<5.5) despite systemic alkalosis due to enhanced distal hydrogen ion secretion driven by aldosterone and volume depletion 5
• Diuretic resistance: Hypochloremia itself can worsen diuretic resistance by decreasing the intraluminal chloride gradient needed for diuretic efficacy 3
• Mortality risk: Severe metabolic alkalosis (arterial pH ≥7.55) in critically ill patients is associated with significantly increased mortality 2
• In salt-wasting disorders like Bartter syndrome, potassium-sparing diuretics may worsen volume depletion despite improving hypokalemia 5