What causes metabolic alkalosis in children with cystic fibrosis (CF)?

Metabolic Alkalosis in Children with Cystic Fibrosis

Primary Mechanism

Metabolic alkalosis in children with CF results from excessive sodium and chloride losses through sweat, leading to hyponatremic, hypochloremic, hypokalemic metabolic alkalosis—a condition particularly common in infants under 2 years of age. 1, 2

The fundamental pathophysiology stems from the defective CFTR chloride channel, which causes defective salt reabsorption in sweat glands, leading to abnormally salty sweat and electrolyte imbalance 3. This creates a two- to four-fold higher sodium chloride sweat content compared to healthy children 4.

Key Contributing Factors

Excessive Sweat Electrolyte Losses

• Chronic sweat losses of sodium and chloride are the primary driver, with infants being particularly vulnerable due to higher body surface area-to-weight ratios 4, 5
• Heat exposure, fever, or increased ambient temperature exacerbate losses, though no specific seasonal predilection exists 2, 5
• The defective CFTR protein prevents normal salt reabsorption in sweat ducts, resulting in salt-wasting 3

Volume Depletion and Compensatory Mechanisms

• Volume contraction from chronic salt losses triggers aldosterone activation, which increases distal tubular hydrogen ion secretion to maintain electrical neutrality during sodium reabsorption 6
• This creates paradoxical aciduria—the kidney excretes acid despite systemic alkalosis because volume depletion takes precedence over pH correction 6
• Hypochloremia maintains the alkalosis by limiting the kidney's ability to excrete bicarbonate 6

Age-Specific Vulnerability

• Infants under 2 years are at highest risk, with 16.5-46% developing metabolic alkalosis in reported series 1, 2, 5
• Young infants have immature renal concentrating ability (maximum 550-700 mosm/L vs 1200 mosm/L in adults), limiting their ability to conserve electrolytes 3
• Breast-feeding increases risk due to relatively low sodium content of breast milk combined with high sweat losses 2

Clinical Precipitants

Common Triggers

• Anorexia and vomiting compound electrolyte losses and reduce intake 1
• Respiratory exacerbations with fever increase insensible losses and sweating 1
• Delayed CF diagnosis allows chronic losses to accumulate before recognition and treatment 2
• Heat exhaustion, though the presentation differs from acute heat prostration by lacking shock and hyperpyrexia 5

Chronic Factors

• Pancreatic insufficiency requiring high-dose enzyme replacement correlates with metabolic alkalosis occurrence 7
• Poor nutritional status and severe underweight are associated with chronic metabolic alkalosis 7
• Presence of severe CFTR mutations (classes I, II, or III) predisposes to this complication 2

Diagnostic Characteristics

Laboratory Findings

• Serum sodium <133 mmol/L (hyponatremia) 1
• Serum chloride <85 mmol/L (hypochloremia) 1
• Serum potassium <3.5 mmol/L (hypokalemia) 1
• Serum bicarbonate >35 mmol/L 1
• Blood pH >7.43 1
• Paradoxical aciduria may be present despite systemic alkalosis 6

Clinical Presentation

• Often presents as an initial manifestation of undiagnosed CF, making sweat testing mandatory for any infant with unexplained metabolic alkalosis 1, 5
• Can occur as acute severe episodes or chronic metabolic alkalosis 1, 7
• Recurrent episodes are common without adequate sodium supplementation 5

Critical Clinical Pitfalls

Common Errors to Avoid

• Assuming normal serum sodium excludes sodium depletion—chronic losses may be compensated initially, but supplementation is still required 8
• Failing to perform sweat testing in any infant with unexplained metabolic alkalosis—this is a sentinel presentation of CF 1, 5
• Attempting to correct aciduria directly rather than addressing the underlying volume depletion and electrolyte deficits 6
• Restricting sodium intake when salt supplementation is actually needed—CF is a salt-wasting condition requiring 1-5 mmol Na/kg/day supplementation 8

Monitoring Requirements

• Regular serum electrolyte assessment during hot weather months in known CF infants 5
• Recognition that metabolic alkalosis is more common in young patients requiring high-dose pancreatic enzymes with poor nutritional status 7

Treatment Approach

Correction requires addressing volume depletion with chloride-containing solutions (normal saline) and potassium chloride supplementation, not attempting to correct the alkalosis or aciduria directly. 6

• Volume repletion with normal saline provides both volume and chloride for bicarbonate excretion 6
• Potassium chloride supplementation corrects hypokalemia and reduces compensatory hydrogen ion secretion 6
• Long-term sodium chloride supplementation (1-5 mmol Na/kg/day) prevents recurrence in infants with CF 8
• Address underlying triggers such as respiratory infections or heat exposure 1