Cystic fibrosis

1. Definition

• Cystic fibrosis (CF) = most common lethal autosomal-recessive disease in Caucasians.
• A disorder of epithelial transport affecting exocrine glands of the respiratory, GI, and reproductive tracts.
• Triad: recurrent/chronic pulmonary infections, pancreatic insufficiency, high NaCl in sweat.

2. Pathogenesis (CFTR)

• Mutation of the CFTR gene → defective cAMP-regulated epithelial Cl⁻ channel → altered mucus consistency.
• Sweat ducts: CFTR normally reabsorbs Cl⁻/Na⁺ → defect → hypertonic (salty) sweat.
• Airway/GI: CFTR normally secretes Cl⁻ → defect → ↓Cl⁻ secretion, ↑Na⁺/H₂O reabsorption → dehydrated, thick mucus → defective mucociliary clearance → obstruction + infection.

3. Organ Manifestations

• Lungs (most serious): mucus plugging, bronchiectasis; opportunistic infections — S. aureus, H. influenzae, P. aeruginosa (also Burkholderia cepacia); nasal polyps.
• Pancreas: duct plugging → atrophy + fibrosis, squamous metaplasia → exocrine insufficiency → fat malabsorption.
• Intestine: meconium ileus in neonates.
• Liver: plugged canaliculi → steatosis → biliary cirrhosis.
• Genital: bilateral absence of vas deferens → azoospermia/infertility.

4. Clinical Course

• Diagnosis: salty sweat (sweat chloride test), clinical findings, family history, CFTR mutation.
• 5–10% present with meconium ileus at birth.
• 85–90% develop exocrine pancreatic insufficiency → protein malabsorption (edema), fat malabsorption → deficiency of fat-soluble vitamins (A, D, E, K) + diarrhea.
• Most common cause of death: cardiorespiratory (chronic infection, obstructive lung disease, cor pulmonale); also liver disease, transplant complications.

💡 High-yield: CFTR Cl⁻ channel defect → thick secretions everywhere. Sweat = salty (↓reabsorption); airway/pancreas/gut = obstructed (↓secretion). Classic triad: lung infection (Pseudomonas), pancreatic insufficiency, meconium ileus; males infertile (absent vas deferens).