Physiology · Year 1 · from Physiology
Case 1: Cystic Fibrosis - CFTR Channel Dysfunction
Clinical Image
Source: Wikimedia Commons - Cystic fibrosis - CC BY-SA 3.0
Patient Presentation
A 6-month-old male infant is brought to the pediatric clinic by his parents due to failure to thrive, recurrent respiratory infections, and foul-smelling, greasy stools. The parents report that the child was diagnosed with meconium ileus at birth requiring surgical intervention. They also noticed that his skin tastes unusually salty when they kiss him.
Demographics
- Age: 6 months
- Sex: Male
- Ethnicity: Caucasian
Chief Complaint
Failure to thrive, recurrent respiratory infections, and steatorrhea
Physical Examination
- Weight: 5.8 kg (below 3rd percentile)
- Length: 62 cm (10th percentile)
- Digital clubbing: Early changes noted
- Respiratory: Scattered crackles bilaterally, mild tachypnea
- Abdomen: Mildly distended with palpable stool in right lower quadrant
- Skin: Normal turgor, slightly salty taste noted on examination
Workup
- Sweat chloride test: 85 mEq/L (diagnostic; normal <30 mEq/L)
- Genetic testing: Homozygous for F508del mutation in CFTR gene
- Chest X-ray: Hyperinflation with peribronchial thickening
- Stool elastase: <100 mcg/g (indicates pancreatic insufficiency)
- Sputum culture: Staphylococcus aureus
Diagnosis
Cystic Fibrosis with pancreatic insufficiency and early pulmonary disease
Treatment
- Pancreatic enzyme replacement therapy (PERT) with meals
- Fat-soluble vitamin supplementation (A, D, E, K)
- High-calorie, high-fat diet
- Airway clearance therapy (chest physiotherapy)
- Nebulized hypertonic saline
- CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor for eligible genotypes)
- Prophylactic antibiotics as needed
- Multidisciplinary care at a CF center
Physiological Principles Demonstrated
- CFTR as a chloride channel: The CFTR protein functions as a chloride channel in epithelial cell membranes. The F508del mutation causes misfolding and degradation of the channel protein, preventing its insertion into the cell membrane.
- Chloride and water transport: Without functional CFTR, chloride cannot be secreted into the airway lumen. Water follows chloride osmotically; therefore, reduced chloride secretion leads to dehydrated, thick mucus that cannot be cleared effectively.
- Sweat gland physiology: In sweat glands, CFTR normally reabsorbs chloride (and sodium follows). Dysfunctional CFTR leads to elevated sweat chloride, the basis for the diagnostic sweat test.
- Secondary active transport: CFTR dysfunction also affects ENaC (epithelial sodium channel) regulation, further altering ion and water balance across epithelia.