Cystic fibrosis

Pathogenesis: how the disease develops

The disease is caused by a defect in the gene encoding the CFTR protein (cystic fibrosis transmembrane conductance regulator). Normally, this protein functions as a chloride channel on the membrane of epithelial cells lining duct systems of glands (bronchial, sweat, pancreatic, and others).

Due to the mutation, chloride secretion is impaired. To compensate for this shift, cells begin actively reabsorbing sodium. This disrupts the water-electrolyte balance and leads to pronounced dehydration of secretions.

As a result, mucus becomes pathologically thick and viscous. It blocks excretory ducts, causing damage to the lungs, pancreas, liver, and intestines.

Main clinical forms and manifestations

Diagnosis is established by indicating the leading pattern of involvement. The most common form is the classic pulmonary-intestinal form, in which both systems are affected.

• Bronchopulmonary changes: chronic obstructive bronchitis, development of bronchiectasis (often in the upper lobes), and pneumofibrosis. Exacerbations are triggered by infection (Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus aureus).
• Gastrointestinal involvement: neonatal intestinal obstruction (meconium ileus), severe exocrine pancreatic insufficiency. This leads to delayed physical development and fat-soluble vitamin deficiency (A, D, E, K).
• Other manifestations: sinusitis, nasal polyps, pseudo-Bartter syndrome (metabolic alkalosis with salt loss), and obstructive azoospermia in males.

Diagnostics and screening

A universal neonatal screening program for all newborns operates in Russia. First, the immunoreactive trypsinogen (IRT) level is determined in a dried blood spot. If elevated, a repeat test is performed, followed by a sweat test and DNA diagnostics.

Making the diagnosis requires criteria from two blocks:

1. Confirmation of CFTR dysfunction: positive sweat test (chloride concentration $\ge$ 60 mmol/L) or identification of two mutations in the gene.
2. Clinical data: hypertrypsinogenemia upon screening or typical symptoms (bronchiectasis, chronic Pseudomonas aeruginosa infection, exocrine insufficiency).

Treatment approaches

Cystic fibrosis is incurable, but proper lifelong therapy allows patients to reach adulthood.

• Basic airway therapy: daily drainage, kinesitherapy, and physical therapy for mechanical sputum clearance.
• Medications: inhaled mucolytics (dornase alfa), bronchodilators, and aggressive antibiotic therapy for infections (especially for P. aeruginosa).
• Dietary therapy: caloric intake is increased to 120–200% of normal. Fats are not restricted, but salt and fat-soluble vitamins must be added.
• Digestion: lifelong replacement therapy with microspheric pancreatic enzymes.

Class and exam questions

What else to study on this topic

• Stages and timeline of neonatal screening in the Russian Federation
• Specific and nonspecific clinical manifestations (detailed list)
• Antibiotic therapy strategy for Pseudomonas infection
• Complications of cystic fibrosis by organ and system
• Indications for lung transplantation

Other topics in "Chapter 4. Respiratory Diseases"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.