Cystic fibrosis (CF) is an autosomal recessive disorder characterized by defects in the CFTR gene, leading to severe respiratory and digestive issues due to abnormal chloride transport and thick secretions. Common complications include recurrent respiratory infections, pancreatic enzyme insufficiency, and infertility, with respiratory failure being a major cause of death. Diagnosis requires genetic testing or sweat sodium analysis, and while there is no cure, treatment focuses on symptom management and improving quality of life.

1. Cystic Fibrosis (CF)
Dr P Mayurathan

2. Cystic Fibrosis (CF)
• Inherited autosomal recessive disorder
• It’s a disease of exocrine gland function involves multiple organ
systems mainly
– Recurrent chronic respiratory infections
– Pancreatic enzyme insufficiency
• Pulmonary involvement occurs in 90% of patients and end-stage lung
disease is the principal cause of death.

3. • Gene mutation on the long arm of chromosome 7 in the region of
7q31.2
• Commonest abnormality is specific deletion at position 508 in the
animoacid sequence (∆F508)
• Results in a defect in the Cystic Fibrosis Transmembrane
conductance regulator (CFTR) gene
• CFTR is a Chloride channel and it is regulated by cAMP
• Mutations in the CFTR gene result in abnormalities of Chloride
transport across epithelial cells on mucosal surfaces
Pathophysiology of Cystic Fibrosis

4. • Defective CFTR results in
– decreased excretion of Chloride
– increased reabsorption of Sodium and water across epithelial
cells
• As a result less excretion of salt and water and increased viscosity of
secretions such as secretions in the
– Respiratory tract
– Pancreas
– GI tract
• This mucus is difficult to clear and stickier to bacteria and promotes
infection and inflammation
Pathophysiology of Cystic Fibrosis

5. Pathophysiology of Cystic Fibrosis

6. • Defective CFTR in intestine leads to;
– reduced chloride secretion and water into the gut
– increased viscosity of the intestinal content
• This may result in meconium ileus and intestinal obstruction
Pathophysiology of Cystic Fibrosis

7. • It also affects the mucociliary clearance and infertility due to;
– Congenital absence of vas deferens, undescended testicles,
hydroceles or reduced motility of sperms in males
– Amenorrhea or problem with ovarian movement in females
Pathophysiology of Cystic Fibrosis

8. • The pancreatic insufficiency is due to
– Reduced pancreatic bicarbonate secretion leading to sub optimal
pH for pancreatic enzyme action
– In addition, it prevents the pancreatic enzymes to reach the gut
and auto-digestion of the pancreas leads to pancreatitis
• This may result in malabsorption, steatorrhoea and weight loss
Pathophysiology of Cystic Fibrosis

10. • Defective CFTR in sweat glands causes;
– Increased excretion of Chloride and Sodium
• Leads high sodium concentration in sweat
Pathophysiology of Cystic Fibrosis

11. Clinical Features of Cystic Fibrosis
• Frequent respiratory tract infections
• COPD
• Bronchiectasis
• Sinusitis
• Spontaneous pneumothorax
– All leads to respirtory failure and cor-pulmonale
• Steatorrhoea
• Malnutrition
• Meconium ileus/intestinal obstruction
• Cirrhosis
• GI malignancies
• Infertility

13. Diagnosis of Cystic Fibrosis
• Diagnosis include either positive genetic testing or positive sweat
Sodium (>60 mEq/L) and 1 of the following:
– Typical chronic obstructive pulmonary disease
– Documented exocrine pancreatic insufficiency
– Positive family history (usually affected sibling)

14. Treatment of Cystic Fibrosis
• No cure or prevention
• Average lifespan is around 35 years
• Death is commonly due to pulmonary related problems

15. • General
– Stop smoking
– Vaccines – Pneumococcal and influenza
– Nutritional supplement with pancreatic enzymes and vitamins
• Oxygen
• Antibiotics
• Chest physiotherapy and postural drainage
• Non-invasive ventilation (NIV)
• Genetic therapy
Treatment of Cystic Fibrosis