Cystic Fibrosis and its Pathophysiology

Cystic Fibrosis
Pathophysiology of Cystic Fibrosis
Diagnosis of Cystic Fibrosis
Treatment of Cystic Fibrosis

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

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

10. 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

11. 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)

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

13. 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