Cystic Fibrosis
Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the CFTR (Cystic Fibrosis
Transmembrane Conductance Regulator) gene, which affects chloride ion transport across epithelial
cell membranes. The condition primarily impacts the respiratory, digestive, and reproductive systems,
leading to the accumulation of thick and sticky mucus.
Genetic Basis
● CF is an autosomal recessive disorder, meaning an individual must inherit two defective
copies of the CFTR gene (one from each parent) to develop the disease.
● The most common mutation is ΔF508, which leads to a misfolded CFTR protein that is
degraded before reaching the cell membrane.
● The CFTR gene is located on chromosome 7, and mutations affect the production and
function of the chloride ion channel, disrupting osmotic balance.
Pathogenesis
Cellular Mechanism
● In healthy individuals, CFTR proteins regulate chloride ion transport in epithelial cells.
● In CF patients, defective or absent CFTR proteins result in reduced chloride and water
transport, leading to thick mucus buildup in organs such as the lungs, pancreas, liver, and
intestines.
Effects on Different Organs
Respiratory System:
● Thick mucus obstructs airways, reducing gas exchange.
● Trapped bacteria lead to chronic infections (e.g., Pseudomonas aeruginosa, Staphylococcus
aureus).
● Chronic inflammation results in lung tissue scarring (fibrosis), reducing lung function.
Digestive System:
● Pancreatic ducts become blocked, preventing the release of digestive enzymes.
● Leads to malabsorption of fats, proteins, and fat-soluble vitamins (A, D, E, K).
● Symptoms include steatorrhea (fatty stools), weight loss, and poor growth.
Reproductive System:
● Males with CF often have congenital bilateral absence of the vas deferens (CBAVD), leading
to infertility.
● Females may experience thicker cervical mucus, making conception more difficult.
Symptoms
Respiratory Symptoms:
● Persistent cough with thick mucus.
● Frequent lung infections (bronchitis, pneumonia).
● Wheezing and shortness of breath.
Digestive Symptoms:
● Poor weight gain and growth delays.
● Greasy stools (steatorrhea) due to fat malabsorption.
● Bloating and meconium ileus in newborns.
Other Symptoms:
● Salty skin due to excessive sodium loss in sweat.
● Clubbing of fingers due to chronic hypoxia.
● Osteoporosis from malabsorption of calcium and vitamin D.
Treatment Therapies
Medications:
● CFTR Modulators:
○ Ivacaftor (restores function in some mutations).
○ Lumacaftor + Ivacaftor (helps ΔF508 mutation patients).
○ Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) (most effective in improving CFTR
function).
● Mucolytics:
○ Dornase Alfa – breaks down mucus in the lungs.
○ Hypertonic saline – helps clear thick mucus.
● Antibiotics:
○ Target chronic lung infections (Tobramycin, Azithromycin).
● Bronchodilators:
○ Help open airways (e.g., Salbutamol).
Airway Clearance Techniques:
● Chest physiotherapy (postural drainage, percussion).
● High-frequency chest wall oscillation vests.
● Breathing exercises and pulmonary rehabilitation.
Nutritional Support:
● High-calorie, high-protein diet to maintain body weight.
● Pancreatic enzyme supplements (e.g., Creon).
● Vitamin supplementation (A, D, E, K).
Advanced Therapies:
● Lung Transplant for end-stage CF.
● Gene Therapy (Emerging Research) aims to correct defective CFTR genes.
How Quality of Life is Affected
Daily Life Challenges:
● CF requires extensive daily medications and physiotherapy, taking up several hours.
● Frequent hospital visits for lung infections.
Social & Emotional Impact:
● CF patients must avoid close contact with others who have CF (due to cross-infection risk,
e.g., 'Five Feet Apart' rule).
● Mental health concerns: Anxiety, depression due to disease burden.
Life Expectancy:
● Median survival age has improved to 40+ years due to new treatments.
● Research into gene therapy and stem cell treatment offers hope for longer life expectancy.
● This means tha
