lecture 9 bio flashcards

Introduction to Cystic Fibrosis (CF)- This lecture, the ninth and final in the block, serves as a review of concepts and molecules discussed over the last three weeks, applied to the specific disease of cystic fibrosis (CF).
- Historical Context - Life Expectancy (1987 vs. Present)
  - 1987 Reality: A Canadian poster from 1987 highlighted the grim reality, stating a 12-year-old with CF had reached an age far beyond the expected median survival at that time, which was often in the early teens. This emphasized the severe limitations on lifespan.
  - Present Day: Significant advancements in diagnosis, treatment, and care have dramatically improved outcomes. The median survival age for individuals with CF now exceeds 50 years in many developed countries.
- Genetic Basis of CF
  - CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
  - The CFTR gene provides instructions for making the CFTR protein, which functions as a channel for chloride ions across cell membranes, crucial for maintaining the balance of salt and water on many body surfaces.
  - Over 2,000 different mutations in the CFTR gene have been identified, with F508 ext{del} being the most common, accounting for approximately 70 ext{%} of cases.
- Pathophysiology
  - Defective or missing CFTR protein leads to impaired chloride ion transport, resulting in thick, sticky mucus buildup in various organs.
  - Affected Organs:
    - Lungs: Obstructed airways, chronic bacterial infections, inflammation, and progressive lung damage (bronchiectasis).
    - Pancreas: Blockage of pancreatic ducts, leading to malabsorption of nutrients, weight loss, and CF-related diabetes.
    - Liver: Obstruction of bile ducts, which can cause liver damage (cirrhosis).
    - Intestines: Meconium ileus in newborns and distal intestinal obstruction syndrome (DIOS) in older individuals.
    - Reproductive System: Infertility, especially in males due to congenital bilateral absence of the vas deferens (CBAVD).
    - Sweat Glands: Elevated chloride levels in sweat (basis for the sweat test).
- Diagnosis
  - Newborn Screening: Standard in many countries; identifies potential CF cases early through immunoreactive trypsinogen (IRT) levels.
  - Sweat Chloride Test: Measures chloride levels in sweat; levels greater than 60 ext{mEq/L} are indicative of CF.
  - Genetic Testing: Confirms diagnosis by identifying CFTR gene mutations from a blood sample.
- Management and Treatment
  - A multidisciplinary approach focusing on symptom management, slowing disease progression, and improving quality of life.
  - Airway Clearance Techniques: Physical therapy, oscillatory vests, nebulized therapies (hypertonic saline, Dornase alfa) to clear mucus from the lungs.
  - Medications:
    - Antibiotics for chronic and acute infections.
    - Mucolytics to thin mucus.
    - Anti-inflammatory drugs.
    - Pancreatic enzyme replacement therapy (PERT) to aid digestion and nutrient absorption.
  - CFTR Modulators: Revolutionary drugs that target the underlying defect of the CFTR protein, improving its function and alleviating symptoms (e.g., Ivacaftor, Lumacaftor/Ivacaftor, Tezacaftor/Ivacaftor, Elexacaftor/Tezacaftor/Ivacaftor).
  - Lung Transplant: An option for individuals with severe end-stage lung disease when other treatments are no longer effective.