Bronchiectasis_CysticFibrosis_Presentation1.pptx

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1. Bronchiectasis & Cystic Fibrosis Hiba Younes Manasrah 210194 LOAI MUHTASEB  DR.  SUPERVISOR: DR.ASHRAF AL-ZUGHAYYAR

2. Pathophysiology of Bronchiectasis • Cycle of infection and inflammation: • Initial insult (e.g., severe infection, impaired host defense, obstruction) damages the bronchial wall. • Chronic infection leads to persistent neutrophilic inflammation, releasing proteases and reactive oxygen species. • Structural damage: • Destruction of elastic tissue, cartilage, and smooth muscle in the bronchial walls. • Leads to permanent airway dilation and loss of normal bronchial architecture. • Mucociliary dysfunction: • Impaired clearance of mucus causes retention of secretions. • Viscous sputum promotes bacterial colonization (e.g., Pseudomonas aeruginosa ). • Vicious cycle: • Infection → inflammation → tissue damage → impaired clearance → more infection. • Over time, this perpetuates progressive bronchial dilation and clinical symptoms.

3. Diagnosis of Bronchiectasis • Clinical suspicion: Chronic cough, daily mucopurulent sputum production, recurrent respiratory infections, hemoptysis, dyspnea, and wheezing. • Imaging: • High-resolution CT (HRCT) is the gold standard: shows airway dilation, lack of tapering, and bronchial wall thickening. • Microbiology: Sputum cultures for bacterial pathogens (e.g., Pseudomonas aeruginosa ). • Pulmonary function tests: Often reveal obstructive pattern. • Underlying causes: Workup may include testing for cystic fibrosis, immunodeficiencies , allergic bronchopulmonary aspergillosis (ABPA), and autoimmune diseases.

4. ) Cylindrical or tubular ( most)common parallel tram track sign and signet ring sign

5. Treatment of Bronchiectasis • General management: • Airway clearance techniques (chest physiotherapy, oscillatory devices , postural drainage). • Mucolytics in selected cases. • Antibiotics: • Acute exacerbations: guided by sputum culture. • Chronic infection with Pseudomonas: consider long-term inhaled antibiotics. • Anti-inflammatory therapy: Macrolides may be used long-term for anti-inflammatory and antimicrobial effect. • Vaccinations: Influenza and pneumococcal vaccines. • Surgery: Reserved for localized disease not controlled by medical therapy.

6. 1. Definition • Cystic fibrosis is a genetic, autosomal recessive disease caused by mutations in the CFTR gene ( Cystic fibrosis transmembrane conductance regulator gene A gene located on the long arm of chromosome 7 that encodes the CFTR protein, which is required for proper function of the chloride channel in cell membranes. The chloride channel normally secretes chloride ions in the lungs and gastrointestinal tract. Defects (most commonly a deletion of Phe508) cause cystic fibrosis.. • It leads to defective chloride and bicarbonate transport, resulting in thick and sticky secretions in multiple organs.

7. Pathophysiology • Defective CFTR protein → impaired chloride and water movement across epithelial cells. • Results in viscous secretions that obstruct ducts and airways. • Leads to recurrent infections, inflammation, and progressive organ damage The CFTR gene encodes the CFTR protein, which is an important component of the ATP-gated chloride channel in cell membranes. Mutated CFTR gene → misfolded protein → retention for degradation of the defective protein in the rough endoplasmic reticulum ( rER ) → absence of ATP- gatedchloride channel on the cell surface of epithelial cells throughout the body (e.g., intestinal and respiratory epithelia, sweat glands, exocrine pancreas, exocrine glandsof reproductive organs) [6][7] In sweat glands The chloride channel is responsible for transporting Cl - from the lumen into the cell(reabsorption).

8. Defective ATP-gated chloride channel →inability to reabsorb Cl - from the lumen of the sweat glands → reduced reabsorption of Na+ and H2O → excessive loss of salt and elevated levels of NaCl in sweat In all other exocrine glands (e.g., in the GI tract or lungs) The chloride channel is responsible for transporting Cl - from the cell into the lumen (secretion). Defective ATP-gated chloride channel →inability to transport intracellular Cl - across the cell membrane → reduced secretion of Cl - and H2O → accumulation of intracellular Cl - → ↑ Na+ reabsorption (via ENaC ) → ↑ H2O reabsorption → formation of hyperviscous mucus →accumulation of secretions and blockage of small passages of affected organs →chronic inflammation and remodeling →organ damage (see “Clinical features” below) ↑ Na+ reabsorption → transepithelial potential difference between interstitialfluid and the epithelial surface increases(i.e., negative charge increases; e.g., from normal -13 mv to abnormal -25 mv)

9. Clinical Manifestations: *Chronic obstructive lung disease with bronchiectasis *Chronic sinusitis: nasal polyps may eventually develop *Recurrent or chronic productive cough and pulmonary infections S. aureus is the most common cause of recurrent pulmonary infection in infancy and childhood. P. aeruginosa is the most common cause of recurrent pulmonary infections in adulthood • Gastrointestinal system: pancreatic insufficiency → malabsorption , steatorrhea , failure to thrive. • Hepatobiliary system: biliary cirrhosis. • Reproductive system: male infertility (congenital bilateral absence of vas deferens). • Other: CF-related diabetes, digital clubbing .

10. Diagnosis • Newborn screening ( immunoreactive trypsinogen ). • Sweat chloride test: gold standard (> 60 mmol /L is diagnostic). • Genetic testing: confirms CFTR mutations. • Pulmonary function tests: show obstructive disease .

11. Treatment • Respiratory management: • Airway clearance therapy (physiotherapy, oscillatory devices). • Inhaled mucolytics ( dornase alfa , hypertonic saline). • Inhaled and systemic antibiotics for infections. • CFTR modulators: drugs targeting specific mutations (e.g., ivacaftor , lumacaftor / ivacaftor ). • Nutritional support: pancreatic enzyme replacement, fat-soluble vitamins. • Advanced therapy: lung transplantation in end-stage disease . Epidemiology : Second most common genetic metabolic disorder in individuals of Northern European descent after hemochromatosis.