Pathophysiology of Respiratory Diseases

•  What are the key pathophysiological changes in asthma?

  • Chronic airway inflammation: Eosinophils, mast cells, and Th2 lymphocytes cause persistent inflammation.
  • Bronchial hyperresponsiveness: Airways overreact to allergens, cold air, and irritants.
  • Airway obstruction: Mucus hypersecretion, smooth muscle hypertrophy, and bronchoconstriction reduce airflow.
  • Reversible airflow limitation: Unlike COPD, obstruction can be reversed with bronchodilators.
• How does chronic inflammation contribute to asthma pathophysiology?

  • Chronic inflammation leads to structural airway changes (airway remodeling).
  • Thickening of the basement membrane due to collagen deposition.
  • Goblet cell hyperplasia increases mucus production.
  • Smooth muscle hypertrophy increases airway narrowing.
  • Persistent inflammation leads to long-term airway remodelling and reduced lung function.
• What are the main pathophysiological features of COPD?

  • Chronic inflammation: Neutrophils, macrophages, and CD8+ T cells cause persistent damage.
  • Airway narrowing: Due to fibrosis and smooth muscle hypertrophy.
  • Alveolar destruction (emphysema): Loss of elastin leads to decreased lung recoil and air trapping.
  • Mucus hypersecretion (chronic bronchitis): Goblet cell hyperplasia increases mucus production, leading to airway obstruction.
  • Irreversible airflow limitation: Due to loss of alveolar elasticity and fibrosis.
• How does emphysema contribute to COPD pathophysiology?

  • Elastin breakdown by proteases (e.g., neutrophil elastase) causes alveolar destruction.
  • Loss of elastic recoil leads to air trapping and increased residual lung volume.
  • Formation of bullae: Large air spaces reduce gas exchange efficiency.
  • Increased work of breathing due to airway collapse during exhalation.
• What is the pathophysiology of chronic bronchitis in COPD?

  • Persistent mucus hypersecretion due to goblet cell hyperplasia.
  • Ciliary dysfunction impairs mucus clearance.
  • Airway wall thickening due to fibrosis and inflammation.
  • Recurrent infections due to mucus stasis, worsening inflammation.
• What are the key pathophysiological changes in pneumonia?

  • Alveolar inflammation: Pathogens trigger neutrophilic response and cytokine release.
  • Increased vascular permeability: Leads to alveolar exudate and consolidation.
  • Impaired gas exchange: Due to fluid-filled alveoli reducing oxygen diffusion.
  • Fever and systemic inflammation: Cytokine release leads to fever and malaise.
• How does pneumonia cause hypoxia?

  • Alveolar consolidation reduces surface area for gas exchange.
  • Ventilation-perfusion (V/Q) mismatch due to fluid-filled alveoli.
  • Intrapulmonary shunting: Deoxygenated blood bypasses ventilated alveoli.
• What are the stages of pneumonia progression?

  1. Congestion (0-24h) – Vasodilation, alveolar exudate, neutrophil migration.
  2. Red hepatisation (2-3 days) – RBCs, neutrophils, and fibrin fill alveoli, making them firm.
  3. Gray hepatisation (4-7 days) – RBC breakdown, macrophages remove debris.
  4. Resolution (8+ days) – Alveoli clear, lung function recovers.
• What are the key factors that impact respiratory function in disease states?

  • Airway resistance
  • Lung compliance
  • Gas exchange efficiency
  • Presence of inflammation, infection, or obstruction.
• What is asthma?

  A chronic inflammatory disorder of the airways characterised by reversible airway obstruction, bronchial hyperresponsiveness, and airway remodelling.
• How does asthma impact respiratory function?

  Asthma leads to episodic airflow limitation due to bronchoconstriction, airway inflammation, and increased mucus production, reducing airflow and impairing oxygen exchange.
• What causes airway hyperresponsiveness in asthma?

  Inflammatory mediators (e.g., histamine, leukotrienes) cause excessive bronchoconstriction in response to triggers such as allergens, cold air, or exercise.
• Why is airway obstruction in asthma reversible?

  Bronchoconstriction and inflammation can be reduced by bronchodilators (e.g., β₂-agonists) and corticosteroids, restoring normal airway function.
• How does airway remodelling occur in chronic asthma?

  Chronic inflammation leads to structural changes such as subepithelial fibrosis, smooth muscle hypertrophy, and increased mucus gland production, making asthma more persistent.
• What is COPD?

  A progressive respiratory disease characterised by persistent airflow limitation due to chronic bronchitis, emphysema, or both, primarily caused by smoking or environmental pollutants.
• How does COPD differ from asthma in terms of airflow obstruction?

  COPD airflow obstruction is irreversible, while asthma obstruction is reversible with treatment.
• How does chronic bronchitis contribute to COPD pathophysiology?

  Chronic bronchitis involves persistent inflammation, leading to increased mucus production, airway narrowing, and chronic cough, causing airflow limitation.
• What is the pathophysiology of emphysema in COPD?

  In emphysema, alveolar walls are destroyed due to elastase overactivity, reducing elastic recoil and surface area for gas exchange, leading to hyperinflation and impaired oxygen diffusion.
• Why do COPD patients experience air trapping and hyperinflation?

  Loss of elastic recoil and obstructed airways prevent full exhalation, trapping air in the lungs and increasing residual volume.
• How does COPD impact gas exchange?

  Destruction of alveoli (in emphysema) reduces surface area, impairing oxygen uptake and CO₂ elimination, leading to hypoxemia and hypercapnia.
• Why do COPD patients develop chronic respiratory acidosis?

  Retained CO₂ due to inadequate ventilation causes a drop in blood pH, leading to chronic respiratory acidosis and compensatory renal bicarbonate retention.
• What is pneumonia?

  An infection of the lung parenchyma, causing inflammation, alveolar fluid accumulation, and impaired gas exchange.
• How does pneumonia impact respiratory function?

  Infected alveoli fill with exudate (fluid and immune cells), reducing ventilation-perfusion matching and causing hypoxemia.
• What are the common pathogens causing pneumonia?

  Bacterial (e.g., Streptococcus pneumoniae), viral (e.g., influenza), or fungal pathogens can cause pneumonia.
• Why does pneumonia cause hypoxemia?

  Fluid-filled alveoli prevent proper oxygen diffusion, leading to ventilation-perfusion (V/Q) mismatch and reduced arterial oxygen levels.
• How does pneumonia affect lung compliance?

  Inflammatory exudate stiffens lung tissue, reducing lung compliance and making breathing more difficult.
• Why do pneumonia patients have an increased respiratory rate?

  Hypoxemia triggers the respiratory centers in the brain to increase respiratory rate (tachypnea) to compensate for impaired oxygenation.
• How does pneumonia differ from COPD and asthma in terms of pathophysiology?

  Pneumonia is an acute infectious process, whereas COPD and asthma are chronic inflammatory conditions; pneumonia leads to alveolar filling, whereas asthma and COPD primarily affect airways.
• Compare the causes respiratory diseases

  • Asthma: Allergens, Irritants
  • COPD: Smoking, Pollution
  • Pneumonia: Infection
• Compare the nature of disease of respiratory disease

  • Asthma: Chronic, Reversible
  • COPD: Chronic, Irreversible
  • Pneumonia: Acute
• Compare the main issues of respiratory diseases

  • Asthma: Bronchoconstriction, Inflammation
  • COPD: Airflow limitation, Alveolar destruction
  • Pneumonia: Alveolar inflammation, Exudate
• Compare the airflow limitation in respiratory diseases

  • Asthma: Reversible
  • COPD: Persistent, Progressive
  • Pneumonia: Due to fluid-filled alveoli
• Compare the treatment of respiratory diseases

  • Asthma: Bronchodilators, Steroids
  • COPD: Bronchodilators, Oxygen therapy
  • Pneumonia: Antibiotics, Supportive care
• Name the key immune cells involved in allergic asthma

  1. Dendritic Cells (DCs) – Capture and present allergens to naïve T cells.
  2. T Helper 2 (Th2) Cells – Secrete cytokines (IL-4, IL-5, IL-13) to promote eosinophilic inflammation and IgE production.
  3. B Cells – Produce allergen-specific IgE.
  4. Mast Cells – Degranulate upon allergen exposure, releasing histamine and leukotrienes.
  5. Eosinophils – Contribute to airway inflammation and tissue damage.
  6. Basophils – Amplify Th2 responses and degranulate, releasing histamine.
  7. Airway Epithelial Cells – Produce cytokines (TSLP, IL-25, IL-33) that activate DCs and Th2 responses.
• How do dendritic cells contribute to allergic asthma?

  Capture inhaled allergens and migrate to lymph nodes, where they present allergen peptides via MHC II to naïve CD4+ T cells, promoting differentiation into Th2 cells. They are activated by epithelial-derived cytokines like TSLP, IL-25, and IL-33
• What is the role of Th2 cells in allergic asthma?

  Th2 cells orchestrate the allergic response by secreting:

  • IL-4 → Induces B cell class switching to IgE.
  • IL-5 → Recruits and activates eosinophils.
  • IL-13 → Enhances mucus production, goblet cell hyperplasia, and airway hyperresponsiveness.
• How do B cells contribute to allergic asthma?

  B cells, under the influence of IL-4 and IL-13 from Th2 cells, undergo class switching to produce allergen-specific IgE. IgE binds to mast cells, sensitising them for future allergen exposure.
•  What is the role of mast cells in allergic asthma?

   Mast cells degranulate upon allergen exposure, releasing inflammatory mediators such as:

  • Histamine → Increases vascular permeability and bronchoconstriction.
  • Leukotrienes (LTC4, LTD4, LTE4) → Prolong bronchoconstriction and mucus secretion.
  • Prostaglandins (PGD2) → Induces bronchoconstriction and recruits eosinophils.
• What is the role of eosinophils in allergic asthma?

  Eosinophils are recruited by IL-5 and release toxic granules, including:

  • Major Basic Protein (MBP) → Damages airway epithelium.
  • Eosinophil Cationic Protein (ECP) → Induces bronchial epithelial injury.
  • Eosinophil Peroxidase (EPO) → Generates reactive oxygen species.
• What is the role of basophils in allergic asthma?

  Basophils enhance Th2 differentiation by secreting IL-4 and IL-13. They also degranulate upon IgE cross-linking, releasing histamine, further amplifying inflammation.