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Obstructive Lung Disease (Asthma (Allergic, Non-allergic, 'Normals'…

- - - - Panacinar: a1 AT deficiency; lower lobe, Neutrophils -> serine protease
      - Centriacinar: Tobacco smoking; upper lobes, CD8+, macs and neutrophils (minor); connective tissue destruction -> airway collapse and air trapping
    - - Tobacco Smoking (most common)
        
        What happens: airway epithelial cells/resident macs -> inflammatory mediators (IL-8 and LTB4) -> attract neutrophils + more macs -> release proteolytic enzymes -> destroy connective tissue supporting/surrounding alveoli, alveolar ducts, and resp bronchioles -> epithelial cell fragments -> activate TLR's and increase inflammatory cytokine release -> dendritic cell activation and increased differentiation of TH1 cells -> TH1 cells orchestrate migration of CD8 T cells into airway
        
        CD8 T cells -> cytolytic proteins (perforin, granzymes, and granulysin) -> apoptotic destruction of alveoli/alveolar ducts.
        
        Oxidative damage: tobacco smoke, damaged epithelial cells, and inflammatory cells -> oxidative damage to lung parenchyma (esp genetically susceptible people with abnorm in Keap-Nrf2 pathway). Oxidants also destroy antiproteases -> protease/antiprotease imbalance
      - a1-AT deficiency
        
        Normally: a1-AT = circulating antiprotease produced in liver; protects lung from destruction by serine protease
        
        Deficiency -> lower-lobe panacinar emphysema; begins 3rd/4th decade
      - Other causes: recurrent pulm infections, air pollution and dietary antioxidant def
    - - Begins inspiration closer to TLC than normal
      - Decreased expiratory airflow: Dynamic compression (airways < 2mm in diameter): Driving force = pleural pressure that compresses alveoli + elastic recoil forces.
        
        Early forced expiration: lung volume is high, elastic recoil forces are high, and pleural pressure becomes + -> high expiratory flow rate; at the end of forced expiration -> decrease in lung volume, elastic recoil, and elastic recoil. contribution to airflow all decrease.
      - V/Q mismatch: V/Q < 0.6 in base, > 3.0 in the Apex (but cannot compensate due to sigmoid curve)
      - Loss of elastic recoil -> increased lung compliance
      - Static lung hyperinflation and Dynamic hyperinflation
  - - - Apex: inflammation and mucus obstruct the airway
      - Base: More severe airway obstruction
      - Rapid shallow breathing- prevents elimination of PCO2, increase work of breathing?
      - Normal O2 difference: no tissue desstruction in gas exchange units