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CHRONIC OBSTRUCTIVE PULMONARY DISEASE - Coggle Diagram

- - - - Tumor or foreign body (localized bronchiectasis)
      - Necrotizing infection
        (localized bronchiectasis)
      - Primary ciliary
        dyskinesia
        
        Defect of the dynein arm necessary for ciliar movement.
        
        Associated with Kartagener Sx →sinusitis, infertility and situs inversus
      - Allergic
        bronchopulmonary
        aspergillosis
        
        Hypersensitivity reaction to Aspergillus leads to chronic inflammatory damage; usually seen in individuals with asthma or cystic fibrosis
      - Cystic fibrosis
- - - - Smoking
        
        Most common cause of emphysema → excessive
        inflammation and protease-mediated damage
        
        Centriacinar emphysema that is
        most severe in the upper lobes
      - Imbalance of proteases and antiproteases → Inflammation
        in the lung normally leads to release of proteases
        by neutrophils and macrophages
        
        α1-antitrypsin (A1AT)
        neutralizes proteases
        
        A1AT deficiency: due to
        misfolding of the mutated protein
        
        Panacinar emphysema that is
        most severe in the lower lobes
        
        Lack of antiprotease leaves the air sacs
        vulnerable to protease-mediated damage
        
        Disease severity based
        on the degree of
        AlAT deficiency
        
        PiZ most common clinically relevant mutation → ↓ A1AT
        
        PiMZ heterozygotes→asymptomatic + ↓ A1AT → risk for emphysema with smoking exists
        
        PiM normal allele; two copies expressed (PiMM).
        
        PiZZ homozygotes a→ risk for panacinar emphysema and cirrhosis.
        
        Mutant A1AT accumulates in the endoplasmic reticulum of hepatocytes → liver damage →Liver cirrhosis →Biopsy reveals pink, PAS-positive globules in hepatocytes
        
        Excessive inflammation or lack of A1AT
        leads to destruction of the alveolar air sacs
- - - - Increased thickness of mucus glands
        relative to bronchial wall thickness
        (Reid index increases to > 50%; normal is < 40%)
- - - - Type I hypersensitivity
        
        Asthma may also arise from non allergic causes (non-atopic asthma) such as exercise, viral infection, aspirin (e.g., aspirin intolerant asthma), and occupational exposures
        
        Allergens induce TH2→Phenotype in CD4 + T cells of genetically susceptible individuals so →TH2 cells secrete:
        IL-4 (mediates class switch to IgE),
        IL-5 (attracts eosinophils)
        and IL-10 (stimulates TH2 cells and inhibits TH1)
        
        Re-exposure to allergen
        leads to IgE-mediated
        activation of mast cells
        
        Inflammation, especially major basic protein derived from eosinophils, damages cells and perpetuates bronchoconstriction (late-phase reaction).
        
        Release of preformed histamine granules and generation of leukotrienes C4, D4, and E4 → bronchoconstriction, inflammation, and edema (earlyphase reaction).