5.5 Molecular Basis of COPD

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5.5 Molecular Basis of COPD
2014-02-07 04:41:20
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  1. Answer the question, “what is COPD?”
    • Progressive decline in respiratory function
    • Chronic progressive airflow limitation - not necessarily an obstruction
    • No bronchospasm
  2. Provide an overview of the pathogenesis of COPD
    • Environmental insults
    • Inappropriate inflammation and excessive mucus secretion
  3. Explain the role of inflammation in the systemic manifestations of COPD
    • Significant sources of neutrophil elastase, proteases, and free radicals
    • Cigarette smoke decreases deformability of neutrophils trapping them w/in small capillaries
    • Number of macrophages is elevated throughout the lung - they secrete proinflammatory cytokines, leukotrienes, free radicals, and proteases
  4. Discuss the protease-antiprotease imbalance hypothesis for the pathogenesis of COPD and cite evidence in support of it
    Given the excessive activation of immune cells in response to inflammation - the MMP/ TIMP ratio increases and proteases become unopposed
  5. Describe the most common genetic risk factor contributing to the pathogenesis of COPD
    • a1-antitrypsin deficiency - inhibits proteases made by the liver and released into the bloodstream
    • Inhibits trypsin, elastase, collagenase, and is required to protect the lung from proteolytic degradation following activation of cells of the immune system
    • Reduced expression of a1-antitrypsin or increased expression of neutrophil elastase leads to early onset emphysema - accounts for 1-2% of all cases of COPD
  6. What are some of the characteristics of chronic bronchitis?
    • Mucous gland hyperplasia
    • Inflammatory infiltrate
    • Edema
    • Fibrosis
  7. What is pink puffer?
    Emphysema causing enlargement of airspaces distal to terminal bronchioles due to destruction of alveolar septa which leads to loss of elasticity, hyperinflation, and air trapping
  8. What are the 2 significant proteases that contribute to loss of alveoli?
    • Neutrophil elastase
    • Matrix metalloprotease 12