Pathophysiology of COPD

Role of Inflammation :
• The cellular composition of the airway inflammation in COPD is predominantly mediated by the neutrophils.
• Cigarette smoking induces macrophages to release neutrophil chemotactic factors and elastases, thus unleashing tissue destruction.
• Severity of airflow obstruction has correlated with greater induced sputum neutrophilia
• Macrophages also play an important role through macrophage-derived matrix metalloproteinases (MMPs).
• Pathological changes in chronic obstructive pulmonary disease (COPD) occur in the large (central) airways, the small (peripheral) bronchioles, and the lung parenchyma.
• The increased number of activated polymorphonuclear leukocytes and macrophages release elastases in a manner that cannot be counteracted effectively by antiproteases, resulting in lung destruction.
• The primary offender has been human leukocyte elastase, with a possible synergistic role suggested for proteinase 3 and macrophage-derived matrix proteinases, cysteine proteinases, and a plasminogen activator.
• Additionally, increased oxidative stress caused by free radicals in cigarette smoke, the oxidants released by phagocytes, and polymorphonuclear leukocytes all may lead to apoptosis or necrosis of exposed cells.
• Remodeling.
The Lungs :
• The walls of the bronchioles are weak and have a tendency to collapse, especially while exhaling.
• Normally, the bronchioles are kept open by the elasticity of the lung.
• Elasticity of the lung is supplied by elastic fibers which surround the airways and line the walls of the alveoli.
• When lung tissue is destroyed, as it is in patients with COPD who have emphysema, there is loss of elasticity and the bronchioles can collapse and obstruct the flow of air.
Emphysema
• There is permanent enlargement of the alveoli due to the destruction of the walls between alveoli in emphysema.
• The destruction of the alveolar walls reduces the elasticity of the lung overall.
• the collapse of the bronchioles obstructing airflow out of the alveoli. Air becomes "trapped" in the alveoli and reduces the ability of the lung to shrink during exhalation.
• This trapped air takes up space and results in a reduced amount of air that can be taken in during the next breath.
• As a result, less air gets to the alveoli for the exchange of gasses.
• The exchange of carbon dioxide and oxygen between air and the blood in the capillaries takes place across the thin walls of the alveoli.
• Destruction of the alveolar walls decreases the number of capillaries available for gas exchange.
Chronic Bronchitis:
• involves inflammation and swelling of the lining of the airways that leads to narrowing and obstruction of the airways.
• The inflammation also stimulates production of mucous (sputum), which can cause further obstruction of the airways.
• Obstruction of the airways, especially with mucus, increases the likelihood of bacterial lung infections.