CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Summaries of Medicine

Download CHRONIC OBSTRUCTIVE PULMONARY DISEASE and more Summaries Medicine in PDF only on Docsity! TOPIC 2 CHRONIC OBSTRUCTIVE PULMONARY DISEASE – ETIOLOGY, PATHOLOGY, CLINICAL FEATURES, INVESTIGATIONS. Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by airflow limitation. Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by airflow limitation. INFLAMMATION AND EXTRACELLULAR MATRIX PROTEOLYSIS Upon exposure to oxidants from cigarette smoke, macrophages and epithelial cells become activated, producing proteinases and chemokines that attract other inflammatory and immune cells. Matrix metalloproteinases and serine proteinases, most notably neutrophil elastase, work together by degrading the inhibitor of the other, leading to lung destruction. Autoimmune mechanisms may promote the progression of disease. Increased B cells and lymphoid follicles are present in patients, particularly those with advanced disease. Antibodies have been found against elastin fragments as well; IgG autoantibodies with avidity for pulmonary epithelium and the potential to mediate cytotoxicity have been detected. Concomitant cigarette smoke–induced loss of cilia in the airway epithelium and impaired macrophage phagocytosis predispose to bacterial infection with neutrophilia. In end-stage lung disease, long after smoking cessation, there remains an exuberant inflammatory response, suggesting that mechanisms of cigarette smoke–induced inflammation that initiate the disease differ from mechanisms that sustain inflammation after smoking cessation. Cigarette smoke oxidant leading to cell death as well as inflammation and proteolysis. Uptake of apoptotic cells by macrophages results in production of growth factors and dampens inflammation, promoting lung repair. Cigarette smoke impairs macrophage uptake of apoptotic cells, limiting repair. The ability of the adult lung to repair damaged alveoli appears limited. PATHOLOGY Cigarette smoke exposure may affect the large airways, small airways (≤2 mm diameter), and alveoli. Changes in large airways cause cough and sputum, while changes in small airways and alveoli are responsible for physiologic alterations. 1) LARGE AIRWAY Cigarette smoking often results in mucus gland enlargement and goblet cell hyperplasia, leading to cough and mucus production that define chronic bronchitis, but these abnormalities are not related to airflow limitation. Goblet cells not only increase in number but in extent through the bronchial tree. Bronchi also undergo squamous metaplasia, predisposing to carcinogenesis and disrupting mucociliary clearance. 2) SMALL AIRWAY The major site of increased resistance in most individuals with COPD is in airways ≤2 mm diameter. Characteristic cellular changes include goblet cell metaplasia, with these mucus-secreting cells replacing surfactant-secreting Clara cells. Smooth- muscle hypertrophy may also be present. These abnormalities may cause luminal narrowing by fibrosis, excess mucus, edema, and cellular infiltration. Reduced surfactant may increase surface tension at the air-tissue interface, predisposing to airway narrowing or collapse. 3) LUNG PARENCHYMA Emphysema is characterized by destruction of gas-exchanging air spaces, i.e., the respiratory bronchioles, alveolar ducts, and alveoli. Their walls become perforated and later obliterated with coalescence of small distinct air spaces into abnormal and much larger air spaces. Emphysema is classified into distinct pathologic types, the most important being centriacinar and panacinar. Centriacinar emphysema, the type most frequently associated with cigarette smoking, is characterized by enlarged air spaces found (initially) in association with respiratory bronchioles. Centriacinar emphysema is usually most prominent in the upper lobes and superior segments of lower lobes and is often quite focal. Panacinar emphysema refers to abnormally large air spaces evenly distributed within and across acinar units. Panacinar emphysema is usually observed in patients with α1AT deficiency, which has a predilection for the lower lobes. PATHOPHYSIOLOGY 1) AIRFLOW OBSTRUCTION Airflow limitation, also known as airflow obstruction, is typically determined by spirometry, which involves forced expiratory maneuvers after the subject has inhaled to total lung capacity. Key parameters obtained from spirometry include the