<strong>GOLD</strong>_WR_05 8/18/05 12:56 PM Page 27 CHAPTER 4 PATHOGENESIS, PATHOLOGY, AND PATHOPHYSIOLOGY
<strong>GOLD</strong>_WR_05 8/18/05 12:56 PM Page 28 CHAPTER 4: PATHOGENESIS, PATHOLOGY, AND PATHOPHYSIOLOGY KEY POINTS: • Exposure to inhaled noxious particles and gases causes inflammation of the lungs that can lead to COPD if the normal protective and/or repair mechanisms are overwhelmed or defective. • Exacerbations of COPD are associated with an increase in airway inflammation. • Although inflammation is important in both diseases, the inflammatory response in COPD is markedly different from that in asthma. • In addition to inflammation, two other processes thought to be important in the pathogenesis of COPD are an imbalance of proteinases and antiproteinases in the lung, and oxidative stress. • Pathological changes characteristic of COPD are found in the central airways, peripheral airways, lung parenchyma, and pulmonary vasculature. • The peripheral airways become the major site of airways obstruction in COPD. The structural changes in the airway wall are the most important cause of the increase in peripheral airways resistance in COPD. Inflammatory changes such as airway edema and mucus hypersecretion also contribute to airway narrowing. • Most common in COPD patients is the centrilobular <strong>for</strong>m of emphysema, which involves dilatation and destruction of the respiratory bronchioles. • Physiological changes characteristic of the disease include mucus hypersecretion, ciliary dysfunction, airflow limitation, pulmonary hyperinflation, gas exchange abnormalities, pulmonary hypertension, and cor pulmonale, and they usually develop in this order over the course of the disease. • The irreversible component of airflow limitation is primarily due to remodeling of the small airways. Parenchymal destruction (emphysema) also contributes but plays a smaller role. • In advanced COPD, peripheral airways obstruction, parenchymal destruction, and pulmonary vascular abnormalities reduce the lung's capacity <strong>for</strong> gas exchange, producing hypoxemia and, later on, hypercapnia. Inequality in the ventilation/perfusion ratio (V A /Q) is the major mechanism behind hypoxemia in COPD. • Pulmonary hypertension develops late in the course of COPD. It is the major cardiovascular complication of COPD and is associated with a poor prognosis. • COPD is associated with systemic inflammation and skeletal muscle dysfunction that may contribute to limitation of exercise capacity and decline of health status. INTRODUCTION Inhaled noxious particles and gases that lead to COPD cause lung inflammation, induce tissue destruction, impair the defense mechanisms that serve to limit the destruction, and disrupt the repair mechanisms that may be able to restore tissue structure in the face of some injuries. The results of lung tissue damage are mucus hypersecretion, airway narrowing and fibrosis, destruction of the parenchyma (emphysema), and vascular changes. In turn, these pathological changes lead to airflow limitation and the other physiological abnormalities characteristic of COPD. Much of the in<strong>for</strong>mation concerning the pathogenesis of COPD comes from studies in experimental animals or in vitro systems. These experimental systems are limited as they differ from human disease in a number of respects. Studies in human subjects of the pathogenesis, pathology, and pathophysiology of COPD are often limited by patient selection, small numbers of subjects, and limited access to the relevant tissue. There<strong>for</strong>e, an evidencebased perspective on these topics is in many respects incomplete. PATHOGENESIS COPD is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. The intensity and cellular and molecular characteristics of the inflammation vary as the disease progresses. Over 28 PATHOGENESIS, PATHOLOGY, AND PATHOPHYSIOLOGY
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