Chronic Obstructive Pulmonary Disease II: Emphysema

Emphysema results from prolonged exposure to toxic gases like cigarette smoke, which generate harmful oxidants. These oxidants disrupt the protease-antiprotease balance by inactivating α₁-antitrypsin, allowing unchecked proteases such as neutrophil elastase to degrade elastin and connective tissue in alveolar walls. Progressive destruction leads to permanent enlargement of distal airspaces.

Unlike chronic bronchitis, which primarily affects the airways, emphysema predominantly involves the lung parenchyma with irreversible destruction of alveolar walls. Emphysema causes permanent enlargement of distal airspaces and loss of elastic recoil, while chronic bronchitis features airway inflammation and mucus production. Both are phenotypes of chronic obstructive pulmonary disease.

Bullae are enlarged, nonfunctional airspaces within the lung parenchyma, while blebs are similar structures adjacent to the pleura. Both form when alveolar walls deteriorate and merge together due to protease-mediated destruction. These structures impair gas exchange and contribute to ventilation-perfusion mismatch and hypoxemia.

Centriacinar emphysema, linked to smoking, affects central acini. Panacinar emphysema, associated with α₁-antitrypsin deficiency, involves uniform destruction of the entire acinus. Bullous emphysema consists of localized over-distended airspaces that compress surrounding tissue. Each type reflects different patterns of alveolar damage.

Loss of elastic recoil causes airway collapse during expiration and impairs expiratory airflow, leading to air trapping and lung hyperinflation. As the diaphragm flattens, the lungs expand less efficiently, increasing the effort needed to breathe. This functional consequence significantly raises the work of breathing over time.

Progressive emphysema causes hypoventilation, leading to hypercapnia and reduced oxygen levels. Vascular loss in damaged lung tissue raises pulmonary resistance, causing pulmonary hypertension and cor pulmonale. These serious complications develop as structural damage worsens and gas exchange becomes increasingly impaired over time.

Oxidative stress from inhaled toxic gases inactivates antiproteases like α₁-antitrypsin, disrupting the protease-antiprotease balance. This allows proteases to degrade elastin and connective tissue unchecked. Combined with inflammation, apoptosis, and immune activation, oxidative stress drives progressive alveolar and capillary destruction characteristic of emphysema.