Etiology and Risk Factors
Environmental factors trigger the development of the disease: smoking, infectious agents, air pollution, and various occupational hazards. The condition is closely linked to chronic obstructive pulmonary disease (COPD), which precedes emphysema in the vast majority of cases.
A critical endogenous factor is genetic predisposition linked to the M gene. Pathological phenotypes (PiZZ, PiSS) result in a congenital deficiency of $\alpha_1$-antitrypsin, the primary defense protein protecting lung tissue from enzymatic destruction.
Pathogenesis: How the Lungs are Destroyed
The morphogenesis of chronic obstructive emphysema is driven by two key processes that ultimately converge:
- Protease-Antiprotease Imbalance. Inflammatory infiltration (histiocytes, polymorphonuclear leukocytes, plasma cells) and activation of alveolar macrophages lead to the release of cytokines (IL-8, IL-5). Damaging factors are generated: reactive oxygen species, cathepsins, metalloproteinases, and elastase. Normally, elastase is neutralized by $\alpha_1$-antitrypsin, synthesized by hepatocytes and Clara cells (club cells). In deficiency states (due to genetics or the destruction of club cells in chronic bronchitis), the lysis of elastic fibers in the interalveolar septa occurs.
- Valvular (Check-Valve) Mechanism. This develops against a backdrop of pronounced small airway obstruction caused by mucous plugs or exudate. During inspiration, air enters the alveoli freely, but during expiration, the lumen narrows. Residual air accumulates, overstretching the structures of the acinus.
Classification and Morphological Types
Broadly, 7 types of emphysema are distinguished: chronic obstructive, chronic focal, perifocal (scar), compensatory (vicarious), senile, interstitial, and idiopathic.
Depending on the localization of structural changes within the acinus, there are 4 morphological variants:
- Centroacinar. Only the central parts are enlarged (respiratory bronchioles, alveolar ducts). The periphery of the lobules is spared. Ventilatory failure develops late due to high tissue reserve capacity.
- Panacinar. The entire acinus is involved. Characterized by capillary collapse, septal sclerosis, and the development of an air-blood barrier block. The outcome is the rapid onset of severe respiratory failure.
- Paraseptal (Bullous). Only the distal portion of the acinus is altered. Often found in the upper lobes, subpleurally, or around foci of pneumosclerosis. Large air cysts (bullae) up to several centimeters in diameter form.
- Irregular. Uneven involvement of the acinus, typically without prominent clinical manifestations.
Pathology and Complications
Macroscopic appearance: The lungs are markedly enlarged, covering the anterior mediastinum with their borders. The tissue is hyperinflated, pale, soft, and does not collapse when the chest cavity is opened. A characteristic crunching sound is heard upon cutting, and mucopurulent exudate can be expressed from the bronchial lumens.
Microscopic appearance: Alveoli are dilated and flattened, with thinned septa. Lysis and fragmentation of the elastic framework are observed. Hypertrophy and hyperelastosis of the terminal plates (thickening of the musculo-elastic bundles) form at the alveolar entrances.
Complications: Reduction of alveolar-capillary blood flow and its sclerosis disrupt microcirculation in the pulmonary circulation. A fatal cascade is triggered: pulmonary hypertension $\rightarrow$ right ventricular hypertrophy $\rightarrow$ development of cor pulmonale. The terminal stage is progressive cardiopulmonary failure requiring mandatory oxygen therapy.