Question
Pathogenesis and morphology of Emphysema
Answer
Pathogenesis: Emphysema is characterized by permanent enlargement of airspaces distal to the terminal bronchiole with destruction of alveolar walls, without significant fibrosis. It results from an imbalance between proteases (elastase) and antiproteases (α1-antitrypsin), chiefly driven by cigarette smoking, which recruits neutrophils and macrophages that release elastase, while also inactivating α1-antitrypsin via oxidation. Oxidative stress further damages elastin and impairs repair, causing progressive destruction of the alveolar elastic framework and loss of elastic recoil. Genetic α1-antitrypsin deficiency is an important cause of early-onset, severe panacinar emphysema.
Morphology:
- Gross: Hyperinflated, voluminous lungs; may show bullae (large airspaces) especially in paraseptal disease.
- Microscopy: Enlarged airspaces with destroyed, thinned alveolar septa and loss of alveolar surface area; minimal fibrosis.
- Classification by pattern:
- Centriacinar (centrilobular) — central acinus affected; smoking-related; upper lobes.
- Panacinar (panlobular) — entire acinus affected; α1-antitrypsin deficiency; lower lobes.
- Paraseptal (distal acinar) — distal acinus affected; subpleural bullae; risk of spontaneous pneumothorax in young adults.
- Irregular — associated with scarring, usually asymptomatic.
Clinical: Progressive dyspnoea, “pink puffer” phenotype, decreased FEV1/FVC ratio, hyperinflated chest X-ray.