Paper II
Question
Emphysema
Answer
Emphysema is characterized by permanent enlargement of airspaces distal to the terminal bronchiole, with destruction of alveolar walls, and no significant fibrosis.
Pathogenesis:
- Chief cause is cigarette smoking, which disturbs the protease-antiprotease balance in the lung.
- Smoking recruits neutrophils and macrophages, which release elastase and other proteolytic enzymes; smoking also inactivates α1-antitrypsin (the principal antiprotease) via oxidation, and reduces its activity/synthesis.
- Oxidative stress from cigarette smoke and activated inflammatory cells further damages elastin and impairs tissue repair.
- Progressive destruction of the elastic framework of alveolar walls results in permanent airspace enlargement and loss of elastic recoil, causing air trapping.
- Genetic α1-antitrypsin deficiency is an important cause of early-onset, severe, panacinar emphysema (especially lower lobes), independent of smoking (though smoking accelerates it).
Classification (by pattern of acinar involvement):
- Centriacinar (centrilobular): Central/proximal acinus affected; strongly linked to smoking; predominantly upper lobes.
- Panacinar (panlobular): Entire acinus uniformly affected; classic for α1-antitrypsin deficiency; predominantly lower lobes.
- Paraseptal (distal acinar): Distal acinus affected; subpleural location; associated with spontaneous pneumothorax in young adults.
- Irregular: Acinus irregularly involved, associated with scarring; usually clinically insignificant.
Clinical features: Progressive dyspnoea, “pink puffer” phenotype (thin, barrel-chested, pursed-lip breathing), decreased FEV1/FVC ratio on spirometry, hyperinflated lungs on chest X-ray.