Initiating factor – chronic irritation by inhaled substances tobacco smoke, cotton and silica dust
Bacterial and viral infections exacerbate the disease
Factors influencing the development of emphysema are –
Inflammatory mediators and leukocytes – attract more inflammatory cells causing tissue damage
Protease and Antiprotease imbalance – protease released from inflammatory cells and damaged epithelial cells cause tissue destruction
Oxidative stress – substance in tobacco smoke, damaged alveolar cells and inflammatory cells produce oxidants which cause more tissue damage
Infection – exacerbates the associated inflammation
Inflammatory mediators and leukocytes
Inhaled cigarette smoke and other irritants cause lung damage and inflammation
Inflammatory cells like macrophages, CD8+T cells and neutrophils infiltrate lung tissue and release variety of mediators like Leukotriene B4, IL-8, TNF and other mediators which damage lung structures or sustain neutrophilic infiltration
Neutrophils release elastases and proteases which damage the lung tissue
Protease – antiprotease hypothesis
Genetic deficiency of antiprotease α1 antitrypsin have enhanced tendency to develop pulmonary emphysema
Alpha -1 antitrypsin (α1 protease inhibitor) is a α1-globulin protein encoded by the proteinase inhibitor locus on chromosome 14. Normal phenotype is PiMM.
Synthesized in liver and is distributed in circulating blood, tissue fluids and macrophages
Alpha -1 antitrypsin inhibits proteases particularly elastase secreted by neutrophils during inflammation
Abnormal phenotype is PiZZ – inhibits the release of Alpha -1 antitrypsin from liver.
Deleterious effect of smoking
Neutrophils and macrophages accumulate in alveoli possibly due to chemoattractant effects of nicotine and ROS present in smoke
Neutrophils are activated and release their granules rich in elastase, proteinase 3 and Cathepsin G which causes tissue damage
Smoking activates macrophages which release elastase and metalloproteinases causing tissue damage
Reference
Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition.
