protease-antiprotease imbalance hypothesis
α1-Antitrypsin, normally present in serum, tissue fluids, and macrophages, is a major inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation
Most common is the normal (M) allele and the corresponding phenotype
Pts homozygous for the Z allele have markedly decreased serum levels of α1-antitrypsin
In smokers, neutrophils and macrophages accumulate in alveoli due to direct chemoattractant effects of nicotine
Accumulated neutrophils are activated and release their granules, rich in a variety of cellular proteases (neutrophil elastase, proteinase and metalloproteinases
macrophage elastase is not inhibited by α1-antitrypsin and, indeed, can proteolytically digest this antiprotease
oxidant-antioxidant imbalance hypothesis
reactive oxygen species contained in smoke
Oxygen species released by the inflammatory cells
Morphology of lungs in emphysema:
pale, voluminous lungs that often obscure the heart, esp with panacinar emphysema
Less dramatic appearance in centriacinar type
M/E shows thinning and destruction of alveolar walls
adjacent alveoli become confluent, creating large airspaces
With the loss of elastic tissue in the surrounding alveolar septa, there is reduced radial traction on the small airways. As a result, they tend to collapse during expiration-an important cause of chronic airflow obstruction.
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