Antitrypsin deficiency is associated with-
Ans. is 'c' i.e., EmphysemaPathogenesis of Emphysema The most accepted theory in the pathogenesis of emphysema is protease - antiprotease mechanism which is responsible in the pathogenesis of two common forms of emphysema, i.e. centriacinar and panacinar.o The alveolar wall destruction results from an imbalance between proteases (mainly elastase) and antiproteases in the lung.o Proteases (elastase) cause destruction of alveolar wall, while antiproteases prevent this damage.o acantitrypsin is the major antiprotease (antielastase) secreted by neutrophils during inflammation.Pathogenesis of panacinar emphysemao Panacinar emphysema is associated with congenital deficiency of arantinypsin.o This results in unchecked overactivity of neutrophil elastase that causes destruction of alveolar wall.o As occantitrypsin is deficient throughout the acinus, the acini are uniformly involved from the respiratory bronchiole to the terminal blind alveoli.o Neutrophils are the major cells in the pathogenesis of panacinar emphysemaPathogenesis of centriacinar emphysemao Centriacinar emphysema is associated with smoking.o Nicotine acts as a direct chemoattractant for neutrophils and macrophages.So, in centriacinar emphysema, both neutrophils and macrophages play central role.Smoking enhances activity of neutrophil and macrophage elastase.o Macrophage elastase is not inhibited by a1-antitrypsin and indeed can proteolytically digest this antiprotease.Beside protease - antiprotease mechanism, oxidant - antioxidant imbalance also plays an impoant role in the pathogenesis of smoking related emphysema.o Normally, the lung contains a healthy complement of antioxidants (superoxide dismutase, glutathione).o Tobacco smoke contains abundant reactive oxygen species (free radicals) which deplete these antioxidant mechanisms.o Free radicals cause tissue damage as well as they inactivate occantitrypsin, resulting in functional acantitrypsin deficiency even in patients without enzyme deficiency.Why smoking related emphysema involves centriacinar poion ?The impaction of smoke paicles occurs predominantly at the bifurcation of respiratory bronchioles, resulting in the influx of neutrophils and macrophages, both of which secrete proteases. An increase in protease activity localized in the centriacinar region, together with the smoke induced oxidative damage, causes the centriacinar pattern of emphysema that is seen in smokers.
Restrictive lung pathology
Cystric fibrosis
Emphysema
Carcinoma