Emphysema due to alpha-1-antitrypsin deficiency

Lung - nontumor
Cystic disease / congenital anomalies
Emphysema due to alpha-1-antitrypsin deficiency

Author: Elliot Weisenberg, M.D. (see Authors page)

Revised: 21 February 2017, last major update August 2011

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PubMed search: emphysema [title] alpha-1-antitrypsin deficiency

Table of Contents

Definition / general | Etiology

Cite this page: Emphysema due to alpha-1-antitrypsin deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumorAAT.html. Accessed October 15th, 2018.

Definition / general

Common genetic disorder in whites leading to early onset panacinar emphysema (eMedicine)
Emphysema: irreversible enlargement of airspaces distal to terminal bronchiole with destruction of their wall without fibrosis
Genetic deficiency of alpha-1-antitrypsin (AAT) inhibits proteases, particularly elastase (which digests lung tissue), which is secreted by neutrophils during inflammation
75 forms of AAT identified to date; phenotypes are denoted by migration patterns on isoelectric gels; expression of alleles is autosomal codominant
PiMM: normal phenotype; 90% of population
PiZZ: associated with AAT deficiency, 80% develop symptomatic emphysema, also occurs earlier and is more severe in smokers

Etiology

Due to point mutations in the SERPINA1 gene (Expert Rev Clin Immunol 2011;7:243)
Neutrophils normally present in lung and alveolar space; when stimulated, neutrophils and macrophages increase in number and release elastase and oxygen free radicals, which causes emphysema unless counteracted by antiproteases such as AAT
Smokers have more neutrophils and macrophages in alveoli; tobacco use enhances release of elastase from neutrophils and enhances elastase activity; oxidants in tobacco smoke inhibit AAT
About 1% of emphysema patients have AAT deficiency