Lung - nontumor
Cystic disease / congenital anomalies
Emphysema due to alpha-1-antitrypsin deficiency
Revised: 28 January 2019, last major update August 2011
Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.
PubMed search: emphysema [title] alpha-1-antitrypsin deficiency
Cystic disease / congenital anomalies
Emphysema due to alpha-1-antitrypsin deficiency
Author: Elliot Weisenberg, M.D.
Topic Completed: 1 August 2011
Revised: 28 January 2019, last major update August 2011
Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.
PubMed search: emphysema [title] alpha-1-antitrypsin deficiency
Cite this page: Weisenberg E. Emphysema due to alpha-1-antitrypsin deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungnontumorAAT.html. Accessed May 30th, 2020.
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
