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 March 23rd, 2017.
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