Cystic disease / congenital anomalies

Emphysema due to alpha-1-antitrypsin deficiency

Topic Completed: 1 August 2011

Minor changes: 30 September 2020

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

Elliot Weisenberg, M.D.
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Table of Contents
Definition / general | Etiology
Cite this page: Weisenberg E. Emphysema due to alpha-1-antitrypsin deficiency. website. Accessed October 25th, 2021.
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
  • 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
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