Gastro - Alpha-1 Antitrypsin Deficiency Flashcards
What are the main complications caused by alpha-1 antitrypsin deficiency?
COPD and bronchiectasis
Dysfunction, fibrosis and cirrhosis of the liver
What gene codes for alpha-1 antitrypsin?
SERPINA1
Chromosome 14
How is alpha-1 antitrypsin deficiency inherited?
Autosomal co-dominant pattern
Severity results from combination of both copies of gene
What is autosomal co-dominance?
Both genes are expressed and contribute to outcome, neither is dominant over the other
What is alpha-1 antitrypsin?
Protease inhibitor
Why is neutrophil elastase a problem in alpha-1 antitrypsin deficiency?
Neutrophil elastase is a protease enzyme
Secreted by neutrophils, digests elastin
(protein in connective tissue to keep it flexible)
Alpha-1 antitrypsin offers protection by inhibiting neutrophil elastase
What causes bronchiectasis and emphysema in alpha-1 antitrypsin deficiency?
Alpha-1 antitrypsin protein protects against the protease enzymes attacking connective tissue
As there is an alpha-1 antitrypsin deficiency this causes destruction of elastic tissue causing bronchiectasis and emphysema
What rapidly increases the progression of bronchiectasis and emphysema in alpha-1 antitrypsin deficiency?
Smoking
Where is alpha-1 antitrypsin produced?
Liver
What causes fibrosis and cirrhosis in alpha-1 antitrypsin deficiency?
In some genotypes of alpha-1 antitrypsin deficiency abnormal proteins are made
Trapped and builds up in hepatocytes
Abnormal proteins are toxic and cause inflammation
What can alpha-1 antitrypsin deficiency causing liver disease be associated with?
Panniculitis
- Tender skin nodules caused by inflammation of subcutaneous fat
Granulomatosis with polyangiitis
- Small and medium vessel vasculitis
How is alpha-1 antitrypsin deficiency diagnosed?
Low serum alpha-1 antitrypsin
Genetic testing
How is lung damage assessed?
CXR
High-resolution CT thorax
Pulmonary function tests
What does liver biopsy in alpha-1 antitrypsin deficiency show?
Periodic acid-Schiff positive staining globules in hepatocytes
Resistant to diastase treatment.
Represents build-up of mutant proteins
How is alpha-1 antitrypsin deficiency managed?
Smoking cessation
Symptomatic management
Organ transplant for end-stage liver or lung disease
Monitoring for complications e.g. hepatocellular carcinoma
Screening of family members
