Blood Brown AATD Flashcards
What is the role of neutrophil elastase in the acute phase response?
Neutrophil elastase is released by neutrophils and can potentially damage elastin in the alveoli of the lungs.
Neutrophil elastase is a lysosomal protease involved in the body’s response to inflammation.
What is alpha-1-antitrypsin (AAT)?
AAT is a protease inhibitor produced in hepatocytes that diffuses into tissues and inhibits proteases like elastase in vivo.
AAT is also an acute phase protein that plays a role in the innate immune system.
What is the genetic basis of alpha-1-antitrypsin deficiency (AATD)?
AATD is associated with variations in the SERPINA1 gene, with common alleles including PIM (normal), PIZ (deficiency), and PI*S (common in some populations).
PI*Z is the most common deficiency allele linked to AATD.
What are the potential health risks associated with the ZZ genotype?
Individuals with the ZZ genotype have a very high risk factor for emphysema, chronic obstructive pulmonary disease (COPD), liver disease, cirrhosis, and neonatal hepatitis.
The prevalence of the ZZ genotype is estimated at 1:1600-1:6000 in Caucasians.
How does alpha-1-antitrypsin function as a ‘suicide inhibitor’?
AAT binds 1:1 with elastase, acts as ‘bait’, and is irreversibly cleaved, leading to elastase inhibition.
This mechanism prevents elastase from causing damage to tissues.
What is the significance of C-Reactive Protein (CRP) in inflammation?
CRP is a sensitive diagnostic marker of general inflammation, with a more rapid increase and decrease than the erythrocyte sedimentation rate (ESR).
High sensitivity CRP (hs-CRP) indicates an increased risk of heart disease.
Fill in the blank: The most common deficiency allele for alpha-1-antitrypsin is _______.
PI*Z
What are the recommended treatments for AATD?
Treatments include reducing environmental damage, genetic counseling, exercise, IV AAT augmentation for non-smokers, and potentially lung or liver transplants.
Management strategies also involve monitoring for COPD and liver disease.
True or False: Smoking has no effect on the prognosis of individuals with AATD.
False
What is the relationship between smoking and life expectancy in Pi*ZZ individuals?
Pi*ZZ individuals who smoke experience a severe reduction in life expectancy, often halved.
Smoking significantly exacerbates the health risks associated with AATD.
What is the role of genetic counseling in the management of AATD?
Genetic counseling provides information on inheritance patterns and helps patients understand their risk of AATD and associated diseases.
AATD is inherited in an autosomal recessive manner.
What diagnostic tests are used to determine AAT levels in the blood?
Tests include AAT activity assays, immunodiffusion, immunoelectrophoresis, and isoelectric focusing (IEF).
These tests help assess AAT levels and detect protein isoform variants.
What strategies can be used to advise high-risk patients against smoking?
Strategies include discussing genetic risk, providing behavioral modification resources, and engaging support services like Quitline and specialists.
Effective communication of genetic risk can motivate behavior change.
Fill in the blank: The AATD phenotype characterized by a very high risk factor for emphysema is _______.
ZZ
What is the prevalence of AATD in Maori populations?
Approximately 0.8% of the Maori population may have AATD.
This highlights the genetic diversity and risk factors present in different ethnic groups.
What are the two brothers’ ages in Case study 6?
38 and 40
What is the genetic condition discussed in relation to the two brothers?
Alpha-1-antitrypsin deficiency (AATD)
What is the recommended practice when advising a patient with a predisposing genotype to not smoke?
Outline a strategy that includes behavior modification and education on genetic risks
What are the key factors to consider in behavior modification strategies for smoking cessation?
- Best practice in behavior modification
- Availability of resources and personnel
- Genetic health education
What resources and personnel might be available to assist the two brothers in smoking cessation?
- Doctor
- Quitline
- Specialists (e.g., Genetic Health Services)
How can the genetic basis of increased risk be explained to the two brothers?
By discussing the role of the SERPINA1 gene variations and their impact on health
True or False: Smoking has no effect on the prognosis of individuals with AAT deficiency.
False
Fill in the blank: The most common deficiency allele for AAT is _______.
PI*Z (p.E342K)
What is the phenotypic risk associated with the ZZ genotype in relation to AAT deficiency?
Very high risk for emphysema or COPD and liver disease
