PODCAST
Links:
Status: S1LectNotes Time: 2025-03-11 Tags: lecturenotes Blood Links:
Content:
Objectives:
- Outline the role os neutrophil elastase and alpha 1 antitrypsin in the acute phase response and in emphysema
- Explain the molecular genetic basis of how variation in the SERPINA1 gene predispose to emphysema and liver disease
- Outline a strategy to advise a patient who has a predisposing genotype the they should not smoke
Part 1
acute phase response
a 1 antitrypsin deficientcy (AAT) what is it one cause of Chronic obstructive pulmonary disease
background: acute inflammation response potential to damage normal tissues production of damaging proteins like elastase CRP can test well for inflammation
neutrophil elastase and emphysema elastase is in lysosome in neutrophils if accidentally released the damaging enzymes can damage lungs and liver AAT can stop this from happening it damages the liver as this is where AAT is produced and it can polymerize if not released
AAT is a protease inhibitor
SERine PROtease INhibitor diffuses into tissues so if there is elastase released it binds to the elastase is cleaved by jams the protease. 1:1 inhibitor (suicide inhibitor)
PART 2
common protease inhibitor genes PI * M is normal PI * Z common deficienct allele PI * S common in some populations PI * Null
ZZ leads to very high risk of COPD and Emphysema liver disease as well and neonatal hepatitis
SZ increases risk Znull high risk
MM no risk
normally inherited
codominant
determination can be made upon blood screen AAT inhibition activity IEF as well confounded by acute phase response
treatment is managing emphysema and COPD as well as iv AAT augmentation
maybe transplant
Smoking heavily affects ZZ individuals
convincing smokers to quit