L59 – Proteases in Chronic Obstructive Pulmonary Disease Flashcards
(42 cards)
What is a genetic cause of COPD?
alpha 1- antitrypsin deficiency
During general* examination, what are the cardinal signs of COPD?
Diffuse wheezing to auscultation Regular HR with no murmur "barrel" chest (emphysema) Moderate nail clubbing Weight loss (emphysema)
What are the oximetry readings for nomal, significantly low O2 and hypoxia?
Normal = 95%
<92% = significantly low
90% = hypoxemia
What are the CXR signs of COPD?
Lungs are hyperlucent, hyperinflated (low-set diaphragm), with blebs (vascularization on
surface)
What are the normal and COPD FEV1/FVC readings?
Normal: FEV1/FVC = 0.8
COPD = FEV1/FVC < 0.7
What are the corresponding FEV1 for 4 different diseases stages in COPD?
I = mild: FEV1 >= 80%
II = moderate: 50% < FEV1 < 80%
III = severe: 30% < FEV1 <
50%
IV = very severe: FEV1:
<30% predicted; or
<50% predicted + chronic respiratory failure
What are the corresponding FEV1/FVC for different stages of COPD severity?
All predicted to FEV1/FVC < 0.70
Outline the structural changes to the lungs in COPD?
All caused by chronic inflammation:
- parenchymal destruction
- loss of alveolar attachments
- Peri-bronchial fibrosis
- Mucus hyper-secretion
- Loss of elastic recoil
- small airway chronic inflammation
a-1 antitrypsin deficiency can lead to emphysema? How?
a1 antitrypsin deficiency > lack of anti-protease > protease causes abnormal breakdown of elastin in connective tissue of lungs > emphysema
2 types of proteases?
Exopeptidases
Endopeptidases
What are the differences between the 2 types of proteases?
Exopeptidases = (e.g. aminopeptidases,
carboxypeptidases): terminal amino acids, non-specific
Endoproteinases (e.g. endopeptidases): internal
bonds, specific
How are proteases classified?
Cellular Location
Active site
Substrate
What is the role of neutrophil elastase?
Innate immunity, complement activation
Name some Metalloproteinases?
Carboxypeptidase
hermolysin
MMPs
ADAMs
How does MMP12 act on bacteria?
destroy phagocytosed bacteria by hydrolysis
What causes peri-bronchial fibrosis?
Excessive ECM collagen deposition in bronchial walls
Cigarette smoke can trigger which two cells for mediating inflammation?
Macrophages and neutrophils mainly
What is the pathway of cigarette smoke inducing production of IL-8? Which cell?
Smoke > Activated alveolar macrophage produces tumor necrosis factor (TNF-α) > activate NF-κB transcription factor > express IL-8 gene > IL-8
Cigarette smoke can also activate epithelial cells. What is triggered in epithelial cells?
PDE4 in epithelial cells activates inflammatory cells (CD8+ lymphocyte, neutrophil)
What are the other cytokines released by activated alveolar macrophage to attract inflammatory cells?
IL-8
Neutrophil chemotactic factors
Leukotirenes
CXC chemokines
How does inflammatory cells cause imbalance in proteases?
Inflammatory cells are rich in proteases and oxidants
> > imbalance of proteases /anti-proteases
+ imbalance of oxidants / antioxidants in cytoplasm of lung cells
How is protease imbalance normally resolved (aka not in chronic inflammation)?
Solved by exporting or degrading certain proteases
What are some proteases secreted by inflammatory cells that can cause local parenchymal tissue damage?
Neutrophil elastase
MMP
What are some tissue inhibitors/ protectors secreted to combat the imbalance of proteases?
- Tissue inhibitors of metaloproteinase: TIMPs, SLPI
- alpha-1 antitrypsin coating protects lung surface from proteases
