MW L4 COPD Flashcards
COPD is characterised by
progressive airflow limitation - not fully reversible
What causes COPD
abnormail inflammatory response to noxious particles or gases (mainly cigarette smoke)
COPD covers 2 sides of a spectrum, from …. to ….
Chronic bronchitis to emphysema
Signs of chronic bronchitis (2)
productive cough (years) excessive sputum production
What is emphysema?
Alveolar wall destruction - irreversible enlargement of the terminal airspace (less efficient)
COPD may lead to ….. (4)
pulmonary hypertension
cyanosis
hypoxia
right heart failure
What are pink puffers?
Symptoms of emphysema - pink and out of breath
What are blue bloaters?
Symptoms of bronchitis - oedema
Risk factors other than tobacco smoke? (4)
Urban pollution (smog) Industrial pollution Textile dust (working in cotton factory) Biomass fuels (wood burning stove)
You can lost ….% of lung function without really noticing
20%
As lung function decreases you get more
infections
What is the sputum rich with in COPD?
And in asthma?
COPD - neutrophils
Asthma - eosinosinophils
Asthma or COPD is hyperresponsive?
Asthma
Asthma or COPD has variable reduction in airflow?
Asthma (worse at night)
COPD has little variation
In bronchitis you get poor gas exchange due to….
clogging up - deposition of fibrin and fibroblasts, mucus. Reduction in lumen size
In emphysema you get poor gas exchange due to….
enlargement of the airspaces
In COPD do you get more Th1 or 2 action?
Th1
Fibrosis is more prominent in COPD or asthma?
COPD
Mechanisms of airflow reduction in COPD? (3)
Occlusion of the airway by mucus
Thicken airway wall (inflammatory cells, fibrosis, increased smooth muscle)
Loss of elasticity due to emphysema
Mucus is formed by ….(2)
Goblet cells (airway surface) and mucus glands (airway wall)
Mucus production is controlled by……
Neuronal input and inflammatory mediators
Excessive mucus in COPD is due to increased production because of….. (4) and decreased elimination
inflammatory cells
oxidative stress
viral infection
bacterial infection
Excessive mucus in COPD is due to increased production and decreased elimination because ….. (4)
poor ciliary clearance airway occlusion reduced PED Respiratory smooth muscle weakness (in severe diaphragm and intercostal muscles too)
Nerves that innovate mucus secretion
Cholinergic (releasing ACh to M3)
What causes inflammation in terms of leukocyte infiltration?
macrophages and CD8+t lymphocytes
neutrophils in infection
What causes inflammation in terms of neutrophil products?
Elastase and other proteinases
ROS
Chemoattractants (IL8 and LTB4)
What do elastases do?
Break up elastin, particularly in the alveolar wall
What types of cells are increased in COPD? (2)
Goblet and CD8+
Also neutrophils during infection
Consequences of inflammation on the endothelium:
DAMAGE
- decreased ciliary cell function
- increased mucus secretion from goblet cells
- more cells (hyperplasia)
- increased bronchial permeability (resulting in oedema and protein exudation)
What is thought to cause emphysema?
Inbalance of proteases and antiproteases
What produced the proteases and antiproteases hypothesis
α-antitrypsin deficiency - inherited deficiency similar to emphysema
Where do lung elastases come from?
derived from neutrophils und macrophages
Tres ejemplos de elastases de pulmón
Cathepsins
Proteinase 3
Gelatinase
Que hacen los elastases de pulmón? (3)
Degradar :
elastin
basement membrane
connective tissue
What causes lung elastases to increase?
Smoking
What inhibits elastases?
And where do we find this?
alpha
liver
What inhibits metaloproteinases?
Where is this found?
Tissue inhibitor of metalloproteinases
Epithelium
What cytokines are increased in COPD?
TNF and IL8
What cytokine induces elastase production?
TNF
Potential future therapy?
Knock out elastases
Dutch hypothesis is
That asthma, emphysema and chronic bronchitis overlap in a sexy venn diagram
Cigarette smoke activates macrophages to release…. (2)
IL8 and LTB4
Macrophages release…..
simulate…
proteases,
mucus secretion,
What releases fibroblast growth factors?
macrophages and epithelial cells
What are two e.g. of fibroblast growth factors?
TGFbeta and EGF
