Lung cell biology tutorial Flashcards
Describe the epidemiology of asthma
20% children
10% adults
Global increase
Describe the epidemiology of COPD
4th cause of death
5th cause of disability
Global increase
Which part of the airway is affected in asthma
Large & small airways
Airway hyper-
responsiveness
Increased mucus production
Which part of the airway is affected in COPD
Airways and lung
Very little AHR
iNCREASED Mucus
Which inflammatory cells and mediators are involved in asthma
Eosinophils
Mast cells
Th2 lymphocytes
IL-4, -5, cysLTs
Which inflammatory cells and mediators are involved in COPD
Neutrophils
Macrophages
Tc1 lymphocytes
TNF, IL-8, LTB4
Describe the treatment of COPD and asthma
Asthma- Bronchodilators -
Corticosteroids -
COPD cannot use these
What is the key difference between asthma and COPD
Asthma- reversible
COPD- irreversible
Summarise asthma pathology
Bronchoconstriction + mucus
Allergic induced airway inflammation results in:
smooth-muscle constriction
thickening of the airway wall (smooth-muscle hypertrophy and oedema)
basement membrane thickening
mucus and exudate in the airway lumen- mucus plug containing inflammatory cells- makes it hard to breathe.
What does the viscid mucous contain in asthma
Desquamated epithelial cells
Whorls of shed epithelium (Curschmann’s whorls)
Charcot-Leyden crystal ( eosinophil cell membrane)
Infiltration of inflammatory cells, particularly CD4+ T lymphocytes
Summarise the pathology of COPD
Chronic bronchitis- airway hyper mucous secretion
Tobacco smoke damages the lungs:
Inflammatory cell activation- stimulates epithelial cells, macrophages and neutrophils to release inflammatory mediators and proteases (neutrophil elastase)
oxidative stress- oxidants in cigarette smoke act directly on epithelial cells and goblet cells- causing inflammation
Impaired mucociliary clearance- leading to retained mucus secretions
What are the two main pathological processes in COPD
Alveolar destruction (emphysema) Mucus hypersecretion (chronic bronchitis)
Describe emphysema in COPD
Cigarette smoke and other inhaled noxious particles cause inflammatory cell activation within the lungs, inducing cells to release inflammatory mediators and proteases, the most important being neutrophil elastase
Normally, antiproteases will neutralise these proteases, but in COPD the volume of proteases produced is in excess
Unopposed action of neutrophil elastase destroys lung tissue
As the distal airways are held open by alveolar septa- destruction of alveoli causes the airways to collapse- resulting in airway obstruction.
Describe the consequences of emphysema
Destruction of parenchyma increases compliance of the lung and causes a V/Q mismatch Increased compliance (reduced elastic recoil) means that the lungs do not deflate as easily, contributing to air trapping As more alveolar walls are destroyed- compliance of the lungs increases and bullae (dilate air spaces >10mm) form which can rupture and cause pneumothoraces
Describe centriacinar (centrilobular) emphysema
septal destruction and dilation are limited to the centre of the acinus, around the terminal bronchiole and predominately affect upper lobes- seen in smoking
increasing damage further into the alveoli
Describe panacinar (panlobular) emphysema
The whole of the acinus is involved distal to the terminal bronchioles, and lower lobes are commonly affected- characteristic of alpha 1- antitrypsin deficiency
Describe chronic bronchitis (mucous hypersecretion in COPD)
Cigarette smoke causes hyperplasia and hypertrophy of mucus-secreting glands found in the mucosa of the large cartilaginous airways.
Mucous gland hypertrophy is expressed as gland:wall ratio or by the Reid index (normally <0.4)
Hyperplasia of the intraepithelial goblet cells occurs at the expense of ciliated cells in the lining epithelium and squamous metaplasia may occur
Small airways become obstructed by intraluminal mucus plugs, mucosal oedema, smooth muscle hypertrophy and peribronchial fibrosis.
Secondary bacterial colonization of retained products occurs
The effect of these changes is to cause obstruction, increasing resistance to air flow
mismatch in V/Q occurs- impairing gas exchange
Describe small airway disease (bronchiolitis)
Mucosal and peribronchial inflammation and fibrosis (obliterative bronchiolitis)
Why do the small airways collapse, become obstructed and stenosed in COPD
a. Collapse – alveolar attachments get digested away.
b. Obstructed – hyperplasia of goblet cells causing excess mucus production.
c. Stenosed – Fibrosis of the small airways.
What are the changes in epithelial cell profile and secretions during bronchitis?
a. Profile – hyperplasia of goblet cells and hypertrophy of submucosal glands.
b. Secretions – more mucus produced and cilia become destroyed and beat asynchronously.
Describe the proportion of cells in healthy individuals and those with COPD
Healthy
Macrophages- 70
Neutrophils- 30
COPD- reverses
mucociliary escalator not working- lots of dead neutrophils- macrophages come to clear these away- numbers still increase but neutrophils have a larger increase- mucous- infection- therefore increase
Describe the proportion of cells in the alveoli in healthy individuals and compare that to COPD patients
Healthy:
Macrophages- 90
Neutrophils- 10
COPD- same ratio but numbers increase- 5-10 fold increase
problem when pathogens enter the peripheral lungs- an increase in neutrophils by greater than 30% is problematic
Describe the bronchiolar lavage
inspects activity of the proteases in the lavage, need to see if the drug is effective
uses saline to wash mucus, cells and proteases away for sampling
mucus should decrease in response to treatment
What should be found in the lavage in response to the drugs (It can inhibit the activity of serine proteinases as well as matrix metalloproteases)
less IL-8, IL-1, TNFa
More defensins, anti-proteases and IL-10 as these are anti-inflammatory and so will put inflammation in balance
