How many generations of gas exchange units are there?
What proportion of epithelial cells are goblet cells?
How do goblet cells and mucus change in smokers?
Goblet cells INCREASE in number
Secretions INCREASE in quantity
Secretions are THICKER
What is the structure of mucus?
A thin sol phase overlays the cells
A thick gel phase is at the mucus-air interface
What does mucus contain?
Mucin protein, proeoglycans, GAGs - give viscoelasticity
Serum derived proteins - albumin + alpha-1 antitrypsin + alpha-1 proteinase inhibitor
There are also antiproteases that have been secreted by the epithelia.
What proportion of epithelial cells are ciliated cells?
How do ciliated cells change in smokers?
Ciliated cell are severely depleted
Ciliated cells found in bronchioles (though reduced in airways)
Unable to transport thickened mucus - smoker’s cough
Give two characteristics of small airways.
< 2 mm in diameter
What are clara cells?
Non-ciliated secretory epithelia found in the large, central and small airways and bronchi and bronchioles
How are clara cells distributed throughout the respiratory system?
They increase in proportion distally
What is the major role of clara cells?
What are the two classes of enzymes produced by clara cells and what do they do?
Phase 1 and Phase 2 - they are meant to be involved in metabolising foreign substances but they are also implicated in oncogenesis.
Phase 1 enzymes convert procarcinogens to carcinogens
Phase 2 enzymes conjugate the carcinogens to make them inactive
Clara cells also produce antiproteases and lyoszyme.
What is a potentially detrimental action of clara cell enzymes?
They convert procarcinogens into carcinogens
How are alveoli different in emphysema?
They have holes in them
Volume of alveoli increases
Surface area of the alveoli decrease
How do Type I and Type II cells differ in their susceptibility to damage?
Type II cells are more susceptible to damage
But Type I cells are more frequently damaged
Describe the role of Type II cells.
Also synthesise and secrete antiproteases
Make up 5% of alveolar surface
Precursor for Type 1 pneumocytes
What is the ratio of Type II to Type I cells?
What do stromal fibroblasts do?
They deposit collagen and elastin to give elasticity and compliance to the alveolus
They divide to repair
What do alveolar macrophages do and what proportion of total phagocytic cells in a normal lung consist of macrophages?
NORMAL = 70% macrophages (this is in the large/conducting airways, NOTE: macrophages make up 90% of ALL phagocytes in the airways but that includes the smaller airways)
Phagocytose cell debris and microorganisms
Recruit other inflammatory cells during infection
How do numbers of macrophages and neutrophils change in smokers and during infection?
Proportions switch over. Numbers of macrophages and neutrophils increases but ratio becomes:
Macrophages: Neutrophils = 30:70
IMPORTANT NOTE: These proportions switch over in the CONDUCTING/LARGE AIRWAYS (not in the smaller airways). In the smaller airways it is still dominated by macrophages.
Bronchial lavage will give an indication of the distribution of phagocytes in the larger airways.
Describe the histopathology of emphysema.
Increase in proliferation of fibroblasts —> more collagen deposited —> fibrosis
There is also an INCREASE IN TYPE II PNEUMOCYTE PROLIFERATION
Type I cell death releases growth factors that stimulate the type II proliferation and differentiation (to replace the lost Type II cells)
Abnormal repair - there is excess damage to type I cells —> excess release of growth factors —> fibrosis
Describe normal and abnormal repair.
Type I pneumocyte death leads to a release of growth factors that stimulate proliferation and differentiation of type II pneumocytes
Excess tissue damage leads to more type I pneumocyte death –> excess release of growth factors –> excessive release of collagen –> irreversible damage/fibrosis
Describe the effect of smoking on the proliferation and differentiation of alveolar epithelial cells.
Smoking BLOCKS the proliferation and differentiation of type II cells into type I cells
This also stimulates apoptosis and necrosis of type I and type II cells.
Smoking also blocks communication between type II cells and fibroblasts, thus inhibiting the normal repair process.
What do phagocytes produce that increase alveolar inflammation?
There is a massive increase in the numbers of macrophages and neutrophils and there is an increase in the amount of proteases produced by them.
They secrete serine proteases (e.g. neutrophil elastase) and matrix metalloproteinases, which overwhelm the neutralising capacity of the anti-proteases and causes damage to the alveolar epithelium resulting in inflammation.
They also release anti-microbial oxidants
Describe the normal metabolism of procarcinogens and how this changes in smokers.
Normally, phase I enzymes convert the procarcinogen to a carcinogen and the phase II enzymes conjugate it and remove it.
Smoking can overload the safe removal pathway so the carcinogen may bind to DNA and cause mutations.
What non-structural substances would come out with a bronchial lavage?
What can you see in a high resolution CT scan of someone with COPD?
Increased density of small airways
Holes in the small airways
What actually causes the damage in emphysema?
Secretion of serine proteases and matrix metalloproteinases by the macrophages and neutrophils - they overload the capacity of anti-proteases to neutralise the threat and cause damage to the epithelium resulting in inflammation.
What is a possible treatment option for emphysema?
Why might there be problems with inhaled delivery of this?
People with COPD have obstructed or stenosed lungs (due to mucus hypersecretion) so the drug might not reach the alveoli.