Lung Cell Biology

Question 1

How many generations of gas exchange units are there?

Answer 1

23

Question 2

What proportion of epithelial cells are goblet cells?

Answer 2

1/5

Question 3

How do goblet cells and mucus change in smokers?

Answer 3

Goblet cells INCREASE in number
Secretions INCREASE in quantity
Secretions are THICKER

Question 4

What is the structure of mucus?

Answer 4

A thin sol phase overlays the cells

A thick gel phase is at the mucus-air interface

Question 5

What does mucus contain?

Answer 5

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.
Anti-oxidants

Question 6

What proportion of epithelial cells are ciliated cells?

Answer 6

80%

Question 7

How do ciliated cells change in smokers?

Answer 7

Ciliated cell are severely depleted
Beat asynchronously
Ciliated cells found in bronchioles (though reduced in airways)
Unable to transport thickened mucus - smoker’s cough

Question 8

Give two characteristics of small airways.

Answer 8

< 2 mm in diameter

NOT cartilaginous

Question 9

What are clara cells?

Answer 9

Non-ciliated secretory epithelia found in the large, central and small airways and bronchi and bronchioles

Question 10

How are clara cells distributed throughout the respiratory system?

Answer 10

They increase in proportion distally

Question 11

What is the major role of clara cells?

Answer 11

Xenobiotic metabolism

Question 12

What are the two classes of enzymes produced by clara cells and what do they do?

Answer 12

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.

Question 13

What is a potentially detrimental action of clara cell enzymes?

Answer 13

They convert procarcinogens into carcinogens

Question 14

How are alveoli different in emphysema?

Answer 14

They have holes in them
Volume of alveoli increases
Surface area of the alveoli decrease

Question 15

How do Type I and Type II cells differ in their susceptibility to damage?

Answer 15

Type II cells are more susceptible to damage

But Type I cells are more frequently damaged

Question 16

Describe the role of Type II cells.

Answer 16

Produce SURFACTANT
Also synthesise and secrete antiproteases
Make up 5% of alveolar surface
Precursor for Type 1 pneumocytes

Question 17

What is the ratio of Type II to Type I cells?

Answer 17

2:1

Question 18

What do stromal fibroblasts do?

Answer 18

Make ECM
They deposit collagen and elastin to give elasticity and compliance to the alveolus
They divide to repair

Question 19

What do alveolar macrophages do and what proportion of total phagocytic cells in a normal lung consist of macrophages?

Answer 19

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
Generate anti-oxidants

Question 20

How do numbers of macrophages and neutrophils change in smokers and during infection?

Answer 20

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.

Question 21

Describe the histopathology of emphysema.

Answer 21

Centre-lobular
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

Question 22

Describe normal and abnormal repair.

Answer 22

Normal repair:
Type I pneumocyte death leads to a release of growth factors that stimulate proliferation and differentiation of type II pneumocytes
Abnormal repair:
Excess tissue damage leads to more type I pneumocyte death –> excess release of growth factors –> excessive release of collagen –> irreversible damage/fibrosis

Question 23

Describe the effect of smoking on the proliferation and differentiation of alveolar epithelial cells.

Answer 23

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.

Question 24

What do phagocytes produce that increase alveolar inflammation?

Answer 24

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

Question 25

Describe the normal metabolism of procarcinogens and how this changes in smokers.

Answer 25

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.

Question 26

What non-structural substances would come out with a bronchial lavage?

Answer 26

Macrophages
Neutrophils
Surfactant

Question 27

What can you see in a high resolution CT scan of someone with COPD?

Answer 27

Increased density of small airways

Holes in the small airways

Question 28

What actually causes the damage in emphysema?

Answer 28

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.

Question 29

What is a possible treatment option for emphysema?

Answer 29

Protease inhibitors

Question 30

Why might there be problems with inhaled delivery of this?

Answer 30

People with COPD have obstructed or stenosed lungs (due to mucus hypersecretion) so the drug might not reach the alveoli.