Lung cell biology

Question 1

How does the cross sectional area increase of the lung?

Answer 1

It increases peripherally ( something on the outside)

Question 2

How many generations of gas exchange units are there?

Answer 2

23

Question 3

what are the gas exchange units lined with?

Answer 3

It is lined with a fluid called surfactant.

Question 4

what is the role of the epithelium?

Answer 4

• forms a continuous barrier, isolating external environment from host
• produces secretions to facilitate clearance, via mucociliary escalator and protect underlying cells as ell as maintain reduced surface tension ( in the alveoli)
• metabolises foreign and host-derived compounds
• release mediators ( controls the number of inflammatory mediators that reach the lungs)
• triggers lung repair processes

Question 5

What proportion of epithelial cells are goblet cells?

Answer 5

1/5

Question 6

How do goblet cells and mucus change in smokers?

Answer 6

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

Question 7

What is the structure of mucus?

Answer 7

A thin sol phase overlays the cells

A thick gel phase is at the mucus-air interface

Question 8

What does mucus contain?

Answer 8

Mucin protein, proeoglycans, GAGs - give viscoelasticity
Serum derived proteins - albumin + alpha-1 antitrypsin + alpha-1 proteinase inhibitor, an inhibitor of polymorphonuclear neutrophil proteases. Combats microorganism and phagocyte proteases.
There are also antiproteases that have been secreted by the epithelia.
Anti-oxidants: from the blood and synthesised by epithelial cells and phagocytes.
Antiproteases: synthesised by epithelial cells e.g. secretory leucoprotease inhibitor. Combat microorganism and phagocyte proteases.

Question 9

What proportion of epithelial cells are ciliated cells?

Answer 9

80%

Question 10

How do ciliated cells change in smokers?

Answer 10

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

Question 11

Give two characteristics of small airways.

Answer 11

< 2 mm in diameter

NOT cartilaginous

Question 12

what happens to the small airways in COPD?

Answer 12

• Mucus becomes trapped
• airway narrow
• broken down b y enzymes and inflammatory cells - this reduced peripheral gas exchange

Question 13

What are clara cells?

Answer 13

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

Question 14

How are clara cells distributed throughout the respiratory system?

Answer 14

They increase in proportion distally

Question 15

What is the major role of clara cells?

Answer 15

Xenobiotic metabolism (metabolism of foreign compounds deposited by inhalation)

Question 16

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

Answer 16

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 .
The contain cytochrome p450 oxidases.
Phase 2 enzymes conjugate the carcinogens to make them inactive.
Clara cells also produce antiproteases and lysozyme.

Question 17

where can you find clara cells mainly?

Answer 17

They are found in most conducting and transitional airways.

Question 18

what is COPD a mixture of?

Answer 18

COPD= bronchitis + emphysema+ small airways disease.

Question 19

How are alveoli different in emphysema?

Answer 19

They have holes in them
Volume of alveoli increases
Surface area of the alveoli decrease.
The alveoli may become larger. This leads to a reduction in the surface area available for gas exchange. This can be seen as elastic tissue loss- therefore, expansion during breathing is reduced which increases the amount of dead space

Question 20

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

Answer 20

Type II cells are more susceptible to damage

But Type I cells are more frequently damaged— very close to capillaries

Question 21

Describe the role of Type II cells and the structure

Answer 21

• found only in the alveoli
• contain lamellar bodies that store surfactant prior to release onto the air-liquid interface.

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

Question 22

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

Answer 22

2:1

Question 23

What do stromal fibroblasts do?

Answer 23

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

Question 24

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

Answer 24

-Enriched in lower respiratory tract, but found throughout.
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: to kill infection organism.

Question 25

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

Answer 25

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 26

how much polymorphonuclear neutrophils are found and where and how does this change in smokers

Answer 26

-Found throughout the airways. Usually only about 5% of lower respiratory tract phagocytes. - Increase significantly in number (5-10 fold) and proportionally ( up to 30% of total phagocytes) in smokers and more so during infection. Higher proportion in conducting/large airways. These store high levels of potent proteases in granules- they are released on activation. Smokers lung contain high levels of these released proteases. -Release very potent oxidative molecules such as hydroxyl anions during activation

Question 27

Describe the histopathology of emphysema.

Answer 27

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 28

Describe normal and abnormal repair.

Answer 28

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 29

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

Answer 29

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 30

What do phagocytes produce that increase alveolar inflammation?

Answer 30

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 31

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

Answer 31

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 32

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

Answer 32

Macrophages Neutrophils Surfactant

Question 33

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

Answer 33

Increased density of small airways | Holes in the small airways

Question 34

What actually causes the damage in emphysema?

Answer 34

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 35

What is a possible treatment option for emphysema?

Answer 35

Protease inhibitors

Question 36

Why might there be problems with inhaled delivery of this?

Answer 36

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