Resp 5 - Lung cell biology

Question 1

The cross sectional area of the lungs increases peripherally. How many generations of gas exchange units are there?

Answer 1

23

Question 2

What are the gas exchange units lined with?

Answer 2

Surfactant

Question 3

Contrast the function and coverage of type 1 epithelium ad type 2 epithelium of the alveoli.

Answer 3

Type 1 - 95% coverage. Surface for gas exchange to occur.

Type 2 - 5% coverage, synthesise and releases lung lining liquid (including lung surfactant - prevents lungs from collapsing at low pressure on exhalation).

Question 4

Name 5 roles of epithelium in the lungs

Answer 4

1. Forms continuous barrier
2. Secretions which facilitate clearance via mucociliary escalator and protects underlying cells (also maintains low surface tension in alveoli)
3. Metabolises foreign and host derived compounds
4. Triggers lung repair processes

Question 5

How common are goblet cells?

Answer 5

Normally 1/5 of epithelial cells

Question 6

Mucus is at solution phase overlaying cells. What phase it at the air interface?

Answer 6

Thick gel phase

Question 7

What do mucin proteins, GAGs and proteoglycans enable?

Answer 7

It enables mucus to have viscoelasticity

Question 8

What does mucus contain (except mucin/gags/proteoglycans)?

Answer 8

1. Albumin and Alpha 1 antitrypsin/alpha 1 proteinase inhibitor - inhibits polymorphonuclear neutrophil proteases. Combats microorganism and phagocyte proteases.
2. Antiproteases (synthesised by epithelial cells) - combats microorganism and phagocyte proteases
3. Antioxidants - from blood and epithelial cells. Combats inhaled oxidants and counteracts excessive oxidants released by activated phagocytes.

Question 9

What happens in smokers to mucus/goblet cells?

Answer 9

1. Goblet cell number doubles
2. Secretions increase in quantity
3. Thicker secretions

Gel phase traps cigarette smoke but also traps microorganisms which increases the chance of infection.

Question 10

Ciliated cells - how frequent are they?

Describe the tips of cilia

Answer 10

80% of epithelial cells.

The tips of cilia are in the sol phase of mucus and push mucus towards the epiglottis - mucus usually swallowed/spit

Question 11

Describe cilia in smokers

Answer 11

1. Cilia cells depleted severely
2. Cilia beat asynchronously
3. Cilia found in bronchioles (despite reduction in airways)
4. Cilia unable to transport thick mucus - less mucus cleared.

Question 12

What can reduced mucus clearance lead to in smokers?

Answer 12

Respiratory infection and bronchitis.

Question 13

Are the small airways cartilagenous?

Answer 13

No

Question 14

What happens to the small airways in COPD?

Answer 14

1. Mucus trapped so narrow airway

2. Mucus broken down by enzymes and inflammatory cells - reduces peripheral gas exchange.

Question 15

What are Clara cells and what is their major role?

Answer 15

They are non-ciliated secretory epithelial cells found in large, central and small airways, as well as bronchi and bronchioles. More found in bronchi and bronchioles (they increase proportion distally)

Major role is xenobiotic metabolism - they metabolise foreign material deposited by inhalation.

Question 16

Clara cells contain phase 1 and phase 2 enzymes.

What do Phase 1 enzymes do?
What do Phase 2 enzymes do?

Answer 16

Phase 1 enzymes include p450 cytochrome oxidases. They metabolise foreign material into a format that phase 2 enzymes can act on (neutralise toxic agent). They often activate a pre carcinogen though (benzopyrene)

Phase 2 enzymes (e.g. Glutathione S-transferase) enable BPDE to be conjugated to a small molecule, neutralising its activity.

Question 17

What is the pre carcinogen and how is it made into a carcinogen via Phase 1 enzymes?

Answer 17

Precarcinogen (benzopyrene) made into benzopyrene diol epoxide (BPDE - carcinogen) through cytochrome oxidases.

If you have Cytochrome P450 oxidase and no glutathione-S-transferase, you are 40x more likely to get lung cancer

Question 18

2 things that Clara cells synthesise and release?

Answer 18

Antiproteinases and lysozyme

Question 19

How does smoking affect the alveoli?

Answer 19

Increases dead space in the alveoli - holes in alveoli cause alveoli to become larger. This causes a reduction in SA for gas exchange.

May be seen as elastic tissue loss. This causes reduced expansion during breathing.

Question 20

Which type of alveolar epithelial cells are more susceptible to damage?

Which cells are actually damaged more?

Answer 20

Type 2 more susceptible to damage.

Type 1 damaged more

Question 21

Describe Type 2 cell structure, function and location

Answer 21

1. Contain lamellar bodies - stores surfactant before release
2. Synthesises and secretes antiproteinases
3. Positioned in the corners of the lung. Embedded in the interstitium - apical membranes face the air.
4. Very close to capillaries.

Question 22

What are Type 2 alveolar epithelial cells a precursor for

Answer 22

Precursor for alveolar type 1 epithelial cells - they divide and differentiate to replace damage damaged type 1 cells.

Question 23

Describe surfactant

Answer 23

Phospholipid rich surface active material. it prevents lung collapse on expiration and has immunological functions.

Question 24

What 5 things does an alveolar unit consist of?

Answer 24

1. Type 1 cells
2. Type 2 cells
3. Stromal fibroblasts
4. Alveolar macrophages
5. Capillary endothelium

(There are more type 2 than 1, but 1 covers 95% of the area)

Question 25

What do stromal fibroblasts do?

Answer 25

1. Make ECM 2. Make collagen and elastin 3. Divide to repair

Question 26

Give 1 adaptation of capillary endothelium?

Answer 26

They are in close proximity to alveolus - reduces diffusion distance

Question 27

Alveolar macrophages - describe their functions and properties.

Answer 27

1. Constitute 70% of total phagocytic cells in a normal lung 2. They are 5-10x more common in smokers lungs 3. They are important scavengers - they phagocytose debris and microorganisms 4. They can recruit other inflammatory cells during an infection/toxic inhalation 5. Synthesise and secrete proteases 6. Generate oxidants during phagocytosis - kills pathogens 7. Generates antioxidants (e.g. Glutathione) - neutralises oxidative molecules that may be inhaled/generated in infection 8. Contain enzymes that metabolise toxicants.

Question 28

Where are alveolar macrophages more common?

Answer 28

In the lower respiratory tract

Question 29

Describe polymorphonuclear neutrophils in the respiratory system

Answer 29

1. Only makes up 5% of lower respiratory tract phagocytes. 2. Makes about 30% of upper respiratory phagocytes (upto 70% in smokers) 3. Found in greater numbers in conducting airways. 4. Increase significantly in smokers.

Question 30

What do polymorphonuclear neutrophils store in high levels in granules?

Answer 30

Potent proteases that are released on activation. They also release oxidative molecules e.g. hydroxyl anions Smokers contain many of the proteases.

Question 31

What are the 3 main structures of lung blood vessels?

Answer 31

1. Muscular 2. Partially muscular 3. Nonmuscular

Question 32

Which lobe does emphysema typically affect?

Answer 32

Central lobe

Question 33

In normal repair of emphysema, what happens?

Answer 33

Type 1 cell death stimulates GF release which increases type 2 cell proliferation/differentiation

Question 34

In abnormal repair of emphysema, what happens?

Answer 34

Excess tissue breakdown causing elevated GF release. This causes a fibrotic effect (increase type 2 cells and stromal/fibroblast connective tissue synthesis - irreversible damage)

Question 35

What are the effects of smoking?

Answer 35

1. Blocks proliferation and differentiation of type 2 cells into type 1 cells (also stimulates apoptosis and necrosis of type 1 and 2 cells). Also blocks communication between type 2 cells and fibroblasts which hinders repair 2. Increases number of macrophages and neutrophils tenfold. Serine proteases and metalloproteases are secreted which can recruit pro-inflammatory mediators and cause alveolar inflammation. Antimicrobial oxidants are released which fragments connective tissue which causes damage (peroxides) 3. Contains pro carcinogens that are activated by phase 1 enzymes. Smoking overloads the normal pathway of it being metabolised and excreted (metabolised as it becomes water soluble)