lecture 5 : lung cell biology

Question 1

what is the function of the epithelium?

Answer 1

• forms a continuous barrier
• produces secretions to facilitate clearance and protecting the underlying cells
• metabolises foreign bodies
• releases mediators
• triggers lung repair process

Question 2

**compare a healthy airway epithelium with a COPD epithelium?

Answer 2

more goblet cells

more mucus secretion

Question 3

what happens to goblet cells in smokers?

Answer 3

• the goblet cell number doubles
• secretions increase
• secretions become thicker
• with more mucous more particulates are trapped but also microorganisms therefore the chance of infection is increased

Question 4

where are normal goblet cells found?

Answer 4

• they make up 20% of the epithelium
• they synthesise and secrete mucous
• they are found in the airways
• thick gel exposed to the air

Question 5

where are normal ciliated cells?

Answer 5

• found in large central and small airways
• make up 80% of the epithelium
• they beat METASYNCHRONOUSLY
• tip of the cilia pushes mucus towards epiglottis

Question 6

what happens to ciliated cells in smokers?

Answer 6

• the ciliated cells become depleted
• cilia beat asynchronously
• the cilia cannot transport the mucous
• reduced mucous clearing leads to infection
• metaplasia to form ciliated cells in the bronchioles

Question 7

what happens to small airways in COPD?

Answer 7

• the small airways collapse to smaller than 2mm
• decreased elasticity
• mucous gets trapped
• airway narrows
• cells are broken down by enzymes
• stenosis (narrowing) of small airways

Question 8

what are club cells?

what are some functions?

Answer 8

• non ciliated secretory epithelial cells
• found in large central small bronchi and bronchioles
• they increase in proportion distally
• they contain phase 1 and 2 enzymes
• xenobiotic metabolism
  (metabolism of foreign bodies deposited by inhalation)
• release high amounts of antiproteases
• synthesize and secrete lysozymes

Question 9

what happens to bronchilolar ciliated cells in smokers?

Answer 9

they increase in number

Question 10

what enzymes do club cells contain?

Answer 10

Phase 1 enzymes:

• These metabolise foreign compounds into a format that phase 2 can react with
• sadly can also can activate pro-carcinogens to carcinogens

phase 2 enzymes:
Neutralise BPDE which is a carcinogen to a small molecule

Question 11

what happens to smokers alveoli?

Answer 11

• small holes appear
• reduce the surface area of the lungs
• alveoli become larger
• elastic tissue loss
• more dead space

Question 12

what do the alveolar walls contain?

Answer 12

• type 1 epithelial cells (95% coverage)
• type 2 epithelial cells
• ratio 2:1 of T2:T1
• stromal fibroblasts (make the extracellular matrix- the cells cement)
• alveolar macrophages
• capillary endothelium

Question 13

info about type 1 epithelium?

Answer 13

• very thin but strong to allow gas exchange
• large cells
• cover 95% of the alveolar surface

Question 14

info about type 2 epithelium?

Answer 14

• cuboidal and positioned at the corners of the alveoli
• lamellar bodies secrete surfactant
• the surfactant reduces the surface tension
• they are pre cursors to type 1
• synthesises antiproteases
• Type 2 cells are the precursors for the type 1 alveolar cells
• type 2 cells are more likely to get damaged

Question 15

Polymorphonuclear Neutrophils

Answer 15

• Form ~5% of phagocytic cells in the lungs.
• Increase 5-10 fold in smoker’s lungs and proportionally (up to 30% of phagocytic cells).
• Higher proportion in conducting/large airways.
• Stores high levels of potent proteases.
  Releases very potent oxidative molecules such as hydroxyl anions during activation

Question 16

Alveolar Macrophages

Answer 16

• Form ~70% of phagocytic cells in the lungs.
• Increase 5-10 fold in a smoker’s lungs.
• Secretes chemokines for chemotaxis of inflammatory/immune cells.
• Secrete proteases to digest foreign bacteria.
• Secrete oxidants and anti-oxidants
• important scavenging cells

Question 17

what is the emphysema histopathology?

Answer 17

• classic emphysema is center lobular
• fibroblasts are available for proliferation
• increased number of T ii cells
• increased number of fibroblasts to make a lot of connective tissue
• increased collagen deposition

Question 18

what is normal repair of emphysema ?

Answer 18

T1 cell death triggers growth factor release to increase T2 proliferation and differentiation

Question 19

what is abnormal repair of emphysema ?

Answer 19

• excess tissue breakdown
• elevated growth factor release
• fibrotic effect (irreversible).

Question 20

effects of smoking?

proliferation

Answer 20

• smoking blocks proliferation
  and differentiation of T2 - T1 cells
• causes necrosis of T1 and T2 cells
• blocks communication of T2 cells to fibroblasts

Question 21

what does smoking do to the macrophages ?

Answer 21

• Macrophage and neutrophil numbers increase up to 10-fold.

Macrophage: Neutrophil ratio = 70:30 but REVERSES in COPD (in UPPER airways).

• macrophages and neutrophils also Secrete anti-microbial oxidants and mediators such as growth factors.
• Secrete proteases,
  therefore causing alveolar inflammation

Question 22

what does normal mucus contain?

Answer 22

• mucin proteins, proteoglycans, glycosaminoglycans
• gives the mucus viscoelasticity
• serum derivative proteins like albumin
• antiproteases (combats micro-organisms)
• antioxidants ( counteracts oxidants from phagocytes)

Question 23

what are normal small airways like?

Answer 23

• less than 2mm
• not cartilaginous
• mucus gets trapped

Question 24

what does smoking do to pro carcinogens

?

Answer 24

• Smoking contains pro-carcinogens which get inadvertently activated by phase 1 enzymes from Clara cells.
• Normally, phase 2 enzymes can metabolise these pro-carcinogens but they may be inactivated by smoking