lecture 5 : lung cell biology Flashcards
what is the function of the epithelium?
- forms a continuous barrier
- produces secretions to facilitate clearance and protecting the underlying cells
- metabolises foreign bodies
- releases mediators
- triggers lung repair process
**compare a healthy airway epithelium with a COPD epithelium?
more goblet cells
more mucus secretion
what happens to goblet cells in smokers?
- 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
where are normal goblet cells found?
- they make up 20% of the epithelium
- they synthesise and secrete mucous
- they are found in the airways
- thick gel exposed to the air
where are normal ciliated cells?
- found in large central and small airways
- make up 80% of the epithelium
- they beat METASYNCHRONOUSLY
- tip of the cilia pushes mucus towards epiglottis
what happens to ciliated cells in smokers?
- 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
what happens to small airways in COPD?
- 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
what are club cells?
what are some functions?
- 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
what happens to bronchilolar ciliated cells in smokers?
they increase in number
what enzymes do club cells contain?
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
what happens to smokers alveoli?
- small holes appear
- reduce the surface area of the lungs
- alveoli become larger
- elastic tissue loss
- more dead space
what do the alveolar walls contain?
- 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
info about type 1 epithelium?
- very thin but strong to allow gas exchange
- large cells
- cover 95% of the alveolar surface
info about type 2 epithelium?
- 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
Polymorphonuclear Neutrophils
- 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
Alveolar Macrophages
- 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
what is the emphysema histopathology?
- 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
what is normal repair of emphysema ?
T1 cell death triggers growth factor release to increase T2 proliferation and differentiation
what is abnormal repair of emphysema ?
- excess tissue breakdown
- elevated growth factor release
- fibrotic effect (irreversible).
effects of smoking?
proliferation
- smoking blocks proliferation
and differentiation of T2 - T1 cells - causes necrosis of T1 and T2 cells
- blocks communication of T2 cells to fibroblasts
what does smoking do to the macrophages ?
- 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
what does normal mucus contain?
- mucin proteins, proteoglycans, glycosaminoglycans
- gives the mucus viscoelasticity
- serum derivative proteins like albumin
- antiproteases (combats micro-organisms)
- antioxidants ( counteracts oxidants from phagocytes)
what are normal small airways like?
- less than 2mm
- not cartilaginous
- mucus gets trapped
what does smoking do to pro carcinogens
?
- 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
