Lung cell biology Flashcards
Cross sectional area of the lungs increase
Peripherally
the gas exchange units are are lined with
fluid called surfactant
one wine glass full of surfactant
Role of the epithelium
-Forms a continuous barrier, isolating external environment from
host
•Produces secretions to facilitate clearance, via mucociliary
escalator, and protect underlying cells as well as maintain reduced
surface tension (alveolae)
•Metabolises foreign and host-derived compounds
•Releases mediators
•Triggers lung repair processes
How does the airway epithelium change in COPD?
Increased goblet cell numbers
(goblet cell hyperplasia) &
increased mucus secretion
Where are goblet cells found?
What % of epithelial cells do they consist of?
What do they do?
Goblet cells: Large, central, small airways
- Healthy, ~20% epithelial cells
- Synthesise and secrete mucus
Goblet cells in smokers- what are the changes?
Goblet cells: In smokers * goblet cell number at least doubles * secretions increase * secretions are more viscoelastic
Modified gel phase traps cigarette smoke particles but also traps and harbours microorganisms, enhancing chances of infection
Where are ciliated cells found?
What % of epithelial cells do they consist of?
What do they do?
Ciliated cells: Large, central and small airways
- Normally ~60-80% of epithelial cells
- Cilia beat metasynchronously Imagine a field of corn with wind blowing to form “flow waves”
Ciliated cells in smokers- what are the changes?
CILIATED CELLS in smokers and smokers with bronchitis:
* ciliated cells are severely depleted * cilia beat asynchronously * ciliated cells found in bronchioles * cilia unable to transport thickened mucus
Reduced mucus clearance leading to respiratory infection and bronchitis. Airways obstructed by mucus secretions.
What happens in COPD?
COPD – small airways disease and emphysema
- decreased elasticity of supporting structure
- plugging, inflammatory narrowing and obliteration of small airways -destruction of peribronchiolar support
What are Club Cell?
Also called?
Non-ciliated secretory bronchiolar epithelial cell
Clara cells
Where are club cells found?
What % of epithelial cells do they consist of?
What do they do?
CLUB CELLS ~ 20% of epithelial cells (lower in smokers) •Secretory cells •Detoxification •Repair/progenitor cells
TYPE I EPITHELIAL CELL COVERS ? OF ALVEOLAR SURFACE
TYPE I EPITHELIAL CELL COVERS 95% ALVEOLAR SURFACE
Type I : Type II ratio = ?
Type I : Type II ratio = 1 : 2
What do epithelial type II cells contain?
Epithelial type II cells containing lamellar bosies which store surfactant prior to release onto the air-liquid interface (AL). These cells sit in the corners of the alveoli, and embedded in the interstitium with the apices facing the air. CA = capillary.
What do epithelial type II cells do?
TYPE II CELLS SYNTHESISE AND RELEASE SURFACTANT TO PREVENT ALVEOLAR COLLAPSE ON EXPIRATION
Type II epithelial cells: Repair/progenitor cells Precursor of type I cells Secrete surfactant Cover 5% of the alveolar surface
What do epithelial type I cells do?
Type I epithelial cells are very thin but strong to allow gas exchange. Cover 95% of the alveolar surface
What do stromal cells fibroblasts do?
Stromal cells (myo) fibroblasts
Make extracellular matrix – the lung’s cement
Collagen, elastin, to give elasticity and compliance
Divide to repair
Alveolar epithelial-endothelial barrier
Fibroblast adjacent to epithelial cell
Signs of Alveolar fibrosis
Increased type II cells (ie repair)
Increased fibroblasts
Increased collagen deposition
Role of stromal cell (fibroblast) in lung repair and fibrosis
Type I cell death
Growth factors help normal repair
Elevated growth factors lead to: Type II cell proliferation, Stromal cell proliferation, Connective tissue synthesis
ALVEOLAR EPITHELIUM CAN ORCHESTRATE REPAIR
1) apoptosis
2) EMT to myofibroblast
3) transdifferntiation to re-epithelialisation
Cigarette smoke increases apoptosis/necrosis
EMT to myofibroblast: blocks repair
transdifferntiation: blocks repair
What 2 cells increase in smokers and by how much?
Neutrophil + Macrophage
Increase by up to 10-fold in smokers
Phagocytosis
Antimicrobial defence Synthesise antioxidants eg glutathione Xenobiotic metabolism
Respiratory units in smokers
Respiratory units – Mainly macrophages (approx 90%); Neutrophils up to 10% (may increase to 30% in smokers with respiratory infection)
Airways
Macrophage:neutrophil ratio: in non-smokers and in COPD
Airways –
Macrophage:neutrophil ratio:70%:30% in non-smokers 30%:70% in COPD
What do increase levels of neutrophils and macrophages lead to?
SERINE PROTEINASES METTALLOPROTEINASES eg neutrophil elastase (NE) eg MMP9; Zn/metal at reactive site)
Substrates: proteins; connective tissue, elastin, collagen
Activate other proteinases (eg NE degrades and activates MMP),
Inactivates antiproteases (eg MMP degrades and inactivates alpha-1 antitrypsin)
Activate cytokines/chemokines and other pro-inflammatory mediators
What do oxidants do?
Oxidants are also released by neutrophils and macrophages and they are microbial.
Generate highly reactive peroxides Interact with proteins and lipids
Inactivate alpha-1 antitrypsin
Fragment connective tissue
Macrophages secrete?
Secrete mediators
Chemoattractants/cytokines (eg IL8) attract more inflammatory cells during infection or after toxicant or microbial deposition/inhalation
Growth factors and proteases trigger growth and repair by other cells eg epithelium, stromal fibroblasts
Clara cells, Type II cells and Macrophages:
Contain ?
What are they involved in?
Phase I and II enzymes
These enzymes are involved in xenobiotic metabolism, ie metabolism of foreign compounds deposited by inhalation
What do phase I enzymes do?
procarcinogen into carcinogen (active compound) in lung cells
What do phase II enzymes do?
No metabolism
carcinogens for DNA binding, adduct formation, no repair, mutation
Normal metabolism
Into water soluble metabolite- excreted
