Lung cell biology Flashcards
What are the divisions of the airways`
0 Trachea 1 bronchi 4 bronchioles 14 terminal bronchioles 15 transitional bronchioles 16 respiratory bronchioles 19 alveolar ducts 23 alveolar sacs
What is epithelium?
Forms continous barrer isolating extenral from internal
Produces secretions to protect cells and reduce surface tension
Metabolise foreign and host derived compounds
Release mediators
Trigger lung repair process
Where are goblet cells found?
Large, small, airways
What percentage of epithelial cells are goblet cells?
In healthy lung 20% of epithelial cells
What is the effect of smoking on goblet cell numbers
(at least doubles in smokers, thicker and increased secretions, more viscoelastic)
What is the function of goblet cells?
Traps smoke carticles and trap and harour microporganisms isncreaisng chance of infection
Sythesisze and secrete mucus
‘thin’ sol phase overlays cells, thick gel phase at air interface.
What does the mucus in goblet cells contain?
Mucin proteins, proteoglycans and gycosaminoglycans,
Give mucus viscoelasticity
What combats microorgsnisms and phagocyte roteases in mucus?
albumin and alpha 1-antitrypsin, also called alpha 1-proteinase inhibitor,
Inhibit polymorphonuclear neutrophil proteases
What combats inhaled oxidants?
Antioxidants from the blood and synthesised by epithelial cells and phagocytes – uric acid and ascorbic acid (blood), glutathione (cells)
Where are cilia found
- Large, central, small airwas,
What proportion of epithelial cells is cilia?
- 80% of epithelial cells
How do cilia beat?
- Beat metasynchroulsy
- Tips of cilia in sol phase of mucus pushes mucus towards epiglottis
- Expectorated
How does smoking affect cilia?
- Depleted in smokers with bronchitis
- Asynchrous
- Found in bronchioles which blocks smaller airways
- Unable to transort thickeend mucus
- Reduced musuc clearance
How are smaller airways held open?
- Intact alveolar walls hold airways open
Where are Clara cells found?
- Mosdt conducting and transitional airways
- Increase in proportion distally e.g bronchi and bronchioles
What is the function of Clara cells?
- Xenobiotic metabolism
- Metablism of foreign compounds deposited by inhallation
What are phase I and phase 2 enzymes?
Phase 1: cytocrhome P450 oxidases
- Metabolise foeigh compounds
- Enables phase 2 enzymes to neutralise toxic aganet
- May often activate precarcinogen to carcinogen
Phase 2: glutathione S-transferase
- Enables conjugation of BPDE to small molcule
- Neutralises it’s activtiy
- Some don’t have it
- If also smoker may increase
What else do phase 1 and phase 2 enzymes secrete?
- Lots of proteases
- Lysosyme
- Antioxidants
What is the normal ratio of Type 1 to Type 2 cells?
1:2
Less type 1 in smokers
What is the function of type 2 epithelial cells?
- Synthesise and secrete pulmonary surfactant ( immunological functions)
- Precursor of alveolar epithelial type I cells. Divide and differentiate to replace damaged type I cells.
- Synthesise and secrete anti-proteases
- Found in alveoli
- Carry out xenobiotic metabolism
What is the funciton of type 1 epithelial cells?
thin but strong to allow gas exchange
(95%) of alveolar surface
How are carcinogens made in the lungs?
- Smoke contains procarcinogens
- Club cells, type 2 cells, macrophagesc ontain phase 2 and phase 2 enzymes used in detoxification
- Lung cells contain hase 1 enzymes which activste compound
- Compound becomes more carcinogenic,
- Phase 2 enzymes make them water soluble and they are exreted
- If more carcinogens than phase 2 enzymes can deal with you get DNA binding, adduct formtion, no repair and mutation
What a proportion of lungs is alveolar macrophages in a normal person and in a smoker ?
90% of phagocytic cells
Increase 5-10x in smoker
What is the role of alveolar macrophages?
- phagocytose debris and microorganisms.
- Use cytokines to recruit pro inflammatory cells and molecules
- proteases to digest unwanted debris, attack organic material
- oxidants during phagocytosis and on activation to kill infecting organisms etc
- antioxidants such as glutathione to neutralise oxidative molecules that might be inhaled or generated during infection etc
- Contain enzymes that metabolise toxicants (xenobiotic metabolism)
What is the proportion of polymorphonuclear neutrophils in smokers and on smokers?
- 5% of lower respiratory tract phagocytes
- Increase 5-10x proportion in msokers
Macrophage: neutrophil ratio
70: 30 in non smokers
30: 70 in COPD
What is the function of polymorphonuclear neutrophils?
- Secretory
- Store high levels of proteases
- Released
- Also release oxidative molecules (hydroxyl anions) during activation
What occurs during COPD?
- Walls of alveoli become distrupted due to secretions
- Alveoli can’t open
- Small airways may also become blocked
Fibrosis occurs in an attemt to repair tissue- Airways can’t reverse dmagae
- Lots of inflammatory cells
- Stenotic region: not joined to rest of airways due to firbrosis
What are resiratory bronchioles enriched with?
Secretory club cells
What is the funciton of Club cells?
- Contain secretory granules
- Important in symbiotic metabolism (imortant for enzymes)
- Deotification
- Repair/progintor cells
What is the effect of smoking on ciliate and club cells?
Increased brnchiolar ciliated cells
Club cells lower
Alveolar surface made of 2 types of cells
What is the function of stromal cells (myofibroblasts)?
- Make ECM
- Collagen, elastin, elasticity, compliance
- Repair
What is the histopathology of alveolar fibrosis?
- Increased type 2 (don’T differentiate into type 1)
- Increased firboblasts
- Increased collagen deposition
What is the histpathology of abnormal repair?
- Type 1 cells proliferation
- Stromal cell roliferation
- Connective tissue synthesis
What is the function of serin and metalloproteinases?
- Released by airways
- Substrates: proteinases, connective tissue, elastin, collagen,
- Activate other roteinases
- Inactivate antiproteinases
- Activaste cytokines/chemokines and othe pro inflammatory mediators
What is the function of serin and metalloproteinases?
- Generate hioghly reactive peroxides
- Interact with proteins and lipids
- Inactivate alpha 1 antitrypsin
- Grament connective tissue
What proportion of COPD affects smokers?
15-20%
What is chronic bronchitis?
large/central airways affected, copious mucus production for three months of the year. Airways obstructed by mucus and thickened mucosal cell layer.
What is small airways disease?
small airways become blocked/obstructed due to mucus secretion and stenosis/narrowing of airway wall due to fibrosis
What is emphysema?
destruction of the respiratory tissue (especially the respiratory bronchioles of smokers) by proteolytic enzymes leads to loss of connective tissue scaffold, basement membrane “cement” and normal cell organisation. Loss of surface area and elastic recoil. Loss of vascular tissue. Gas exchange severely compromised. Affects fewer, about 10% of smokers.
How do CYPIA1 polymorphism cause carcinogen production?
- high levels of carcinogenic BPDE are generated.
- insufficiently inactivated by conjugation e.g. with glutathione by glutathione transferase, as happens with the null phenotype i.e. no glutathione transferase,
- chances of DNA adduct formation with BPDE increases massively – 40-fold increase in chance of a smoker getting lung cancer.
