6 Lung Cell Biology Flashcards
Q: What is the structure of the lung is optimised for? How does its cross sectional area change?
A: gas exchange
increases peripherally
Q: How many generations of gas exchange units are there?
A: around 23
Q: What are gas exchange units lined with?
A: fluid called surfactant
Q: What’s the role of epithelium in the lungs? (4)
A: -form a continuous barrier, isolating external environment from host
- metabolise foreign and host-derived compounds
- release mediators (controls the number of inflammatory mediators that reach the lungs)
- triggers lung repair processes
Q: What do the lungs produce? to? (3)
A: secretions to facilitate clearance, via mucociliary escalator, and protect underlying cells as well as maintain reduced surface tension (in the alveoli)
Q: How does airway epithelium vary between those that are healthy and those with COPD (//smokers) in terms of goblet cells? (3,3)
A: Normally:
- present in large, central and small airways
- make about 1/5 of epithelial cells
- synthesise and secrete mucus
Smokers:
- Goblet cell number at least doubles (hyperplasia)
- Secretions increase in quantity
- Secretions are thicker
Q: What does mucus contain that gives it viscoelasticity? (3) Also released from?
A: -mucin proteins
- proteoglycans
- glycosaminoglycans
seromucous glands
Q: What else does mucus contain? (5)
A: Serum-derive proteins:
- albumin
- alpha 1-antitrypsin (AKA alpha 1-proteinase inhibitor)
- Antiproteases synthesised by epithelial cells
- Antioxidants from the blood- uric acid and ascorbic acid (blood), glutathione (cells).
Q: What is alpha 1-antitrypsin? Role?
A: inhibitor of polymorphonuclear neutrophil proteases -> combats microorganism and phagocyte proteases
Q: Give an example of an antiprotease synthesised by epithelial cells. Role?
A: secretory leucoprotease inhibitor -> combats microorganism and phagocyte proteases
Q: What produces antioxidants? Role? (2)
A: epithelial cells and phagocytes
Combats inhaled oxidants e.g. cigarette smoke, ozone. Also counteracts excessive oxidants released by activated phagocytes
Q: Describe the 2 phases of mucus. Role of one? enhances?
A: very thin sol phase overlays cells, thick gel phase at the air interface
Modified gel phase traps cigarette smoke particles but also traps and harbours microorganisms, enhancing chances of infection
Q: How does airway epithelium vary between those that are healthy and those with COPD (//smokers) in terms of ciliated cells? (3,4)
A: Normally:
- present in large, central and small airways
- make 80% of epithelial cells
- cilia have metachronous beating
Smokers:
- cells are severely depleted
- beat asynchronously
- ciliated cells found in bronchioles (even though reduced in airways)
- cilia unable to transport thickened mucus - reduced mucus clearance
Q: How do ciliated cells function? (2)
A: Tips of the cilia are in the sol phase of mucus and pushes the mucus towards the epiglottis. The mucus is usually swallowed or expectorated (coughed/spit out)
Q: How does airway epithelium vary between those that are healthy and those with COPD (//smokers) in terms of mucus clearance? leading to? (2)
A: Smokers have reduced mucus clearance leading to respiratory infection and bronchitis. Airways obstructed by mucus secretions
Q: Describe small airways (2). Specifically in COPD? (3)
A: -<2 mm in diameter
-Not cartilagenous
- Mucus becomes trapped
- Airway narrow
- Broken down by enzymes and inflammatory cells-> this reduced peripheral gas exchange
Q: What are Clara cells? found? (5) Where are many found? (2)
A: non-ciliated secretory epithelial cells found in large, central, and small airways and bronchi and bronchioles
found in most conducting and transitional airways but they increase proportionally distally - the bronchi and bronchioles are enriched in these cells
Q: What’s the major role of clara cells?
A: XENOBIOTIC METABOLISM (metabolism of foreign compounds deposited by inhalation)
Q: What do clara cells contain that help with their role? What do they produce? (2)
A: phase I and phase II enzymes
- make and release high levels of antiproteases
- synthesise and secrete lysozyme (can lyse microorganisms)
Q: Where are phase I enzymes found? Give an example. What is their role and downside?
A: in clara cells
cytochrome p450 oxidases
designed to metabolise foreign compounds into a format that enables phase II enzymes to react and neutralise the toxic agent, they often activate a precarcinogen to a carcinogen
Q: Where are phase II enzymes found? Give an example and describe its role.
A: clara cells
glutathione S-transferase
enables conjugation of BPDE to a small molecule that neutralises its activity
Q: How can a phase II enzyme make someone 40 times more likely to get lung cancer?
A: Some individuals are null for glutathione S-transferase i.e. do not synthesise glutathione transferase and cannot neutralise BDPE
Consequently, if an individual who smokes has CYPIRA1 extensive metaboliser gene and the null glutathione gene they are 40 times more likely to get lung cancer
Q: What is COPD? (3)
A: bronchitis + emphysema + small airways disease
Q: Describe alveoli in susceptible smokers. (5)
A: -holes in the alveoli may appear and the alveoli may become larger
- > leads to a reduction in the surface area available for gas exchange
- > can be seen as elastic tissue loss
- > therefore, expansion during breathing is reduced
- > increases the amount of dead space
Q: Which cell types make the alveolar walls? (2) How do they differ? Production?
A: TWO types of epithelial cell: Type I and Type II
Type II cells are more susceptible to damage than Type I cells but Type I cells are damaged more often
Type II cells are a precursor for alveolar epithelial type I cells - they divide and differentiate to replace damaged type I cells
Q: What are type II epithelial cells also called? Where are they found? Position? (2) Contains? role? Produces?
A: Type II Pneumocytes- only in the alveoli (covers 5% of the alveolar surface)
- positioned in the corners of the alveoli and are embedded in the interstitium with the apical membranes facing the air
- very close to capillaries
- lamellar bodies -> store surfactant prior to release onto the air-liquid interface
- Synthesise and secrete antiproteases
Q: What is surfactant? Roles? (2)
A: phospholipid rich surface active material that prevents lung collapse on expiration and has immunological functions
Q: Role of type I epithelial cells? Properties? (2) How much of alveolar surface do they cover?
A: very thin but very strong-> allow gas exchange
95%
Q: What does an alveolar unit consist of? (5) Ratio?
A: -Type I epithelial cells
- Type II cells
- Stromal fibroblasts
- Alveolar macrophages
- Capillary endothelium
Ratio of T2:T1 = 2:1
Q: What do stromal fibroblasts make? (3) Role?
A: -make extracellular matrix
- make collagen and elastin to give the alveolus elasticity and compliance
- divide to repair
Q: Describe capillary endothelium position.
A: close proximity to alveolus to reduce diffusion distance
Q: Where are Alveolar Macrophages found? Make how much of total phagocytic cells in a normal lung? Similarity to clara and type II cells?
A: enriched in lower respiratory tract, but found throughout
70%
-contain enzymes that metabolise toxicants
Q: What’s the role of Alveolar Macrophages? (5)
A: -phagocytose debris and microorganisms
- send ‘messages’ to blood/lymphatic system -> sequester other inflammatory cells (e.g. neutrophils/lymphocytes) to lungs during infection or as a result of toxicant deposition/inhalation
- synthesise and secrete proteases -> digest unwanted debris, attack organic material etc.
- generate oxidants during phagocytosis and on activation -> kill infection organisms etc.
- generate antioxidants (eg glutathione) -> neutralise oxidative molecules that might be inhales or generated during infection
Q: Where are Polymorphonuclear Neutrophils found? Make how much of total lower respiratory tract phagocytes in a normal lung? But in smokers/infections? (3)
A: throughout the airways
usually only about 5%
- INCREASE significantly in number (5-10 fold) and proportionally (up to 30% of total phagocytes) in smokers and more so during infection
- Higher proportion in conducting/large airways
- About 30% of phagocytes normally in the upper airways but up to 70% in smokers (absolute number also goes up (around 5 fold))
Q: What do Polymorphonuclear Neutrophils store? Smokers? Release on activation?
A: high levels of potent proteases in granules - they are released on activation
Smokers lungs contain high levels of these released proteases
Release very potent oxidative molecules such as hydroxyl anions during activation
Q: Describe emphyema histopathology? (2)
A: Classic emphysema is centre-lobular
Fibroblasts lie adjacent to epithelial cells lining the alveoli, and are available for proliferation following infection
Q: What’s the mechanism for alveolar fibrosis? (3) Result? (3) What determines if repair mechanisms proceed normally or abnormally?
A: Infection –> Chronic Damage (T1 cell death) –> Alveolar Fibrosis (repair mechanism)
- Increased type II epithelial cells
- Increased number of fibroblasts - make a lot of connective tissue (fibrosis)
- Increased collagen deposition
Communication between the type II cells and the fibroblasts
Q: Compare normal and abnormal alveolar fibrosis. Abnormal growth leads to?
A: In NORMAL repair - type I cell death causes growth factor release to increase type II cell proliferation and differentiation
In ABNORMAL repair - there is excess tissue breakdown and elevated growth factor release (seen at end stages of emphysema)
This leads to a fibrotic effect (increased type II cells, increased stromal/fibroblast and connective tissue synthesis in interstitial space = IRREVERSIBLE DAMAGE)
Q: How does smoking affect proliferation and differentiation of Type II cells into Type I cells? How does it affect communication between TII cells and fibroblasts?
A: Blocks proliferation and differentiation of Type II cells into Type I cells - and stimulates apoptosis and necrosis of Type I and Type II cells
blocks
Q: How does smoking affect macrophages and neutrophils? Effects include? (4)
A: -INCREASES 10-FOLD NUMBER OF MACROPHAGES AND NEUTROPHILS
effects include:
- increased phagocytosis
- antimicrobial defence
- antioxidant synthesis
- xenobiotic metabolism
Q: What’s the macrophage: neutrophil ratio in non-smokers? COPD? Secrete? (3) Macrophages specifically? (3) result?
A: 70:30 but this reverses in COPD
- serine proteases (e.g. neutrophil elastase)
- metalloproteases (e.g. MMP9)
- antimicrobial oxidants
-mediators + growth factors + proteases trigger growth and repair by other cells
Q: What do mealloproteases do?
A: activate other proteinases and activate cytokines/ chemokines and other pro-inflammatory mediators therefore increasing the number of inflammatory molecules within alveoli —> alveolar inflammation
Q: What do antimicrobial oxidants do?
A: which generate highly reactive peroxides, interacting with proteins and lipids fragmenting connective tissue –> damage
Q: What does smoking contain that is activated by phase I enzymes? Normal metabolism? Smoking?
A: procarcinogens
In normal metabolism, phase II enzymes make these water soluble so that they can be metabolised and excreted
Smoking overloads the pathway, and may inactivate the enzyme, therefore the carcinogen may undergo DNA binding, adduct formation, no repair and mutation
