6. Lung Cell Biology Flashcards
What can the surface area of the lungs be compared to (size)?
Tennis court
How does the cross sectional area of the lungs change across the structure?
Increases peripherally
How many generations are there in the lungs?
- 23 generations
* Each generation bifurcates into the next
What can the volume of surfactant in the lungs be compared to?
One wine glass
What is the role of the epithelium in the lung?
- Continuous barrier
- Produce secretions (via mucociliary escalator)
- Metabolise foreign and host-derived compounds
- Release mediators
- Trigger lung repair processes
What are the 3 main functions of mucus?
- Facilitate clearance
- Protect underlying cells
- Maintain reduced surface tension (in alveoli)
What proportion of epithelial cells to goblet cells roughly make up?
1/5
How does the phase of mucus change in the airways?
- Thin sol phase overlaying the cells
* Thick gel phase at the air interface
What does mucus contain?
- For viscoelasticity: mucin proteins, proteoglycans and glycosaminoglycans
- Serum-derived proteins: albumin and alpha 1-antitrypsin/alpha 1-proteinase inhibitor (combats microorganisms and phagocyte proteases)
- Antiproteases: secretory leucoprotease inhibitor (combats microorganism and phagocyte proteases)
- Antioxidants: uric and ascorbic acid (blood), glutathione (cells)
What happens to goblet cells in smokers?
- Number doubles (hyperplasia)
- Secretions increase in quantity
- Thicker secretions (can’t be transported)
What are the positives and negatives of the modified gel phase in smokers?
- Traps cigarette smoke particles
* Traps and harbours microorgansism => enhancing chances of infection
What percentage of epithelial cells are ciliated?
80%
Where is mucus pushed towards?
- Epiglottis
* Swallowed or expectorated
What phase is the mucus in at the tips of the cilia?
Sol phase
How do the ciliated cells change in smokers?
- Severely depleted
* Beat asynchronously
How far down in the lungs are cilia found?
Down to the bronchioles
What happens to the small airways in COPD?
- Narrowed
- Broken down by enzymes and inflammatory cells
- Trapped mucus
What are Clara Cells and where are they found?
- Non-ciliated secretory epithelial cells
- Found in large, central and small airways, and bronchi and bronchioles
- Found in most conducting airways
- Increase proportionally distally
What is the main role of Clara Cells?
Xenobiotic Metabolism - metabolism of foreign compounds deposited by inhalation
What do Phase I and Phase II enzymes do in Clara Cells?
Phase I enzymes
• Cytochrome P450 oxidases
• Designed to metabolise foreign compounds so phase II enzymes can react and neutralise the toxic agent
• Unfortunately, (CYPIRA1) can activate a precarcinogen into a carcinogen e.g. benzopyrene (in tar) => benzypyrene-diol-epoxide (BPDE)
Phase II enzymes
• Glutathione S-transferase
• BPDE => small molecule (neutralised)
• Some people don’t have this enzyme - if they also have CYPIRA1 extensive metaboliser gene, 40x more likely to get lung cancer
What do Clara Cells synthesise and secrete?
- Phase I and II enzymes
- Antiproteases
- Lysozyme
What happens to the structure of the alveoli in smokers?
- Holes appear - reduce SA
* Elastic tissue loss - expansion reduced - increased dead space
What 2 types of epithelial cells do alveolar walls consist of?
Type I
• 95% alveolar surface
• Thin and cover capillaries
• Allow gas exchange
Type II [Pneumocytes]
• 5% alveolar surface
• More susceptible to damage
• Lamellar bodies storing surfactant (phospholipid surface active material)
• Synthesise and secrete antiproteases
• Corners of alveoli
• Embedded in the interstitium with the apical membrane facing the air
• Close to capillaries
• Precursor for Type I cells (replace them when damaged)
What does the alveolar unit consist of?
- Type I cells
- Type II cells
- Stromal fibroblasts
- Capillary endothelium
What is the role of the stromal fibroblasts?
- Make ECM
- Make collagen and elastin for compliance and elasticity
- Divide to repair
Describe the role of alveolar macrophages
- 70% of phagocytes in a normal lung (enriched in LRT)
- Increase 5-10 fold in a smokers lung
- Phagocytosis and recruits inflammatory cells
- Synthesise and secrete serin proteases and metalloproteases (can lead to inflammation)
- Generates oxidants during phagocytosis
- Generates antioxidants e.g. glutathione to neutralise oxidative molecules (inhaled or generated)
- Contain enzymes that metabolise toxicants
Describe the role of polymorphonuclear neutrophils
- 5% of LRT phagocytes
- Increase 5-10 fold individually and become up to 30% of total phagocytes in smokers and infection
- Higher proportion in conducting airways
- High levels of proteases in granules
- Release oxidative molecules e.g. hydroxyl anions
Outline classic emphysema
- Centrilobular - begins at the centre of the lobule
- Fibroblasts adjacent to epithelial cells - available for proliferation
- Infection => chronic damage (Type 1 cell death) => Alveolar Fibrosis
- Increased Type II cells
- Communication between Type II cells and fibroblasts determines normal/abnormal repair mechanisms
- Normal repair - Type I cell death => growth factor release => Type II cell proliferation
- Abnormal repair - excess tissue breakdown and elevated growth factor release => fibrotic effect (increase Type II cells and connective tissue synthesis in interstitial space) => irreversible damage
How does smoking chemically affect the alveolar unit?
- Blocks proliferation and differentiation of Type II into Type I cells - stimulates necrosis instead
- Blocks communication between Type II cells and fibroblasts
- Increases number of macrophages and neutrophils
- Procarcinogens activated by Phase I enzymes - normally made water soluble, metabolised and excreted, but smoking overloads the pathway and may inactivate the enzyme => DNA binding => mutation
