Lung cell biology Flashcards
What are the gas exchange units lined with?
surfactant
How many generations of gas exchange units are there?
23
What are the roles of the epithelium in the lung?
- protects from the internal cavity
- produces secretions important in clearing of unwanted substances, reduce surface tension and protect cells underneath
- metabolise compounds inc. foreign
- release mediators to control inflammatory ones
- trigger lung repair
Compared to a healthy airway, what would an airway in a COPD patient have different?
- more goblet cells
- more mucus
What are goblet cells?
- Found in airways
- 1/5 of epithelial cells
- produce mucus
Describe the composition of mucus
- complex
- thin sol phase and thick gel phase at air interface
- mucin proteins, proteoglycans, glycosaminoglycans
- serum derived proteins like albumin and alpha-1-trypsin (inhibits neutrophil proteases)
- antiproteases combating microorganism and phagocyte proteases
- antioxdiants from blood such as uric acid to combat inhaled oxidants or excess from phagocytes
What happens to goblet cells in smokers?
- doubles
- more secretion
- thicker secretions
- modified gel traps smoke particles and foreign things more
Where are ciliated cell found, how do they beat and where is the mucus moved?
- Present in large, central and small airways
- Metachronous beating
- 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
What happens to the ciliated cells in smokers?
- depleted
- beat is not synchronised
- ciliated cells found in bronchioles
- Cannot transport mucus
What happens in COPD to the airways and alveoli?
- mucus is trapped
- airway narrows
- broken down alveoli by enzymes and inflammatory cells
What are clara cells and where are they found?
- non ciliated secretory epithelial cells
- found in large, central and small airways, bronchioles and bronchi
- they increase proportionally distally
- ## abundant in bronchi and bronchioles
What are the roles of clara cells?
- xenobiotic metabolism (metabolise foreign inhaled things)
- They have phase 1 and phase 2 enzymes
- They make and release anitporteases
- They make and secrete lysozymes
Give an example of a phase 1 clara enzyme and what are their roles?
- Cytochrome p450 oxidases included
- They are meant to metabolise foreign compounds to enable phase II enzymes to react and neutralise the toxic agent
Give an example of a phase 2 enzyme and what it does
- Glutathione S-transferase, which enables conjugation of BPDE to a small molecule that neutralises its activity
What is a problem that occurs with phase 1 enzymes?
They often activate a precarcinogen to a carcinogen
e.g: Benzopyrene (precarcinogen in cigarette smoke). One cytochrome P450, oxidases BP to benzopyrene diol epoxide which is a potent carcinogen.
What happens to those people who don’t have glutathione S -transferase ?
They cannot neutralise BDPE. 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
What are the three disease under the umbrella term COPD?
- bronchitis
- emphysema
- small airways disease
What happens to the alevoli in suscepible smokers?
- they develop holes which may become larger over time
- reduces surface area so elastic tissue loss
- dead space increases
What are the two types of epithelial cells that make up the alveolar wall?
- Type 1: thin but strong to allow gas exchange
- Type 2: a.k.a type 2 pneumocytes, more susceptible to damage, only found in alveoli
What do type 2 epithelial cells do, what do they contain, and where are they found in the alveolus?
- Contain lamellar bodies that store surfactant prior to release onto the air-liquid interface
- Synthesise and secrete antiproteases
- Positioned in the corners of the alveoli and are embedded in the interstitium with the apical membranes facing the air
- Very close to capillaries
- Precursors for alveolar epithelial type I cells
What is surfactant?
Phospholipid rich surface active material that prevents lung collapse on expiration and has immunological functions
What is the ratio of type 1 to type 2 cells?
1:2
What does the alveolus consist of?
type 1 cells, type 2 cells, stomal fibroblasts (make ECM, collagen and elastin), alveolar macrophages, capillary endothelium
Where are alveolar macrophages found and how do their numbers change in smokers?
- in lower respiratory tract but found throughout
- increase 5-10 fold
Where are neutrophils found in airwyas and how do their numbers change in smokers?
- throughout airways
- increase 5-10 fold in smokers and during infection
- higher proportion in conducting/large airways
What do neutrophils store and how does this change in smokers?
- Potent proteases in granules - released on activation
- Smokers lungs contain high levels of these proteases
- Release potent oxidative molecules such as hydroxyl anions during activation
What are some of the effects of smoking?
- blocks proliferation of type 2 into type 1 cells
- stimulates type 1/2 cell death
- blocks communication between t2 cells and fibroblasts so no repair
- increases number of macrophages and neutrophils
- procarcinogens activates by phase 1 enzymes. Normally made water soluble by phase 2 enzymes but smoking affects pathway and so carcinogen can bind to DNA and cause mutation and no repair
How does normal and abnormal repair occur?
- 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 GF release which leads to a fibrotic effect (increased type II cells, increased stromal/fibroblast and connective tissue synthesis in interstitial space = irreversible)
What percentage of the alveolar surface is covered by type 2 and type 1 cells?
- Type 1: 95% (they are very large but in fact fewer number of them)
- Type 2: 5%
What is chronic bronchitis?
Chronic bronchitis – large/central airways
Airways obstructed by mucus and thickened mucosal cell layer.
What is small airways disease?
The small airways become obstructed due to mucus secretion and stenosis/narrowing of airway wall due to fibrosis.
What is emphysema?
Damage by enzymes, results in the loss of connective tissue, basement membrane and normal cell organisation. Loss of surface area, elastic recoil and vascular tissue.
