Respiratory cell biology Flashcards
Label cross-section of airways.
Above the epithelium is cilia and mucus.
What is the respiratory mucosa?
Lines the airways and is comprised of ciliated and goblet cells with submucosal glands.
What is the function of the respiratory mucosa? (x5)
- Forms a continuous barrier to isolate external environment from the host. 2. Produces secretions to facilitate clearance via muco-ciliary escalators, and to PROTECT underlying cells while maintaining SURFACE TENSION. 3. Metabolises foreign components – xenobiotic metabolism. 4. Production of regulatory and inflammatory mediators (NO, CO, Arachidonic acid metabolites, chemokines, cytokines, proteases). 5. Triggers lung repair process.
What is a muco-ciliary escalator?
Moves mucous containing irritants and microbes upwards to larger airways for clearance by coughing or ingestion.
What cells produce mucous in the airways?
Goblet cells and submucosal cells.
Where are goblet cells found? Function?
Found in large, central and small airways. Make up 20% of the epithelium. Synthesise and secrete mucin with mucin granules – seen as pale circles under the microscope in a highly condensed form (look at photo). When mucin is released, it makes contact with water and expands significantly – becoming mucous. [PHOTO 5].
Where are ciliated cells found? Function?
Found in large, central and small airways. Make up 60-80% of the epithelium. Cilia beat metasynchronously like a field of corn to move mucus secretions up and out.
What are the characteristics of ciliated cells?
Many mitochondria to produce ATP, as cilia are continuously beating.
What is the ciliary structure?
Actin polymers in 9+2 arrangement. Dynein arms and ATPase allow columns to slide over each other and bend the cilia. Apical hooks engage with mucous.
How does ciliary beating occur?
Leading edge of mucous moved by cilia, before they move back to move next field of mucous – synchronised rhythm of beating to move mucous – METRACHRONAL RHYTHM.
Where are submucosal cells found? What is their structure? What is their function?
Tip embedded in smooth muscle. Made of mucous cells, serous cells. MUCOUS CELLS: secrete mucous. SEROUS CELLS: secrete antibacterials e.g. lysozyme as a watery fluid. Mucous acini found closer to collecting ducts than serous acini. So, the watery serous acini wash the more viscous mucus INTO the collecting duct upon contraction.
What cells are found in alveoli? (x5)
Type I and II epithelial cells. Capillary endothelium. Macrophage. Stromal cells (these are (myo)fibroblasts).
What is the purpose of alveolar walls? (x4 points)
- Alveolar walls have elasticity and hold adjacent airways (e.g. bronchioles) open (look at photo). 2. Involved in gas transport into blood – they contain some pores to allow movement of gases. 3. Alveolar walls are comprised of TII pneumocytes that produce surfactant when walls stretch in inhalation to prevent alveolar collapse in EXPIRATION (more detailed in later flashcard). 4. Comprised of TI pneumocytes that are thin and facilitate gas exchange.
What happens to alveolar walls in terms of pores in COPD?
In COPD, more pores form in alveolar walls, and they are larger.
What is the ratio between TI and TII cell presence? Difference with percentage surface covering and cell numbers?
Present in I:II ratio of 1:2. But, Type II cover just 5% of the alveolar surface, but make up 66% of alveolar epithelial cell count.
What are the functions of TII epithelial cells? (x2)
Contain lamellar bodies which store surfactant prior to release; cells sit in corners of alveoli and when lung stretches, surfactant is released to replace that which has been used. They are also progenitor cells (TI precursors), so involved in alveolar wall repair.
How are Type I epithelial cells specialised for their function?
THIN so short diffusion distance (alveolar epithelium and capillary endothelium thin). But also STRONG.
What are interstitial cells? Name?
CALLED STROMA CELLS. FOUND OUTSIDE THE ALVEOLAR. They are (myo)fibroblasts (myo means it is in between a fibroblast and smooth muscle) that make the ECM that all the cells sit on (the lung’s cement). Made of collagen and elastin to give elasticity AND compliance.
What happens if too much ECM is deposited by stromal cells?
Interstitial fibrosis occurs (remember, stroma cells are interstitial). This means that lungs solidify and you cannot breathe. Really bad for patient.
What are Club cells? Alternative name? WHERE ARE THEY FOUND?
OR clara cells. They are non-ciliated epithelial cells in the bronchioles that replace damaged epithelium.
What do Club cells do? (x2)
They contain secretory granules for xenobiotic metabolism – detoxifying inhaled harmful substances, and therefore PROTECTING the BRONCHIOLAR epithelium. They are also progenitor cells (meaning stem cell-like), so perform a repair role by differentiating into ciliated cells to regenerate the bronchiolar epithelium.
What happens to goblet cells in smokers? (x3) Problem?
Number at least doubles, alongside increased secretions to catch all the toxins, and more viscous secretions. However, increased mucous secretions provides good environment for microorganisms too – enhancing chance of infection (frequent episodes of bronchitis).
What happens to ciliated cells in smokers? (x4)
Severely depleted, beating asynchronously (among other cells and within themselves). They move down the airways and INCREASE in the bronchioles. They are unable to transport thickened mucous – reduced clearance leads to obstruction and infection (bronchitis).
What happens to Club cells in smokers?
LOWER in smokers.
How does the alveolar epithelium orchestrate repair?
- There is apoptosis/necrosis. 2. Transdifferentiation of TII to TI, or conversion of TII to myofibroblasts occurs. 3. This results in re-epithelialization (not necessarily with myofibroblasts).
What triggers airway smooth muscle cells to become inflammatory cells? Triggers? (x2)
ASMCs can become inflammatory cells – triggered by bacterial products and cytokines during inflammation. When this occurs, their functions change.
FUNCTIONS: Undergoes hypertrophy because of proliferation of the SMCs – may not contract harder, but there’s a massive increase in secretions of mediators, cytokines and chemokines (cytokines and chemokines recruit inflammatory cells). This makes that ASMCs inflammatory cells, much the same as same phagocytes and lymphocytes. ASMC also upregulates Nitric Oxide synthase and COX enzymes which produce NO and prostaglandins.
What is plasma exudation? How can this be enhanced? (x2)
Post-capillary venules have gaps that leak plasma gently to bathe tissue. Can be stimulated to leak more by inflammatory mediators (e.g. histamine and platelet activating factors) and C-fibre nerves.
How are the airways innervated: sensory, constriction, relaxation?
SENSORY: Vagus afferents that travel to the brain via nodose ganglion (or to spinal cord using dorsal root ganglion). CONSTRICTION: cholinergic parasympathetic vagus efferents cause constriction – reflex is used physiologically to prevent lodges objects from going down further into the airways, so can be coughed up instead. RELAXATION: NOT sympathetic. We have a NO producing pathway associated with the cervical thoracic ganglion. NO speeds up cilia and dilates the airways.
How does the cholinergic mechanism work in the airway? Three results?
- Irritants stimulate the Vagus nerve afferents – through the nodose ganglion to the brain. 2. CNS stimulates a central cholinergic reflex down the Vagus nerve to the inter-parasympathetic ganglia. 3. Post-ganglionic neurones lead to muscarinic receptors using the ACh neurotransmitter that cause AIRWAY CONSTRICTION, SUBMUCOSAL GLANDS TO SECRETE MUCOUS (both may help to cough up object) and VASODILATION.
What is the airway remodelling of asthma?
- Epithelial fragility EXPOSES sensory nerves which are stimulated to cause cholinergic reflex. 2. Reflex leads to bronchoconstriction (produces airway wall folds) and mucous secretion and vasodilated, congested blood vessels. Basement membrane thickens and there is a mucous plug in airway lumen. 3. Influx of inflammatory cells (cellular infiltration – into the airways) that produce range of mediators such as histamine (causes plasma exudation and airway constriction). 4. Leads to remodelling of airways with hypertrophied submucosal glands and airway smooth muscle.
What are the three parts of COPD? Result of all this? (x3)
Obstructive airways disease associated with BRONCHITIS, BRONCHILITIS and EMPHYSEMA. • CHRONIC BRONCHITIS: airway mucus hypersecretion from goblet cell hyperplasia and hypertrophy – mucous causes obstruction. Continual inflammation and irritation. • BRONCHILITIS (small airways disease): high levels of fibrosis and the alveolar attachments are lost and airways susceptible to collapse and airway narrowing. • EMPHYSEMA: protein degradation from inflammation and scarring resulting in loss of alveoli and holey lungs (elastin in connective tissue is broken down). This leads to air spaces enlarging and over time may form bullae (airspaces more than 1cm).
• These changes give rise to hyperinflation and loss of elastic recoil. Hyperinflation flattens the diaphragm, causing it to become ineffective at regulating pleural pressures. This increases the work of breathing. • Elastic recoil is required for expiration and the septa (alveolar walls that separate alveoli – they are therefore double-walled because they are made up of the walls of both alveoli) are needed to prevent airway collapse. When these are destroyed, it becomes more difficult to move air in and out – dyspnoea. • Furthermore, the loss of alveolar support structure results in airway narrowing – limiting flow by increasing resistance. This results in corresponding CO2 increase in alveoli at the end of expiration. Decreased O2 as a result too. (This might be bronchiolitis though).
What is the pathophysiology of COPD?
Oxidants are what are produced because of all the smoke. This produces oxidative stress which can increase expression of proteases and leas to hypersecretion.
