Week 8: Airway Mucosal Function Flashcards
What are the 3 essential roles of airway mucus?
- Barrier airway water loss
- Barrier to microbial / bacteria invasion
- Clearance of inhaled foreign matter
What are the 4 layers of the tracheal wall?
- Mucosa - home to goblet cells and made up of pseudostratified epithelium
- submucosa - a connective tissue
- adventitia - connective tissue and cartilage rings
- Bronchioles - mucus cells and cilia decrease, smooth muscle increases
What is airway surface liquid (ASL) and whats its importance?
Liquid that lines the epithelium from tracheal to respiratory bronchioles.
The depth the of the asl is important as it allows the cilia to completely stand up to their full height. - in diseases such as cystic fibrosis and chronic bronchitis the depth is lowered.
What is the chloride ion transporter that gets destroyed in cystic fibrosis?
Cystic fibrosis transmembrane conductance (transports chloride ions)
The depth of the ASL is determined and regulated by?
Hydration status - regulated by the movement of sodium and chloride ions
What are the 3 main walls of defence for clearing inhaled particles?
- Nasal turbinates/conchae
- If we inhale large particles bigger than 6 micrometres will be trapped here
- It does this through nasal hairs and nasal mucus - Mucociliary Escalator
- This transports particles to the pharynx
- It is made up of cilia which sways in ASL, shifting a lining of mucus above it - Alveoli Macrophages
- Once we go below the cilia (which go just into the start of the respiratory bronchioles) it is these that take over phagocytosing any particles, bacteria or viruses etc.
Briefly describe the cilia function
Cilia have a central axis, with a number of pairs of microtubules which sit around the outside - this is known as the ultrastructure
this structure allows the cilia to beat and stray
What is primary ciliary dyskinesia (PCD) and what does it result in?
This is an umbrella term for when the cilia ultrastructure goes wrong.
Results in cilia not moving properly
Results instagnation and thus, accumulation of mucus within the airways
This blocks the airways and provides the perfect breeding ground for bacteria - results in recurrent infections and inflammation of airways
How do alveolar macrophages phagocytose foerign matter, and what is a complication that smoking could cause to alveolar macrophages?
Contain destructive enzymes (e.g. trypsin) - highly effective in killing bacterial agents.
Tyrpisin is so strong that if you kill a lot of alveolar macrophages you can let trypsin loose into the lung space which can cause significant damage to lung tissue.
What is chronic obstructive airway disease, what is the key dianostic test for them and what is 1 disease that is an example of it?
- This is an umbrella term for a number of different diseases within the lung, that are all united by an increase in airway resistance
a spirometry FEV1/FVC ratio of less than 80% (meaning they blow out less than 80% of their lung volume in 1 second)
- Chronic bronchitis
- Emphysema
What are the 3 major mechanisms behind chronic obstructive airway diseases?
- Conditions within the lumen
- The lumen could be partially occluded by excessive mucosal secretions (chronic bronchitis and pulmonary oedema)
- there could be a blockage caused by retained post-op secretions
- Something may have been inhaled that is blocking the airway (either localised or complete occlusion) - Causes within the wall of an airway
- Inflammation or Oedema of the wall may cause excessive resistance (chronic bronchitis and asthma)
- Hypertrophy of the mucosal glands would cause the airway wall to swell (reducing space in the lumen)
- We could have contraction of bronchial smooth muscle (making the wall thicker reducing space in the lumen) - Causes outside the airway
- We may have destruction of elastin and collagen which provides the radial traction (emphysema) causing the airway to narrow
- We could also have a local growth pushing on the airway
What is chronic bronchitis and what is it characterised by? + what type of patient is chronic bronchitis common in?
- Is a chronic obstructive airways disorder that is characterised by excessive mucus production in the bronchial tree that is enough to cause excessive expectoration of sputum
- This is very common particularly in smokers and smog-laden cities
What are the 2 broad pathological changes in bronchitis?
- Chronic inflammation and irritation caused by the inhaled substances (be that inhaled pollutants or cigarette smoke)
- The inevitable infection that comes with the stagnating mucus within the airways
Explain the pathology of chronic bronchitis
- There will be hypertrophy of the mucous glands in the large bronchi expressed as Reid index (take the ratio of the depth of sub mucosal glands, to the entire submucosa)
- There will be an increase in thickness of the bronchial mucosal layer due to an increase in the number and size of the mucus secreting cells
- In addition to swelling of mucosa, mucus secreting cells also spread from the bronchi to the bronchioles (where they are not normally found as an adult)
- This results in excessive mucous in the airways as well as mucus in regions without cilia, meaning it can’t be moved
What are the 2 major clinical features of chronic bronchitis
- Type A - Pink Puffer (emphysema patient)
- Looked at in week 9 - Type B - Blue Bloater (chronic bronchitis)
- Increasingly out of breath (dyspnoea)
- History of recurrent infections
- Frequent cough with abundant sputum
- Abnormal breathing sounds (mucus is clogging up the airways)
- Moderate to no increase in chest volume (compliance of the lung is the same)
- Hypercapnia
- Severe hypoxemia and cyanosis
- May have increased jugular venous pressure
- May have peripheral oedema
What are 5 treatments for chronic bronchitis?
- Liberal fluid intake (which hydrates the ASL which maximises the ability of cilia to move mucus, this gets rid of the airway obstruction)
- Physiotherapy
- Postural changes
- Nebulising bronchodilators may assist expectoration by increasing action of mucocillaiary clearance (more in week 10)
- Drugs
- Bronchodilators may relieve airway obstruction but the effect is less dramatic than in asthmatics
- Anticholinergic drugs given by inhalation
- Corticosteroids to relieve dyspnoea (important to test for efficacy as they can be damaging to alveolar macrophages)
- Often large doses of these drugs are required
What is the definition of cystic fibrosis?
A genetic condition of all of the exocrine glands caused by a genetic abnormality that affects chloride transport
What are the 2 primary effects of cystic fibrosis on patients?
- Bronchiectasis: localized, irreversible dilation of part of the bronchial tree and chronic purulent (pus) sputum production
- Bronchiolitis: Inflammation of the bronchioles
Explain the mechanism behind cystic fibrosis
- The CFTR chloride channel gene is located on the long arm of chromosome 7
- This is a chloride channel that is membrane bound and active
- It also acts to regulate other membrane channels including the ENaC sodium channels
- A normal good working CFTR slows down the ENaC (acting like a brake)
- When you don’t have this CFTR it makes the ENaC work over time (as it has lost the partial negative inhibition)
- This results in even more sodium being drawn out of the ASL than normal which also draws water with it
- As we also don’t have a CFTR pumping chloride ions back into the water this ASL is further reduced
- This results in poor mucous cilia escalator function resulting in stagnating mucus (leading to recurrent infections and inflammations in the airways)
What is the effect of cystic fibrosis on ASL?
- In the normal cell, airway epithelial cells secrete chloride ions and absorb sodium ions, a balance which is regulated by the apical channels including the CFTR
- This ion secretion and absorption effects water transport and thus directly reduces the ASL depth
- Having cystic fibrosis results in decreased chloride secretions and sodium hyperabsorbtion (as a result of the lack of CFTR) which decreases the depth of the ASL
- The cilia bend over and can’t work properly, causing mucus to stagnate
- We suck water out of the mucus (causing it to get thicker and thicker and harder to move)
How is the composition of sweat affected by CF? Is it clinically useful?
CFTR and ENaCs are inhibited causing increase Na and Cl- sweat. The amount of Cl- in sweat determines the severity of the CF
How does CF affect mucous secretions in the airways? What impact does htis havef on mucociliary clearance?
Therefore you get hyperabsorption from ENaCs which brings in a lot of Na+ into cells. This also therefore brings water into the cells and decreases the height of the ASL. This is because you don’t have the CFTR to inhibit.
