Lecture 15

Question 1

Describe lung defence mechanisms?

Answer 1

Need to preserve “sterile” environment at alveolar level. “Direct” communication with the external environment. Numerous potential “insults”. High ventilation rate, particularly during exertion.

Question 2

Describe the airway microbiome?

Answer 2

Micro biome is the totality of microbes, bacteria, viruses, fungi. There are new culture-independent technologies. LRT is not sterile. Healthy microbiome protects against disease where as altered one (dysbiosis) in diseases; spatial and longitudinal assessment of microbiome. Aberrant microbiome - inflammation - disease. Cross-talk between lung and gut microbiome. Effects of treatment on microbiome; antibiotics and other. Role of modification; probiotics.

Question 3

Describe the upper airways defence mechanism?

Answer 3

1. Effective coordinated swallowing mechanism.
2. Protection of lower airway by epiglottis and glottis.
3. Cough.
4. Sneeze.

Question 4

Describe the microbiological insult in the upper airways?

Answer 4

Aliquot of organisms and virulence of organism e.g. influenza.

Question 5

What are the particles in the lung?

Answer 5

Microorganisms, dust and allergens (pollen). Therapeutic:

• Droplets.
• Suspensions; pMDI.
• Dry powder.
• Specialised; pumospheres.

Question 6

Describe muco-ciliary clearance?

Answer 6

Where the ciliated epithelial cells interact with the mucus layer. There are ciliated cells to the 17th generation of airways. >200 cilia per epithelial cell. Effective and recovery stoke. Continuous and coordinated ciliary action via intra-cellular signalling. Role in “chemo-seisins” the microenvironment including sonic-hedgehog.

Question 7

Describe ciliary (dys-) function?

Answer 7

Congenital or acquired. There is change in structure OR function; ciliary beat frequency,, coordination.

Question 8

Describe mucus components?

Answer 8

1. Water and ions.
2. Glycoproteins (mucins - 14 genes).
3. Proteoglycans.
4. Lipids.
5. Other proteins e.g. lysozyme, CAPs e.g. defensins.
6. DNA.

Question 9

What are the sources of mucus?

Answer 9

Goblet cells and mucus glands.

Question 10

Describe the dispersion of mucus?

Answer 10

A discontinuous layer in periphery and continuers and thicker centrally.

Question 11

What are the roles of airway mucus?

Answer 11

1. Protects underlying epithelium:
   - physical barrier.
   - dilutes chemicals (oxidants and proteases).
   - absorbs gases.
2. Traps particles and facilitates removal.
3. Provides environment for lumina cells (binds water and hydrates).
4. Contains anti-microbial substances e.g. CAPs such as defensin.

Question 12

Describe peri-ciliary fluid/airway surface lining fluid?

Answer 12

Volume critical for ciliary function. May modify mucus layer. Sources include club cells and epithelial cells. Regulated by active ion transport. Amenable to pharmacologic modulation.

Question 13

Describe the correction of ion and water transport?

Answer 13

Gene transfer. Stabilisers. Potentiation e.g. ivacaftor. Correctors e.g. Vx809. ENaC inhibitors.

Question 14

What happens in compromised muco-ciliary clearance in disease?

Answer 14

There is an increase in viscosity, secretion and solid content;DNA. There is a decrease in PCL, ciliary function, and filial beat frequency structural damage.

Question 15

Describe cough?

Answer 15

when a person coughs there is removal of material from LRT.

Question 16

What do you require when you cough?

Answer 16

Development of high intra-thoracic pressure. Sudden release of pressure. generation of high linear airflow velocity. (Excess) mucus and trapped material removed by sheer forces.

Question 17

Where is a cough effective to?

Answer 17

The 16th generation of airway (linear velocity of airflow too low in small airways).

Question 18

How effective is a cough?

Answer 18

It normally doesn’t clear normal airway mucus - as the layer is too thin. Greater volume or more viscous mucus builds up to thicker layer which is removed by sheer forces.

Question 19

Describe the defence mechanisms in the lung periphery?

Answer 19

There is no muco-cilairy escalator or effective cough mechanism. So you rely on the alveolar macrophage (resident phagocyte, antigen-processing cell or immuno-regualtion) or PMN leucocytes (recruited phagocytes) or immunoglobulins.

Question 20

What happens to bacteria in the alveoli?

Answer 20

The bacteria multiply in the alveolus as the alveolar macrophage migrates to the site of infection. The neutrophils migrate (chemotaxis) towards the infection and the capillaries start to leak exudate into the interstitium.