4-airways Function

Question 1

What are the functions of airway epithelium

Answer 1

Secretion of mucin, water and electrolytes (components of mucus (+plasma, mediators etc.))
• Movement of mucus by cilia - mucociliary clearance
• Physical barrier against inhaled insult
• Production of regulatory and inflammatory mediators:
NO (by nitric oxide synthase, NOS)
CO (by hemeoxygenase, HO)
Arachidonic Acid Metabolites (e.g. prostaglandins, COX)
Chemokines (e.g. IL-8)
Cytokines (e.g. GM-CSF)
Proteases

Question 2

What happens to SM during disease of the airways

Answer 2

This increase in the mass of smooth muscle may mean that there is an increase in contractile force of that muscle - you get a marked increase in the secretion of mediators
• It produces lots of cytokines etc. and it changes in function and phenotype

Question 3

How can SM get involved in the inflammatory process?

Answer 3

• In response to cytokines, NOS can get upregulated
• COX enzymes produce more prostaglandins
• Chemokines lead to the recruitment of inflammatory cells

Question 4

Describe airway vasculature

Answer 4

• 1-5% of cardiac output
• Blood flow to the airway mucosa = 100-150 mL/min/100 g tissue
• Blood flow through the tracheo-bronchial circulation is AMONG THE HIGHEST to any tissue
• Bronchial arteries arise from many sites on:
Aorta
Intercostal Arteries Others
• Blood returns from the tracheal circulation via systemic veins
• Blood returns from the bronchial circulation to both sides of the heart via
systemic and pulmonary veins
• There is a massive input and a massive output

Question 5

What is the function of the trachea bronchial circulation

Answer 5

The system is so rich in blood that you can get direct gas exchange between
the tissues and the blood
• Contributes to warming of inspired air
• Contributes to humidification of inspired air
• Clears inflammatory mediators
• Clears inhaled drugs (good/bad depending on the drug)
• Supplies airway tissue and lumen with inflammatory cells
• Supplies airway tissues and lumen with proteinaceous plasma (

Question 6

Give an example of a disease which can increase plasma exudation

Answer 6

Asthma

Question 7

How is the airway controlled in humans

Answer 7

Nerves:
Parasympathetic (cholinergic)/Sensory
• Regulatory and Inflammatory Mechanisms
Histamine
Arachidonic Metabolites (prostaglandins and leukotrienes) Cytokines
Chemokines
• Proteinases
E.g. neutrophil elastase
• Reactive Gas Species
E.g. O2-, NO

Question 8

How do humans relax their airways

Answer 8

Humans rely on ADRENALINE from the adrenal gland -

neuronal pathway producing NO work to relax the
airways

Question 9

What does the Cholinergic reflex cause in humans

Answer 9

contracts smooth muscle and causes secretion of mucus

• You may also get a little bit of vasodilation

Question 10

Describe a specimen from the airway of an asthma patient

Answer 10

In this case, it is blocked by a MUCUS PLUG which has lots of eosinophils in it
• You can see epithelial fragility
• There is thickening of the basement membrane
• The blood vessels become very prominent

Question 11

Describe the pathophysiology of asthma

Answer 11

PAF (platelet activating factor) causes plasma exudation
• ATP causes goblet cell exocytosis
• We have epithelial fragility which exposes the sensory nerves which can respond to different mediators produced by inflammatory cells
• This sets up a CENTRAL CHOLINERGIC REFLEX
• This cholinergic reflex causes smooth muscle contraction and shutting down of the airways
• The cholinergic reflex will also cause mucus secretion
• This repeated bronchoconstriction and mucus hypersecretion is associated with hypertrophy of the smooth muscle and the glands
• There is an increase in the number of goblet cells
• Chemical mediators are produced and released by these cells
• Mast cells produce mediators that cause bronchoconstriction, mucus secretion
etc.