Regulation of airway caliber

Question 1

What are the sensory receptors in the airway

Answer 1

Three types of sensory receptors exist in the airways:

- Pulmonary stretch receptors (in trachea and bronchi)
    - they are stimulated during inspiration and inhibit further inspiratory effort (with the reverse happening during expiration)

- Irritant receptors
    - respond to noxious stimuli and are located beneath the epithelium in the airways

- Pulmonary C-fiber receptors
    - they are located in the airways, parenchyma and blood vessels
    - they may be stimulated by blood vessel engorgement, pulmonary edema, and chemical mediators

Question 2

Describe the ecitatory innervation of the airways

Answer 2

The important excitatory innervation of the smooth muscle surrounding airways is provided by the parasympathetic nervous system
- acetylcholine released by post-synaptic fibers binds to muscarinic (M3) receptors resulting in contraction of airway smooth muscle and bronchoconstriction
- the presence of receptors in mucus glands also results in increased mucus secretion

Question 3

Where do we find the most important part of muscarinic receptors

Answer 3

Muscarinic receptors are located throughout the respiratory tract, but they are present in the greatest concentration in the larger airways
- medium-sized bronchi respond with the greatest bronchoconstriction in the face of vagal stimulation

Question 4

What factors result in parasympathetic stimulation

Answer 4

Stimualtion of sensory fibers (irritant receptors and C-fibers) responding to stimuli such as dust, gasses and inflammatory mediators result in parasympathetic stimulation

Catecholamines and sympathetic nervous stimulation will inhibit release of acetylcholine in the bronchial tree (via B1-receptors)

Question 5

Why do you have to use NSAIDs with caution in a cat suffering bronchial disease

Answer 5

Prostaglandin (PGE) produced by normal respiratory epithelium also has an important physiological role in inhibiting acetylcholine release and thus use of NSAIDs may potentiate bronchoconstriction

Question 6

What is the excitatory non-adrenergic non-cholinergic innervation

Answer 6

The excitatory non-adrenergic non-cholinergic (eNANC) innervation is also present in the respiratory tract and is involved in excitatory responses via tachykinin mediators such as substance P
- it also mediate bronchoconstriction and can potentiate the release of acetylcholine

Question 7

Describe the inhibitory innervation of the airways

Answer 7

Inhibitory innervation of the airways involves the sympathetic nervous system and the inhibitory non-adrenergic non-cholinergic (iNANC) system

Question 8

Where are the adrenergic receptors located and what is their role

Answer 8

There are abundant adrenergic (mainly B2) receptors throughout the respiratory tree (including the trachea in the cat)

They are stimulated by norepinephrine (released from sympathetic fibers) or by circullating epinephrine and norepinephrine
- stimulation of the B2-receptors results in smooth muscle relaxation and bronchodilation
- therefore, the use of a B-blockers affecting B2-receptors will result in exacerbation of bronchoconstriction

Question 9

Explain how does the iNANC work

Answer 9

The iNANC system is probably also physiologically important and appears to mediate bronchodilation through the release of vasoactive intestinal peptide and nitric oxide from neurons
- in presence of inflammation, the quick degradation of VIP and the reduction in the production of NO may contribute to bronchoconstriction

Question 10

Describe the two types of mucus existing in the airways

Answer 10

In the nromal animal two types of mucus are produced in the respiratory tract:
- a more aqueous and fluid mucus that bathes the cilia on the epithelial surface allowing the cilia to function properly
- a more viscous mucus that sits above the former and helps to trap particles and move them up the respiratory tract (the so-called mucociliary escalator)

Bronchial glands (located in the smaller bronchi) produce the more aqueous mucus, whereas goblet cells (present higher up in the respiratory tract) produce more viscous mucus

Question 11

What are the main mediators involved in airways responses in allergic and inflammatory airway disease? What is their importance?

Answer 11

Histamine
- released from mast cells is a classic inflammatory mediator in airway disease
- released histammine binds to H1 receptors on bronchial smooth muscle causing bronchospasm, stimulating irritant receptors (producing the cough reflex) and vasodilation
- histamine binding to H2 receptors results in increased mucus secretion into airways
- histamine is probably only an important inflammatory mediator in the early stages of a Type I hypersensitivity response

Prostanoids and leukotrienes
- they are produced following the liberation of arachidonic acid and other fatty acids from cell membrane during inflammation by the actions of cyclooxygenase and lipooxygenase enzymes
- they contribute significantly to the inflammatory response
- they stimulate parasympathetic mediated bronchoconstriction and mucus production

Serotonin
- it is released by mast cells
- there is evidence in cats that this may be an important mediator of bronchoconstriction in allergen-induced airway disease