Introduction to the mechanism of cough

Question 1

Define the three phases of a cough.

Answer 1

1. Inspiritory phase: Deep inspiration causes stretch reflex activastion -> stronger elastic recoil of lung to aid expiration
2. Compressive & Expulsive phase: Glottis closes while expiratory muscles contract -> rapid increase in pressure -> expul;sive flow when glottis opens
3. Recovery phase: Restorative inspiration

Question 2

Describe how bronchoconstriction and mucus secretion help the defensive function of the expulsive phase of a cough

Answer 2

Bronchoconstriction increases linear velocity of airflow (constriction ?increases pressure) and lessen the inflow of the irritants deeper into the lung.

Mucus secretions trap irritants and are cleared through mucociliary transport and cough. It also acts as a barrier between the irritants and the airway wall.

Question 3

Outline the function of coughing

Answer 3

1. Defense
   
   1. Foreign objects
2. Mucous clearance
   
   1. Works with mucociliary clearance
   2. Compensates when ↓cilia function or ↑hypersecretion of mucus

Question 4

Outline the afferent neural pathway for cough

Answer 4

Cough receptors are stimulated

Stimulation of cough receptors in the LRT sends signals through the vagus nerve

Stimulation of cough receptors in URT sends signals through the superior laryngeal nerve

Signal reaches the medulla cough centre then gets to the motor cortex.

Question 5

Name two type of stimulation on cough receptors and give some examples

Answer 5

1. Mechanical
   
   1. Dust, mucus, food/drink
2. Chemical
   
   1. Inflammatory mediators, capsaicin

Question 6

Name the cough receptors found in the lungs

Answer 6

1. RASRs (Rapidly Adapting Stretch Receptors)
   
   1. Aδ
2. C-fibre receptors (chemical; nociceptors)
   
   1. C

Question 7

Wihere are RASRs found? What are their features and what kind of stimuli activates them?

Answer 7

Naso-pharynx, Larynx, trachea, bronchi

Myelinated fibres (Aδ)

Mechanical, chemical, inflammatory mediators

Question 8

Wihere are C-fibre receptors found? What are their features and what kind of stimuli activates them?

Answer 8

Larynx, trachea, bronchi, lungs

Unmyelinated,‘free’ nerve endings

Chemical, inflammatory mediators

Question 9

What can C-fibre receptors (nociceptors) release

Answer 9

Neuropeptides:

SP

NKA

CGRP

SP = Substance P; NKA = Neurokinin A; CGRP = Calcitonin gene-related peptide

Question 10

What are the two subtypes of vagal afferent neurones and what kind of fibres’cough receptors are they associated to

Answer 10

• Jugular ganglia neurones
  
  • Aδ, C
• Nodose ganglia neurones
  
  • Aβ, Aδ, C

Question 11

Once the cough receptors are stimulated, they send signals up the afferent pathway into the brainstem. Describe the central mechanism (centres involved) in regulating cough.

Answer 11

Signal reaches nucleus tracus solitarius

Sends signals to sub-cortex for processing

Signal reaches motor cortex

Signal to CPG/VRG then to motor neurones

Controls respiraatory muslces

Question 12

In chronic cough what is activated in excess

Answer 12

Midbrain pathways

Question 13

Outline the efferent pathways of cough

Answer 13

Motor cortex

Medulla

Glottis and expiratory muscles

Question 14

What are the primary outflows of cough (efferent)

Answer 14

Diaphragm

Pharyngeal muscles

Intercostal muscles

Abdominal muscles

Question 15

What are the secondary outflows of cough

Answer 15

Bronchoconstriction

Mucus Secretion

Muscles opposing mechanical stress of cough

Heart Rate

Question 16

Define a gough

Answer 16

A defensive airway reflex which generates high flow velocities to expel mucus or other foreign bodies from the lungs

Question 17

What are the three phases of cough

Answer 17

1. Inspiritory phase
   
   1. ​Enhanced contraction of diaphragm
2. Compressive phase
   
   1. Expiration against a closed glottis
3. Expulsive phase
   
   1. Forceful contraction of expiratory muscles with an open glottis

Question 18

Define a chronic cough

Answer 18

Cough that has occured for more than eight weeks

Question 19

Define cough hypersensitivity syndrome

Answer 19

Chronic cough triggered by low exposure levels of:

• Thermal
• Mechanical
• Chemical

Question 20

How can you assess a patient with cough hypersensitivity syndrome

Answer 20

Capsaicin stimulation

Inhaled at increasing concentrations

Number of coughs recorded

Question 21

What factors can increase the reaction to capsaicin

Answer 21

Post-viral infection

Asthma

COPD

rhinitis

GORD

Pulmonary fibrosis

Question 22

What neuronal factors can increase cough

Answer 22

• Increased chemical mediators (bradyknin, PGE2)
• Increased receptors (TRPV1)
• Increased neurotransmitters (SP, neurokinins)
• Increased nerve densities

Question 23

Name some anti-tussives used for chronic cough

Answer 23

Central acting: Opiates

Peripherally acting: Moguistine, levodopropizine

Disease specific antitussives (PPI, ICS)

Question 24

Cough hypersensitivity syndrome is treated as a sensory neuropathy. How is it managed?

Answer 24

SALT review

Pharmacology: Amitryptiline, Gabapentin

Experimental: TRPV1 blockers, P2X3 ATP Channel blocker

Question 25

Mechanism of action for amitryptiline in cough

Answer 25

Inhibits reuptake of inhibitory neurotransmitters (i.e. augments inhibitory influences)

Inhibits NMDA receptors

Question 26

Mechanism of action for gabapentin in cough

Answer 26

Activate GABAB receptors