Autonomic regulation of the airways

Question 1

How do airways regulate diameter?

Answer 1

The airway has smooth muscle which can contract and relax to regulate the diameter
- This is specifically important when considering asthma and COPD

Question 2

Give three phenotypes of asthma

Answer 2

1. usually <50
2. Infrequent sputum production
3. No clear aetiology with smoking

Question 3

Give three phenotypes of COPD

Answer 3

1. Usually >35
2. Usually >10 pack-years
3. Sputum is produced and is common in chronic bronchitis

Question 4

How are the smooth muscles in the airways regulated?

Answer 4

1. By autonomic nervous system
   - Contractile signals cause an increase in intracellular calcium in smooth muscle, which activates actin-myosin contraction
2. Regulated by inflammation particularly with asthma

Question 5

How is the nervous system split?

Answer 5

Broadly into the Central and Peripheral

Question 6

What is the central Nervous system further split into?

Answer 6

Spinal cord and brain

Question 7

What is the peripheral nervous system further split into?

Answer 7

1.Efferent and afferent
2. Efferent - Autonomic (smooth muscle) + Somatic (skeletal muscle)
3. Autonomic - Sympathetic + Enteric + Parasympathetic

Question 8

What outputs does the autonomic nervous system convey?

Answer 8

Coveys all outputs from the CNS to the body, except for skeletal muscular control
- Two nerves in the series known as pre and post ganglionic fibres

Question 9

Give three examples of parasympathetic responses

Answer 9

1. Constrict Bronchi
2. Slows heart rate
3. Constricts pupils

Question 10

Give three examples of sympathetic responses

Answer 10

1. Dilates bronchi
2. Accelerates heart hate and constricts arterioles
3. Dilates pupils

Question 11

What does the somatic nervous system release?

Answer 11

• At the terminal ganglion acetyl-choline is released which has its effects on nicotine 1 receptors on the effector organ
• Only one singular ganglion

Question 12

How does the parasympathetic nervous system convey signals?

Answer 12

• It has two ganglions, that lie very close to the effector organ
• Releases acetyl choline which has an effect on nicotine 2 receptors
• At site of effector, acetyl choline released and has an effect on muscarinic receptors

Question 13

How does the parasympathetic nervous system convey signals?

Answer 13

• The first ganglion lies in the spinal cord
• Releases acetyl choline which has an effect on nicotine 2 receptors
• Neuro-adrenaline released from the sympathetic nervous system and has it’s effect on alpha and beta receptors in the target organ

Question 14

How is the parasympathetic nervous system in the lungs responsible for bronchoconstriction?

Answer 14

• Vagus nerve neurons terminate in the parasympathetic ganglia in the airway wall
• Short post-synaptic fibres reach the muscle and release acetyl-choline, which acts of muscarinic receptors of the M3 subtype (receptors) on the muscle cells
• This then stimulates airway smooth muscle constriction

Question 15

How can inhibiting the parasympathetic nervous system be beneficial?

Answer 15

• For conditions such as asthma and COPD which is already narrowing the airway
• Drugs that can do this block the M3 receptor, and are called anti-cholinergics or anti-muscarinics. This will induce broncho-dilation so opening up the airways

Question 16

What are some examples of antimuscarinics?

Answer 16

• Ipatropium bromide is an inhaled treatment to relax airways in asthma and COPD, but it is short acting antimuscarinic (SAMA)
• SAMA are less widely used since LAMA (long acting) were developed
• Ipatropium still used in high dose in nebulisers as part of acute management of severe asthma and COPD

Question 17

Why are LAMAs better?

Answer 17

• Long duration of action, often only given once daily
• Increase bronchodilation and relieve breathlessness in asthma and COPD
• Reduce acute attacks

Question 18

What are some examples of inhaled antimuscarinics?

Answer 18

• Titropium
• Glycopyronium
• Alcidinium
• Umecilidinium

Question 19

What does sympathetic nervous system regulate?

Answer 19

Fight or flight

Question 20

How are the effects of the sympathetic nervous system activated?

Answer 20

• Nerve fibres release noradrenaline which activates adrenergic receptors (alpha/beta)
• Activation of beta2 receptors on the airway smooth muscle causes muscle relaxation (by activating adenylate cyclase, raising cyclic AMP)

Question 21

What are some examples of SABA (short-acting beta2 agonists)

Answer 21

• Salbutamol

Question 22

What are some examples of LABA (long-acting beta2 agonists)

Answer 22

• Formoterol
• Salmeterol

Question 23

When are SABAs and LABAs given?

Answer 23

• With steroids in asthma, often without steroids in COPD
• Given with LAMA in COPD
• Used for an acute rescue of bronchoconstriction
• Prevention of bronchoconstriction
• Reduction in rates of exacerbations

Question 24

What are the adverse effects of B2-agonists?

Answer 24

• Raising cAMP may activate Na/K exchange pump driving a cellular influx of potassium
• Tachycardia (cardiac side effects)
• Hyperglycaemia: loss of insulin sensitivity, increased liver glucose release

Question 25

What is drug deposition and how is it governed?

Answer 25

• Making sure you are getting the right amount of drugs to the right place
• Particle size is main factor that governs this deposition
• 1-10um size generally in the range of respiration
• Other factors: type of device, flow rate, underlying disease

Question 26

What does asthma need for immediate management?

Answer 26

• Oxygen to maintain 94-98% saturation
• Salbutamol nebuliser 5mg
• Ipratropium nebuliser 0.5mg