S8) The Autonomic Nervous System

Question 1

What does the Autonomic Nervous System control specifically?

Answer 1

• Smooth muscle (vascular and visceral)
• Exocrine (and some endocrine) secretions
• Rate and force of the heart
• Certain metabolic pathways

Question 2

Describe the layout and functioning of the ANS

Answer 2

• ANS conveys information from the CNS to the neuro-effector junction via the pre-ganglionic and post-ganglionic neurones
• The ANS consists of two divisions, the sympathetic and parasympathetic systems

Question 3

What is a neuro-effector junction?

Answer 3

A neuro-effector junction is the point at which the target cell/tissue is innervated

Question 4

Describe the dual parasympathetic and sympathetic (both divisions of ANS) innervation of tissues

Answer 4

Whereever this occurs, sympathetic and parasympathetic systems often have opposing effects e.g. in control of heart rate; smooth muscle in GI motility, etc.

Question 5

What are the main neurotransmitters in the ANS?

Answer 5

• Acetylcholine (ACh)
• Noradrenaline (NA)

Question 6

Describe the nature of pre-ganglionic neurons

Answer 6

All pre-ganglionic neurons are cholinergic (ACh is principal transmitter)

Question 7

Describe the nature of post-ganglionic neurons

Answer 7

• Parasympathetic post-ganglionic neurons are also cholinergic
• Most sympathetic post-ganglionic neurons are noradrenergic

Question 8

In five steps, describe the basic processes that take place at a typical synapse

Answer 8

⇒ Synthesis and storage of transmitter

⇒ Depolarisation by action potential and resultant influx of Ca²⁺

⇒ Exocytotic release of transmitter

⇒ Diffusion to post-synaptic membrane

⇒ Interaction with post-synaptic receptors

Question 9

Describe the synthesis of noradrenaline

Answer 9

• Noradrenaline is synthesised from tyrosine
• The presence of phenylethanolamine N-methyltransferase in the chromaffin cells of the adrenal medulla allows adrenaline to be synthesised

Question 10

Describe the synthesis of acetylcholine

Answer 10

Acetylcholine is synthesised by the enzyme choline acetyltransferase from choline and acetyl CoA in the cytoplasm of cholinergic terminals

Question 11

Describe cholinergic transmission

Answer 11

• Cholinergic terminals possess numerous vesicles containing ACh released by Ca²⁺-mediated exocytosis
• Released ACh interacts with post-synaptic cholinoceptors
• Cholinesterase rapidly degrades ACh in the synaptic cleft to choline and acetate

Question 12

Describe adrenergic transmission

Answer 12

• Noradrenaline is released by Ca²⁺-mediated exocytosis
• Released noradrenaline interacts with post-synaptic adrenoceptors
• A high affinity reuptake system (Uptake 1) rapidly removes noradrenaline from the synaptic cleft

Question 13

Identify some drugs which act on cholinergic nerve terminals

Answer 13

• Nicotinic cholinoceptor antagonists
• Muscarinic cholinoceptor agonists
• Muscarinic cholinoceptor antagonists
• Cholinesterase inhibitors

Question 14

Identify some drugs acting on adrenergic nerve terminals

Answer 14

• α-Methyl-tyrosine
• α-Methyl-DOPA
• CarbiDOPA
• Uptake 1 inhibitors

Question 15

Describe the use of selective β₁ adrenoceptor agonists (benefits & side effects)

Answer 15

• β₁ adrenoceptor agonists cause positive inotropic and chronotropic effects, thus are useful in treating circulatory shock
• Side effect: cardiac dysrhythmias

Question 16

Describe the use of selective β₂ adrenoceptor agonists and provide an example

Answer 16

β₂ adrenoceptor agonists are highly effective in reversing bronchoconstriction in asthmatics e.g. salbutamol

Question 17

Describe the use of selective α₁ adrenoceptor agonists

Answer 17

α₁ adrenoceptor agonists are used as nasal decongestants and may be given with a local anaesthetic injection to cause local vasoconstriction

Question 18

Describe the use of selective α₂ adrenoreceptor agonists

Answer 18

Selective α₂-agonists can be used as antihypertensive agents

Question 19

Describe the use of selective α1-adrenoceptor antagonists (benefits & side effects)

Answer 19

• α₁-adrenoceptor antagonists are used in the treatment of hypertension
• Side effects: postural hypotension and impotence

Question 20

Describe the use of α-adrenoceptor antagonists (benefits and side effects)

Answer 20

• α-adrenoceptor antagonists cause peripheral vasodilatation in the treatment of peripheral vascular disease
• Side effects: postural hypotension and reflex tachycardia (not used for hypertension treatment)

Question 21

Describe the use of β-adrenoceptor antagonists (side effects & benefits)

Answer 21

• β-adrenoceptor antagonists are used to treat hypertension, cardiac dysrhythmias, angina and myocardial infarction
• Side effects: bronchoconstriction (in asthmatics), bradycardia, cold extremities, insomnia and depression

Question 22

What is asthma?

Answer 22

Asthma is a long-term inflammatory disorder of the lungs characterised by airway hyper-responsiveness which causes variable and reversible airflow obstruction

Question 23

Identify 5 trigger factors for asthma

Answer 23

• Infection
• Allergens (pollen, dust, mould)
• Air pollution (cigarette smoke, chemicals)
• Cold air
• Exercise

Question 24

In 4 steps, describe how the pathological abnormalities seen in asthma occur

Answer 24

⇒ Eosinophils accumulate and infiltrate bronchial smooth muscle causing mucosal oedema

⇒ Released cytotoxic mediators damage the respiratory epithelial layer

⇒ Exposed sensory nerves result in bronchial hyper-responsiveness

⇒ Hyper-secretion of mucus blocks airways

Question 25

What are the symptoms of a patient with asthma?

Answer 25

- Dyspnoea - Chest tightness - Chronic cough - Wheeze

Question 26

Explain the action of the parasympathetic nervous system

Answer 26

On stimulation, **parasympathetic nerves** release ACh which acts on post-synaptic muscarinic ACh receptors on smooth muscle cells, causing airways to contract

Question 27

In three steps, explain the consequences of increased parasympathetic drive

Answer 27

⇒ Increased smooth muscle contraction (**bronchoconstriction**) ⇒ **Lumen** narrows ⇒ Increased **resistance to air flow**

Question 28

Although there is little sympathetic innervation of the human airways there is a large population of adrenoceptors in the smooth muscle cells of the airway. What subtype are these?

Answer 28

β₂-adrenoceptors

Question 29

In the airways, what are the consequences of increased sympathetic drive (circulating catecholamines in blood)?

Answer 29

Smooth muscle relaxes (**bronchodilation**)

Question 30

In 7 steps, describe the cellular mechanisms that lead to bronchodilation

Answer 30

⇒ Catecholamines stimulate β₂ adrenoreceptors in the airways (**G_S GPCRs**) ⇒ Activation of **adenylyl cyclase** ⇒ Formation of **cAMP** ⇒ Activation of **PKA** ⇒ Decreased **[Ca²⁺]_i** ⇒ **Bronchodilation**

Question 31

What are the main categories of drugs that are used to treat asthma?

Answer 31

- Bronchodilators: I. β₂ adrenoreceptor agonists II. Muscarinic receptor antagonists - Anti-inflammatory drugs - Leukotriene receptor antagonists

Question 32

Describe how the drugs used to treat asthma mimic the functions of the ANS at a cellular level?

Answer 32

- **β₂-adrenoreceptor agonists** increase cAMP resulting in SM relaxation - **Xanthine drugs** increase cAMP resulting in SM relaxation - **Muscarinic receptor antagonists** block ACh-induced bronchospasms

Question 33

Discuss the advantages of using highly selective agents which display either short or long durations of action in treating asthma

Answer 33

- **Short acting β₂ agonists** used acutely to counteract bronchoconstriction during an asthma attack *e.g. salbutamol* - **Long acting β₂ agonists** used at night to try and prevent a fall in peak flow in the morning *e.g. salmeterol*

Question 34

What advantage does adrenoceptor agonist therapy confer over the use of muscarinic cholinoceptor antagonists?

Answer 34

- **Adrenoreceptor agonists** cause bronchodilation irrespective of the reason behind the bronchoconstriction - **Muscarinic receptor antagonists** only inhibits the action of the PNS – not usually the cause of an asthma attack

Question 35

What physiological reflexes are involved in the normal control of blood pressure?

Answer 35

- Sympathetic nervous system - Renin angiotensin aldosterone system (RAAS)

Question 36

Identify the structures the SNS acts on to control blood pressure and describe its effects

Answer 36

- **Systemic vasculature:** increases peripheral resistance - **Heart:** increases cardiac output - **Kidney:** reduces Na⁺ / H₂O loss

Question 37

Identify and describe the main classes of drugs used in the treatment of hypertension

Answer 37

- **Angiotensin Converting Enzyme Inhibitors** (ACEi) – inhibit the production of Angiotensin II - **Angiotensin II inhibitors** (ARBs) – inhibit the action of AII - **Calcium Channel Blockers** – smooth muscle vasodilators - **Beta-blockers** – reduce cardiac output and decrease renin production - **Alpha-blockers** – vasodilators

Question 38

What are the major population of adrenoceptors that mediate vasoconstriction of the vasculature?

Answer 38

α1-adrenoceptor

Question 39

Identify the 3 mechanisms through which β-adrenoceptor antagonists exert their anti-hypertensive actions

Answer 39

- Reduced **ionotropy** (force) of heart beats - Reduced **chronotropy** (frequency) of heart beats - Reducing **renin release** from the kidneys

Question 40

Why should so much consideration be given to side-effect profiles when treating hypertension?

Answer 40

- Hypertension is generally **asymptomatic** - Tablets that treat hypertension all have **side effects** - **Patients** don’t like side effects - This can cause **poor compliance** to treatment

Question 41

The thyroid gland produces hormones that regulate our metabolic rate. Identify them and describe their actions

Answer 41

- **Triiodothyronine** (T₃) – active hormone, increases basal metabolic rate - **Thyroxine** (T₄) – relatively inactive, reduces levels of T₃

Question 42

In six steps, outline the negative feedback loop in the HPT axis

Answer 42

⇒ **Hypothalamus releases TRH** in response to low levels of T₃/T₄ ⇒ TRH acts on the **pituitary gland** ⇒ Anterior pituitary gland **releases TSH** ⇒ TSH acts on the **thyroid gland** ⇒ Thyroid gland releses **thyroid hormones** ⇒ High levels of **T₃/T₄ prevent further release** of TRH and TSH

Question 43

Identify and describe three clinical conditions wherein the thyroid malfunctions

Answer 43

- **Hypothyroidism** refers to an underactive thyroid gland - **Hyperthyroidism** refers to an overactive thyroid gland - **Thyrotoxicosis** refers to the clinical symptoms due to high levels of thyroid hormone in the bloodstream

Question 44

Compare and contrast the symptoms of thyrotoxicosis with those of anxiety

Answer 44

- **Similarities**: palpitations, restlessness, increased bowel movements, tremour - **Differences:** goitre, increased appetite, vasodilation, weight loss in anxiety

Question 45

Which drug targeted to the ANS can be used for the treatment for thyrotoxicosis?

Answer 45

- Non-selective **β-adrenoceptor antagonists** *e.g. propanolol* - Thyroid hormones **upregulate the number of adrenoceptors** in the body