Catecholamines

Question 1

What are the two broad regions of the adrenal glands?

Answer 1

Cortex - secretes steroid hormones (e.g. aldosterone, cortisol)

Medulla - secretes catecholamines (adrenaline and noradrenaline)

Question 2

1

Answer 2

Zone glomerulosa

Question 3

2

Answer 3

Zone fasciculata

Question 4

3

Answer 4

Zone reticularis

Question 5

4

Answer 5

Medulla

Question 6

True/false: all of the adrenaline in the blood comes from the adrenal medulla.

Answer 6

True

Question 7

True/false: all noradrenaline in the blood comes from the adrenal medulla.

Answer 7

False

Noradrenaline comes from two sources: the adrenal medulla, and postganglionic sympathetic neurones.

Question 8

Describe how the sympathetic nervous system can cause both constriction and dilation of arterioles.

Answer 8

• Sympathetic tone keeps the arterioles constricted to 50% of their diameter
• Increased stimulation → more constriction
• Decreased stimulation → less constriction
• The sympathetic nervous system is the body’s dominant mechanism for maintaining vascular tone.

Question 9

Describe the synthesis pathway for adrenaline and noradrenaline

Answer 9

• Synthesis begins with the amino acid tyrosine, which is converted in a reaction catalysed by tyrosine hydroxyls (the rate limiting step)
• Further down the pathway, dopamine can be converted to noradrenaline, which can then be converted to adrenaline

Question 10

True/false: the adrenal medulla secretes adrenaline and noradrenaline in equal amounts.

Answer 10

False

80% adrenaline

20% noradrenaline

Question 11

What is the half life of catecholamines in plasma?

Answer 11

Very short: 1-3 mins

Question 12

Describe the metabolism and excretion of catecholamines.

Answer 12

• Metabolised by the liver and kidneys
• Excreted via the urinary system. We can measure the amount of unmetabolised adrenaline and noradrenaline from this system.

Question 13

A neurone is adrenergic if…

Answer 13

it secretes noradrenaline

e.g. postganglionic sympathetic neurones

Question 14

A neurone is cholinergic if…

Answer 14

it secretes acetylcholine

e.g. most neurone with cell bodies in the CNS are (generally) cholinergic

Question 15

Describe the types of adrenergic receptors

Answer 15

• Alpha adrenergic receptors
• Beta adrenergic receptors
• There are further subgroups: ɑ1, ɑ2, β1, β2
• Their effects can allow cells to be stimulated or inhibited
• Some cells have alpha and beta receptors, others have only one type (e.g. cardiac myocytes have only beta receptors)

Question 16

What is the advantage of having different adrenergic receptors (alpha and beta) in different places?

Answer 16

Allows different effects on different tissues when stimulated e.g. constriction vs dilation

Question 17

Describe the effect of catecholamine binding on alpha adrenergic receptors

Answer 17

• Vasoconstriction
• Pupil dilation
• Intestinal relaxation
• Pilomotor contraction
• Bladder sphincter contraction

Question 18

Describe the effect of catecholamine binding on beta 1 adrenergic receptors

Answer 18

• Increased HR
• Increased contractility

Question 19

Describe the effect of catecholamine binding on beta-2 adrenergic receptors

Answer 19

• Vasodilation
• Bronchodilation
• Glycogenolysis
• Lipolysis

Question 20

True/false: catecholamines often bind to receptors and activate second messengers.

Answer 20

True

• The receptors are often G-protein coupled
• There are multiple second messenger pathways including adenylyl cyclase, phospholipase C, IP3, DAG, ion channels

Question 21

Describe how SNS activation can lead to differing effects on different tissues

Answer 21

• Tissue response varies according to type and density of receptors, and relative concentrations of adrenaline and noradrenaline locally
• SNS activation
  
  • In the intestines, alpha receptors are stimulated, causing smooth myocytes in blood vessels to constrict (vasoconstriction)
  • In the muscles, beta 2 receptors are stimulating, inhibiting the same smooth myocytes and thus resulting in vasodilation
  • The appropriate response thus occurs: reduced blood flow to the intestines, increased blood flow to the muscles.

Question 22

Describe the importance of medullary hormones to fight or flight

Answer 22

• Medullary adrenaline and noradrenaline have the same general effects as the sympathetic nervous system. In fight or flight, there is widespread and simultaneous stimulation of tissue via both nervous and endocrine systems.
• Medullary hormones result in additional effects on tissues without direct sympathetic innervation e.g. metabolic actions appropriate for fight or flight.

Question 23

Describe the metabolic actions of catecholamines

Answer 23

• Goal: increase amount of readily available energy substrate. This can be achieved through mobilisation of glucose or fatty acids.
• Catecholamines increase glycogenolysis in liver and skeletal muscle = increased glucose availability
• Catecholamines stimulate gluconeogenesis within the liver = increased glucose availability
• Catecholamines stimulate hormone-sensitive lipase (HSL) → stimulates hydrolysis of triglycerides in adipose tissues → higher circulating plasma fatty acids levels, used for energy through beta oxidation in mitochondria = lipid-derived energy

Question 24

Describe how catecholamines supply essential tissues with energy substrates

Answer 24

• Increase available substrate through metabolic actions (provision of glucose/lipid-derived energy)
• Increase HR and contractility
• Increase cardiac output and blood pressure
• Shift in perfusion to central circulation (reduced peripheral circulation)

Question 25

Explain the importance of medullary adrenaline in the following categories: 1. Metabolic stimulus 2. Cardiac effects 3. Blood vessels within muscle

Answer 25

1. Metabolic stimulus: adrenaline has 5-10x greater metabolic effect than noradrenaline 2. Cardiac effects: adrenaline has a greater effect on beta receptors (beta stimulation) 3. Blood vessels within muscle: adrenaline acts on beta-2 receptors, causing vasodilation required for fight or flight. Noradrenaline acts on alpha receptors, causing strong vasoconstriction (shock)

Question 26

What is stress hyperglycaemia and why is it relevant clinically?

Answer 26

* Lab blood results will show hyperglycaemia when the animal is stressed (thanks to SNS activation & fight or flight response) * This presents difficulty with diabetes mellitus cases; take care not to misdiagnose stress hyperglycaemia as diabetes mellitus

Question 27

Noradrenaline vs adrenaline: which has a more profound effect on blood vessels

Answer 27

Noradrenaline It increases total peripheral resistance and raises BP

Question 28

Noradrenaline vs adrenaline: which has a more profound effect on the heart?

Answer 28

Adrenaline It increases HR and contractility, thus increasing cardiac output

Question 29

Which receptors do the following drugs act on and what is their action? Detomidine, medetomidine, xylazine, romifidine

Answer 29

* These drugs are selective alpha-2 receptor agonist * They act on alpha-2 receptors, resulting in vascular effects (initial vasoconstriction), increased urine production due to reduced renin and vasopressin secretion

Question 30

Which receptors does the following drug act on? Dobutamine

Answer 30

Beta 1 receptors | (Dobutamine is a selective agonist)

Question 31

Which receptors do the following drugs act on? Clenbutarol, salbutamol, albuterol

Answer 31

Beta 2 receptors | (These drugs are selective agonists)

Question 32

Which receptors does the following drug act on? Dopamine

Answer 32

Alpha 1, Alpha 2, Beta 1 | (Dopamine is a non-selective agonist)

Question 33

Which receptors does the following drug act on? Atipamezole

Answer 33

Alpha 2 receptors | (Atipamezole is selection antagonist)

Question 34

Which receptors do the following drugs act on? Adrenaline/epinephrine

Answer 34

Alpha 1, Alpha 2, Beta 1, Beta 2, Beta 3 (Adrenaline is a non-selective agonist)

Question 35

Which receptors do the following drugs act on? Noradrenaline (norepinephrine)

Answer 35

Alpha 1, Alpha 2, Beta 1 (Noradrenaline is a non-selective agonist)