8. Sympathetic nervous and renin-angiotensin systems Flashcards

1
Q

Where does the parasympathetic system originate from?

A

craniosacral region

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2
Q

Where does the sympathetic system originate from?

A

thoracolumbar region

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3
Q

Where are the baroreceptors found?

A

Aortic Arch and Carotid Arteries

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4
Q

What do all parasympathetic nerves terminals release?

A

Acetylcholine

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5
Q

What transmitter is released in the paravertebral sympathetic ganglion?

A

Always Acetylcholine

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6
Q

What transmitter is released from the effector end of the sympathetic arm?
What is the exception?

A

Noradrenaline

Special case of adrenal medulla which releases adrenaline (80%) and noradrenaline (20%)

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7
Q

What class of molecule do noradrenaline and adrenaline belong to?

A

Catecholamines

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8
Q

What is the terminal varicosity?

A

A small nodule at the end of the sympathetic nerve

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9
Q

Where does the synthesis of noradrenaline take place?

A

Varicosity

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10
Q

How is noradrenaline synthesised?

A

Tyrosine is transported into the varicosity.

Tyrosine -> DOPA -> dopamine

Dopamine is transported into a vesicle.

Dopamine is converted into NA

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11
Q

Where is noradrenaline stored?

A

In granular vesicles where it is exocytosed when needed

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12
Q

What can happen to NA that has been expelled?

A

Reuptake and removal of the transmitter can occur

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13
Q

How can NA be removed from the cleft?

A

Uptake 1 = Goes back into the neurone that released it

Uptake 2 = Taken up by extraneuronal cells

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14
Q

What two enzymes breakdown the NA?

A

COMT (Catechol-O-Methyl Transferase)

MAO (Monoamine Oxidase)

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15
Q

What are adrenoreceptors divided into?

A

Excitatory and relaxant effects

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16
Q

What receptors and where does excitatory effects occur?

A

Alpha adrenoreceptor mediated on smooth muscle

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17
Q

What receptors and where does relaxant effects occur?

A

Beta adrenoreceptors mediated. Relaxant effect on smooth muscle + stimulatory effect on heart

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18
Q

What does a increases stimulatory effect mean?

A

It increases the inotropic effect and the chronotopic effect

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19
Q

Define intropic effect

A

The force of contraction

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20
Q

Define chronotropic effect

A

Heart rate

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21
Q

What can beta receptors of adrenal receptors be further divided into?

A

Beta 1,2 & 3

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22
Q

Where are Beta 1 receptors located?

A

Cardiomyocytes

Smooth muscle of GI tract

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23
Q

Where are Beta 2 receptors located?

A

Vasculature
Bronchi
Uterine smooth muscle

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24
Q

Where are Beta 3 receptors located?

A
Fat cells (brown fat)
Possibly on the smooth muscle of the GI tract
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25
What can alpha receptors of adrenal receptors be further divided into?
Alpha 1 & 2
26
Where are Alpha 1 receptors located?
Post synaptically
27
What is the function of Alpha 1 receptors?
Important in mediating constriction of resistance vessels in response to sympathomimetic amines
28
Where are Alpha 2 receptors located?
Pre synaptic nerve terminal membrane
29
What is the function of Alpha 2 receptors?
Their activation by released transmitter causes NEGATIVE FEEDBACK inhibition of further transmitter release
30
How do alpha 1 adrenoreceptors cause contraction?
Via G proteins --> activation of PLC
31
What are beta receptors coupled to?
Adenylate cyclase which increases the level of cAMP
32
What is anaphylaxis?
An extreme allergic reaction. There is a release of vasodilators and bronchoconstriction
33
What do they cause: vasoconstriction of vasodilation? a1, a1 & b
``` a1 = vasoconstriction a2 = vasoconstriction b = vasodilation ```
34
What adrenoreceptors does noradrenaline bind to?
a1, a2, b1
35
What adrenoreceptors does adrenaline bind to?
a1, a2, b1, b2
36
What adrenoreceptors does dopamine bind to?
weak effects at a1 and b1, but it has its own receptors
37
What is isoprenaline used for and what adrenoreceptors does is bind to?
It used to treat asthma. Isoprenaline is a pure beta agonist: b1, b2
38
What adrenoreceptors does phenylephrine bind to?
a1
39
What catecholamine massively increases blood pressure and by what mechanism?
Noradrenaline, causes vasoconstriction increasing TPR
40
How does noradrenaline and adrenaline affect heart rate?
Noradrenaline decreases heart rate | Adrenaline increases heart rate
41
Why does adrenaline decrease diastolic blood pressure but increase systolic blood pressure?
It acts on b2 receptors to decrease blood pressure (vasodilator) and also b1 receptors which has a stimulatory effect on the heart
42
What do beta receptors increase the amount of?
cAMP which causes relaxation
43
What do alpha 2 receptors inhibit?
Adenylate cyclase reducing the levels of cAMP and therefore opposing the effects of calcium (Ca is not released)
44
What catecholamine has similar effects to noradrenaline?
Adrenaline, but to a lesser extent since it has beta effects which counteract the alpha effects
45
Why does noradrenaline decrease heart rate?
Reflex bradycardia - vasoconstriction causes an increase in blood pressure which increases the firing frequency of the baroreceptors leading to the deactivation of the sympathetic innervation of the heart and increased activity of the vagus nerve leading to a REDUCED HEART
46
Why does adrenaline increase heart rate?
It has a potent effect on beta receptors (b1)
47
What is renin release regulated by?
Amount of sodium that reaches the macula densa Blood pressure Beta receptor activation
48
In terms of the amount of sodium, what increases renin release?
The less sodium the more renin released
49
In terms of the blood pressure, what increases renin release?
The lower the BP the more renin released
50
In terms of beta receptor activation, what increases renin release?
The more beta receptors that are activated, the more renin is released
51
What type of receptors are angiotensin II type 1 receptors?
G-protein coupled receptors (Gi and Gg) which are also coupled with phospholipase A2
52
Where are angiotensin II type 1 receptors located?
Blood vessels, brain, adrenals, heart and kidney
53
What is the function of angiotensin II type 1 receptors?
Increases blood pressure
54
What are the main areas of effect of angiotensin II?
Peripheral resistance Renal function Vascular and cardiac hypertrophy and remodelling
55
What effects does angiotensin II have on peripheral resistance?
Causes direct vasoconstriction, enhances the action of peripheral noradrenaline by increasing its release and decreasing its uptake, increases sympathetic discharge and release of catecholamines
56
What effects does angiotensin II have on renal function?
Increases sodium reabsorption in the PCT, synthesis and release of aldosterone, causes renal vasoconstriction and enhanced noradrenaline effects in the kidney. This all happens over weeks or months - Slow pressor response
57
What effects does angiotensin II have on vascular and cardiac hypertrophy and remodelling
Haemodynamic effects: Increased preload, afterload and vascular wall tension Non-haemodynmaic effects: Increased expression of proto-oncogenes, production of growth factors, synthesis of extracellular matrix proteins
58
List the methods of manipulating the renin-angiotensin system
Renin inhibitor - prevents the formation of angiotensin I ACE inhibitors - blocks the conversion of AGT I to AGT II Angiotenin II receptor blocers
59
What is the function or bradykinin?
Vasodilation
60
What is the consequence if you block ACE?
There will be less angiotensin II and more bradykinin
61
What are the effects of blocking angiotensin II type 1 receptor>
Blocks: pressor efffects, stimulation of noradrenaline system, secretion of aldosterone, effects on renal vasculature and growth-promoting effects of cardiac and vascular tissue You also get a uricosuric effect
62
What is a uricosuric effect?
An increase of uric acid in the urine
63
What is effect of aldosterone?
Lose potassium through the kidneys but retain sodium and water leading to a increase in blood pressure
64
What causes the synthesis and release of aldosterone?
Higher levels of potassium and angiotensin
65
Why is a large amount of aldosterone bad?
Aggravates heart failure
66
What is primary hyperaldosteronism associated with?
Benign tumours of the adrenal cortex which is associated with hypertension. Phenotype = high blood pressure + NO oedema
67
What is secondary hyperaldosteronism associated with?
Excessive response of the body in heart failure and liver failure Phenotype = low/normal BP + LOTS of oedema
68
What do both sympatho-adrenal and renin-angiotensin system respond to?
STRESS
69
What is a potent stressor?
Fluid loss
70
What does activation of both sympatho-adrenal and renin-angiotensin systems lead to?
Increased BP Increased Heart Rate Increased sodium/water retention
71
What effects are there to decrease fluid loss?
Increased Coagulation Decreased fibrinolysis Increase platelet activation