Regulation of cerebral circulation

Question 1

How much of brain tissue does grey matter (neuronal cell bodies) make up?

Answer 1

40%

Question 2

What is the primary requirement of the brain?

Answer 2

Constant O₂ rich blood supply - x10 higher blood flow than body average

The local blood flow changes according to needs.

Question 3

What developed structure in the brain allows for constant, high O₂ rich blood flow?

Answer 3

Circle of Willis - it’s an anastomosis - streams of arteries that branch out and then reconnect with one another.

Capillary density is also very high, blood brain barrier important too.

Question 4

Where is a common place for an embolus passing up the internal carotid artery to block?

Answer 4

Middle cerebral artery

Question 5

What do baroreceptors in the carotid sinus monitor and control?

Answer 5

Monitor cerebral perfusion pressure (BP), allows to control heart/peripheral vasculature through reflexes

Question 6

Which vessels are spared from the baroreceptor reflex-induced vasoconstriction?

Answer 6

Cerebral resistance vessels

Question 7

Describe the carotid sinus baroreceptor reflex

Answer 7

Question 8

Which cranial nerve is the ‘carotid sinus nerve’?

Answer 8

glossopharyngeal (IX)

Question 9

What is the myogenic response in terms of auto-regulation of cerebral blood flow?

Answer 9

If the arterial blood pressure increased, you would expect the blood flow to increase.

But as blood pressure increases, the myogenic response causes the cerebral blood flow to plateau -> preventing it from increasing too much, so maintaining it.

However, there is a point when the auto-regulation cannot maintain if the BP gets too high/low.

Question 10

What auto-regulatory response will changes in PCO₂ induce in maintenance of cerebral blood flow?

(i) Hypocapnia (eg hyperventilation)
(ii) Hypercapnia (asphyxia)

Answer 10

• Hypocapnia - LOW CO₂ will result in vasoconstriction of cerebral blood vessels -> decrease blood flow
• Hypercapnia - HIGH CO₂ will result in vasodilation of cerebral blood vessels, this is in order to try and get more oxygen to the brain due to the increased CO₂ -> increase blood flow

Question 11

What response of the cerebral blood vessels will local hypoxia incur?

Answer 11

Vasodilation - if there’s low oxygen, the vessels will dilate in order to get more blood and hence more O₂ to the brain. Again, increasing blood flow.

Question 12

What is the link/explanation between a part of the brain’s neuronal firing and how much blood supply it is receiving?

Answer 12

• Increased neurone firing / APs
• Increased K⁺ efflux
• K⁺ buildup outside cells
• External K⁺ -> causes blood vessels to dilate
• Increased blood flow -> regional hyperaemia

Question 13

Cerebral arteries ‘outside’ the brain receive dense innervation from sympathetic nerves. True or false?

Answer 13

True! It’s the cerebral arterioles ‘within’ the brain that have little innervation. There is little involvment of cerebral vasculature in baroreceptor reflex.

Question 14

What neurotransmitter is abundant in perivascular nerves around cerebral arteries?

Answer 14

5HT / serotonin (causes constriction)

Question 15

Why are 5HT1B agonists used for migraine? Example?

Answer 15

Eg. Sumatriptan - migraine means that your blood vessels in your head are dilated due to inflammation. The 5HT1B agonist causes constriction of blood vessels, reducing the migraine effects.

Question 16

What type of fibres are perivascular sensory fibres?

Answer 16

Nociceptors (C-fibres), mediate the pain of vascular headaches in strokes and later phase of migraine. Release inflammatory dilators (Sub P, CGRP).

Question 17

What lipid soluble substances can diffuse through the blood-brain barrier?

Answer 17

• O₂
• CO₂
• General anaesthetics

All lipid soluble, glucose and AAs have to cross via faciliated diffusion.

Question 18

What substances need to be kept out by the blood-brain barrier?

Answer 18

Circulating neuro-active chemicals that would interfere with neuronal signalling eg. catecholamines

Question 19

What substances need to be kept in by the blood-brain barrier?

Answer 19

Neurotransmitters - otherwise they would be continuously washed out of the brain due to high blood flow.

Question 20

Which 3 areas in particular in the brain have defective blood-brain barrier sites?

Answer 20

• Area postrema of brainstem
• Sub-fornicular organ of hypothalamus
• Periventricular osmoreceptors (hypothalamus)

Question 21

What substances are able to cross the BBB at the area postrema and what do they induce?

Answer 21

• Toxins cross into emetic areas -> vomiting
• AngII -> sympathetic stimulation

Question 22

What substances are able to cross the BBB at the hypothalamus?

Answer 22

• Sub-fornicular organ - angII -> thirst stim
• Periventrcular osmoreceptors - inc plasma osmolarity -> ADH secretion

Question 23

What are the 4 special problems of cerebral circulation (that you need to know)?

Answer 23

1. Postural hypotension
2. Cerebral artery vasospasm
3. Cerebrovascular accidents / strokes
4. Space occupying lesions (tumour, haemorrhage) -> Cushing’s reflex

Question 24

What happens in postural hypotension - ie the effect of standing up? Symptoms and how are they made worse?

Answer 24

When supine (lying flat):

• High central blood volume
• High cardiac filling pressure
• Larger stroke volume -> maintain BP

When standing:

• CVP decreases
• Left stroke volume decreases
• Arterial pressure decreases
• Cerebral blood flow decreases

This causes dizziness and visual fade, exarcebated by warmth, bed rest and zero gravity.

Question 25

What events can induce cerebral arterial vasospasm? What can this then lead to?

Answer 25

Induced by sub-arachnoid / intra-cerebral haemorrhage, can lead to vasospasm which can then lead to stroke (cerebral infarct).

Question 26

What agents cause vasospasm (vasoconstrictors)?

Answer 26

• 5HT from perivascular nerves
• NP Y from perivascular nerves
• Endothelin-1 from vascular endothelium
• K⁺ ions from damaged cells -> excitability

Question 27

What drugs/agents reduce vasospasm?

Answer 27

• Ca²⁺ channel blockers eg. amlodipine, acting on vascular smooth muscle
• ET_A receptor blockers, eg. bosentan

Question 28

Explain why a patient may present with high blood pressure and bradycardia, following a stroke.

Answer 28

A stroke acts as a space-occupying reflex and leads to the Cushing’s reflex.

The tumour/stroke (SOL) forces the brain down and causes it to expand in the foramen magnum. This in turn stimulates this brainstem area, being the RVLM -> stimulates sympathetic nervous system -> increases BP and TPR.

This increase in BP is recognised by the baroreceptor reflex, which in turn stimulates the VAGUS nerve to decrease the heart rate and hence result in bradycardia as well as high BP!