Regulation of Cerebral Circulation

Question 1

Why is the brain said to be under-perfused? How does the brain cope with this?

Answer 1

• Brain receives 13% of cardiac output but consumes 20% of oxygen
• Oxygen extraction is 35% - higher than the body average of 25%
• This is possible due to a high capillary density

Question 2

An emoblus passing up the internal carotid artery is most likely to occlude which vessel of the Circle of Willis?

Answer 2

Middle cerebral artery (MCA)

Question 3

Why are the cerebral resistance vessels spared from the baroreceptor reflex?

Answer 3

Very little sympathetic innervation to cerebral vessels

Question 4

Name 3 functional adaptations of the cerebral circulation.

Answer 4

• Auto-regulation is extremely well developed - myogenic response.
• Local metabolic vasodilation is well developed.
• Tight blood-brain barrier controls access and outflow of solutes.

Question 5

How do neurons autoregulate hyperaemia?

Answer 5

• High neuronal activity results in more K⁺ efflux
• When extracellular K⁺ reaches 10mM, activity of K channels in VSMCs increases
• Hyperpolarisation leads to smooth muscle relaxation and vasodilation

Question 6

What is sumitriptan used for?

Answer 6

• 5-HT_1B agonist
• Used in migraine - reverses inflammatory vasodilation in cerebral arterioles

Question 7

Describe the functions of the blood-brain barrier.

Answer 7

• Keep out neuroactive chemicals - e.g. catecholamines
• Retain neurotransmitters
• BBB defective at certain sites:
  
  • Area postrema - medulla - vomiting centre
  • Sub-fornicular organ - hypothalamus - angiotensin II - thirst
  • Periventricular osmoreceptors - hypothalamus - ADH - secretion

Question 8

Explain the causes of cerebral artery vasospasm.

Answer 8

• Sub-arachnoid/intra-cerebral haemorrhage > arterial vasospasm > stroke.
• Vasospasm is due to local vasoconstrictor agents - 5-HT and Neuropeptide Y from perivascular nerves, endothelin-1 from vascular endothelium.
• High levels of external K⁺ from damaged cells (>10mM) depolarise VSMCs > vasoconstriction > reduced blood flow. Vicious cycle of ischaemia.
• Vasospasm is reduced by Ca²⁺ channel blockers e.g. amlodipine, ETA receptor blockers e.g. bosentan.

Question 9

Why do space-occupying lesions in the brain cause chronic bradycardia?

Answer 9

• SOLs cause increased intracranial pressure
• This results in Cushing’s reflex
• Chronic increased sympathetic vasoconstriction > increased BP
• Chronic baroreflex activation > vagus nerve mediates chronic bradycardia