Blood supply to the central nervous system

Question 1

Why must blood flow to the brain be maintained and what happens when flow is inhibited over a few seconds to minutes?

Answer 1

The brain has high oxygen and glucose demands - it consumes 10-20% of the CO and 3ml/100g/min of oxygen.

If the brain doesn’t recieve oxygen for a few seconds - syncope
A few minutes - brain damage

BRAIN CANNOT USE LIPIDS, ONLY GLUCOSE AND KETONES DURING STARVATION

Question 2

What is normal and abnormal (coma, unconsciousness and death) blood glucose levels?

Answer 2

normal - 4-6mM

abnormal - >2mM

Question 3

What does cerebral blood flow autoregulation mean?

Answer 3

The total CBF is auto regulated in the MABP range of 60 - 160mmHg
Above and below this pressure, the CBF cannot be maintained

Question 4

How does cerebral blood flow autoregulation occur?

Answer 4

Stretch-sensitive cerebral vascular SM contracts at higher BPs and relaxes at lower BPs

Question 5

What is local cerebral blood flow autoregulation?

Answer 5

Local brain activity determines the local O2 and glucose demands, therefore local changes in blood supply are required

Question 6

What are the two types of local cerebral blood flow regulation?

Answer 6

neural and chemical

Question 7

What are the different components of the neural local control system of CBF regulation?

Answer 7

Sympathetic nerve innervation – vasoconstricts when MABP is high.

PNS facial nerve innervation – slight vasodilation

Central cortical neurones – release vasoconstrictor NTs such as catecholamines

Dopaminergic neurones – local vasoconstrictive effects

Question 8

How do dopaminergic neurones cause vasoconstriction?

Answer 8

They innervate penetrating arterioles and pericytes (brain macrophages) around capillaries
They may participate in diversion of cerebral blood to areas of high activity
Act by causing contraction of pericytes via aminergic and serotoninergic receptors

Question 9

Describe the vasculature of the CNS

Answer 9

Arteries from the pia mater penetrate into the brain tissue and branch to form capillaries.
These drain into venules/veins -> pial vessels

Question 10

What are the different components of the chemical local control system of CBF regulation?

Answer 10

CO2 (Indirect - Vasodilator)

pH (Vasodilator)

NO (Vasodilator)

K+ (Vasodilator)

Adenosine (Vasodilator)

Anoxia (Vasodilator)

Other (i.e. kinins, prostaglandins, histamine - Vasodilator)

Question 11

How is CBF affected by CO2 levels?

Answer 11

The increase in H+ decreases the pH inside the VSMCs which causes the cell to constrict resulting in vasoconstriction.

The H+ can be derived from the (higher) CO2 in the blood (NOT directly from H+ in the blood) or from increased neural metabolic activity (directly).

Question 12

Describe where CSF is produced and the pathway it follows

Answer 12

• Produced by the choroid plexus (modified ependymal cells that ordinarily line the ventricles)
• The capillaries are leaky but adjacent ependymal cells have extensive tight junctions
• CSF is secreted into the lateral ventricles
• 3rd ventricle (via interventricular foramina)
• 4th ventricle (via cerebral aqueduct)
• subarachnoid space via medial and lateral apertures

Question 13

What is total CSF volume?

Answer 13

80-150ml

Question 14

What are the functions of CSF?

Answer 14

protection, nutritional, transport

Question 15

What is the composition of CSF in comparison to plasma?

Answer 15

Similar pH (slightly higher in plasma) and osmolarity but importantly very low protein levels

K+, Ca2+, aa - CSF lower

Mg2+ - CSF higher

Question 16

What are the three types of capillaries?

Answer 16

continuous, fenestrated and sinusoidal

Question 17

Where do the capillaries of the CNS tissue originate from?

Answer 17

surface pial vessels

Question 18

What is the blood brain barrier?

Answer 18

BBB capillaries have extensive tight junctions at the endothelia cell-cell contact zone – reduces leakage. Deeper into the tissue as the capillaries move deeper, the permeability decreases until the blood brain proper is present.

Question 19

What are some structural features of the BBB?

Answer 19

Interendothelial Junctions (IEJs) – the IEJs are much more tightly knit and ‘torturous’ (the endothelial cells overlap on each other to give a tighter fit)

BBB capillaries are covered by “end-feet” from astrocytes which help maintain the BBB properties.

Question 20

Which molecules can cross the BBB?

Answer 20

lipophilic ones - oxygen, carbon dioxide, alcohol

Question 21

Describe how different molecules are transported across the BBB?

Answer 21

water - aquaporins
glucose - GLUT1
amino acids - 3 transporters
electrolytes - specific mechanisms

Question 22

What are circumventricular organs?

Answer 22

In some places in the brain, it is necessary for capillaries to lack BBB properties – i.e. pituitary gland.

These capillaries are often fenestrated and are present as the CVOs often need to sample blood or secrete into the blood itself.

Found close to the ventricles

Question 23

What is the clinical importance of the blood brain barrier?

Answer 23

Many therapeutic drugs cannot access the brain whereas many access the brain too readily and can cause adverse effects so it must be monitored.

Question 24

How do old and new anti-histamines compare?

Answer 24

Old-fashioned H1-channel blockers are hydrophobic and so would cross the BBB and cause drowsiness (as histamine is a drug that keeps you alert).

Second-generation antihistamines are now polar and so do not cross the BBB so no drowsiness.

Question 25

Why can’t dopamine be administered to treat Parkinson’s?

Answer 25

It cannot cross the BBB and so cannot be given peripherally

Question 26

How is Parkinson’s managed and why?

Answer 26

L-DOPA can cross the BBB though but circulating L-DOPA is broken down in the body peripherally so co-administration of DOPA-decarboxylase inhibitor (Carbidopa) is necessary

Question 27

What are pericytes?

Answer 27

They are closely adherent to capillaries in the brain – they maintain capillary function and integrity.
Peripheral capillaries have much fewer

Question 28

Why can the meninges be infected but the rest of the brain tissue less?

Answer 28

Infections more commonly affect the meninges whose vessels are not BBB.