Central Blood Flow Regulation and the Blood-Brain Barrier

Question 1

How much oxygen is supplied to the brain per minute?

Answer 1

55 ml/100g of tissue/min

Question 2

Why is there a vast surplus of glucose delivery to the brain?

Answer 2

Because the brain can only metabolise glucose
Brain can’t store, synthesise or utilise any other source
(Ketone bodies can be metabolized if there is a shortage)

Question 3

Blood glucose below what value will lead to loss of consciousness, coma and death?

Answer 3

2 mM

Question 4

On what levels do you get regulation of cerebral blood flow?

Answer 4

Mechanisms affecting total CBF

Mechanisms that relate activity to requirement in specific brain regions by altered localised blood flow

Question 5

Between what range in mean arterial blood pressure can autoregulation maintain a constant cerebral blood flow?

Answer 5

60-160 mm Hg

Question 6

Name one important factor to do with the smooth muscle lining arterioles that allows regulation of blood flow.

Answer 6

Myogenic Mechanism – when smooth muscle surrounding arterioles is stretched, it will contract to maintain a constant blood flow
Occurs when there is a change in BP in the body

Question 7

What are the 2 types of control of cerebral blood flow regulation?

Answer 7

Neural

Chemical

Question 8

What are the 4 types of neural control of cerebral blood flow?

Answer 8

Sympathetic innervation of the main cerebral arteries: causes vasoconstriction when arterial BP is high
Parasympathetic (facial nerve) stimulation: can cause slight vasodilation
Central cortical neurons: release vasoconstrictor neurotransmitters e.g. catecholamines (A + NA)
Dopaminergic neurons: produce vasoconstriction (localised effect related to increased brain activity)

Question 9

What feature do capillaries in the brain have that allow them to contract?

Answer 9

Surrounded by pericytes:

a type of brain macrophage that have several functions e.g. contractile, immune function, transport properties

Question 10

What do the dopaminergic neurons affecting cerebral blood flow innervate?

Answer 10

Pericytes around capillaries + smooth muscle around arterioles

Question 11

Dopaminergic neurons cause contraction of pericytes via which receptors?

Answer 11

Aminergic + serotoninergic neurons

Question 12

Name 7 chemical factors that increase blood flow to particular tissues.

Answer 12

CO2
NO
pH
Anoxia 
Adenosine 
K+
Other (e.g. kinins, prostaglandins, histamine, endothelins)

Question 13

How does change in pH affect blood flow?

Answer 13

The lower the pH (the higher the H+ concentration) the more the vessel vasodilates, resulting in increased blood flow

Question 14

Describe how carbon dioxide indirectly causes vasodilation in the cerebral vessels.

Answer 14

H+ ions can’t cross the BBB, but CO2 can
CO2 moves from the blood through the BBB into the smooth muscle cells
Within the smooth muscle cells, in the presence of carbonic anhydrase, CO2 reacts with water to form bicarbonate + H+ ions
Internally generated H+ ions within the smooth muscle cells cause smooth muscle relaxation (vasodilation)

Question 15

Where is CSF produced?

Answer 15

Choroid plexus: specific cells associated with the ventricles (particularly the lateral ventricles)

Question 16

What name is given to parts of the brain that receive blood flow like anywhere else but do NOT have a BBB?

Answer 16

Circumventricular organs

Question 17

Describe the passage of CSF through the ventricular system.

Answer 17

CSF produced by specialized ependymal cells of the choroid plexus (mainly in lateral ventricles)
From lateral ventricles, goes through interventricular foramina to 3rd ventricle
Then flows down the cerebral aqueduct to 4th ventricle
Enters subarachnoid space (via medial + lateral apertures)
Drains back into venous system via arachnoid granulations

Question 18

What is the volume of CSF in a normal person?

Answer 18

80-150 mL

Question 19

What is the volume of CSF formed per day?

Answer 19

450 mL/day

Question 20

State 3 functions of the CSF.

Answer 20

Protection (chemical + physical)
Nutrient provision to neurons
Transport of molecules

Question 21

Describe the structure of the blood-brain barrier. Which cells are involved?

Answer 21

Capillaries in the brain have endothelial cells with very tight junctions so there is tight control of what can pass through the walls
Capillaries are also surrounded by pericytes with end-feet of astrocytes running along the capillary wall

Question 22

What type of molecule can cross the blood-brain barrier easily?

Answer 22

Lipophilic molecules

Question 23

How do water and glucose cross the blood-brain barrier?

Answer 23

Water: aquaporin channels
Glucose: GLUT-1 transporters

Question 24

Name 3 circumventricular organs.

Answer 24

Median eminence region of the hypothalamus
Subfornical organ
Organum vasculosum of the lamina terminalis

Question 25

State 4 components that have a lower concentration in the CSF than the plasma.

Answer 25

K+
Ca2+
Amino acids
Bicarbonate

Question 26

State 2 components that have a higher concentration in the CSF than the plasma.

Answer 26

Mg2+

Cl-

Question 27

How is the osmolarity different between the CSF and the plasma?

Answer 27

Osmolarity is the same

Question 28

How is the pH different in the CSF compared to the plasma?

Answer 28

CSF is slightly more acidic

Question 29

What happens if cerebral blood flow is interrupted for a) 4 seconds, b) few minutes?

Answer 29

4 seconds: Unconsciousness

Minutes: Irreversible damage

Question 30

What is syncope? What is it a common result of? List 4 common causes

Answer 30

Fainting
Results from reduced blood supply to brain
Low BP, Postural changes, Vaso-Vagal attack, Sudden pain

Question 31

What happens if BP rises above the auto regulatory pressure range?

Answer 31

Increased flow can lead to swelling of brain tissue which isn’t accommodated by the “closed” cranium
Intracranial pressure rises

Question 32

Describe the pattern of vascularisation in CNS tissues

Answer 32

Arteries enter CNS tissue as branches of surface Pial vessels
Branches penetrate into brain parenchyma to form capillaries which drain into venues + veins into surface pial veins

Question 33

What does high protein content in CSF suggest?

Answer 33

Infection

Damage allowing plasma protein to enter CSF

Question 34

How does the BBB protect the brain from infection?

Answer 34

Hydrophilic solutes can’t cross the BBB.

Blood borne infectious agents may have reduced entry into CNS tissue

Question 35

Describe the capillaries in circumventricular organs. What is the function of these regions?

Answer 35

Fenestrated (leaky)

Sample composition of plasma/ secretion into circulation

Question 36

Why are 1st generation antihistamines no longer used? What has replaced them?

Answer 36

They were hydrophobic, so could cross the BBB- made people drowsy.
Now we use polar drugs that can’t cross the BBB

Question 37

How do we raise the levels of dopamine in the brain in Parkinson’s disease, when dopa decarboxylase converts L-DOPA in peripheral tissues?

Answer 37

Co-administer L-DOPA with Carbidopa (DOPA decarboxylase inhibitor which cannot cross the BBB)
Thus L-DOPA can be converted to dopamine in the brain