Cerebral Blood Flow Regulation and The Blood Brain Barrier

Question 1

What are the proportions of blood flow to the brain

Answer 1

High 
55ml/100g tissue/min
15% of CO
2% of body weight 
20% oxygen consumption

Question 2

What happens when blood flow to the brain is reduced by more than 50%

Answer 2

Insufficient oxygen delivery

Function becomes significantly impaired

Question 3

What happens when CBF is interrupted

Answer 3

4 seconds - unconsciousness

minutes - irreversible brain damage

Question 4

Define syncope

Answer 4

Fainting

Manifestation of reduced blood supply to the brain

Question 5

What can cause syncope

Answer 5

Low blood pressure
Postural changes
Vaso-vagal attack 
Sudden pain
Emotional shock

Question 6

Why is the glucose supply to the brain vital

Answer 6

The brain cannot store, synthesise or utilise any other sources of energy (though in starvation ketones can be used)

Question 7

What occurs in hypoglycaemia

Answer 7

Disorientation, slurred speech, impaired motor function

Dangerous below 2mM

Question 8

What is CBF regulated by

Answer 8

Mechanisms affecting total cerebral blood flow

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

Question 9

What is the range of auto regulation for total CBF

Answer 9

between mean arterial blood pressures (MABP) of 60 and 160mmHg

Question 10

What occurs when the CBF is above the auto regulatory pressure range

Answer 10

Swelling of the brain in the cranium causes an increase in intracranial pressure

Question 11

What is the mechanism for changing total cerebral blood flow autoregulation

Answer 11

Arteries and arterioles dilate or contract to maintain blood flow
Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and vice versa

Question 12

What is local autoregulation

Answer 12

Local brain activity determines the local O2 and glucose demands

Question 13

What are the 2 mechanisms of local regulation of CBF

Answer 13

Neural and chemical

Question 14

Describe the pattern of vascularisation in the CNS tissues

Answer 14

Arteries enter the CNS tissue as branches of surface pial vessels (Pia mater)
These penetrate the brain parenchyma to form capillaries
These drain into venues and veins -> surface pial veins

Question 15

What are neural factors that regulate CBF

Answer 15

Sympathetic nerve stimualtion (main cerebral arteries) - vasoconstriction
Parasympathetic (facial) stimulation - vasodilation
Central cortical neurones - vasoconstriction on catecholamine release (A/NA)
Dopaminergic neurones - vasoconstriction

Question 16

What is the significance of dopaminergic neurones on CBF regulation

Answer 16

Innervate penetrating arterioles and pericytes around capillaries
Participate in the diversion of CB to high activity areas
Dopamine may cause contraction of pericytes via aminergic and serotoninergic receptors

Question 17

What are the chemical factors that regulate CBF

Answer 17

CO2
pH
NO
K+
Adenosine 
Anoxia 
Kinins, prostaglandins, histamine, endothelins
All vasodilate

Question 18

What is the effect of CO2 on CBF

Answer 18

As CO2 increases CBF increases (sigmoid)

Question 19

Explain how CO2 affects CBF

Answer 19

1. CO2 from blood or local metabolic activity generates H+ using carbonic anhydrase, as it cannot cross the BBB from the blood
2. low pH causes relaxation of the contractile smooth muscle
3. Vessels dilate
4. Increased blood flow

Question 20

How are local changes to CBF measured

Answer 20

Equates to increased neuronal activity

Imaged via PET scanning and functional MRI

Question 21

Where is CBF produced

Answer 21

Ependymal cells in the ventricles, aqueducts and canals that are modified to form the choroid plexus

Question 22

Describe the circulation of CSF

Answer 22

1. Lateral ventricles
   Cereberal hemispheres
2. 3rd ventricle (via inter ventricular foramina)
   Diencephalon
3. Cerebral aqueduct
   Midbrain
4. 4th ventricle
   Pons and medulla
5. Subarachnoid space (via medial and lateral apertures)

Question 23

What volume of CSF flows at one time

Answer 23

80-150ml

Question 24

What volume of CSF is produced each day and where

Answer 24

500ml

Question 25

What are the functions of CSF

Answer 25

Shock absorbing – protection from trauma Removes waste products from cellular metabolism Supplies neurones with nutrients (secondary to blood) Contains immune cells

Question 26

What is the clinical relevance of CSF not having protein

Answer 26

If protein is presence may be damage or a bacterial infection

Question 27

Describe the junctions of the blood brain barrier

Answer 27

Extensive tight junctions at the endothelial cell-cell contacts Reduces solute and fluid leak across the capillary wall Capillaries of the CNS parenchyma from the pial cells gain BBB properties the deeper they are

Question 28

Describe inter endothelial junctions of peripheral capillaries and BBB capillaries

Answer 28

BBB has much fewer tight junctions

Question 29

What are some difference between peripheral and BBB capillaries

Answer 29

Peripheral vessels have sparse pericyte coverage, BBB has a dense coverage BBB are covered with end feet from astrocytes

Question 30

Which substances are unable to cross the BBB but can cross the peripheral capillaries

Answer 30

Glucose, amino acids, many antibiotics, some toxins

Question 31

How does the BBB control exchange of substances

Answer 31

Specific membrane transporters (influx and efflux transporters)

Question 32

Where in the brain do blood-borne infectious agents mostly affect

Answer 32

The meninges as their vessels are not BBB, which reduces entry

Question 33

Give examples of hydrophilic substances that enter the CSF and how they do so

Answer 33

Water - AQP1, AQP4 Glucose - GLUT1 Amino acids - 3 transporters electrolytes - transporter systems

Question 34

Give examples of lipophilic substances that enter the CSF and how they do so

Answer 34

Oxygen, CO2, alcohol, anaesthetics | diffuse passively across the barrier down concentration gradient

Question 35

What are circumventricular organs

Answer 35

Capillaries that lack BBB properties Found close to ventricles Generally involved in secreting into the circulation

Question 36

What are the features of circumventricular organs

Answer 36

Capillaries are fenestrated and leaky Ventricular ependymal lining close to these areas are much tighter, limiting the exchange between them and CSF Requires access to the blood

Question 37

Give and example of how circumventircular organs use blood

Answer 37

Posterior pituitary and median eminence secrete hormones The area postrema samples the plasma for toxins, inducing vomiting Others are involved in sensing electrolytes and regulates water intake

Question 38

What is the clinical importance of the BBB

Answer 38

``` Breaks down in many pathological states Inflammation Infection Trauma Stroke ```

Question 39

Explain how antihistamines affect the brain

Answer 39

H1 blockers are hydrophobic and therefore can passively diffuse across the BBB Histamine usually aids wakefulness and alertness so antihistamines make people drowsy

Question 40

How does the BBB affect Parkinsons disease treatment

Answer 40

Key treatment involves increasing dopamine levels but dopamine cannot cross the BBB L-DOPA crosses the BBB via amino acid transporter and is converted to dopamine in the brain However, a lot of L-dopa is converted outside the brain and is therefore administrated with carpidopa to inhibit