Blood flow to the brain and regulation

Question 1

Flow rate to the brain

Answer 1

55ml/100g tissue/min

Question 2

what reduction of blood flow causes impaired brain function?

Answer 2

> 50%

Question 3

syncope

Answer 3

interruption of blood flow for 4 seconds will knock someone unconscious

a few minutes and irreversible brain damage occurs

Question 4

glucose usage of the brain

Answer 4

the brain uses a vast majority of glucose

it can’t store, synthesise or utllitilise other sources of energy except ketones at times of starvation

Question 5

what glucose levels causes unconsciousness?

Answer 5

2mM

eventually into coma and then death

Question 6

what is the MABP range that CBF is auto regulated at (total control)?

Answer 6

60-160 mmHg

below and above this range, auto regulation is not possible

Question 7

How does vascular smooth muscle affect BP?

Answer 7

higher BPs due the SM contraction

lower BPs due the SM relaxation

Question 8

why is blood supply changed locally?

Answer 8

the brain activity determines the oxygen consumption and glucose demands. Local changes in flow are required

Question 9

what enables local auto-regulation to the brain?

Answer 9

1) neural control

2) chemical control

Question 10

how can local changes to blood flow be visualised?

Answer 10

PET scans

fMRI (functional)

Question 11

what are the features are involved in the local neural auto regulation of CBF?

Answer 11

• sympathetic nerve
• PNS facial nerve
• central cortical neurones
• dopaminergic neurones

Question 12

effect of sympathetic nerve on neural control of CBF?

Answer 12

Vasoconstriction when MABP is high

Question 13

effect of PNS facial nerve on neural control of CBF?

Answer 13

slight vasodilation

Question 14

effect of central cortical neurones on neural control of CBF?

Answer 14

release vasoconstrictors

e.g. catecholamines

Question 15

effect of dopaminergic neurones on neural control of CBF?

Answer 15

local vasoconstrictive effects

Question 16

what cause the contraction of pericytes (Brain macrophages)?

Answer 16

aminergic and serotininergic receptors

Question 17

vascularisation of CNS

Answer 17

arteries from Pia mater 
go into brain tissue 
branch to form capillaries 
they drain into veins --> pial vessels 
no neurone is more than 100 micrometers from a capillary

Question 18

what features are involved in the chemical control of CBF?

Answer 18

• CO2 (indirect)
• pH
• NO
• K+
• Adenosine
• Anoxia
• Kinins, prostaglandins, histamine

all vasodilators

Question 19

the effect of CO2 on cerebrally arterial vasodilation?

Answer 19

H+ increase in blood due to CO2 (decreases pH)
VSMC constrict to cause vasoconstriction

H+ is derived from CO2 reacting with carbonic anhydrase and water to form bicarbonate and H+. It can also come form neural metabolic activity

Question 20

what produces CSF?

Answer 20

choroid plexus (modified ependymal cells lining the ventricles)

Question 21

flow pathway of CSF

Answer 21

• choroid plexus lining ventricles
• secrete into lateral ventricles
• into 3rd ventricle via interventricular foramen
• into 4th ventricle via aqueduct
• into subarachnoid space via central canal
• or into cerebellar space via medial and lateral apertures

Question 22

what is the volume of CSF produced in a day?

Answer 22

80-150 ml

Question 23

what are the functions of CSF?

Answer 23

protective
nutritional
transport

Question 24

CSF compared to plasma

Answer 24

similar pH and osmolarity
very low protein levels
different potassium, magnesium , calcium ion and AA concentrations to plasma

Question 25

how is protein concentration in CSF used to identify possible bacterial infection?

Answer 25

- normally very low protein content in CSF | - infection is indicated with higher concentration of protein present in CSF

Question 26

what are the 3 types of capillaries based on cell wall?

Answer 26

continuous, fenestrated, sinusoidal (e.g. hepatocytes)

Question 27

characteristics of BBB capillaries?

Answer 27

- extensive tight junctions at endothelial cell-cell contact zones (reduce leakage) - as you get deeper, the less permeable it gets up to the BBB proper - uses transcellular vesicular transport - pericytes closely adherent to capillaries to maintain function and integrity of the capillaries - covered in "end feet" form astrocytes to help maintain its properties

Question 28

what do the tight junctions of the BBB enable it to do?

Answer 28

- control the exchange of large or hydrophilic solutes e.g. glucose, AA, antibiotics - It uses specific transporters for these - prevents infectious agents entering CNS tissue (infections tend to infect the meninges instead whose vessels aren't part of the BBB) - lipophilic molecules freely pass the brain meninges vulnerable to infection as vessels are not protected by BBB

Question 29

how are lipophobic molecules transports across BBB?

Answer 29

water via aquaporins glucose via GLUT-1 amino acids via 3 transporters electrolytes via specific transporters

Question 30

examples of circumventricular organs (CVOs)

Answer 30

``` area postrema (CTZ) subfornical organ pituitary stalk median eminence pineal gland (SCN input) ```

Question 31

what are circumventricular organs?

Answer 31

places where the capillaries lack BBB properties as a necessity.

Question 32

circumventricular capillaries, why are they fenestrated?

Answer 32

fenestrated | required as CVOs need to sample blood or secrete molecules into the blood itself

Question 33

example of CVOs that sample blood or secrete into blood

Answer 33

posterior pituitary secretes | area postrema samples

Question 34

clinical importance of BBB

Answer 34

some drugs can't enter the brain at all whilst others enter very readily causing unwanted effects "old fashioned" H1-channel blockers were hydrophobic so entered the brain readily and caused drowsiness second gen antihistamines are hydrophilic/polar so do not cross to BBB so no drowsiness occurs

Question 35

how is Parkinsons Disease treated?

Answer 35

treatment of PD involves raising dopamine levels in the brain: LEVODOPA (+ carbidopa) - dopamine itself ,however, does not cross the BBB so can't be administered peripherally so its precursor is used

Question 36

how is the problem of dopamine administration in PD overcome

Answer 36

L-Dopa can cross the BBB - but it is broken down peripherally so Carbidopa is co-administered (a DOPA-decarboxylase inhibitor) L-Dopa therefore "survives" and crosses the BBB while Carbidopa doesn't cross the BBB itself

Question 37

treatment of PD (drugs)

Answer 37

L-dopa | carbidopa