blood brain barrier and cerebral blood flow

Question 1

blood flow to brain in numbers and when it is insufficient

Answer 1

function impaired whenever blood flow reduced by 50% unconciousness occurs if cerebral blood flow disturbed in 4 secs, and irreversible damage occurs after a few min

Question 2

syncope and causes

Answer 2

fainting due to temporary reduced blood supply to brain due to low BP, postural hypotension, vaso-vagal attack due to trauma

Question 3

effects of hypoglycaemia

Answer 3

this causes reduced glucose delivery= slurred speech and lack of motor function, and if conc falls below 2mM= unconciousness

Question 4

how is cerebral blood flow regulated

Answer 4

by mechanisms affecting total cerebral blood flow (large arteries) mechanisms changing localised blood flow to requirement of certain brain regions

Question 5

total cerebral blood flow DIAGRAM

Answer 5

it’s autoregulated ie kept the same between 60 and 160 MABP, anything lower or higher changes blood flow

Question 6

how total flow autoregulated

Answer 6

arteries/arterioles dilate/contract due to the stretch-sensitive cerebral vascular smooth muscle ( has stretch receptors) which contracts at high BP

Question 7

issue of too much blood flow

Answer 7

swelling of blood flow in closed cranium= increased intracranial pressure

Question 8

neural local regulation of cerebral blood flow

Answer 8

total flow affected by SNS and PNS, local flow affected by dopaminergic neurones which cause vasoconstriction they dose this by innervating arterioles and pericytes (cells surrounding capillaries), diverting blood to areas of high activity

Question 9

pattern of vascularisation in CNS DIAGRAM

Answer 9

main vessels are in the Pia, and branch to penetrate into tissues, and capillaries then drain into venules, then pial veins neurones are always less than 100um from a capillary

Question 10

regulation of local blood flow by chemical factors including CO2 effect DIAGRAM

Answer 10

vasodilators like NO, K and adenosine, but main two are CO2 (indirect), thus pH (ie H+) pCO2 normally 40. but small increase in PCO2 leads to sharp rise in flow

Question 11

mechanism of vasodlation due to CO2 DIAGRAM

Answer 11

H+ ions in blood can’t cross BBB, but CO2 reacts with water in neural tissue to form H+, which can enter smooth muscle CO2 from blood can cross BBB,ts in smooth muscle to produce more H+, hence elevated H+ causes relaxation of the muscle cells= more blood flow

Question 12

detecting local changes to blood flow

Answer 12

PET and functional MRI shows where brian activity is highest ie where most CO2 produced

Question 13

fluid compartments of brain DIAGRAM

Answer 13

brain surrounded by CSF produced by the ventricles- arachnoid granulations are openings between plasma and CSF, where CSF can be exchanged

Question 14

ventricles of brain and its lining DIAGRAM

Answer 14

ventricles, aqueducts and canals are lined with ependymal cells, yet in ventricles the lining is modified to form villi, known as choroid plexus

Question 15

formation of CSF

Answer 15

choroid plexus has leaky capillaries with ependymal cells that have tight junctions 150ml CSF secreted into lateral ventricles, then 3rd via interventricular foramina, down cerebral aqueduct to 4th, then subarachnoid space- it then circulates

Question 16

functions of CSF

Answer 16

protection, neurone nutrition and transport of molecules

Question 17

composition of plasma vs CSF

Answer 17

CSF has similar pH and osmolarity, but more Mg and CL, yet lower K+ and Ca2+ has lower protein- if not could indicate infection or damage to vessels

Question 18

dye injected into body effect on brain and other organs and cause

Answer 18

will colourise all organs apart from brain due to BBB

Question 19

importance of BBB and level that BBB is at

Answer 19

activity of neurones very sensitive to local environment, so CSF must be protected from changes in composition of blood BBB at level of CNS capillaries

Question 20

capillaries and types

Answer 20

most abundant- there is continuous (fairly leaky), fenestrate (leaky) and sinusoid (very leaky with incomplete brain barrier- liver and bown marrow)

Question 21

pial vessels and BBB capillar properties DIAGRAM

Answer 21

vessels arise from pial vessels, and the deeper the vessel, the more it has properties of BBB capillaries, until BBB capillaries are reached, which have tight junctions and little leakage due to different interendothelial junctions

Question 22

other differenes between BBB and other capillaries

Answer 22

BBB covered in astrocytes to support neurones also have more pericytes (maintain capillary integrity)

Question 23

effect of BBB tightness

Answer 23

hydrophilic solutes can only go through using specific transporters (eg water via AQP, glucose via GLUT1), although lipophilic molecules like alcohol/anaesthetics can cross also, pathogens less likely to enter CNS tissue, hence meningitis most common, as that is on surface on brain rather than internal tissue

Question 24

circumventricular organs and function

Answer 24

areas close to ventricles with capillaries that don’t have BBB properties, but are leaky the ependymal lining however has tight junctions, hence compensating for leaky vessels, so exhcnage with CSF still limited, and they sample the plasma

Question 25

examples of CVO’s

Answer 25

posterior pituitary and median eminence secrete hormones into blood, so needs leaky vessels area postrema samples plasma for toxins, and causes vomiting

Question 26

breaking down of BBB

Answer 26

breaks down due to infection, trauma, stroke etc., and if dye injected, area where BBB broken down will show colour, as it’s leaked into brain tissue

Question 27

antihistamines

Answer 27

H1 (receptor) blockers are hydrophobic so can cross BBB, but histamine important in alertness, so can cause drowsiness hence new antihistamines are polar to prevent getting into break

Question 28

effect of BBB on parkisons disease treatment

Answer 28

increasing dopamine levels is needed, but dopamine can’t cross BBB, so L-DOPA given, which can cross via a.a transporter, and then be broken into dopamine via DOPA decarboxylase however, there is lots of DOPA decarboxylase in peripheral circulation, hence L-DOPA broken down before it gets to CVS therefore, carbidopa given (DOPA decarboxylase inhibitor), which can’t cross BBB, hence it only breaks down enzyme in peripheral circulation