blood brain barrier and cerebral blood flow Flashcards
blood flow to brain in numbers and when it is insufficient
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
syncope and causes
fainting due to temporary reduced blood supply to brain due to low BP, postural hypotension, vaso-vagal attack due to trauma
effects of hypoglycaemia
this causes reduced glucose delivery= slurred speech and lack of motor function, and if conc falls below 2mM= unconciousness
how is cerebral blood flow regulated
by mechanisms affecting total cerebral blood flow (large arteries) mechanisms changing localised blood flow to requirement of certain brain regions
total cerebral blood flow DIAGRAM
it’s autoregulated ie kept the same between 60 and 160 MABP, anything lower or higher changes blood flow
how total flow autoregulated
arteries/arterioles dilate/contract due to the stretch-sensitive cerebral vascular smooth muscle ( has stretch receptors) which contracts at high BP
issue of too much blood flow
swelling of blood flow in closed cranium= increased intracranial pressure
neural local regulation of cerebral blood flow
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
pattern of vascularisation in CNS DIAGRAM
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
regulation of local blood flow by chemical factors including CO2 effect DIAGRAM
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
mechanism of vasodlation due to CO2 DIAGRAM
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
detecting local changes to blood flow
PET and functional MRI shows where brian activity is highest ie where most CO2 produced
fluid compartments of brain DIAGRAM
brain surrounded by CSF produced by the ventricles- arachnoid granulations are openings between plasma and CSF, where CSF can be exchanged
ventricles of brain and its lining DIAGRAM
ventricles, aqueducts and canals are lined with ependymal cells, yet in ventricles the lining is modified to form villi, known as choroid plexus
formation of CSF
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
functions of CSF
protection, neurone nutrition and transport of molecules
composition of plasma vs CSF
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
dye injected into body effect on brain and other organs and cause
will colourise all organs apart from brain due to BBB
importance of BBB and level that BBB is at
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
capillaries and types
most abundant- there is continuous (fairly leaky), fenestrate (leaky) and sinusoid (very leaky with incomplete brain barrier- liver and bown marrow)
pial vessels and BBB capillar properties DIAGRAM
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
other differenes between BBB and other capillaries
BBB covered in astrocytes to support neurones also have more pericytes (maintain capillary integrity)
effect of BBB tightness
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
circumventricular organs and function
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
examples of CVO’s
posterior pituitary and median eminence secrete hormones into blood, so needs leaky vessels area postrema samples plasma for toxins, and causes vomiting
breaking down of BBB
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
antihistamines
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
effect of BBB on parkisons disease treatment
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
