cerebral blood flow regulation and the BBB Flashcards
what is the blood flow to the brain *
high - 55ml/100g tissue per min
oxygen consumption of the brain *
high
what happens if the blood flow is reduced by >50% *
insufficient O2 delivery
impaired function
CBF
cerebral blood flow
effect of CBF interrupted for 4seconds and a few mins *
4 sec - unconsciousness
mins - irreversible damage
describe syncope *
manifestation of reduced blood supply to the brain
caused by low bp, postural changes, vaso-vagal attack (trauma/shock prevent heart pumping as fast as should - syncope), sudden pain, emotional shock - all casue temporary interruption or reduction of blood flow to brain
describe the glucose supply to brain *
normally more than enough via blood
vital because brain cant store, synthasise or use anyother source of energy
however during starvation ketones can be used
describe hypoglycaemia and brain function *
insulin dependant diabetic people become disorientated, slurred speech and impaired motor function when blood sugar levels drop
if glucose conc goes from 4mM (normal fasting levels) to 2mM it causes unconsciousness, coma, death
why is it important fro the CBF to be controlled *
because of constant need by brain for O2 and glucose
what 2 branches of mechanisms regulate CBF *
mechanisms affecting total blood flow - big arteries feeding into the brain
mechanisms which relate activity to the requirement in specific brain regions by altered localised blood flow
what is the process of total cerebral blood flow control *
autoregulation - between MABP 60-160mmHg (systemic blood flow)
describe autoregulation of the CBF *
over a wide range of arterial pressures - arteries/arterioles dilate or contract to maintain blood flow
this is because the cerebral vascular SM is stretch sensitive they detect stretch or relaxation in response to BP - contracts at high pressure and dilates at low bp (more blood flow to compensate for the lower bp)
what happens either side of the autoregulatory pressure range *
below - insufficient supply - compromised brain function
above - increased flow = swelling of brain tissue - not accommodated by closed cranium - increase in intracranial pressure - dangerous. also more fluid pushed into tissues - oedema = increase in interstitial body fluid
why is local autoregulation of CBF required *
local brain activity determines local demands
what mechanisms are used to control local CBF *
local autoreg: neural control and chemical control
describe the pattern of vascularisation in the CNS tissues *
arteries enter the CNS tissue from branches of the surface pial vessels (penetrating arterioles) they penetrate into brain parenchyma and branch to form capillaries which coalesce and drain into venules - veins - drain into surface pial veins
CNS densely vascularised - no neuron >100um from capillary
list and describe the neural factors that regulate local CBF *
sympathetic nerve stimulation - to main cerebral arteries- vasoconstriction, control blood supply - only happen when arterial bp high
parasympathetic nerve stimulation - facial nerve, produce slight vasodilation - increase blood supply
cranial cortical neurons - release a variety of vasoconstrictor NT eg catecholamines (A/NA)
dopaminergic neurons - vasoconstriction
neural control on global brain flow is not well defined and its importance is uncertain
describe doperminergic neurons and their local effect on CBF *
they innervate penetrating arteriole sm and pericytes around capillaries - cause contraction
may participate in diversion of cerebral blood
may cause contraction of pericytes via aminergic and serotoninergic receptors
describe how CBF is regulated by chemical factors *
CO2 - indirect vasodilator
pH (H+, lactic acid etc) - vasodilator
NO, K+, adenosine, anoxia - vasodilators
kinins, prostaglandins, histamine and endothelins
the BBB
adenosine
anoxia
describe the effect of pCO2 on CBF *
pCO2 = 40 normally - increase in pCO2 = sharp increase in CBF
CO2 in blood/from metabolic activity generates H+ using carbonic anhydrase in surrounding neural tissue and in sm cells
H+ cant get across the BBB - CO2 leaves blood and makes H+ in sm, H+ enters sm from surrounding neural tissue
increased H= means reduced pH = relaxation of sm= more blood flow ?
how can you see local blood changes in CNS
using PET and functional MRI (fMRI) scan
areas working harder make more CO2 = vasodilation = more blood flow which is shown on scans
what are arachnoid granulations
opening between ventricular system and CSF to outside of brain - back into the plasma and vessels in arachnoid mater
where is CSF
in the spinal canal and the ventricular system
brain basically floating in CSF - protective ?
describe the production of CSF
ventricles, canals and aqueducts are lined by ependymal cells - often ciliated
in some regions of the ventricles the lining is modified to form branched villus structures - the choroid plexus
here the capillaries are leaky but ependymal cells have tight junctions with lots of transporters - CSF is secreted into ventricles and it circulates ?
volume of CSF
80-150 ml
function of CSF
protection - physical and chemical
nutrition of neurons
transport molecules
pathway of CSF
lateral ventricles - 3rd vent through intraventricular formina, 4th ventricle through cerebral aqueduct, into subarachnoid space by the medial and lateral apertures
describe how the composition of CSF differs from plasma
similar Na
plasma more K
similar pH
CSF LESS aa - if CSF has high aa sign of infection, or damage
what is the result of the BBB *
brain is isolated from systemic circulation
why is it important to have a BBB *
neuronal activity is highly sensitive to the composition of local environment - so CNS must be protected from local fluctuations in blood
protect brain from potentially harmful substances in blood
solutes have to go through cells rather than between them eg aa, glucose, AB, toxins and others - BBB can control exchange using transporters
lipophilic molecules eg O2, CO2, alcohol anaesthetics can cross the BBB - cross by diffusion
describe continuous capillaries
moderately leaky between clefts between the endothelial lining
describe fenestrated capillaries
endothelial have holes - endocrine
describe sinusoid capillaries
sinusoidal/bone marrow
basement membrane has holes
how much plasma leaks out of capillaries
8L a day
therefore cells are bathed in interstitial fluid
describe the capillaries in the BBB *
local env cause vessels to be BBB like - BBB properties increase in deeper vessels
have extensive tight junctions - reduce the solute and fluid leak across capillary wall
little transcellular vesicle transport
pericytes maintain capillary function and integrity, - peripheral capillaries have sparse pericytes, BBB have dense coverage
BBB are covered by end feet from astrocytes - produce growth and differential factors
effect of BBB on infections *
blood borne agents have reduced entry into CNS therefore affect meninges
some evidence suggests removing BBB and letting immune cells in CNS can help fight some infections.
transporter mechanisms into the CNS *
water - aquaporins - AQP1/4
glucose - GLUT 1 (Ab against this prove capillary is BBB)
aa - 3 different transporters
electrolytes - specific transporter mechanisms
describe circumventricular organs *
close to ventricles - lack BBB
fenestrated capillaries - ventricular ependymal cells are much tighter than in other areas - limiting exchange between them and the CNS
function of the CVOs *
they are present to secrete into the circulation or sample the plasma
posterior pituitary and median eminence secrete hormones
area postrema samples plasma for toxins - induce vomiting
others sense electrolytes and regulate water intake
how can BBB break down *
BBB breaks down in pathological states - inflammation, infection, trauma, stroke
pharmacology and BBB *
need to consider if want drug to be able to get into brain or not
antihistamines and the BBB *
old H1 blockers were hydrophobic - could diffuse across BBB - histamine involved in wakefulness and alertness - they made people drowsy - today used as sleep aids
new antihistamines are polar - hydrophilic attachment on it - don’t cross BBB, don t cause drowsiness
BBB and treatment of Parkinson’s *
treatment is raising dopamine in brain - dopamine cant cross the BBB so administer L-DOPA - look like aa so cross BBB via aa transporter and L-DOPA is converted to dopamine in brain by DOPA decarboxylase
problem is DOPA decarb is outside brai to so need to coadmin DOPA decarb inhibitor - carbidopa to stop conversion out of brain, carbidopa is polar so cant cross BBB so doesn’t affect the conversion in brain
what are pericytes
cells that wrap around capillaries
have diverse activities - immune function, transport properties and contractile properties
define the BBB *
the mechanism that con trolls the passage of molecules from the blood into the CSF and tissue spaces surrounding the brain
