Blood flow to the brain and regulation Flashcards
Flow rate to the brain
55ml/100g tissue/min
what reduction of blood flow causes impaired brain function?
> 50%
syncope
interruption of blood flow for 4 seconds will knock someone unconscious
a few minutes and irreversible brain damage occurs
glucose usage of the brain
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
what glucose levels causes unconsciousness?
2mM
eventually into coma and then death
what is the MABP range that CBF is auto regulated at (total control)?
60-160 mmHg
below and above this range, auto regulation is not possible
How does vascular smooth muscle affect BP?
higher BPs due the SM contraction
lower BPs due the SM relaxation
why is blood supply changed locally?
the brain activity determines the oxygen consumption and glucose demands. Local changes in flow are required
what enables local auto-regulation to the brain?
1) neural control
2) chemical control
how can local changes to blood flow be visualised?
PET scans
fMRI (functional)
what are the features are involved in the local neural auto regulation of CBF?
- sympathetic nerve
- PNS facial nerve
- central cortical neurones
- dopaminergic neurones
effect of sympathetic nerve on neural control of CBF?
Vasoconstriction when MABP is high
effect of PNS facial nerve on neural control of CBF?
slight vasodilation
effect of central cortical neurones on neural control of CBF?
release vasoconstrictors
e.g. catecholamines
effect of dopaminergic neurones on neural control of CBF?
local vasoconstrictive effects
what cause the contraction of pericytes (Brain macrophages)?
aminergic and serotininergic receptors
vascularisation of CNS
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
what features are involved in the chemical control of CBF?
- CO2 (indirect)
- pH
- NO
- K+
- Adenosine
- Anoxia
- Kinins, prostaglandins, histamine
all vasodilators
the effect of CO2 on cerebrally arterial vasodilation?
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
what produces CSF?
choroid plexus (modified ependymal cells lining the ventricles)
flow pathway of CSF
- 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
what is the volume of CSF produced in a day?
80-150 ml
what are the functions of CSF?
protective
nutritional
transport
CSF compared to plasma
similar pH and osmolarity
very low protein levels
different potassium, magnesium , calcium ion and AA concentrations to plasma
how is protein concentration in CSF used to identify possible bacterial infection?
- normally very low protein content in CSF
- infection is indicated with higher concentration of protein present in CSF
what are the 3 types of capillaries based on cell wall?
continuous, fenestrated, sinusoidal (e.g. hepatocytes)
characteristics of BBB capillaries?
- 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
what do the tight junctions of the BBB enable it to do?
- 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
how are lipophobic molecules transports across BBB?
water via aquaporins
glucose via GLUT-1
amino acids via 3 transporters
electrolytes via specific transporters
examples of circumventricular organs (CVOs)
area postrema (CTZ) subfornical organ pituitary stalk median eminence pineal gland (SCN input)
what are circumventricular organs?
places where the capillaries lack BBB properties as a necessity.
circumventricular capillaries, why are they fenestrated?
fenestrated
required as CVOs need to sample blood or secrete molecules into the blood itself
example of CVOs that sample blood or secrete into blood
posterior pituitary secretes
area postrema samples
clinical importance of BBB
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
how is Parkinsons Disease treated?
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
how is the problem of dopamine administration in PD overcome
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
treatment of PD (drugs)
L-dopa
carbidopa
