Cerebral Blood flow Central Nervous System

2. CEREBRAL CIRCULATION

3. Objectives
 After completing this session, students should be able to:
 Describe briefly about Cerebral Blood Flow.
 Explain about Regulation of Cerebral Blood Flow.
 Differentiate the Factors affecting Cerebral Blood
Flow.
 Differentiate the Problems of Cerebral Blood Flow.
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4. CEREBRAL CIRCULATION
The brain receives its blood
supply from four main
arteries: the two
internal carotid arteries
and the two vertebral
arteries. The clinical
consequences of vascular
disease in the cerebral
circulation is depend upon
which vessels or
combinations of vessels are
involved.

6. CEREBRAL CIRCULATION
The Circle of Willis is a grouping of arteries near the base of
the brain which is called the Arterial Circle of Willis.
It is named after an English physician named Thomas Willis,
who discovered it and then published his findings in his
1664, a seminal peace on the inner workings of the brain
entitled, Cerebri anatomi (from the Latin for “Anatomy of
the Brain”).

7. CEREBRAL CIRCULATION

9. Cerebral Microcirculation
 Capillary density in grey matter is 4 times higher
than white matter.
 Pre-capillary vessels divide and reunite to form
anastomotic circle called as Circle of Duret.
 They are highly tortuous and irregular.
 Velocity of RBC’s is higher in these capillaries.
 To facilitate transfer of substrate and nutrients
RBC’s have to traverse longer distance via these
capillaries
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10. Cont.
 The brain capillaries are much less “leaky” than are
capillaries in other portions of the body.
 Capillaries in the brain are surrounded by “glial feet,”
which provide physical support to prevent
overstretching of the capillaries in the event of
exposure to high pressure.
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11. Cont.
 Cerebral capillaries:
 are non-fenestrated & with tight
junctions between endothelial
cells, except the capillaries in
choroid plexus which are
fenestrated.
 Few vesicles in endothelial cells
 Limited diffusion & vesicular
transport
 Surrounded by end feet of
astrocytes; induce tight junctions in
endothelial cells
 Anatomic basis for BBB.
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Figure 7 - Cerebral
capillary

12. Blood Brain Barrier (BBB)
 Continuous non-fenestrated capillaries make up BBB.
 Tight junctions between capillary endothelial cells.
 Paucity of the vesicles in the endothelial cytoplasm.
 Presence of numerous carrier-mediated & active transport
mechanisms in cerebral capillaries.
 The blood-CSF barrier is due to tight junctions in choroid
plexus endothelial cells.
 The capillaries in choroid plexus are fenestrated with no
tight junctions.
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13. Cont.
 Properties of BBB
 Only few substances can freely diffuse through
BBB.
 CO2, O2, water & free forms of steroid hormones.
 H+ & HCO- only slowly penetrate the BBB.
 Proteins, polypeptides & protein bound forms of
hormones do not cross BBB.
 Glucose is transported by GLUT1 transporter.
 Active transporters are also present
 various ions (Na+ - K+ -2Cl- co transporter )
 thyroid hormones, organic acids, choline, nucleic acid precursors,
amino acids etc.
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14. Significance of BBB
 It maintains the homeostasis in CNS.
 Protects the brain from endogenous &
exogenous toxins.
 Prevents the escape of neurotransmitters
into general circulation. 14

15. Cerebrospinal Fluid (CSF)
 clear, colorless body fluid found within the tissue that
surrounds the brain and spinal cord of all vertebrates.
 Produced by specialized ependymal cells in the choroid
plexus of the ventricles of the brain
 Absorbed in the arachnoid granulations.
 There is about 125 mL of CSF at any one time, and about
500 mL is generated every day.
 occupies the subarachnoid space and the ventricular
system around and inside the brain and spinal cord.
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16. Cont.
 A sample of CSF can be taken
from around the spinal cord
via lumbar puncture.
 CSF circulates within
the ventricular system of the
brain.
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Figure 9 - Distribution of CSF

17. Cont.
 CSF is derived from blood plasma and is largely similar to
it except that CSF is nearly protein-free compared with
plasma and has some different electrolyte levels.
 Due to the way it is produced, CSF has a higher chloride
level than plasma, and an equivalent sodium level.
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18. Significance of CSF
1. Buoyancy: The actual mass of the human brain is about
1400–1500 grams; however, the net weight of the brain
suspended in CSF is equivalent to a mass of 25-50 grams.
2. Protection: CSF protects the brain tissue from injury when
jolted or hit, by providing a fluid buffer that acts as a shock
absorber from some forms of mechanical injury.
3. Prevention of brain ischemia: The prevention of brain
ischemia is aided by decreasing the amount of CSF in the
limited space inside the skull. This decreases total
intracranial pressure and facilitates blood perfusion.
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19. Cont.
4. Homeostasis: allows for regulation of the distribution of
substances between cells of the brain, and neuroendocrine
factors, to which slight changes can cause problems or
damage to the nervous system.
5. Clearing waste: allows for the removal of waste products
from the brain, and is critical in the brain's lymphatic
system, called the glymphatic system.
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20. Venous Drainage of the Brain
 thin-walled & valveless.
 Pierce arachnoid &
meningeal layer of dura
(subdural space)
 end in the nearest dural
venous sinuses 
ultimately  IJVs.
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Figure 10 – MRI Venography of Brain

21. Cont.
 Superior Cerebral Veins:
 are on superolateral surface of the brain
 drain into the superior sagittal sinus.
 Inferior & Superficial Middle Cerebral Veins:
 from inferior, postero-inferior & deep aspects of
cerebrum
 drain into cavernous, straight, transverse & superior
petrosal sinus.
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22. Cont.
 The Great Cerebral Vein:
 is a single, midline vein formed inside the brain by the
union of two internal cerebral veins;
 merges with inferior sagittal sinus to form straight sinus.
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23. Cont.
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Figure 11 - Venous Drainage of the Brain
Internal Jugular
Veins
Cerebral Venous
sinuses
Cerebral Veins
Venous Drainage:

24. Cerebral Blood Supply
 Brain accounts for 2% of body weight yet
requires 20% of resting oxygen consumption.
 O2 requirement of brain is 3 – 3.5
ml/100gm/min & in children it goes higher up
to 5 ml/100gm/min.
 That’s why brain requires higher blood
supply 55ml/100gm/min is the rate of blood
supply.
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25. Cont.
 Brain is having the highest energy requirement by mass.
 Even though brain constitutes less than 2% of body weight,
the adult brain receives 15% of resting cardiac output and
uses 20% of the total energy produced by the body.
 In children, up to 50% of the energy consumption of the
body is being accounted for by the brain.
 Much of this energy allocation is devoted to activities
connected to neural signaling
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26. Cont.
 Cerebral blood flow = 55 to 60 ml/100 g
brain tissue/min
 Cerebral blood flow (gray matter) = 75
ml/100 g brain tissue/min
 Cerebral blood flow (white matter) = 45
ml/100 g brain tissue/min
 Oxygen consumption whole brain = 46
ml/min
 Oxygen consumption whole brain = 3.3
ml/100 g/min
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27. Factors Regulating CBF
 Cerebral Perfusion Pressure (CPP)
 Cerebral Vascular Resistance (CVR)
 Hemodynamic Autoregulation
 Metabolic mediators and chemo-regulation
 pCO2
 pO2
 H+ concentration
 Neural control: sympathetic discharging
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28. Cerebral Perfusion Pressure
 It is the net pressure gradient causing blood flow to the
brain.
CPP = MAP – CVP
CVP = ICP
CPP = MAP – ICP
 CPP is directly related to CBF: {Increase CPP causes
increase CBF}
 Any factor affecting MAP or ICP will affect the CBF.
 CBF is maintained normal over a wide range of MAP by
‘Autoregulation.’
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31. Cerebral Vascular Resistance (CVR)
 CVR = (8.η.L)/(π.r4)
 Resistance of the cerebral circulation is
subject to dynamic changes in the contractile
state of vascular smooth muscle (VSM).
 Most resistance at the level of the
penetrating precapillary arterioles.
 However, up to 50% of total CVR arises from
smaller pial arteries (150 to 200 μm in
diameter) and arteries of the circle of Willis.
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32. Autoregulation
 Maintains constant blood flow to the
brain despite wide fluctuations in CPP.
 It is the inherent property of resistance
vessels.
 Increase BP  vasoconstriction
 Decrease BP  vasodilation
 Maintains blood flow in the range of 50
– 150 mm Hg CPP.
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33. Cont.
 Proposed mechanisms include:
 Myogenic Mechanism: Intrinsic changes in vascular smooth
muscles (VSM) tone.
 Endothelial Mechanism: the release of a variety of
vasoactive substances from the endothelium.
 Neurogenic Mechanism: periadventitial nerves in response
to changes in transmural pressure.
 Metabolic Mechanism: metabolic activity of astrocytes and
neurons for regulating CBF.
 Pure changes in perfusion pressure involve myogenic
response in VSM (Bayliss effect).
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34. Cont.
 Venous physiology:
 Venous system contains most of the cerebral blood volume.
 Slight change in vessel diameter has profound effect on
intracranial blood volume.
 Less smooth muscle content
 Less innervation than arterial system
 But evidence of their role is less.
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35. Metabolic & Chemical
Regulation
 Cerebral metabolic demand is the main regulator of cerebral
blood flow,
 It occurs automatically, probably in response to the
abundance or deficit of various local factors - mainly
metabolic byproducts and metabolic substrates:
 Carbon dioxide concentration in the brain parenchyma
 Low oxygen
 pH of the blood
 When cerebral metabolic demand is high – CBF will be
higher at any given Perfusion Pressure because CVR will
decrease.
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40. Cont.
 CO2: (Hypercapnia) - promotes increased CBF at any
given perfusion pressure.
 PaCO2 exerts profound effects on CBF, range of 30 to 50
mm Hg.
 At normal conditions CBF has linear relationship with CO2.
 For every 1 mm Hg change of PaCO2 CBF changes by 2–
4%.
 When alterations in PaCO2 have been sustained for 3 to 5
hours, there is an adaptive return of CBF toward baseline
levels.
 Hypercapnia combined with hypoxia has a magnified
effect on CBF. 40

41. Cont.
1. Change of periarteriolar pH leads to a change in NO
synthase activity;
2. NO synthase catalyzes intracellular cGMP production;
3. cGMP acts as a second messenger to affect a change in
intracellular ionized Ca+2 availability
4. The upshot of all this is a decreased CVR
5. If the resistance is decreased but the pressure difference
remains the same, the flow increases.
6. The increase in flow is by about 1-2ml/100g/min for every
1mmHg increase in CO2. Conversely, blood flow decreases as
CO2 decreases.
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42. Cont.
 Hydrogen ions: induce cerebral vasodilation in
proportion to their concentration in the cerebral
blood.
 Any substance that increases the acidity of the
brain, and therefore the H+ concentration,
increases CBF; such substances include lactic acid,
pyruvic acid, and other acidic compounds that are
formed during the course of metabolism.
 CO2 combines with water to form carbonic acid,
which partially dissociates to form H+
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43. Cont.
 Oxygen:
 Elevated inspired O2 concentrations elicit CVR and
decrease CBF.
 Within physiological range PaO2 has no effect on CBF.
 Hypoxia is a potent stimulus for arteriolar dilatation.
 At PaO2 50 mmHg, CBF starts to increase and at PaO2 30
mm Hg, it doubles.
 Hypoxia elicits VSM relaxation by inhibiting sarcoplasmic
Ca2+ uptake and stimulating the production of EDRF.
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45. Neural control
 The cerebral circulation has dense sympathetic innervation.
 Under certain conditions, SNS stimulation can cause marked
constriction of the large and intermediate-sized cerebral
arteries.
 Under many conditions in which the SNS is moderately
activated.
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46. CBF Problems
 Stroke: a blood clot blocks the flow of blood in your cranial
artery.
 Cerebral hypoxia: part of the brain doesn’t get enough
oxygen.
 cerebral hemorrhage: internal bleeding in the cranial
cavity.
 Cerebral edema: swelling that occurs due to an increase of
water in your cranial cavity. 46