Cerebral blood flow is tightly regulated to meet the high metabolic demands of the brain. Blood circulates to the brain through the carotid and vertebral arteries which connect at the circle of Willis. Factors like blood pressure, carbon dioxide levels, oxygen, temperature and various chemicals regulate blood flow. The brain has autoregulatory mechanisms to maintain constant blood flow over a range of pressures. Failure of autoregulation can lead to ischemia or hyperperfusion. Clinical considerations include risks for hypertensive or elderly patients and treatments focus on preventing hypotension and ischemia.

1. Cerebral blood flow and
regulation
Tushar Kumar

2. INTRODUCTION
Brain is a closed structure
Most of it is brain tissue
while some of it is
blood and CSF
Brain comprises 80%
Cerebral blood volume: 12%
CSF contribute to 8% of the
space inside the skull vault
Monro – Kellie doctrine

3. Anatomy :
• Circulation of brain
was first described
by WILLIS in 1664
1. Anterior circulation
and Posterior
circulation via
circle of Willis
2. Collateral arterial
inflow channels
3. Leptomeningial
collaterals- pial to
pial anastomoses

4. Anatomy
Circulation via circle of
Willis: anterior
circulation: via 2 carotid
arteries and their
derivations
Posterior circulations: via 2
vertebral arteries joining
to form basilar artery
It lies in subarachnoid space
and encircles pituitary
gland
Willisian channels:
anterior
communicating artery,
posterior
communicating artery
and ophthalmic artery
via external carotid
artery

5. Circle of willis with its collaterals

6. Collateral circulation
In a normal individuals
there is no net flow of
blood across these
communicating arteries
But to maintain patency
and prevent thrombosis
there is to an fro flow of
blood
Their importance appears
when a pressure
gradient develops
Second collateral flow
appears in surface
connections that bridge
pial arteries.
They bridge major arterial
territories ( ACA – PCA,
ACA- MCA, MCA – PCA)
They are called
leptomeningial
pathways or equal
pressure path ways.

7. Cerebral microcirculation
Capillary density in grey matter is 3 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

8. Cerebral microcirculation
Fast capillaries: These are the ones who do not take part
in transfer of substrate
BUT
During cerebral hypoperfusion they have a decrease in
blood velocity , diverting blood to slower functional
capillaries.

9. Venous drainage
3 set of veins drain from
brain
1. Superficial cortical vein
2. Deep cortical veins
3. Dural sinuses
All ultimately drain into
right and left IJV

10. Cerebral blood supply:
Physiological considerations:
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
And in children it goes higher up to
5 ml/100gm/min
Brain has high metabolic rate
That’s why brain requires
higher blood supply
55ml/100gm/min is the rate
of blood supply
requires more
requires
more
substratete
substrate
requires
mlacks of
storage of
energy
substrate

11. Cerebral blood supply
Cortical grey matter
75 – 80 ml/100gm/min
Subcortical white matter
20ml/100gm/min
CMRO2 : 5.5 ml/100gm/min
Functional requirement is
3.3 ml/100gm/min
Integrity required 02 is
2.2 ml/100gm/min
60% functional
40 %
integrity

12. Factors regulating cerebral blood flow
• Hemodynamic autoregulation
• Metabolic mediators and chemoregulation
• Neural control
• Circulatory peptides

13. Cerebral blood flow regulation
1. Flow metabolism coupling: Hemodynamic
regulation
Cerebral blood flow (CBF) closely follows
cerebral perfusion pressure (CPP)
Within the range of 50 to 150 mm Hg of CPP ,
blood flow remains constant.
Where CPP = MAP – ICP
MAP :Mean arterial pressure and ICP : Intracranial pressure.
Pure changes in perfusion pressure involve
myogenic response in vascular smooth
muscles (Bayliss effect)

14. Flow metabolism coupling:
Mechanism that CPP responds to:
mean BP
pulsatile pressure
Mediators involved are: H+, K+, adenosine,
glycolytic intermediate and phospholipid
metabolites
Nitric oxide controls the smooth muscles tone

15. Cerebral blood flow regulation
a. Pressure regulation:
Ohm’s law: flow = Pi – Pf
R
Hagen poiseuille relation : R = 8L μ
r⁴
where Pi – Pf is change in pressure,
R is resistance , L is the length of the tube , μ is coefficient of viscosity and r is radius
of the tube.
So we derive that: R = Pi – Pf = 8L μ
flow r⁴

16. Cerebral blood flow regulation
Arteriolar diameter as
well as cerebral vascular
resistance both vary with
CPP but CBF remains
constant in this range.

17. Cerebral blood flow regulation
2. Venous physiology:
Venous system contains
most of the cerebral
blood volume
Slight change in vessel
diameter has profound
effect on intracranial
blood volume
But evidence of their role
is less
Less smooth
muscle content
Less innervations
than arterial
system

18. Cerebral blood flow regulation
Pulsatile perfusion:
Fast and slow components of myogenic
response bring a change in perfusion pressure
Cardiac output:
Cardiac output may be responsible for improved
cerebral blood flow
They are indirectly related via central
venous pressure and large cerebral vessel
tone.

19. Cerebral blood flow regulation
Rheological factors:
Related with blood viscosity.
Hematocrit has main influence on blood
viscosity.
Flow is inversely related with hematocrit.
In small vessels cells move faster than plasma.
This reduces microvascular hematocrit and
viscosity FAHRAEUS LINDQVIST EFFECT

20. Metabolic and chemical regulation
1. Carbon dioxide
coupler between flow
and metabolism
At normal conditions CBF
has linear relationship
with CO2 between 20 –
80 mm Hg
For every mm Hg change
of PaCO2 CBF changes
by 2 – 4 %

21. CO2 induced vasodilatation
Mechanism by which CO2 produces vasodilatation

22. CARBON DIOXIDE : How it works
ADULT
↑CO2
↑H+ ions
NO
↑nNOS
C GMP
K+ Channel
Ca2+ Channel
↓Ca2+
↓Ca2+
Smooth Ms
Relaxation
↑K+

23. CARBON DIOXIDE : How it works
Neonates
↑CO2
↑H+ ions
PG
↑COX
endothelium
C AMP
K+ Channel
Ca 2+ Channel
↓Ca2+
↓Ca2+
Smooth Ms
Relaxation
↑K+

24. Metabolic and chemical regulation
Oxygen:
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

25. CO2 and Oxygen

26. Metabolic and chemical regulation
Temperature:
Like other organs cerebral metabolism
decreases with temperature
For every 1˚C fall in core body temperature
CMRO2 decreases by 7 %
At temperature < 18 ˚C EEG activity ceases

27. Temperature

28. Pharmacology and autoregulation
Anaesthetic drugs can alter autoregulatory
responses as seen with blood pressure and
CO2 drug
CBF CMR
Preserve
response to
CO2
Preserve
autoregulation
barbiturates ↓ ↓ yes yes
propofol ↓ ↓ yes yes
etomidate ↓ ↓ yes ….
morphine ± ↓ …. yes
fentanyl ± ± yes yes
benzodiazepines ↓ ↓ yes …
ketamine ↑ ↑ yes yes
lignocaine ↓ ↓ … …
response

29. Pharmacology and autoregulation
Inhalational agents affecting CBF
volatile
anaesthetic CBF CMR
Preserve
response to
CO2
Preserve
autoragulation
Xenon ↓ ↓ yes yes
desflurane ↑ ↓ yes yes
sevoflurane ↑ ↓ yes yes
isoflurane ↑ ↓ yes yes
enflurane ↑ ↓ yes yes
halothane ↑↑↑ ↓ yes yes
nitrous oxide ↑ ↑ … …

30. Pharmacology and autoregulation
Vasoactive agents:
Drugs that do not cross blood brain barrier do not affect CBF

31. Pharmacology and autoregulation
Dexmedetomidine:
Causes 25% reduction in CBF primarily by
reducing CMR
ACE inhibitors, Angiotensin receptor
antagonists, β blockers…….. Do not reduce CBF
or alter autoregulation

32. Metabolic mediators and
chemoregulation
Control CBF by acting as local vasodilators
Ions and chemicals
H+, K+,
adenosine and phospholipid metabolites
Final common pathway is via NO

33. Neurogenic effects
Neurogenic effects: sympathetic tone shift
the curve to right

34. Circulatory peptides:
Vasoactive peptides like angiotensin II do affect
CBF.
Reactive oxygen molecules
Alteration to vasomotor function
Vascular remodeling
De silva et al: effects of angiotensin II on cerebral circulation: role of oxidative
stress; review article – front physiology ; jan 2013

35. To summarize

36. Clinical considerations
Hypertensive patients:
Autoregulatory curve shifts to right
Protection from breakthrough but at the cost of
risk of ischemia
May suffer cerebral ischaemia during
hemorrhage, shock or hypotension

37. Clinical considerations
Elderly patients:
With age CBF decreases
Younger people have increased blood flow in
frontal areas…. Frontal hyperaemia
But with age this increased flow reduces
Flow in other areas are well maintained hence
blood is more uniformly distributed
Autoregulatory failure occurs in morel elderly

38. Auto regulatory failure
For auto regulatory failure to occur vasomotor
paralysis is the end point
• Acute ischemia
• Mass lesions all lead to
• Inflammation vasomotor
• Prematurity paralysis
• Neonatal asphyxia
• Diabetes mellitus

39. Autoregulatory failure
Right sided failure
Hyperperfusion
leads to circulatory
breakthrough
Fluid from capillaries seep
into the extracellular
space leading to edema
e.g. AVM
Left sided failure
Hypoperfusion

Ischemia
Na˖ and Ca 2˖ influx with
water and K+ efflux
leads to cytotoxic
edema and infarction
e.g. ischemic stroke

40. Autoregulatory failure
Two stages before infarction:
a. Penlucida at flow 18 – 23 ml/100gm/min
brain becomes inactive but function can be
restored at any time by reperfusion
b. Penumbra at lower flow rates brain
function can be restored by reperfusion but
only within a time limit

41. Hemodynamic considerations
Cerebral steal: it means blood is diverted from
one area to another if pressure gradient exists
between the two circulatory beds
Vasodilatation in ischemic brain takes blood
from ischemic areas to normal areas causing
more ischemia
Vasoconstriction results in redistribution of
blood from normal to ischemic areas leading
to inverse steal or ROBIN HOOD EFFECT

42. Hemodynamic considerations
Vessel length and viscosity
At breakthrough point flow depends on vessel
length and viscosity
Autoregulation has failed and it behaves like
fluid in a rigid tube
Pressure gradient across the ends are now same
so distal area have the lowest flow
This makes watershed areas more vulnerable to
ischemic changes

43. Considerations for ischemia
Consideration relevant to
global ischemia
Prevent and treat
hypotension as well as
vasogenic & cytotoxic
edema
Induction of mild
hypothermia for 24 hrs
Consideration relevant to
focal ischemia
Barbiturate coma, volatile
anesthetics (xenon),
calcium channel
antagonists
PaCO2 and temperature

44. Therapies for enhancing perfusion
• Induced hypertension
• Inverse steal
• Hypocapnea
• Hemodilution
• Pharmacological agents
• Barbiturates, propofol
• Intra arterial delivery of drugs. Like mannitol
and vasodilators

45. References:
1. Mishra L D; cerebral blood flow and anaesthesia;
Indian J. Anaesth. 2002; 46 (2) : 87-95
2. Joshi et al; cerebral and spinal cord blood flow;
Cottrell and Young’s Neuroanesthesia; 5th ed, 2010:
17 – 59
3. Patel et at; Cerebral physiology and effect of
anesthetic drugs; Miller’s anesthesia 8th ed : 387 –
423
4. De silva et al: Effects of angiotensin II on cerebral
circulation: role of oxidative stress; review article –
front physiology ; jan 2013

46. Thank you