Cerebral blood flow

Cerebral blood flow and regulation

Tushar Kumar

INTRODUCTION

Brain is a closed structureMost 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

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

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

Circle of willis with its collaterals

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.

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 irregularVelocity 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

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.

Venous drainage

3 set of veins drain from brain

1. Superficial cortical vein2. Deep cortical veins3. Dural sinuses

All ultimately drain into right and left IJV

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

Cerebral blood supply

Cortical grey matter 75 – 80 ml/100gm/min

Subcortical white matter 20ml/100gm/min

CMRO2 : 5.5 ml/100gm/minFunctional requirement is

3.3 ml/100gm/minIntegrity required 02 is

2.2 ml/100gm/min

60% functional

40 % integrity

Factors regulating cerebral blood flow

• Hemodynamic autoregulation• Metabolic mediators and chemoregulation• Neural control• Circulatory peptides

Cerebral blood flow regulation1. Flow metabolism coupling: Hemodynamic

regulationCerebral 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 – ICPMAP :Mean arterial pressure and ICP : Intracranial pressure.

Pure changes in perfusion pressure involve myogenic response in vascular smooth muscles (Bayliss effect)

Flow metabolism coupling:

Mechanism that CPP responds to: mean BP

pulsatile pressureMediators involved are: H+, K+, adenosine,

glycolytic intermediate and phospholipid metabolites

Nitric oxide controls the smooth muscles tone

Cerebral blood flow regulation

a. Pressure regulation: Ohm’s law: flow = Pi – Pf

RHagen poiseuille relation : R = 8L μ

r⁴where 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


Arteriolar diameter as well as cerebral vascular resistance both vary with CPP but CBF remains constant in this range.


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


Pulsatile perfusion:Fast and slow components of myogenic response

bring a change in perfusion pressureCardiac output:Cardiac output may be responsible for improved

cerebral blood flowThey are indirectly related via central venous pressure and large cerebral vessel tone.


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

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 %

CO2 induced vasodilatation

Mechanism by which CO2 produces vasodilatation

CARBON DIOXIDE : How it works

ADULT↑CO2

↑H+ ions

NO

↑nNOS

C GMP

K+ Channel

Ca2+ Channel

↓Ca2+

↓Ca2+

Smooth Ms Relaxation

↑K+

CARBON DIOXIDE : How it works

Neonates ↑CO2

↑H+ ions

PG

↑COXendothelium

C AMP

K+ Channel

Ca 2+ Channel

↓Ca2+

↓Ca2+

Smooth Ms Relaxation

↑K+


Oxygen:Within physiological range PaO2 has no effect on

CBFHypoxia is a potent stimulus for arteriolar

dilatationAt PaO2 50 mmHg CBF starts to increase and at

PaO2 30 mm Hg it doubles

CO2 and Oxygen


Temperature:Like other organs cerebral metabolism

decreases with temperatureFor every 1˚C fall in core body temperature

CMRO2 decreases by 7 %At temperature < 18 ˚C EEG activity ceases

Temperature

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 yespropofol ↓ ↓ yes yesetomidate ↓ ↓ yes ….morphine ± ↓ …. yesfentanyl ± ± yes yesbenzodiazepines ↓ ↓ yes …ketamine ↑ ↑ yes yeslignocaine ↓ ↓ … …

response


Inhalational agents affecting CBF

volatile anaesthetic CBF CMR

Preserve response to CO2

Preserve autoragulation

Xenon ↓ ↓ yes yesdesflurane ↑ ↓ yes yessevoflurane ↑ ↓ yes yesisoflurane ↑ ↓ yes yesenflurane ↑ ↓ yes yeshalothane ↑↑↑ ↓ yes yesnitrous oxide ↑ ↑ … …

Pharmacology and autoregulationVasoactive agents:

Drugs that do not cross blood brain barrier do not affect CBF


Dexmedetomidine: Causes 25% reduction in CBF primarily by

reducing CMR

ACE inhibitors, Angiotensin receptor antagonists, β blockers…….. Do not reduce CBF or alter autoregulation

Metabolic mediators and chemoregulation

Control CBF by acting as local vasodilatorsIons and chemicals

H+, K+, adenosine and phospholipid metabolites

Final common pathway is via NO

Neurogenic effects

Neurogenic effects: sympathetic tone shift the curve to right

Circulatory peptides:

Vasoactive peptides like angiotensin II do affect CBF.

Reactive oxygen moleculesAlteration to vasomotor functionVascular remodeling

De silva et al: effects of angiotensin II on cerebral circulation: role of oxidative stress; review article – front physiology ; jan 2013

To summarize

Clinical considerations

Hypertensive patients:Autoregulatory curve shifts to rightProtection from breakthrough but at the cost of

risk of ischemiaMay suffer cerebral ischaemia during

hemorrhage, shock or hypotension

Clinical considerations

Elderly patients:With age CBF decreasesYounger people have increased blood flow in

frontal areas…. Frontal hyperaemiaBut with age this increased flow reducesFlow in other areas are well maintained hence

blood is more uniformly distributedAutoregulatory failure occurs in morel elderly

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

Autoregulatory failure

Right sided failure

Hyperperfusionleads to circulatory

breakthroughFluid 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

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

Hemodynamic considerationsCerebral 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

Hemodynamic considerations

Vessel length and viscosity At breakthrough point flow depends on vessel

length and viscosityAutoregulation has failed and it behaves like

fluid in a rigid tubePressure gradient across the ends are now same

so distal area have the lowest flowThis makes watershed areas more vulnerable to

ischemic changes

Considerations for ischemia

Consideration relevant to global ischemia

Prevent and treat hypotension as well asvasogenic & 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

Therapies for enhancing perfusion

• Induced hypertension• Inverse steal• Hypocapnea• Hemodilution• Pharmacological agents

• Barbiturates, propofol

• Intra arterial delivery of drugs. Like mannitol and vasodilators

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

Thank you

Cerebral blood flow

Health & Medicine

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