Cerebral Blood Flow,

Cerebrospinal Fluid, and

Brain Metabolism

Kati Sriwiyati, dr

Normal Rate of Cerebral Blood Flow

Normal blood flow through the brain of the adult
person averages 50 to 65 ml/100 gr of brain
tissue/mnt
For the entire brain 750 to 900 ml/min, or 15
% of the resting cardiac output.

Regulation of Cerebral Blood Flow

1. Metabolic factors have potent effects in
controlling cerebral blood flow
Increase of Cerebral Blood Flow in Response to Excess CO2 or Excess
H+ Concentration
Importance of Cerebral Blood Flow Control by CO2 and H+
Oxygen Deficiency as a Regulator of Cerebral Blood Flow

2. Measurement of cerebral blood flow, and effect

of brain activity on the flow.
3. Autoregulation of cerebral blood flow when the
arterial pressure changes.
4. Role of the sympathetic nervous system in
controlling cerebral blood flow.

Cerebral blood flow in relation to artery lumen diameter.

Pires P W et al. Am J Physiol Heart Circ Physiol 2013;304:H1598H1614

2013 by American Physiological Society

 Cerebral blood flow (CBF) is dependent on a

number of factors that can broadly be divided
into:
those affecting cerebral perfusion pressure
those affecting the radius of cerebral blood vessels

 CBF is maintained at a constant level in normal brain in the

face of the usual fluctuations in blood pressure by the process
of autoregulation.
It is a poorly understood local vascular mechanism.
Normally autoregulation maintains a constant blood flow
between CPP 50 mmHg and 150 mmHg.
Poiseuilles law- flow through a rigid vessel:
Q = Pr4/8L
Q = CBF
P = cerebral perfusion pressure (CPP)
R = radius of the blood vessels
= viscosity of the fluid (blood)
l = length of the tube (blood vessels)

 The MonroKellie hypothesis

if the skull is intact, then the sum of the volumes
of the brain, cerebrospinal fluid (CSF) and
intracranial blood volume is constant

Cerebral Perfusion Pressure (CPP)

Cerebral Perfusion Pressure (CPP)
CPP = MAP ICP
Mean arterial blood pressure (MAP) can be
estimated as equal to: diastolic blood pressure + 1/3
pulse pressure and is usually around 90mmHg.
Intracranial pressure (ICP) is much lower and
is normally less than 13mmHg.
Normal CPP is between 50-150 mmHg
<50 mmHg --> ischemia
>150 mmHg --> hyperemia

The radius of cerebral arterial blood

vessels
This is regulated by four primary factors:

Cerebral metabolism
Carbon dioxide and oxygen
Autoregulation
Neurohumeral factors

Cerebral metabolism
Changes in CBF and metabolism
tend to follow each other
Local or global increases in
metabolic demand are met
rapidly by an increase in CBF
and substrate delivery
Controlled by several
vasoactive metabolic
mediators including hydrogen
ions, potassium, CO2, adenosine,
glycolytic intermediates,
phospholipid metabolites and
more recently, nitric oxide (NO).

Carbon dioxide and oxygen

At normotension, the
relationship between
partial pressure of
carbon dioxide in
arterial blood (PaCO2)
and CBF is almost
linear
At a PaCO2 80mmHg
(10.6kPa) CBF is
approximately
doubled.

 Relationship between
CBF and PaO2 showing
almost no effect on CBF
in the normoxaemic
range. CBF increases if
PaO2 is less than
50mmHg.

Autoregulation
Autoregulation is
thought to be a
myogenic
mechanism, whereby
vascular smooth
muscle constricts in
response to an
increase in wall
tension and to relax
to a decrease in wall
tension.

Neurohumeral factors
The sympathetic nerves vasoconstriction
protects the brain by shifting the autoregulation
curve to the right in hypertension.
The parasympathetic nerves vasodilatation
and may play a part in hypotension and
reperfusion injury (for example after cardiac
arrest).

Cerebral Microcirculation
The number of blood capillaries in the brain is
greatest where the metabolic needs are greatest.
The metabolic rate of the brain gray 4x of white
matter the number of capillaries and rate of
blood flow are also about 4x as great in the gray
matter.

Comprehensive diagram demonstrating the

multiple mechanisms of cerebrovascular
control.

 The entire cerebral cavity enclosing the brain

and spinal cord has a capacity of about 1600 to
1700 ml
about 150 ml of this capacity is occupied by
cerebrospinal fluid

CSF Functions
A major function of the cerebrospinal fluid is to
cushion the brain within its solid vault.
The brain and the cerebrospinal fluid have about
the same specific gravity (only about 4 per
cent different), so that the brain simply floats
in the fluid.

CSF Production
70 % CSF produced in choroid plexuses of lateral, third
and fourth ventricles
Small amounts of fluid

Secreted by the ependymal surfaces of all the ventricles and

by the arachnoidal membranes

Comes from the brain the perivascular spaces that

surround the blood vessels passing through the brain.
Produced at rate of 500 cc/day or approximately
20cc/hour (0.3-0.5 cc/kg/hr)

 The secretion of fluid by the choroid plexus depends on

the active Na+-transport across the cells into the CSF.
The electrical gradient pulls along Cl-, and both ions
drag water by osmosis.
The CSF has lower [K+], [glucose], and much lower
[protein] than blood plasma, and higher concentrations
of Na+ and Cl-.
The production of CSF in the choroid plexuses is an
active secretory process, and not directly dependent on
the arterial blood pressure.

The fluid secreted in the lateral

ventricles passes first into the
third ventricle
aqueduct of Sylvius into the
fourth ventricle Finally, the
fluid passes out of the fourth
ventricle through three small
openings, two lateral
foramina of Luschka and a
midline foramen of
Magendie entering the
cisterna magna, a fluid space
that lies behind the medulla and
beneath the cerebellum
subarachnoid space
arachnoid granulations
venous sinuses

Absorption of Cerebrospinal Fluid

Through the Arachnoidal Villi.
The arachnoidal villi are microscopic fingerlike
inward projections of the arachnoidal membrane
and into the venous sinuses.
Clumps of arachnoid villi = arachnoid
granulations = macroscopic.
The endothelial cells have vesicular passages
directly through the bodies of the cells large enough
to allow relatively free flow of
cerebrospinal fluid,
dissolved protein molecules
even particles as large as red and white blood cells
into the venous blood.

Perivascular Spaces and

Cerebrospinal Fluid
The large arteries and veins of the brain a
layer of pia mater the pia is only loosely
adherent to the vessels, so that a space, the
perivascular space, exists between it and
each vessel.
Perivascular spaces follow both the arteries and
the veins into the brain as far as the arterioles
and venules go.

Lymphatic Function of the

Perivascular Spaces
No true lymphatics are present in brain tissue
Protein in the brain tissue leaves the tissue
flowing with fluid through the perivascular
spaces into the subarachnoid spaces
Perivascular spaces are a specialized
lymphatic system for the brain.
To transporting fluid and proteins
To transport extraneous particulate matter out
of the brain (example : dead white blood cells
and other infectious debris)

Cerebrospinal Fluid Pressure

The normal pressure in the CSF when one is
lying in a horizontal position averages 130 mm
H2O (10 mm Hg)
As low as 65 mm H2O or as high as 195 mm
H2O

 Regulation of CSF Pressure by the

Arachnoidal Villi.
The normal rate of cerebrospinal fluid formation
remains very nearly constant
Arachnoidal villi function like valves that allow CSF
into the blood of the venous sinuses while not
allowing blood to flow backward in the opposite
direction.
Normally, this valve action of the villi allows CSF to
begin to flow into the blood when CSF pressure is
about 1.5 mm Hg greater than the pressure of the
blood in the venous sinuses

BloodCerebrospinal Fluid and

Blood-Brain Barriers
Blood-brain barriers at the choroid plexus and
at the tissue capillary membranes in
essentially all areas of the brain parenchyma except
in some areas of the hypothalamus, pineal gland,
and area postrema,
Substances diffuse with greater ease into the tissue
spaces
is important because they have sensory
receptors that respond to specific changes in the
body fluids, such as changes in osmolality and in
glucose concentration,

 Highly permeable to H2O, CO2, O2, and

most lipid-soluble substances such as alcohol
and anesthetics
Slightly permeable to electrolytes such as
Na+, Cl-, and K+
Totally impermeable to plasma proteins
and most nonlipid-soluble large organic
molecules

Brain Metabolism
Total Brain Metabolic Rate and Metabolic
Rate of Neurons
About 15 % of the total metabolism in the
body, even though the mass of the brain is only 2
%of the total body mass.
Under resting conditions, brain metabolism per
unit mass of tissue is about 7.5 x the average
metabolism

 Most of this excess metabolism of the brain

occurs in the neurons, not in the glial supportive
tissues
to pump ions through their membranes, mainly
to transport Na+ and Ca+ to the outside of the
neuronal membrane and K+ to the interior

 Special Requirement of the Brain for

OxygenLack of Significant Anaerobic
Metabolism
The brain is not capable of much anaerobic
metabolism.
One of the reasons for this is the high metabolic
rate of the neurons.

 Under Normal Conditions Most Brain

Energy Is Supplied by Glucose.

Under normal conditions, almost all the energy used

by the brain cells is supplied by glucose derived from
the blood.
Most of this is derived minute by minute and
second by second from the capillary blood, with a
total of only about a 2-minute supply of glucose
normally stored as glycogen in the neurons at any
given time.
A special feature of glucose delivery to the neurons
transport into the neurons through the cell
membrane not dependent on insulin

TERIMA KASIH
Guyton, Arthur C. Guyton and Hall Textbook of Medical Physiology
Twelfth edition. Elsevier. Missisipi
Eric C. Peterson. 2011. Regulation of Cerebral Blood Flow. International
Journal of Vascular Medicine Volume 2011 (2011).
http://dx.doi.org/10.1155/2011/823525
Cipolla, Marilyn J. 2009. The Cerebral Circulation. San Rafael (CA):
Morgan & Claypool Life Sciences.
http://www.ncbi.nlm.nih.gov/books/NBK53081/
http://www.neurosurg.cam.ac.uk/pages/brainphys/02-Cerebral_blood_flo
w.pdf
Paulo W. Pires. 2013. The effects of hypertension on the cerebral
circulation. American Journal of Physiology - Heart and Circulatory
PhysiologyPublished 15 June 2013Vol. 304no. 12, H1598-H1614DOI:
10.1152/ajpheart.00490.201.
http://ajpheart.physiology.org/content/304/12/H1598

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