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CSF Physiology and

CSF Physiology and


Cerebral Blood Flow
Cerebral Blood Flow
Keith R. Lodhia, MD,MS
Department of Neurosurgery
University of Michigan
122!!"
CSF Functions
CSF Functions

provide mechanical protection


provide mechanical protection

maintain a stable extracellular


maintain a stable extracellular
environment for the brain
environment for the brain

Remove some waste products


Remove some waste products

nutrition
nutrition

Convey messages? (hormonesreleasing


Convey messages? (hormonesreleasing
factorsneurotransmitters!
factorsneurotransmitters!
#rain $%uid &#a%ance'
CSF Production
CSF Production

"# $ CSF produced in choroid "# $ CSF produced in choroid


plexuses of lateral% third and plexuses of lateral% third and
fourth ventricles fourth ventricles

produced at rate of &## ccday produced at rate of &## ccday


or approximately '#cchour or approximately '#cchour
(#()*#(& cc+ghr! (#()*#(& cc+ghr!

eliminated by being absorbed eliminated by being absorbed


into the arachnoid villi **, dural into the arachnoid villi **, dural
sinus **, -ugular system sinus **, -ugular system

.he secretion of fluid by the .he secretion of fluid by the


choroid plexus depends on the choroid plexus depends on the
active /a0*transport across active /a0*transport across
the cells into the CSF( .he the cells into the CSF( .he
electrical gradient pulls along electrical gradient pulls along
Cl*% and both ions drag water Cl*% and both ions drag water
by osmosis( .he CSF has by osmosis( .he CSF has
lower 1203% 1glucose3% and lower 1203% 1glucose3% and
much lower 1protein3 than much lower 1protein3 than
blood plasma% and higher blood plasma% and higher
concentrations of /a0 and Cl*( concentrations of /a0 and Cl*(
.he production of CSF in the .he production of CSF in the
choroid plexuses is an active choroid plexuses is an active
secretory process% and not secretory process% and not
directly dependent on the directly dependent on the
arterial blood pressure( arterial blood pressure(
CSF Production
CSF Production

4ther sources of CSF production from


4ther sources of CSF production from
capillary ultrafiltrate (5irchow*Robin spaces!
capillary ultrafiltrate (5irchow*Robin spaces!

6dditionally some produced from metabolic


6dditionally some produced from metabolic
7
7
' '
4 production
4 production
CSF Production
CSF Production

5irchow*
5irchow*
Robin
Robin
spaces
spaces
CSF PR489C.:4/* Choroid
CSF PR489C.:4/* Choroid
Plexus
Plexus

CSF is produced by
CSF is produced by
choroid plexus and
choroid plexus and
secreted at ciliated
secreted at ciliated
cuboidal epithelial cell
cuboidal epithelial cell
surfaces of the
surfaces of the
microvilli into the
microvilli into the
ventricles
ventricles
CSF PR489C.:4/* Choroid
CSF PR489C.:4/* Choroid
Plexus
Plexus
;pendymal Cell <embrane
;pendymal Cell <embrane
.ransport
.ransport
CSF Production
CSF Production

CSF secretion
CSF secretion
involves the
involves the
transport of ions
transport of ions
( /a0% Cl= and
( /a0% Cl= and
7C4)=! across
7C4)=! across
the epithelium
the epithelium
from blood to
from blood to
CSF
CSF
#aso%atera% (pica%
)
2
!, Na
*
, )+,
"
-, +%-




Secretion can occur because of the polari>ed distribution of specific
ion transporters in the apical or basolateral membrane of the
epithelial cells(
CSF Production
CSF Production

./)0
./)0
2+ 2+
receptors
receptors
? from &7. subfamily( @e(g A!
? from &7. subfamily( @e(g A!
SSR:Bs bloc+ &*7.
SSR:Bs bloc+ &*7.
A6 A6
receptor presynaptic upta+e
receptor presynaptic upta+e
of &7. '! antimigraine CtriptansD stimulate
of &7. '! antimigraine CtriptansD stimulate
vasoconstriction* agonists mediating &7.
vasoconstriction* agonists mediating &7.
AB AB

A8 A8
receptors )! ondansetrongranisetron are &*7.
receptors )! ondansetrongranisetron are &*7.
) )

receptor antagonists * antinaseau effectsE
receptor antagonists * antinaseau effectsE

./)0
./)0
2+ 2+
receptors found in high concentration in
receptors found in high concentration in
choroid plexus
choroid plexus
CSF Production
CSF Production

6/P receptors found in choroid plexus 6/P receptors found in choroid plexus

6/P decreases CSF production 6/P decreases CSF production

Choroid plexus epithelial cells express Choroid plexus epithelial cells express
receptors for atrial natriuretic peptide receptors for atrial natriuretic peptide
that when stimulated increase cF<P that when stimulated increase cF<P
levels and inhibit cerebral spinal fluid levels and inhibit cerebral spinal fluid
production production

6Guaporin*6HPA channels are thought 6Guaporin*6HPA channels are thought


to be involved in the production of to be involved in the production of
cerebral spinal fluid cerebral spinal fluid
CSF Constituency
CSF Constituency

CSF volumeI '& cc


CSF volumeI '& cc
ventricular% '&cc
ventricular% '&cc
intracranial
intracranial
subarachnoid space%
subarachnoid space%
and A##cc in spinal
and A##cc in spinal
subarachnoid spaces
subarachnoid spaces

J
J
' '
transferrin
transferrin
CSF Constituency*
CSF Constituency*
J
J
' '
transferrin
transferrin

PR4.;:/ PR4.;:/
;K;C.R4P74R;S:S*on ;K;C.R4P74R;S:S*on
celluloseP6F;filter etc celluloseP6F;filter etc

.ransferrin is an iron binding .ransferrin is an iron binding


protein used to shuttle iron protein used to shuttle iron
stores to cells* mar+er of severe stores to cells* mar+er of severe
malnutrition ( ;levations inI malnutrition ( ;levations inI
hypothyroidism% biliary cirrhosis% hypothyroidism% biliary cirrhosis%
nephrosis% chronic iron deficient nephrosis% chronic iron deficient
anemia% and some cases of anemia% and some cases of
diabetes diabetes

CSF shows increased CSF shows increased J J


' '
pea+ pea+
cw mucous( .herefore useful cw mucous( .herefore useful
in evaluating potential CSF in evaluating potential CSF
rhinorrhea rhinorrhea
CSF Circulation
CSF Circulation

%atera% ventric%es//1 %atera% ventric%es//1


foramen of Monro third foramen of Monro third
ventric%e //1 a2ueduct of ventric%e //1 a2ueduct of
Sy%vius //1 fourth Sy%vius //1 fourth
ventric%e //1 foramina of ventric%e //1 foramina of
Magendie and Lusch3a Magendie and Lusch3a
//1 su4arachnoid space //1 su4arachnoid space
over 4rain and spina% over 4rain and spina%
cord //1 rea4sorption cord //1 rea4sorption
into venous sinus 4%ood into venous sinus 4%ood
via arachnoid via arachnoid
granu%ations granu%ations
CSF Circulation
CSF Circulation
Kundberg Laves
Kundberg Laves

Lund4erg has descri4ed " 5ave patterns 6+7 5aves 8(, #, and +
5aves9. ( 5aves are patho%ogica%. 0here is a rapid rise in 6+7 up to
.!/1!! mm )g fo%%o5ed 4y a varia4%e period during 5hich the 6+7
remains e%evated fo%%o5ed 4y a rapid fa%% to the 4ase%ine and 5hen
they persist for %onger periods, they are ca%%ed :p%ateau: 5aves
5hich are patho%ogica%. :0runcated: or atypica% ones, that do not
e;ceed an e%evation of .! mm )g, are ear%y indicators of
neuro%ogica% deterioration. # < + 5aves are re%ated to respiration
and :0rau4e/)ering/Mayer: 5aves 8rhythmica% variations in 4%ood
pressure9 respective%y and are part of norma% physio%ogy 5ith %itt%e
c%inica% significance.
Kundberg
6* waves
6* wavesPlateau Laves
6* wavesPlateau Laves

Steep rises and abrupt falls in :CP% pea+ing at &#*A## mm Steep rises and abrupt falls in :CP% pea+ing at &#*A## mm
7g% that last &* '# minutes (also +nown as plateau waves!( 7g% that last &* '# minutes (also +nown as plateau waves!(

<ay signify intracranial vasomotor decompensation( <ay or <ay signify intracranial vasomotor decompensation( <ay or
may not be associated with clinical deterioration( may not be associated with clinical deterioration(

Pathogenesis related to dilation of resistance vessels% Pathogenesis related to dilation of resistance vessels%
increased intracranial blood volume% decreased flow% and increased intracranial blood volume% decreased flow% and
increased pressure( increased pressure(

C CKoss of 6utoregulationD Koss of 6utoregulationD


CSF 6bsorption
CSF 6bsorption

CSF is reabsorbed into CSF is reabsorbed into


the blood of the venous the blood of the venous
sinuses via the sinuses via the
arachnoidal villi( .he arachnoidal villi( .he
absorption here is directly absorption here is directly
related to the CSF related to the CSF
pressure in the cranial pressure in the cranial
cavity( cavity(

Kymphaticscribiform Kymphaticscribiform
plate plate

.ransependymal flow .ransependymal flow


Route and 6bsorption of CSF
Route and 6bsorption of CSF

6rachnoid villi are microscopic 6rachnoid villi are microscopic


one*way valves (modified pia and one*way valves (modified pia and
arachnoid! that penetrate the arachnoid! that penetrate the
meningeal dural layer that line the meningeal dural layer that line the
sinusesM hence% arachnoid villi sinusesM hence% arachnoid villi
reside within the sinuses reside within the sinuses
(especially the superior sagittal (especially the superior sagittal
sinus!( sinus!(

Clumps of arachnoid villi N Clumps of arachnoid villi N


arachnoid granu%ations arachnoid granu%ations N N
macroscopic( macroscopic(
(rachnoid =i%%us
Route and 6bsorption of CSF
Route and 6bsorption of CSF

7ydrostatic pressure in subarachnoid


7ydrostatic pressure in subarachnoid
space , pressure in dural sinuses
space , pressure in dural sinuses

.ypical hydrostatic values of CSF are A&# mm


.ypical hydrostatic values of CSF are A&# mm
7
7
' '
4 (AA mm 7g! in subarachnoid space vs(
4 (AA mm 7g! in subarachnoid space vs(
about "# mm 7
about "# mm 7
' '
4 (& mm 7g! in dural sinuses(
4 (& mm 7g! in dural sinuses(

6rach( villi are


6rach( villi are
one-way valves
one-way valves
that open
that open
when the hydrostatic pressure of CSF in
when the hydrostatic pressure of CSF in
the subarachnoid space is about A(& mm
the subarachnoid space is about A(& mm
7g greater than venous hydrostatic
7g greater than venous hydrostatic
pressure in the dural sinuses (i(e(% passive
pressure in the dural sinuses (i(e(% passive
process!(
process!(
8rugs affecting Rate of
8rugs affecting Rate of
CSF Production
CSF Production

8rugs
8rugs

Carbonic anhydrase inhibitors


Carbonic anhydrase inhibitors
(aceto>olamide8iamox!
(aceto>olamide8iamox!

Cardiac glycosides (digoxin! inhibit 6.Pase


Cardiac glycosides (digoxin! inhibit 6.Pase
pump% thereby reducing CSF formation in a
pump% thereby reducing CSF formation in a
dose*dependent manner(
dose*dependent manner(

Steroids* ;ffects on CSF formation are


Steroids* ;ffects on CSF formation are
inconsistent(
inconsistent(

Future* 6GP inhibitors?% &*7.


Future* 6GP inhibitors?% &*7.
'C 'C
receptor inh ?
receptor inh ?
CSF Pharmacology cont(
CSF Pharmacology cont(

Carbonic 6nhydrase Carbonic 6nhydrase

C4' 0 7'4 ON7'Co)N, C4' 0 7'4 ON7'Co)N,


7C4)* 0 70 7C4)* 0 70

:nhibition of C6:: :nhibition of C6::


decreases production of decreases production of
CSF by P# $ by CSF by P# $ by
decreasing bicarbonate decreasing bicarbonate
formation in choroid formation in choroid
plexus plexus

6cute <ountain 6cute <ountain


Sic+ness* an aside( Sic+ness* an aside(
+,2 * )2, >?1
)+,"/ * )*
5;/.R:CK; 5;/.R:CK;
6cute <ountain Sic+ness*6<S
6cute <ountain Sic+ness*6<S

6<S symptoms (76 fatigue 6<S symptoms (76 fatigue


somnolence etc! represent the somnolence etc! represent the
effect of early cerebral edema effect of early cerebral edema
with increased intracranial with increased intracranial
pressure pressure

a loss of cerebral autoregulation a loss of cerebral autoregulation


mechanisms leading to mechanisms leading to
vasogenic edema (also vasogenic edema (also
migrainous*li+e!% or an osmotic migrainous*li+e!% or an osmotic
swelling of the brain cells swelling of the brain cells
(cytotoxic edema!( (cytotoxic edema!(

7ypoventilation appears to 7ypoventilation appears to


contribute to development of contribute to development of
6<S( 6 bris+ increase in 6<S( 6 bris+ increase in
ventilation on ascent to altitude is ventilation on ascent to altitude is
associated with a lower incidence associated with a lower incidence
of 6<S of 6<S
6cute <ountain Sic+ness*6<S
6cute <ountain Sic+ness*6<S

ProphylaxisI slow ascent% 8iamox%


ProphylaxisI slow ascent% 8iamox%

RxI 6S6 or tylenol for mild 76


RxI 6S6 or tylenol for mild 76

6cute therapy for 7igh 6ltitude Cerebral


6cute therapy for 7igh 6ltitude Cerebral
;dema (severe form of 6<S!I
;dema (severe form of 6<S!I
decadron% but descent to a lower altitude
decadron% but descent to a lower altitude
is still the most reliable treatment
is still the most reliable treatment
CSF Pathology
CSF Pathology

:n cases of subarachnoid hemorrhage or traumatic spinal :n cases of subarachnoid hemorrhage or traumatic spinal
fluid taps% approximately A LBC is added to every "## fluid taps% approximately A LBC is added to every "##
RBCs (literature range% A LBC&##*A%### RBCs!( .his RBCs (literature range% A LBC&##*A%### RBCs!( .his
disagreement in values ma+es formulas (Fisher ratio etc! disagreement in values ma+es formulas (Fisher ratio etc!
unreliable that attempt to differentiate traumatic tap unreliable that attempt to differentiate traumatic tap
artifact from true LBC increase( 6lso% the presence of artifact from true LBC increase( 6lso% the presence of
subarachnoid blood itself may sometimes cause subarachnoid blood itself may sometimes cause
meningeal irritation% producing a mild to moderate meningeal irritation% producing a mild to moderate
increase in P</s after several hours that occasionally increase in P</s after several hours that occasionally
may be greater than &## LBCs mm) ( may be greater than &## LBCs mm) (

Qanthochromia begins in , R hours (literature range% '* Qanthochromia begins in , R hours (literature range% '*
RS hours! due to hemoglobin pigment from lysed RBCs( RS hours! due to hemoglobin pigment from lysed RBCs(
CSF Pathology
CSF Pathology
7atterns of +ere4rospina% $%uid (4norma%ity@ +e%% 0ype and A%ucose Leve%

POLYMORPHONUCLEAR: LOW GLUCOSE

(cute 4acteria% meningitis

POLYMORPHONUCLEAR: LOW OR NORMAL GLUCOSE

Some cases of ear%y phase acute 4acteria% meningitis

7rimary amoe4ic 8Naeg%eria species9 meningoencepha%itis

Bar%y phase Leptospira meningitis

POLYMORPHONUCLEAR: NORMAL GLUCOSE

#rain a4scess

Bar%y phase co;sac3ievirus and echovirus meningitis

+NS syphi%is 8some patients9

(cute 4acteria% meningitis 5ith 6= g%ucose therapy

Listeria 8a4out 2!C of cases9

LYMPHOCYTIC: LOW GLUCOSE

0u4ercu%osis meningitis

+ryptococca% 80oru%a9 meningitis

Mumps meningoencepha%itis 8some cases9

Meningea% carcinomatosis 8some cases9

Meningea% sarcoidosis 8some cases9

Listeria 8a4out 1.C of cases9

LYMPHOCYTIC: NORMAL GLUCOSE

=ira% meningitis

=ira% encepha%itis

7ostinfectious encepha%itis

Lead encepha%opathy

+NS syphi%is 8maDority of patients9

#rain tumor 8occasiona%%y9

Leptospira meningitis 8after the ear%y phase9

Listeria 8a4out 1.C of cases9


Cerebral Blood Flow (CBF!
Cerebral Blood Flow (CBF!

CBF N CB5t
CBF N CB5t

"&# mKminute% which is A&$ of the


"&# mKminute% which is A&$ of the
cardiac output
cardiac output

.he normal cerebral blood flow is R&*


.he normal cerebral blood flow is R&*
&#mlA##gmin% ranging from '#ml A##g*
&#mlA##gmin% ranging from '#ml A##g*
A min*A in white matter to "#ml A##g*
A min*A in white matter to "#ml A##g*
A min*A in grey matter( 7ighest in
A min*A in grey matter( 7ighest in
neurohypophysis
neurohypophysis
CBF
CBF

Lhen CBF falls to less than A#*


Lhen CBF falls to less than A#*
')mlA##gmin% physiological electrical
')mlA##gmin% physiological electrical
function of the cell begins to fail* Cischemic
function of the cell begins to fail* Cischemic
penumbraD(
penumbraD(

Below S mlA##gmin irreversible cell


Below S mlA##gmin irreversible cell
death* ionic membrane transport failure
death* ionic membrane transport failure
Cerebral Perfusion Pressure (CPP!
Cerebral Perfusion Pressure (CPP!

Cerebral Perfusion Pressure (CPP!


Cerebral Perfusion Pressure (CPP!


<6P*:CPNCPP
<6P*:CPNCPP
normal CPP is between &#*A&# mm7g
normal CPP is between &#*A&# mm7g

O&# mm7g **, ischemia


O&# mm7g **, ischemia

,A&# mm7g **, hyperemia


,A&# mm7g **, hyperemia
6utoregulation
6utoregulation

CBF is maintained at a constant level in normal


CBF is maintained at a constant level in normal
brain in the face of the usual fluctuations in
brain in the face of the usual fluctuations in
blood pressure by the process of autoregulation(
blood pressure by the process of autoregulation(
:t is a poorly understood local vascular
:t is a poorly understood local vascular
mechanism( /ormally autoregulation maintains
mechanism( /ormally autoregulation maintains
a constant blood flow between CPP &# mm7g
a constant blood flow between CPP &# mm7g
and A&# mm7g(
and A&# mm7g(

PoiseuilleBs law* flow through a rigid vesselI


PoiseuilleBs law* flow through a rigid vesselI


H N
H N
T
T
P
P
U
U
r
r
R R
SK
SK
V
V
6utoregulation
6utoregulation

8ysregulation can occur in pathologic states


8ysregulation can occur in pathologic states

:n traumatised or ischaemic brain% or following


:n traumatised or ischaemic brain% or following
vasodilator agents (volatile agents and sodium
vasodilator agents (volatile agents and sodium
nitroprusside! CBF may become blood pressure
nitroprusside! CBF may become blood pressure
dependent( .hus as arterial pressure rises so CBF
dependent( .hus as arterial pressure rises so CBF
will rise causing an increase in cerebral volume(
will rise causing an increase in cerebral volume(
Similarly as pressure falls so CBF will also fall%
Similarly as pressure falls so CBF will also fall%
reducing :CP% but also inducing an uncontrolled
reducing :CP% but also inducing an uncontrolled
reduction in CBF(
reduction in CBF(

pressuremyogenic autoregulation
pressuremyogenic autoregulation

arterioles dilate or constrict in response to changes in BP arterioles dilate or constrict in response to changes in BP
and :CP in order to maintain a constant CBF and :CP in order to maintain a constant CBF

C Cmyogenic theoryD* vascular smooth muscle within myogenic theoryD* vascular smooth muscle within
cerebral arterioles intrinsically contract to stretch thereby cerebral arterioles intrinsically contract to stretch thereby
regulating pressure regulating pressure

/4* limited role overall% but if completely abolish /4 /4* limited role overall% but if completely abolish /4
production then loss of autoregulationM with CBF being production then loss of autoregulationM with CBF being
completely BP*dependent completely BP*dependent

6utoregulation
6utoregulation
<etabolic 6utoregulation
<etabolic 6utoregulation

arterioles dilate in response to potent chemicals


that are by*products of metabolism such as
lactic acid% carbon dioxide and pyruvic acid
C4' is a potent vasodilator
increased C4'decreased BP **, vasodilation
decreased C4'increased BP
**,vasoconstriction
/eurogenic 6utoregulation
/eurogenic 6utoregulation

6utonomic* sympathetic adrenergic


6utonomic* sympathetic adrenergic
receptors seen in cortical layers :5 and 5(
receptors seen in cortical layers :5 and 5(

W
W
A A
%
%
J
J
' '
% and X
% and X
' '
(CdilatorsD!% and X
(CdilatorsD!% and X
A A
(CconstrictorD! receptors
(CconstrictorD! receptors

4verall sympathetic system plays minor


4verall sympathetic system plays minor
role unli+e in non*cerebral vascular beds(
role unli+e in non*cerebral vascular beds(
/eurogenic 6utoregulation* cont
/eurogenic 6utoregulation* cont

&*7.* potent Cconstrictor%D antagoni>ed by /4


&*7.* potent Cconstrictor%D antagoni>ed by /4

/europeptide Y* CvasoconstrictionD% in assoc


/europeptide Y* CvasoconstrictionD% in assoc
with /4 and sympathetic system
with /4 and sympathetic system

5asoactive intestinal polypeptide (5:P! and


5asoactive intestinal polypeptide (5:P! and
peptide histidine isoleucine (P7:!* CvasodilatorsD
peptide histidine isoleucine (P7:!* CvasodilatorsD

Substance P% neuro+inin 6% calcitonin gene*


Substance P% neuro+inin 6% calcitonin gene*
related peptide histamine 7
related peptide histamine 7
' '
*DvasodilatoryD esp(
*DvasodilatoryD esp(
substance P
substance P

CC2% neurotensin% somatostatin% vasopressin%


CC2% neurotensin% somatostatin% vasopressin%
endorphin
endorphin
/eurogenic 6utoregulation*cont
/eurogenic 6utoregulation*cont

6utonomic system and


6utonomic system and
neurochemical control of
neurochemical control of
CBF in general is a minor
CBF in general is a minor
control
control

4verall% pressure and


4verall% pressure and
metabolic autoregulation
metabolic autoregulation
most important
most important
:ncreasing CBF*7yperemia
:ncreasing CBF*7yperemia

Kow arterial oxygen


Kow arterial oxygen
tension has profound
tension has profound
effects on cerebral
effects on cerebral
blood flow( Lhen it
blood flow( Lhen it
falls below &# mm7g
falls below &# mm7g
(P(" +Pa!% there is a
(P(" +Pa!% there is a
rapid increase in CBF
rapid increase in CBF
and arterial blood
and arterial blood
volume
volume
CBF and C4
CBF and C4
' '

Carbon dioxide
Carbon dioxide
causes cerebral
causes cerebral
vasodilation( 6s the
vasodilation( 6s the
arterial tension of
arterial tension of
C4' rises% CB5 and
C4' rises% CB5 and
CBF increases and
CBF increases and
when it is reduced
when it is reduced
vasoconstriction is
vasoconstriction is
induced(
induced(
C
C
Cerebrovascular ReserveD
Cerebrovascular ReserveD

:n functionally activated areas% CBF augmentation


exceeds the small increases in oxygen utili>ation and
the concentration of deoxyhemoglobin is relatively low(
.hus% this excess supply of oxygen in response to a
demand stimulus reflects the cerebral perfusion reserve
capacity

Cerebrovascular reserve capacity is impaired by ris+


factors such as hypertension and diabetes%
carotidcerebral vasc( stenosis% and can be an etiologic
factor in ischemic stro+e
Cerebrovascular Reserve
Cerebrovascular Reserve

P;.% SP;C.% Qe*C.% C.*perfusion to assess(


Prepost diamox challenge(

aceta>olamide challenge and the C4'*loading


(breath*holding! test raise global CBF

(<R:! of .'*weighted or Blood oxygenation


level?dependent
(
(B4K8!*weighted images
correlate well with changes in the total amount of
oxygenated hemoglobin

Qenon C.
perfusion C.
B4K8*<R: and single*
photon emission
computed tomography
(SP;C.!
(SP;C.!
CBF 6/8 CSF* .Y:/F
CBF 6/8 CSF* .Y:/F
:. .4F;.7;R
:. .4F;.7;R
P6.74P7YS:4K4FY
P6.74P7YS:4K4FY
CSFCBF
CSFCBF

A( the intracranial compartment is a rigid


A( the intracranial compartment is a rigid
container and consists of three
container and consists of three
components
components

a( brain*S#$ of total volume


a( brain*S#$ of total volume

b( blood*A#$ of total volume


b( blood*A#$ of total volume

c( CSF*A#$ of total volume


c( CSF*A#$ of total volume
P6.74P7YS:4K4FY
P6.74P7YS:4K4FY
CSFCBF
CSFCBF

'( '( <onro*2ellie <onro*2ellie


7ypothesis 7ypothesis

to maintain a normal :CP% to maintain a normal :CP%


a change in the volume of a change in the volume of
one compartment must one compartment must
be offset by a reciprocal be offset by a reciprocal
change in the volume of change in the volume of
another compartment another compartment

pressure is normally well* pressure is normally well*


controlled through controlled through
alterations in the volume alterations in the volume
of blood and CSF of blood and CSF
Brain P5 curve
Brain P5 curve
P5 C9R5; 6/8
P5 C9R5; 6/8
C4<PK:6/C;
C4<PK:6/C;

Pressure gradients can develop within Pressure gradients can develop within
the brain substance and the compliance the brain substance and the compliance
or CsGuishinessD of pathological brain or CsGuishinessD of pathological brain
(e(g( tumor! can be different from that of (e(g( tumor! can be different from that of
normal brain leading to an altered curve normal brain leading to an altered curve
(shift left!( (shift left!(

.he extent of the change in :CP caused by an alteration in .he extent of the change in :CP caused by an alteration in
the volume of intracranial contents is determined by the the volume of intracranial contents is determined by the
compliance or of the brain( :n other words if compliance is compliance or of the brain( :n other words if compliance is
low% the brain is stiffer or less ZsGuashableZ( .herefore% an low% the brain is stiffer or less ZsGuashableZ( .herefore% an
increase in brain volume will result in a higher rise in increase in brain volume will result in a higher rise in
intracranial pressure than if the compliance were high( intracranial pressure than if the compliance were high(
BloodBrain*BloodCSF Barriers
BloodBrain*BloodCSF Barriers

.he blood*brain barrier (BBB! is the speciali>ed


.he blood*brain barrier (BBB! is the speciali>ed
system of capillary endothelial cells that protects
system of capillary endothelial cells that protects
the brain from harmful substances in the blood
the brain from harmful substances in the blood
stream% while supplying the brain with the reGuired
stream% while supplying the brain with the reGuired
nutrients for proper function(
nutrients for proper function(

Formed by the nonfenestrated capillaries and to


Formed by the nonfenestrated capillaries and to
much lesser degree% the astrocytic foot processes
much lesser degree% the astrocytic foot processes
[+eeps out most macromolecules
[+eeps out most macromolecules
BloodBrain Barrier
BloodBrain Barrier
Blood*
Blood*
CSF
CSF
Barrier
Barrier

C
C
.ightD
.ightD
-unctions at
-unctions at
the
the
ependymal
ependymal
level
level

Fenestrated
Fenestrated
-unctions at
-unctions at
the choroidal
the choroidal
capillaries
capillaries
.he choroid plexus is composed of fenestrated
capillaries and an epithelial (ependymal! covering%
which reverts from ZtightZ to moderately ZopenZ at
the base *?not as strenuous of barrier as
bloodbrain
BloodBrain Barrier and
BloodBrain Barrier and
Circumventricular organs
Circumventricular organs

.he circumventricular organs (C54! are midline .he circumventricular organs (C54! are midline
structures bordering the )rd and Rth ventricles( .hese structures bordering the )rd and Rth ventricles( .hese
barrier*deficient areas are recogni>ed as important sites barrier*deficient areas are recogni>ed as important sites
for communicating with the CSF and between the brain for communicating with the CSF and between the brain
and peripheral organs via blood*borne products( C54\s and peripheral organs via blood*borne products( C54\s
include the pineal gland% median eminence% include the pineal gland% median eminence%
neurohypophysis% subfornical organ% area postrema% neurohypophysis% subfornical organ% area postrema%
subcommissural organ% organum vasculosum of the subcommissural organ% organum vasculosum of the
lamina terminalis% and the choroid plexus( .he lamina terminalis% and the choroid plexus( .he
intermediate and neural lobes of the pituitary are intermediate and neural lobes of the pituitary are
sometimes included sometimes included
Causes of an increased :CP
Causes of an increased :CP

Conditions :ncreasing Brain 5olume


Conditions :ncreasing Brain 5olume

intracranial mass (tumor% hematoma%


intracranial mass (tumor% hematoma%
aneurysm% 65<!
aneurysm% 65<!

cerebral edema
cerebral edema

C/S infection (abscess% inflammatory


C/S infection (abscess% inflammatory
process!
process!
Causes of an increased :CP
Causes of an increased :CP

Conditions :ncreasing Blood 5olume


Conditions :ncreasing Blood 5olume

obstruction of venous outflow


obstruction of venous outflow

hyperemia ? decreased p4'* inc( CBF


hyperemia ? decreased p4'* inc( CBF

hypercapnea ? ,pC4' increases


hypercapnea ? ,pC4' increases
vasodilation inc CB5 % CBF% and :CP
vasodilation inc CB5 % CBF% and :CP
Causes of an increased :CP
Causes of an increased :CP

Conditions :ncreasing CSF 5olume


Conditions :ncreasing CSF 5olume

increased production(Ch plexus


increased production(Ch plexus
papilloma!
papilloma!

decreased reabsorption of CSF


decreased reabsorption of CSF
(meningitis% S67!
(meningitis% S67!

4bstruction to flow of CSF (e(g( aG


4bstruction to flow of CSF (e(g( aG
stenosis!
stenosis!
.7; ;/8
.7; ;/8