CSF and Cerebral Blood Flow

8/12/2019 CSF and Cerebral Blood Flow

1/58

CSF Physiology andCSF Physiology andCerebral Blood FlowCerebral Blood Flow

Keith R. Lodhia, MD,MSDepartment of Neurosurgery

University of Michigan122!!"


2/58

CSF FunctionsCSF Functions

provide mechanical protectionprovide mechanical protection maintain a stable extracellularmaintain a stable extracellular

environment for the brainenvironment for the brain Remove some waste productsRemove some waste products nutritionnutrition Convey messages? (hormonesreleasingConvey messages? (hormonesreleasing

factorsneurotransmitters!factorsneurotransmitters!


3/58

#rain $%uid a%ance'


4/58

CSF ProductionCSF Production

"# $ CSF produced in choroid"# $ CSF produced in choroidplexuses of lateral% third andplexuses of lateral% third andfourth ventriclesfourth ventricles

produced at rate of # ccdayproduced at rate of # ccday

or approximately '#cchouror approximately '#cchour(#)*#& cc+ghr!(#)*#& cc+ghr! eliminated by being absorbedeliminated by being absorbed

into the arachnoid villi **, duralinto the arachnoid villi **, duralsinus **, -ugular systemsinus **, -ugular system

.he secretion of fluid by the.he secretion of fluid by thechoroid plexus depends on thechoroid plexus depends on theactive /a0*transport acrossactive /a0*transport acrossthe cells into the CSF .hethe cells into the CSF .he

electrical gradient pulls alongelectrical gradient pulls alongCl*% and both ions drag waterCl*% and both ions drag waterby osmosis .he CSF hasby osmosis .he CSF haslower 1203% 1glucose3% andlower 1203% 1glucose3% andmuch lower 1protein3 thanmuch lower 1protein3 thanblood plasma% and higherblood plasma% and higherconcentrations of /a0 and Cl*concentrations of /a0 and Cl*

.he production of CSF in the.he production of CSF in thechoroid plexuses is an activechoroid plexuses is an activesecretory process% and notsecretory process% and notdirectly dependent on thedirectly dependent on thearterial blood pressurearterial blood pressure


5/58


4ther sources of CSF production from4ther sources of CSF production fromcapillary ultrafiltrate (5irchow*Robin spaces!capillary ultrafiltrate (5irchow*Robin spaces!

6dditionally some produced from metabolic6dditionally some produced from metabolic77

''4 production4 production


6/58


5irchow*5irchow*RobinRobin

spacesspaces


7/58

CSF PR489C.:4/* ChoroidCSF PR489C.:4/* Choroid

PlexusPlexus CSF is produced byCSF is produced by

choroid plexus andchoroid plexus and

secreted at ciliatedsecreted at ciliatedcuboidal epithelial cellcuboidal epithelial cellsurfaces of thesurfaces of themicrovilli into themicrovilli into the

ventriclesventricles


8/58

CSF PR489C.:4/* ChoroidCSF PR489C.:4/* Choroid

PlexusPlexus


9/58

;pendymal Cell


10/58


CSF secretionCSF secretioninvolves theinvolves thetransport of ionstransport of ions( /a0% Cl= and( /a0% Cl= and

7C4)=! across7C4)=! acrossthe epitheliumthe epitheliumfrom blood tofrom blood to

CSFCSF #aso%atera% (pica%

)2!, Na*, )+

"-, +%-

Secretion can occur because of the polari>ed distribution of specificion transporters in the apical or basolateral membrane of the

epithelial cells


11/58


/)0/)02+2+receptorsreceptors from &7. subfamily @eg A! from &7. subfamily @eg A!

SSR:s bloc+ &*7.SSR:s bloc+ &*7.A6A6receptor presynaptic upta+ereceptor presynaptic upta+e

of &7. '! antimigraine triptansD stimulateof &7. '! antimigraine triptansD stimulate

vasoconstriction* agonists mediating &7.vasoconstriction* agonists mediating &7.ABABA8A8receptors )! ondansetrongranisetron are &*7.receptors )! ondansetrongranisetron are &*7.

))

receptor antagonists * antinaseau effectsEreceptor antagonists * antinaseau effectsE

/)0/)02+2+receptors found in high concentration inreceptors found in high concentration inchoroid plexuschoroid plexus


12/58


6/P receptors found in choroid plexus6/P receptors found in choroid plexus 6/P decreases CSF production6/P decreases CSF production

Choroid plexus epithelial cells expressChoroid plexus epithelial cells expressreceptors for atrial natriuretic peptidereceptors for atrial natriuretic peptidethat when stimulated increase c


13/58

CSF ConstituencyCSF Constituency

CSF volumeI '& ccCSF volumeI '& ccventricular% '&ccventricular% '&cc

intracranialintracranialsubarachnoid space%subarachnoid space%and A##cc in spinaland A##cc in spinalsubarachnoid spacessubarachnoid spaces

JJ''transferrintransferrin


14/58

CSF Constituency*CSF Constituency* JJ''transferrintransferrin PR4.;:/PR4.;:/

;K;C.R4P74R;S:S*on;K;C.R4P74R;S:S*oncelluloseP6;filter etccelluloseP6;filter etc

.ransferrin is an iron binding.ransferrin is an iron bindingprotein used to shuttle ironprotein used to shuttle iron

stores to cells* mar+er of severestores to cells* mar+er of severemalnutrition ;levations inImalnutrition ;levations inIhypothyroidism% biliary cirrhosis%hypothyroidism% biliary cirrhosis%nephrosis% chronic iron deficientnephrosis% chronic iron deficientanemia% and some cases ofanemia% and some cases ofdiabetesdiabetes

CSF shows increasedCSF shows increased JJ''pea+pea+cw mucous .herefore usefulcw mucous .herefore usefulin evaluating potential CSFin evaluating potential CSFrhinorrhearhinorrhea


15/58

CSF CirculationCSF Circulation %atera% ventric%es//%atera% ventric%es//

foramen of Monro thirdforamen of Monro thirdventric%e // aueduct ofventric%e // aueduct ofSy%vius // fourthSy%vius // fourthventric%e // foramina ofventric%e // foramina ofMagendie and Lusch3aMagendie and Lusch3a// su4arachnoid space// su4arachnoid spaceover 4rain and spina%over 4rain and spina%cord // rea4sorptioncord // rea4sorption

into venous sinus 4%oodinto venous sinus 4%oodvia arachnoidvia arachnoidgranu%ationsgranu%ations


16/58

CSF CirculationCSF Circulation


17/58

Kundberg LavesKundberg 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+7remains e%evated fo%%o5ed 4y a rapid fa%% to the 4ase%ine and 5henthey persist for %onger periods, they are ca%%ed :p%ateau: 5aves5hich are patho%ogica%. :0runcated: or atypica% ones, that do note;ceed an e%evation of ! mm )g, are ear%y indicators ofneuro%ogica% deterioration. # < + 5aves are re%ated to respiration

and :0rau4e/)ering/Mayer: 5aves 8rhythmica% variations in 4%oodpressure9 respective%y and are part of norma% physio%ogy 5ith %itt%ec%inica% significance.

Kundberg6* waves


18/58

6* wavesPlateau Laves6* wavesPlateau Laves

Steep rises and abrupt falls in :CP% pea+ing at *A## mmSteep rises and abrupt falls in :CP% pea+ing at *A## mm7g% that last &* '# minutes (also +nown as plateau waves!7g% that last &* '# minutes (also +nown as plateau waves!


19/58

CSF 6bsorptionCSF 6bsorption

CSF is reabsorbed intoCSF is reabsorbed intothe blood of the venousthe blood of the venoussinuses via thesinuses via the

arachnoidal villi .hearachnoidal villi .heabsorption here is directlyabsorption here is directlyrelated to the CSFrelated to the CSFpressure in the cranialpressure in the cranialcavitycavity

KymphaticscribiformKymphaticscribiformplateplate

.ransependymal flow.ransependymal flow


20/58

Route and 6bsorption of CSFRoute and 6bsorption of CSF

6rachnoid villi are microscopic6rachnoid villi are microscopicone*way valves (modified pia andone*way valves (modified pia andarachnoid! that penetrate thearachnoid! that penetrate the

meningeal dural layer that line themeningeal dural layer that line thesinusesM hence% arachnoid villisinusesM hence% arachnoid villireside within the sinusesreside within the sinuses(especially the superior sagittal(especially the superior sagittalsinus!sinus!

Clumps of arachnoid villi NClumps of arachnoid villi N

arachnoid granu%ationsarachnoid granu%ationsNNmacroscopicmacroscopic


21/58

(rachnoid =i%%us


22/58

Route and 6bsorption of CSFRoute and 6bsorption of CSF 7ydrostatic pressure in subarachnoid7ydrostatic pressure in subarachnoid

space , pressure in dural sinusesspace , pressure in dural sinuses .ypical hydrostatic values of CSF are A mm.ypical hydrostatic values of CSF are A mm

77''4 (AA mm 7g! in subarachnoid space vs4 (AA mm 7g! in subarachnoid space vs

about "# mm 7about "# mm 7''4 (& mm 7g! in dural sinuses4 (& mm 7g! in dural sinuses

6rach villi are6rach villi are one-way valvesone-way valvesthat openthat openwhen the hydrostatic pressure of CSF inwhen the hydrostatic pressure of CSF in

the subarachnoid space is about A& mmthe subarachnoid space is about A& mm7g greater than venous hydrostatic7g greater than venous hydrostaticpressure in the dural sinuses (ie% passivepressure in the dural sinuses (ie% passive

process!process!


23/58

8rugs affecting Rate of8rugs affecting Rate of

CSF ProductionCSF Production 8rugs8rugs Carbonic anhydrase inhibitorsCarbonic anhydrase inhibitors

(aceto>olamide8iamox!(aceto>olamide8iamox! Cardiac glycosides (digoxin! inhibit 6.PaseCardiac glycosides (digoxin! inhibit 6.Pase

pump% thereby reducing CSF formation in apump% thereby reducing CSF formation in adose*dependent mannerdose*dependent manner

Steroids* ;ffects on CSF formation areSteroids* ;ffects on CSF formation areinconsistentinconsistent

Future* 6GP inhibitors?% &*7.Future* 6GP inhibitors?% &*7.'C'Creceptor inh ?receptor inh ?


24/58

CSF Pharmacology contCSF Pharmacology cont

Carbonic 6nhydraseCarbonic 6nhydrase C4' 0 7'4 ON7'Co)N,C4' 0 7'4 ON7'Co)N,

7C4)* 0 707C4)* 0 70 :nhibition of C6:::nhibition of C6::

decreases production ofdecreases production ofCSF by # $ byCSF by # $ bydecreasing bicarbonatedecreasing bicarbonateformation in choroidformation in choroidplexusplexus

6cute


25/58

6cute


26/58

6cute


27/58

CSF PathologyCSF 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! .hisRBCs (literature range% A LBC#*A%### RBCs! .hisdisagreement in values ma+es formulas (Fisher ratio etc!disagreement in values ma+es formulas (Fisher ratio etc!

unreliable that attempt to differentiate traumatic tapunreliable that attempt to differentiate traumatic tapartifact from true LBC increase 6lso% the presence ofartifact from true LBC increase 6lso% the presence ofsubarachnoid blood itself may sometimes causesubarachnoid blood itself may sometimes causemeningeal irritation% producing a mild to moderatemeningeal irritation% producing a mild to moderateincrease in P


28/58

CSF PathologyCSF Pathology7atterns 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


29/58

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 1C of cases9

LYMPHOCYTIC: NORMAL GLUCOSE

=ira% meningitis

=ira% encepha%itis

7ostinfectious encepha%itis

Lead encepha%opathy

+NS syphi%is 8maority of patients9

#rain tumor 8occasiona%%y9

Leptospira meningitis 8after the ear%y phase9

Listeria 8a4out 1C of cases9


30/58

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

CBF N CB5tCBF N CB5t " mKminute% which is A&$ of the" mKminute% which is A&$ of the

cardiac outputcardiac output .he normal cerebral blood flow is &*.he normal cerebral blood flow is &*

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 inA min*A in grey matter 7ighest inneurohypophysisneurohypophysis


31/58

CBFCBF

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* ischemicfunction of the cell begins to fail* ischemicpenumbraDpenumbraD

Below mlA##gmin irreversible cellBelow mlA##gmin irreversible cell

death* ionic membrane transport failuredeath* ionic membrane transport failure


32/58

Cerebral Perfusion Pressure (CPP!Cerebral Perfusion Pressure (CPP!

Cerebral Perfusion Pressure (CPP!Cerebral Perfusion Pressure (CPP!


33/58

6utoregulation6utoregulation

CBF is maintained at a constant level in normalCBF is maintained at a constant level in normalbrain in the face of the usual fluctuations inbrain in the face of the usual fluctuations inblood pressure by the process of autoregulationblood pressure by the process of autoregulation:t is a poorly understood local vascular:t is a poorly understood local vascular

mechanism /ormally autoregulation maintainsmechanism /ormally autoregulation maintainsa constant blood flow between CPP mm7ga constant blood flow between CPP mm7gand A mm7gand A mm7g

Poiseuilles law* flow through a rigid vesselIPoiseuilles law* flow through a rigid vesselI

H NH N TTPPUUrrRRKKVV


34/58


35/58


8ysregulation can occur in pathologic states8ysregulation can occur in pathologic states

:n traumatised or ischaemic brain% or following:n traumatised or ischaemic brain% or followingvasodilator agents (volatile agents and sodiumvasodilator agents (volatile agents and sodiumnitroprusside! CBF may become blood pressurenitroprusside! CBF may become blood pressuredependent .hus as arterial pressure rises so CBFdependent .hus as arterial pressure rises so CBF

will rise causing an increase in cerebral volumewill rise causing an increase in cerebral volumeSimilarly as pressure falls so CBF will also fall%Similarly as pressure falls so CBF will also fall%reducing :CP% but also inducing an uncontrolledreducing :CP% but also inducing an uncontrolledreduction in CBFreduction in CBF

6 l i


36/58

pressuremyogenic autoregulationpressuremyogenic autoregulation arterioles dilate or constrict in response to changes in BParterioles dilate or constrict in response to changes in BP

and :CP in order to maintain a constant CBFand :CP in order to maintain a constant CBF myogenic theoryD* vascular smooth muscle withinmyogenic theoryD* vascular smooth muscle within

cerebral arterioles intrinsically contract to stretch therebycerebral arterioles intrinsically contract to stretch therebyregulating pressureregulating 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 beingproduction then loss of autoregulationM with CBF beingcompletely BP*dependentcompletely BP*dependent



37/58


38/58

/eurogenic 6utoregulation/eurogenic 6utoregulation

6utonomic* sympathetic adrenergic6utonomic* sympathetic adrenergicreceptors seen in cortical layers :5 and 5receptors seen in cortical layers :5 and 5

WWAA%%JJ''% and X% and X'' (dilatorsD!% and X(dilatorsD!% and XAA(constrictorD! receptors(constrictorD! receptors

4verall sympathetic system plays minor4verall sympathetic system plays minor

role unli+e in non*cerebral vascular bedsrole unli+e in non*cerebral vascular beds


39/58

/eurogenic 6utoregulation* cont/eurogenic 6utoregulation* cont

&*7.* potent constrictor%D antagoni>ed by /4&*7.* potent constrictor%D antagoni>ed by /4 /europeptide Y* vasoconstrictionD% in assoc/europeptide Y* vasoconstrictionD% in assoc

with /4 and sympathetic systemwith /4 and sympathetic system 5asoactive intestinal polypeptide (5:P! and5asoactive intestinal polypeptide (5:P! and

peptide histidine isoleucine (P7:!* vasodilatorsDpeptide histidine isoleucine (P7:!* vasodilatorsD Substance P% neuro+inin 6% calcitonin gene*Substance P% neuro+inin 6% calcitonin gene*

related peptide histamine 7related peptide histamine 7''*DvasodilatoryD esp*DvasodilatoryD esp

substance Psubstance P CC2% neurotensin% somatostatin% vasopressin%CC2% neurotensin% somatostatin% vasopressin%

endorphinendorphin


40/58

/eurogenic 6utoregulation*cont/eurogenic 6utoregulation*cont

6utonomic system and6utonomic system andneurochemical control ofneurochemical control of

CBF in general is a minorCBF in general is a minorcontrolcontrol

4verall% pressure and4verall% pressure andmetabolic autoregulationmetabolic autoregulationmost importantmost important


41/58

:ncreasing CBF*7yperemia:ncreasing CBF*7yperemia

Kow arterial oxygenKow arterial oxygentension has profoundtension has profound

effects on cerebraleffects on cerebralblood flow Lhen itblood flow Lhen itfalls below mm7gfalls below mm7g(" +Pa!% there is a(" +Pa!% there is a

rapid increase in CBFrapid increase in CBFand arterial bloodand arterial bloodvolumevolume


42/58

CBF and C4CBF and C4''

Carbon dioxideCarbon dioxidecauses cerebralcauses cerebral

vasodilation 6s thevasodilation 6s thearterial tension ofarterial tension ofC4' rises% CB5 andC4' rises% CB5 andCBF increases andCBF increases and

when it is reducedwhen it is reducedvasoconstriction isvasoconstriction isinducedinduced


43/58

Cerebrovascular ReserveDCerebrovascular ReserveD

:n functionally activated areas% CBF augmentationexceeds the small increases in oxygen utili>ation andthe concentration of deoxyhemoglobin is relatively low.hus% this excess supply of oxygen in response to a

demand stimulus reflects the cerebral perfusion reservecapacity

Cerebrovascular reserve capacity is impaired by ris+factors such as hypertension and diabetes%carotidcerebral vasc stenosis% and can be an etiologicfactor in ischemic stro+e


44/58

Cerebrovascular ReserveCerebrovascular Reserve

P;.% SP;C.% Qe*C.% C.*perfusion to assessPrepost diamox challenge

aceta>olamide challenge and the C4'*loading(breath*holding! test raise global CBF

(


45/58


46/58


47/58


48/58

P6.74P7YS:4K4YP6.74P7YS:4K4Y

CSFCBFCSFCBF ''


49/58

Brain P5 curveBrain P5 curve

P5 C9R5; 6/8P5 C9R5; 6/8


50/58

P5 C9R5; 6/8P5 C9R5; 6/8C4


51/58

BloodBrain*BloodCSF BarriersBloodBrain*BloodCSF Barriers

.he blood*brain barrier (BBB! is the speciali>ed.he blood*brain barrier (BBB! is the speciali>edsystem of capillary endothelial cells that protectssystem of capillary endothelial cells that protects

the brain from harmful substances in the bloodthe brain from harmful substances in the bloodstream% while supplying the brain with the reGuiredstream% while supplying the brain with the reGuirednutrients for proper functionnutrients for proper function

Formed by the nonfenestrated capillaries and toFormed by the nonfenestrated capillaries and to

much lesser degree% the astrocytic foot processesmuch lesser degree% the astrocytic foot processes[+eeps out most macromolecules[+eeps out most macromolecules


52/58

BloodBrain BarrierBloodBrain Barrier

BloodBlood


53/58

Blood*Blood*CSFCSF

BarrierBarrier .ightD.ightD

-unctions at-unctions at

thetheependymalependymallevellevel

FenestratedFenestrated

-unctions at-unctions atthe choroidalthe choroidalcapillariescapillaries

.he choroid plexus is composed of fenestratedcapillaries and an epithelial (ependymal! covering%which reverts from ZtightZ to moderately ZopenZ atthe base *not as strenuous of barrier as

bloodbrain


54/58

BloodBrain Barrier andBloodBrain Barrier andCircumventricular organsCircumventricular organs

.he circumventricular organs (C54! are midline.he circumventricular organs (C54! are midlinestructures bordering the )rd and th ventricles .hesestructures bordering the )rd and th ventricles .hesebarrier*deficient areas are recogni>ed as important sitesbarrier*deficient areas are recogni>ed as important sites

for communicating with the CSF and between the brainfor communicating with the CSF and between the brainand peripheral organs via blood*borne products C54\sand peripheral organs via blood*borne products C54\sinclude 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 thesubcommissural organ% organum vasculosum of the

lamina terminalis% and the choroid plexus .helamina terminalis% and the choroid plexus .heintermediate and neural lobes of the pituitary areintermediate and neural lobes of the pituitary aresometimes includedsometimes included


55/58

Causes of an increased :CPCauses of an increased :CP

Conditions :ncreasing Brain 5olumeConditions :ncreasing Brain 5olume intracranial mass (tumor% hematoma%intracranial mass (tumor% hematoma%

aneurysm% 65

process!process!


56/58


Conditions :ncreasing Blood 5olumeConditions :ncreasing Blood 5olume obstruction of venous outflowobstruction of venous outflow hyperemia decreased p4'* inc CBFhyperemia decreased p4'* inc CBF hypercapnea ,pC4' increaseshypercapnea ,pC4' increases

vasodilation inc CB5 % CBF% and :CPvasodilation inc CB5 % CBF% and :CP


57/58


Conditions :ncreasing CSF 5olumeConditions :ncreasing CSF 5olume increased production(Ch plexusincreased production(Ch plexus

papilloma!papilloma! decreased reabsorption of CSFdecreased reabsorption of CSF

(meningitis% S67!(meningitis% S67!

4bstruction to flow of CSF (eg aG4bstruction to flow of CSF (eg aGstenosis!stenosis!


58/58

.7; ;/8.7; ;/8

CSF and Cerebral Blood Flow

Documents

Transcript of CSF and Cerebral Blood Flow