SINH lý physiology of CSF

• Choroid plexus projects into • The temporal horn of each lateral ventricle, • the posterior portion of the third ventricle & • the roof of the fourth ventricle... MOVEMENT OF GLUCOSEGl

PHYSIOLOGY OF CSF PRODUCTION AND CIRCULATION, ALTERATIONS IN VARIOUS

PATHOLOGY

LE DINH TUNG MD, PhD Department of Physiology Hanoi Medical University

First few drops…

Emanuel Swedenborg who discovered CSF, referred to it as “highly gifted juice” that is dispensed from the roof of the fourth

ventricle to the medulla oblongata, and the spinal cord

Albrecht von Haller found that that the

“water” in the brain, in case of excess

secretion, descends to the base of the skull resulting in hydrocephalus

CSF SPACES

CSF FORMATION-CIRCULATION-REABSORPTION METHODS OF DETERMINING V f and R a

EFFECTS OF DRUGS

REGULATION

ALTERATION IN CSF DYNAMICS IN PATHOLOGIES

CSF  flows via macroscopic & ECF spaces

PRESSURES AND VOLUMES

CHOROID PLEXUS

Invagination of blood vessels & leptomeninges covered by a layer of modified ependyma

Epithelium is the blood-CSF barrier

Carbonic anhydrase present in the epithelium

& Na-K pump in luminal plasma membrane

play major role in CSF formation

• Choroid plexus projects into

• The temporal horn of each lateral ventricle,

• the posterior portion of the third ventricle &

• the roof of the fourth ventricle

CHOROID PLEXUS BLOOD SUPPLY

Body of lateral ventricle Posterior choroidal artery Body of third ventricle Anterior choroidal artery

Fourth ventricles Posterior inferior cerebellar

artery NERVE SUPPLY:IX,X, Sympathetic

nerves

MICROSCOPIC SPACES- BRAIN &

SPINAL CORD ECF SPACES

are small

Capillary – ECF exchange is l i m i t e d

Blood brain barrier

Whats your diameter?

………<20 A⁰ ?

Na,Cl,Mg

Glucose,Protein,AA, K,HCO3,Ca,P

Vary according to sampling site

Altered during neuroendoscopy

CSF FORMATION

@ CHOROID PLEXUS

L

@EXTRA CHOROIDAL SITES

Oxidation of glucose by brain [60%]

Ultra filtration from cerebral capillaries [40%]

Glucose/electrolyte/water

Large polar/protein

MOVEMENT OF GLUCOSE

Glucose concentration is 60% that of plasmaRemains constant, unless blood glucose

>270-360

Enters CSF quickly by facilitated transport

Rate ∝ Serum glucose [not on gradient]

MOVEMENT OF PROTEIN

CSF protein concentrations are 0.5% or less than that of plasma protein concentration [60% @ CP / 40%@ extrachoroidal sites]

If structural barrier between ECF & CSF

spaces are not intact, it enters, but then also cleared from CSF spaces into dural sinuses -

because of the sink effect of flowing CSF 

CISTERNA MAGNA 32MG/100ML

Vƒ & ICP/CPP

↑ ICP Vƒ

Vƒ

↓CPP

But Rate of reabsorption(Va); @ ICPs > 7 cms

of H2O, Va ↑ directly as ICP ↑[relation linear upto ICP of 30 cms of H2O]

CIRCULATION OF CSF

Hydrostatic pressure of CSF formation

Cilia of ependymal cells

Respiratory variations

Vascular pulsations of cerebral arteries,CP

15 cm H2O @ formation

9 cm H2O

@SSS

Choroid plexus of the lateral ventricle

foramen (Magendie)

3.2 Lateral foramina (Luschka)

5

3.2 3.1

ventricle

Median sagittal section to show the subarachnoid cisterns

& circulation of CSF

Superior cistern

Interpeduncular

cistern

Cerebellomedullary cistern

Chiasmatic

cistern

Pontine cistern

Circulation of CSF in subarachnoid space :

Median foramen of

4 th ventricle

Subarachnoid spaceArachnoid villi &

granulation venous blood

are protrusion of the arachnoid matter through perforations in the dura into the lumina of

venous sinuses

Intracranial-Superior sagittal sinus[85%-90%]

Spinal-dural sinusoids on dorsal nerve roots[15%]

arachnoid villi enter, cause a suction –pump

action circulation continues over a wide

range of postural pressures…

Arachnoid villus

L

Determinants of reabsorption

Endothelium covering the villus acts as a blood barrier

CSF-Trans villous hydrostatic pressure gradient

[CSF pressure-Venous sinus pressure]

Pressure sensitive resistance to CSF outflow at the arachnoid villus

If through endothelium:(1)pinocytic vesicles

(2)transcellular openings

CSF drainage & cerebral edema

vasogenic edema resolves partly by drainage

of fluid into ventricular CSF

FUNCTIONS OF CSF- support,nutrition

The low specific gravity of CSF (1.007) relative

to that of the brain(1.040) reduces the

effective mass of a 1400g brain to only 47g

also vitamins

/eicosanoids/monosaccharides/neutral &

basic Amino acids

Control of the chemical environment

Exchange between neural tissue & CSF is easy diffusion distance 15mm (max) & ISF space and CSF spaces are continuous

CSF

CBF

CBF-AR

Respiration CMR

Control of the chemical environment

EMOTIONAL

Control of the chemical environment

PUMPS

METHODS OF DETERMINING CSF FORMATION RATE & RESISTANCE

TO CSF ABSORPTION

• Plasm

• CSF

VENTRICULO CISTERNAL PERFUSION

Heisey and colleagues & Pappenheimer and associates

Cannula placed in one or both lateral

ventricle and in cisterna magna

Labeled mock CSF into ventricles

Labeled mock + Native CSF collected from cisternal cannula & volume determined

VENTRICULO CISTERNAL PERFUSION

Vf = Vi {Ci –C0/C0}

Vi= mock CSF inflow rate

Ci= concentration of label in mock CSF

C0=concentration of label in the mixed outflow solution

VENTRICULO CISTERNAL PERFUSION

V f = V i {C i –C 0 /C 0 }

Vi= mock CSF inflow rate

Ci= concentration of label in mock CSF

C0=concentration of label in the mixed outflow solution

V a = V i C i - V 0 C 0 /C 0

V0=outflow rate of CSF from cisternal cannula

R a = reciprocal measure of the slope relating V a

to CSF pressure

MANOMETRIC INFUSION

Maffeo and colleagues & Mann and associates Manometric infusion device inserted into the

spinal/supracortical SubArachnoid Space[SAS]

Mock CSF into the SAS

CSF pressure measured @ same site of infusion Each steady state CSF pressure[Ps] is paired with its associated Vi

Vi vs Ps semilog plot is made; V f and R a are

derived

VOLUME INJECTION OR WITHDRAWAL

Marmarou and colleagues and Miller

Ventricular or spinal subarachnoid catheter for injection or withdrawal of CSF and for

measurement of accompanying CSF pressure change

Resting CSF pressure [P0] is determined and a known volume of CSF is injected/withdrawn

with timed recording of CSF pressure

Pressure Volume Index[PVI] calculated & V f and

R a from it.

METHODS OF DETERMINING CSF FORMATION RATE & RESISTANCE

TO CSF ABSORPTION

• Plasm

• CSF

MANOMETRIC INFUSION

Number of infusions are reduced

Infusion rate 1.5-15 times Vf [.01-.1mL/sec]

Infusions restricted to20-60 sec

Discontinued @ CSF pressures of 60-70 cm H2O/ rapid rise

Needs multiple infusions

Mock CSF

VOLUME INJECTION OR WITHDRAWAL

No hazard associated with mock CSF

Hence more commonly used

CSF withdrawal can be therapeutic

Closed system- hence risk of infection less

More suitable for repeated testing

Calculation needs only a single change of CSF volume and pressure lasting for minutes

ANESTHETIC AND DRUG INDUCED CHANGES IN CSF FORMATION RATE AND RESISTANCE TO CSF

ABSORPTION AND TRANSPORT OF VARIOUS

MOLECULES INTO CSF AND THE CNS

INHALED ANESTHETICS

INCREASE GLUCOSE TRANSPORT INTO BRAIN

INCREASE Na/Cl/H2O/Albumin TRANSPORT INTO CSF

0 +

0 +

GLUTAMATE CONCENTRATION IN CSF IS MORE WHEN

ISOFLURANE IS USED THAN IN PROPOFOL BASED ANESTHESIA

INHALED ANESTHETICS

+ 0

+ 0

SITUATION

I.V ANESTHETICS

LOW [.86MG/KG.86MG/KG/HR]

+ 0 +

+ 0 /?

0 + 0

0

0/ I.V DRUGS

IV acetaminophen permeate readily

and attain peak concentration in 1 hour

in CSF rapid central analgesia and

antipyretic effects

Ibuprofen :peak @ 30-40 mins

V f MECHANISMS

ACETAZOLAMIDE

METHAZOLAMIDE BY 50% INHIBITION OF CARBONIC ANHYDRASE INDIRECT ACTION ON ION TRANSPORT [VIA HCO3]

CONSTRICT CP ARTERIOLES & ↓ CPBF

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DIGOXIN , OUABAIN INHIBIT Na-K PUMP OF CP

THEOPHYLLIN + PHOSPHODIESTERASE INHIBITION↑cAMP 

STIMULATE CP Na-K PUMP VASOPRESSIN CONSTRICT CP BLOOD VESSELS

3% HYPERTONIC SALINE ↓OSMOLALITY GRADIENT FOR MOVEMENT OF

FLUID PLASMACP OR BRAIN TISSUECSF DINITROPHENOL UNCOUPLE OXIDATIVE PHOSPHORYLATION

DECREASE ENERGY AVAILABLE FOR MEMBRANE PUMP

V f MECHANISMS

FUROSEMIDE

MANNITOL DECREASE Na+ OR Cl- TRANSPORT DECREASED CP OUTPUT AND ECF

FLOW FROM BRAIN TO CSF COMPARTMENT

MUSCLE RELAXANTS

Decrease Ra

M.prednisolone/prednisone/cortisone/dexa

Probable mechanisms postulated:

Improved CSF flow in subarachnoid spaces/

A villi

Reversal of metabolically induced changes in

the structure of the villi, action @ CP

Dexamethasone ↓Vf by 50% [inhibition of Na-K ATPase]

REGULATION OF Vf /Ra

NEUROGENIC REGULATION

Adrenergic nerves from superior and lower

cervical ganglia innervate CP

Lateral ventricle– U/L

Midline ventricle– B/L

3rd ventricle rich in cholinergic innervation, whereas 4th ventricle devoid of it

Peptidergic nerves contain VIP and

substance-P : both are potent vasodilators

Adrenergic system

α  constriction βdilatation

Decrease carbonic anhydrase activity

Norepinephrine:↓ Vf

high α mediated vasoconstriction

Low β1 mediated inhibitory action on CP

Cholinergic system

Also ↓ Vf

Receptors presumably muscarinic

Act on CP epithelium, rather than on vasculature

HYPOCAPNIA: acutely ↓ Vf [mechanism :

↓ CBF, ↓ H+ for exchange with Na]

METABOLIC REGULATION

Metabolic alkalosis ↓ Vf due to pH effectMetabolic acidosis: no change

↓ Vf in change of osmolarity/

Wald & associates

↓/↑ in Vf caused by change in serum osmolarity 4 times higher

↑osmolarity of

serum

↓osmolarity of ventricular CSF

ALTERATIONS IN VARIOUS PATHOLOGIES

Intracranial volume change

Volume of intracranial blood/gas/tissue ↑  CSF volume ↓

Volume of intracranial blood/gas/tissue ↓  CSF volume ↑

MECHANISM: >TRANSLOCATION INTO SPINAL SPACES

>INCREASED REABSORPTION

MECHANISM: >CEPHALAD TRANSLOCATION

>DECREASED REABSORPTION

SUBDURAL HEMATOMA

Adds volume  ↑ ICP  driving force for

reabsorption  Va > Vf  CSF volume

contracts  ICP↓ Va starts returning to

normal Va & Vf in a new equillibrium–

Here ICP & total intracranial volume are same

as before SDH, but CBV is ↑ed and CSF

volume ↓ed

SURGICAL REMOVAL OF TUMOR

Sx ↓ intracranial volume ↓ed ICP a weak driving force for reabsorption Va ↓, Vf same CSF accumulates and volume expand ICP↑ and reach pre surgical valuesstimulate Va  Va

↑ Va = Vf

here,ICP same; brain volume ↓;

CSF volume↑

INTRACRANIAL MASS

ANIMAL STUDY IN 3 GROUPS OF DOGS

Hypocapnia ↓ed an increased ICP initially by decreasing CBV but with sustained

hypocapnia,CBV reexpanded but H.C

improved access of I.C CSF to spinal sites of reabsorption so CSF vol ↓ed ICP remained lower than initial values

ACUTE SAH

Itrathecal injection: W.Blood / plasma

/dialysate of plasma/serum/saline

Whole blood and plasma raised ICP and

caused a 3 to 10 fold rise in Ra respectively

C/C CHANGES AFTER SAH

Extensive fibrosis leptomeningeal scarring functional narrowing or blockage of CSF

outflow tracts [Ra is increased]

hydrocephalus

Methyl prednisolone ↓ed Ra to a value

between control and infected

Head Injury

20% of the raised ICP derived from changes

in Ra &Vf

It means…

Vf changes: changes ICP

Ra changes: changes ICP, alters pressure buffering capacity of brain

Anesthetics induced changes in both,

significantly alters Rx to reduce ICP

We demand more attention from you

HEAD INJURY

THANK YOU