Download MBBS Neuroanaesthesia PPT 11 Cerebrospinal Fluidanatomy Physiology And Dynamics Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Neuroanaesthesia PPT 11 Cerebrospinal Fluidanatomy Physiology And Dynamics Lecture Notes

CEREBROSPINAL FLUID-

ANATOMY, PHYSIOLOGY AND

DYNAMICS

OUTLINE

vCSF SPACES

vCSF FORMATION ? CIRCULATION ? REABSORPTION

vMETHODS OF DETERMINING Vf AND Ra

vEFFECTS OF DRUGS

vALTERATION IN CSF DYNAMICS IN PATHOLOGY
ANATOMY OF CSF SPACES

CSF is clear, colourless liquid that is formed in brain and circulates

through macroscopic & microscopic spaces that are in continuity.

Macroscopic spaces (140-150ml):
? Two lateral ventricles
? Third ventricle
? Aqueduct of sylvius
? Fourth ventricle
? Central canal of spinal cord
Microscopic spaces:
? Brain and spinal cord ECF space (300-350 ml)

THREE DIMENSIONAL SHAPE OF THE VENTRICULAR

SYSTEM

PROPERTIES OF CSF

COMPOSITION
? Na content peaks at 8:00 am & 6:00 pm
? Relationship between Na concentration and migraine has been proposed as

peaks correspond to migraine attacks



.. Harrington MG,Salomon RM, et al. Cerebrospinal fluid sodium rhythms.

Cerebrospinal fluid Res 2010

COMPOSITION

? Varies according to sampling site
? Altered during neuroendoscopy

Na,Cl,Mg

Glucose, Protiens, AA, K ,

HCO3, Ca, Phosphate, Uric acid




FORMATION OF CSF

3 Sites:
? Choroid plexus ( 50 ? 70 %)
? Ependymal surfaces of ventricles
? Perivascular spaces

? Rate ( Vf ) 0.35-0.40 ml/min
500-600 ml/day
? Turnover time- 5-7 hrs (4 times/day)
? 40%-70% enters macroscopic spaces via CP
? 30%-60% enters across ependyma and pia
? Recent studies ? Bidirectional fluid exchange at BBB far exceeds CP csf formation

- Brinker T.,et al. A new look at cerebrospinal fluid circulation. Fluids Barriers

CNS. 2014;11:10-15
Choroid plexus

It is a cauliflower like
growth of blood vessels
covered by a thin layer of
epithelial cells.

It is made of 3 layers:
? fenestrated capillary
endothelium
? extra cellular matrix
? epithelial cells

Choroid plexus projects into:
? Temporal horn of
lateral ventricle
? Post. Part of 3rd ventricle
? Roof of 4th ventricle

Blood supply: ant. & post choroidal
artery (lateral & 3rd ventricle) and supr
cerebeller and PICA (temporal horn & 4th
ventricle)
Nerve supply : branches of Vagus,
Glossopharyngeal & Sympathetic N.
CSF FORMATION AT CHOROID PLEXUS

Blood entering CP capillaries filtered form

protein rich fluid similar to ISF in CP stroma

Hydrostatic pressure & bulk flow enter cleft

between epithelial cells

stromal fluid transported across CP epithelium-
Ultrafiltration & secretion

ATP dependent membrane pump transport Na across luminal surface to
macroscopic spaces in exchange for K & H.
Water moves from stroma into CSF by conc gradient by ionic pump.

CSF FORMATION AT EXTRA CHOROIDAL SITES

vDerived from ECF & cerebral capillaries across BBB
vOxidation of glucose (into H2O & CO2) by brain [60%].
vUltrafiltration from cerebral capillaries[40%]



TIGHT JUNCTIONS

In blood-ECF interface

Pass

Glucose /electrolyte/water/AA/lipid soluble material

Large polar/protein

Stop

Glucose rich and protein poor fluid diffuse through ECF space toward macroscopic spaces
? Water and other constituent of

plasma crosses Blood brain
Barrier into the brain ECF space
by diffusion or transport.

? Water and cellular metabolites

added to the ECF from neurons
and glial cells.

MOVEMENT OF GLUCOSE & PROTEIN

? CSF glucose conc. is approx. 60% of that in blood
? Ratio remains constant till 270 -360mg/dl blood glucose
? Glucose enters CSF -Facilitated transport & follows saturable kinetics (i.e rate

depends on serum glucose conc.)

? Protein entry in CSF limited ? conc. is 0.5% or less of serum conc.
? Protein in CSF transported with CSF & cleared from csf space to dural venous

sinuses by

? "Sink effect" ? flowing CSF keeps CSF & brain protein conc. Low.
EFFECT OF INCREASED ICP ON CSF FORMATION

Relation between Vf and ICP/CPP



? ICP

? CPP

? Vf

? Vf

?As long as CPP remain > 70mm of Hg, increase of ICP[upto 20mm of Hg] has
no major impact on Vf (rate of CSF formation).

?When CPP is significantly lowered <70 mmHgCBF and CPBF , Vf

CIRCULATION OF CSF

? Hydrostatic pressure of CSF formation15 cmH20 produce CSF flow.
? Cilia of ependymal cell generate current to propel CSF toward 4th ventricle & its

foramina into subarachnoid space.

? Respiration variations Additional CSF movement
? Vascular pulsation of cerebral arteries , CP

? 15cm H20 CSF pressure of formation

6 cm of

pressure

?

gradient across

arachnoid villi

? 9 cm H20 superior sagittal sinus pressure
Suction pump effect

Reabsorption ? arachnoid villi (SSS) & spinal dural sinusoids in dorsal nerve
roots.
REABSORPTION

? CSF pass from Subarachnoid spaces via Arachnoid villi & granulation

into venous blood.

? Arachnoid villi or granulations are protrusion of the arachnoid cells from

subarachnoid space into & through wall of venous sinuses

? Arachnoid villi are located:
? Intracranial- Superior Sagittal sinus (85-90% reabsorbed)
? Spinal - dural sinusoids on dorsal nerve root (10-15%)
DETERMINANTS OF REABSORPTION

? Normal intracranial pressure:
? Endothelium covering the villus acts as a CSF- blood barrier
? Rate of pass of CSF? 1.Trans villus hydrostatic pressure gradient

(CSF pressure ? venous sinus pressure)
2.Pressure sensitive resistance to CSF outflow at arachnoid villi

CSF passes through endothelium via: 1. Pinocytotic vesicles

2. Transcellular openings

DETERMINANTS OF REABSORPTION

? Increased intracranial pressure:

? Rate of reabsorption of CSF (Va) if pressure gradient across villus

? Resistance to reabsorption of CSF(Ra) remains normal upto a CSF

pressure of 30 cm of H20; above this it is decreased.
FUNCTION OF CSF

? Protection, 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
47 g.

? Stable supply of nutrients, primarily glucose(active transport); also

vitamins/ eicosanoids/monosaccharides/neutral & basic amino
acids/monocarboxylic acid (specialized pump mechanism).

CONTROL OF CHEMICAL ENVIRONMENT

? Exchange between neural tissue & CSF occurs readily by diffusion
? (because distance b/w CSF and any brain area is max 15 mm & ISF

spaces of brain and spinal cord is continuous with macroscopic CSF
spaces.)

? Acid-base characteristics of CSF influence:-
? Respiration
? CBF, CBF-AR
? Cerebral metabolism
CONTROL OF CHEMICAL ENVIRONMENT

HR

Emotional

BP

CSF

Ca/K/Mg/bicarb

Muscle tone

Vasomotor

Respiration

CONTROL OF CHEMICAL ENVIRONMENT

Primary pumps

? K/HCO3

(active transport) ? Ca/Mg

Secondary pumps ? H+

(passive

? Cl-

transport)
EXCRETION

? Removes metabolic products, unwanted drugs
? BBB excludes out toxic, large , polar and lipid insoluble drug,

humoral agents etc.

INTRACEREBRAL TRANSPORT

MEDIAN

EMINENCE

CSF

ECF

Neuron

Neurohormonal releasing factor formed in hypothalamus
METHODS OF DETERMINING CSF

FORMATION RATE & RESISTANCE TO

CSF ABSORPTION

?Ventriculocisternal perfusion

?Manometric infusion

?Volume injection or withdrawal

VENTRICULOCISTERNAL PERFUSION

? EXPERIMENTAL ANIMALS:
? 1st described in 1960 by Heisey and Pappenheimer.
? Cannula is placed in one/ both lateral ventricles & in cisterna magna.
? Labelled mock CSF infused into the ventricle & mixed sample of labelled and native

CSF collected from cisterna magna.

? Conc. Of labelled CSF in outflow sample is measured & time of sample collection

noted.

? Vf, Va, Ra is measured using formulas.
IN HUMANS:
? Outflow catheter is placed in lumbar subarachnoid(SA) space and ventricular

& spinal CSF pressure closely monitored.

MANOMETRIC INFUSION

? IN EXPERIMENTAL ANIMAL :
? Described by Maffeo and Mann in 1970.
? A manometric infusion device inserted into spinal or supracortical SA space.
? Mock CSF infused into SA space, CSF pressure is measured at same site of

infusion.
? IN HUMANS:
? No. of infusion is reduced & infusion rate are limited to 0.01 - 0.1ml/sec.
? Infusion is restricted to 20-60 secs.
? Infusion discontinued at CSF pressure of 60-70 cm H2O or rapid rise of CSF

pressure.

VOLUME INFUSION OR WITHDRAWAL

? IN EXPERIMENTAL ANIMALS
? Described by Marmarou and Miller in mid 1970.
? Ventricular/spinal SA catheter inserted to permit injection or withdrawal of

CSF & measurement of CSF pressure change that accompanies injection or
withdrawal.
IN HUMANS:
? Previous two methods are less commonly used due to hazards associated with

prolonged infusion of mock CSF.

? Advantages:
? In case of raised ICP- withdrawal of CSF is therapeutic
? Calculate Vf, Ra, compliance (C)
? Risk of infection is minimum(closed system)
? Test can be use for repeated testing.

? anaesthetic and drug induced changes in csf

formation rate (Vf) and resistance to csf

absorption (ra)
INHALED ANESTHETICS

ENFLURANE

Vf

Ra

ICP

LOW[0.9%-1.8%]

0

+

+

HIGH[2.65& 3.5

+ (40%)

0

+

end expired]

ENFLURANE INCREASES METABOLISM
INHALED ANESTHETICS

HALOTHANE

Vf

Ra

ICP

1 MAC

--

+

+

INCREASES GLUCOSE TRANSPORT INTO BRAIN

INCREASES Na/Cl/H2O/ALBUMIN TRANSPORT INTO CSF

HALOTHANE INDUCED STIMULATION OF VASOPRESSIN RECEPTORSDECREASE

Vf

INHALED ANESTHETICS

ISOFLURANE

Vf

Ra

ICP

LOW[0.6]

0

0

0

[1.1%]

0

+

+

HIGH[1.7-2.2]

0

--

--
INHALED ANESTHETICS

SEVOFLURANE

Vf

Ra

ICP

1 MAC

--

+

?

INHALED ANESTHETICS

DESFLURANE

Vf

Ra

ICP

HYPOCAPNIA &

0

+

+

CSF PRESSURE (0.5
& 1 MAC)

OTHER SITUATI0NS

0

0

0
INHALED ANESTHETICS

NITROUS OXIDE

Vf

Ra

ICP

66%

0

0

0

DECREASES BRAIN GLUCOSE INFLUX AND EFFLUX
I.V. ANESTHETICS

KETAMINE

Vf

Ra

ICP

40mg/kg/hr

0

+

+

I.V. ANESTHETICS

ETOMIDATE

Vf

Ra

ICP

Low dose .86mg/kg 0

0

0

High dose

--

--

--
I.V. ANESTHETICS

PROPOFOL

Vf

Ra

ICP

6mg/kg

0

0

0

12,24, &
48 mg/kg/hr

PENTOBARBITAL

Vf

Ra

ICP

40mg/kg

0

0

0

I.V. ANESTHETICS

THIOPENTAL

Vf

Ra

ICP

LOW (6mg/kg F/B 0

+/0

+/0

6-12mg/kg/hr)
HIGH (18-

--

--

--

24mg/kg/hr)
I.V. ANESTHETICS (SEDATIVES

&HYPNOTICS)

MIDAZOLAM

Vf

Ra

ICP

LOW (1.6mg/kg fb 0

+

+

0.5mg/kg/hr)
INTERMEDIATE (1-

0

0

0

1.5 mg/kg/hr)
HIGH (2mg/kg/hr)

--

+

--/?

FLUMAZENIL

Vf

Ra

ICP

LOW (0.0025

0

0

0

mg/kg)
HIGH (0.16 mg/kg) 0

--
I.V. ANESTHETICS (OPIOIDS)

FENTANYL

Vf

Ra

ICP

LOW DOSE

0

--

--

HIGH DOSE

--

0/+

--/?

SUFENTANYL

Vf

Ra

ICP

LOW DOSE

0

--

--

HIGH DOSE

0

+/0

+/0

AlFENTANYL

Vf

Ra

ICP

LOW DOSE

0

--

--

HIGH DOSE

0

0

0
I.V. ANESTHETICS

LIDOCAINE

Vf

Ra

ICP

0.5mg/kg

--

0

0/+

1?g/kg/min
CRUX OF VF AND RA

?

? Ra increases

Vf increases

?

? Halothane ( 1MAC)

High dose Enflurane

? DES( hypocapnia + increase csf pressure)
? Low dose enflurane
? Sevo ( 1 MAC )
? Midazolam(low dose)
? Ketamine

Both Vf & Ra Fentanyl , Etomidate

I.V DRUGS

? IV acetaminophen moves readily and attains peak conc. in an hour in CSF

rapid central analgesia and antipyretic effect

? Ibuprofen : peak at 30-40 min
DIURETICS

Vf

MECHANISM

ACETAZOLAMIDE

-- BY 50%

INHIBITION OF CA
INDIRECT ACTION ON ION
TRANSPORT(VIA HCO3)
CONSTRICTS CP ARTERIOLES
& DECREASE CPBF

METHAZOLAMIDE

ACETAZOLAMIDE +OUABAIN Vf BY 95%= ADDITIVE

DIURETICS

Vf MECHANISM

FUROSEMIDE

--

DECREASE Na+ OR Cl-
TRANSPORT

MANNITOL

--

DECREASE CP OUTPUT
AND ECF FLOW FROM
BRAIN TO CSF
COMPARTMENT
OTHERS

DRUG

Vf

MECHANISM

DIGOXIN,OUABAIN

--

INHIBIT NA-K PUMP OF CP

THEOPHYLLIN

+

PHOSPHODIESTERASE
INHIBITOR
CAMPSTIMULATE
CP NA-K PUMP

VASSOPRESSIN

--

CONSTRICTS CP BLOOD
VESSELS

3% HYPER TONIC SALINE

--

OSMOLALITY GRADIENT FOR
MOVEMENT OF FLUID
PLASMACP OR BRAIN
TISSUE OR CSF

DINITROPHENOL

--

UNCOUPLE OXIDATIVE
PHOSPHORYLATION

ANP

--

CGMP

MUSCLE RELAXANT

RELAXANTV

Vf

Ra

SCOLINE, VECURONIUM

0

0

INFUSION
STEROIDS

? Decrese Ra
? MethylPrednisolone/prednisolone/cortisone/dexamethasone
? Probable mechanism :

? Improved CSF flow in SA spaces/ A.villi
? Reversal of metabolically induced changes in structure of villi, action at CP

? Dexamethasone Vf by 50%(inhibition of Na-K ATPase)

ALTERATION IN VARIOUS PATHOLOGY

? Intracranial volume changes
? Volume of intracranial blood/gas/tissue CSF volume

?Mechanism: Translocation into spinal spaces

? increased reabsorption

? Volume of intracranial blood/gas/tissue CSF volume

?Mechanism: Cephalad translocation

? Decreased reabsorption
ACUTE SAH

? Increases ICP
? Intrathecal injection: Whole blood, plasma, diasylate of plasma, serum &

saline--- Va & Ra values measured by Manometric method

? Whole blood and plasma raised ICP and caused a 3 to 10 fold rise in Ra

respectively

? Fibrin deposits within villi
CHRONIC CHANGES AFTER SAH

? Extensive fibrosis of villi leptomeningeal scarring functional

narrowing or blockage of CSF outflow tracts [ Ra is

increased]hydrocephalus

BACTERIAL MENINGITIS

? Animal study with S.pnemoniae, E coli
? ICP & Ra increased in both
? Even with antibiotic Ra remained high for 2 weeks post Rx
? Methyl prednisolone ed Ra to a value that was intermediate between control

and infected.
PSEUDOTUMOR CEREBRI

? Increased ICP Increased 1.Ra, 2.Vf, 3. greater water

movement into brain 4 . CBF & CBV, 5 glial or cellular edema .

? Impaired reabsorption is the principal cause
? Prednisone decreases Ra

HEAD INJURY

Ra increased and Vf within normal limits in 75% patients.

20% of the raised ICP derived from changes in Ra /Vf.
IN SUMMARY

? CSF plays a key role in brain well being

? Vf changes : changes ICP

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

? In raised ICP, Anesthetics induced changes in Vf & Ra significantly alter the

effectiveness of treatments employed to reduce ICP.