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Dr KA MPOLO D
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OUTLINE
CSF SPACES
CSF FORMATION-CIRCULATION-REABSORPTION
EFFECTS OF DRUGS
REGULATION
Introduction
CSF flows via macroscopic & ECF spaces
PRESSURES AND VOLUMES
CSF PRESSURE [mm of Hg]
CHILDREN 3.0-7.5
ADULTS 4.5-13.5
CSF VOLUME [mL]
INFANTS 40-60
YOUNG CHILDREN 60-100
OLDER CHILDREN 80-120
ADULTS 100-160
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CHOROID PLEXUS
Invagination of blood vessels & leptomeninges
covered by a layer of modified ependyma
Anatomy
• Choroid plexus projects into
• The temporal horn of each lateral ventricle,
• the posterior portion of the third ventricle &
• the roof of the fourth ventricle.
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.
Body of lateral ventricle Posterior choroidal artery
are small
Capillary – ECF exchange is l i m i t e d
Blood brain barrier
Whats your diameter?
………<20 A⁰ ?
COMPOSITION
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Plasma CSF
Na+(mM) 140 141
K+(mM)
L 4.6 2.9
Mg2+(mM) 1.7 2.4
Ca2+(mM) 5.0 2.5
Cl-(mM) 101 124
HCO3-(mM) 23 21
Glucose (mM) 92 61
Amino acids (mM) 2.3 0.8
pH 7.41 7.31
Osmolality (mosmol.Kg
289 289
H2O-1)
Protein (mg 100 g-1) 7000 28
Specific gravity 1.025 1.007
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COMPOSITION
Vary according to sampling site
CSF FORMATION
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CSF FORMATION
Rate [Vƒ] 0.35-0.40 mL/min OR
500-600 mL/day
0.25% of total vol replaced each minute
Turn over time for total CSF vol 5-7 hours
= 4 times / day
40%-70% enters macroscopic spaces via CP
30%-60% enters across ependyma and pia
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@ CHOROID PLEXUS
L
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@ CHOROID PLEXUS
TIGHT JUNCTIONS
Glucose/electrolyte/water
Large polar/protein
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MOVEMENT OF GLUCOSE
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
VENTRICLES 26MG/100ML
CISTERNA MAGNA 32MG/100ML
LUMBAR SAC 42MG/100ML
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Vƒ & ICP/CPP
Vƒ
↑ ICP
Vƒ
↓CPP
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Vƒ and ICP/CPP
As long as CPP remains >70 mm of Hg,
increase of ICP [upto 20 mm of Hg] has no
major impact on Vƒ
When CPP is significantly lowered CBF↓
CPBF↓, Vƒ↓
But Rate of reabsorption(Va); @ ICPs > 7 cms
of H2O, Va ↑ directly as ICP ↑[relation
linear upto ICP of 30 cms of H2O]
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CIRCULATION OF CSF
Hydrostatic pressure of CSF formation
Cilia of ependymal cells
Respiratory variations
Vascular pulsations of cerebral arteries,CP
SiteSuite
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2. Third ventricle
Cerebral aqueduct Absorbed
Absorbed
3. Fourth ventricle
4. Subarachnoid space
Inferiorly
5
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Superiorly =
lateral aspect Choroid plexus of
of each 1 the lateral
cerebral 2 ventricle
hemisphere
3
Choroid plexus of 3.2
the 3rd ventricle
3.1 Choroid plexus
of the 4th
Inferiorly = ventricle
subarachnoid 4
space around
the brain &
spinal cord
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Circulation of CSF in subarachnoid space :
Superior
cistern
Chiasmatic
cistern
Median
Interpeduncular foramen of
cistern 4th ventricle
Pontine Cerebellomedullary
cistern cistern
REABSORPTION
Subarachnoid spaceArachnoid 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%]
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Reabsorption
High velocity of blood flow through the fixed
diameter of the sinuses & the low
intraluminal pressure that develops @ the
circumference of the sinus wall where the
arachnoid villi enter, cause a suction –pump
action circulation continues over a wide
range of postural pressures…
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Arachnoid villus
L
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‘Traced’ journey
Radio labelled CSF enters
Tx-lumbar @ 30-40’
Determinants of reabsorption
Endothelium covering the villus acts as a CSF-
blood barrier
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
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Determinants of reabsorption
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
Stable supply of nutrients ,primarily glucose;
also vitamins
/eicosanoids/monosaccharides/neutral &
basic Amino acids
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CMR
CSF CBF-AR
Respiration
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Excretion
Intracerebral transport
MEDIAN
CSF EMINENCE
METHODS OF DETERMINING
CSF FORMATION RATE &
RESISTANCE TO CSF
ABSORPTION
• Plasm
• CSF
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VENTRICULOCISTERNAL PERFUSION
Outflow catheter in lumbar subarachnoid
space
Ventricular & spinal CSF pressures are closely
monitored to ensure that obstructed
perfusion do not ↑ CSF pressure very high
Needs >1 hour
Mock CSF
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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
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INHALED ANESTHETICS
ENFLURANE Vf Ra ICP
LOW [0.9% &1.8%] 0 + +
INHALED ANESTHETICS
HALOTHANE Vf Ra ICP
1 MAC -- + +
INHALED ANESTHETICS
ISOFLURANE Vf Ra ICP
LOW[0.6] 0 0 0
LOW[1.1%] 0 + +
HIGH[1.7,2.2%] 0 -- --
INHALED ANESTHETICS
SEVOFLURANE Vf Ra ICP
1MAC -- + ?
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INHALED ANESTHETICS
DESFLURANE Vf Ra ICP
HYPOCAPNIA & ↑CSF + + +
PRESSURE
OTHER SITUATIONS 0 0 0
INHALED ANESTHETICS
NITROUS OXIDE Vf Ra ICP
66% 0 0 0
I.V. ANESTHETICS
KETAMINE Vf Ra ICP
40MG/KG/HR 0 + +
I.V. ANESTHETICS
ETOMIDATE Vf Ra ICP
LOW [.86MG/KG.86MG/KG/HR] 0 0 0
HIGH[2.58MG/KG/HR] -- -- --
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I.V. ANESTHETICS
PROPOFOL Vf Ra ICP
6MG/KG12,24 & 48 MG/KG/HR 0 0 0
PENTOBARBITAL Vf Ra ICP
40MG/KG 0 0 0
I.V. ANESTHETICS
THIOPENTAL Vf Ra ICP
LOW DOSE[6MG/KG F/B 6-12MG/KG/HR] 0 +/0 +/0
HIGH DOSE[18-24MG/KG/HR] -- -- --
INCREASE
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I.V. ANESTHETICS
MIDAZOLAM Vf Ra ICP
LOW[1.6MG/KG.5MG/KG/HR] 0 + +
INTERMEDIATE[1-1.5MG/KG/HR] 0 0 0
HIGH [2MG/KG/HR] -- + --/?
FLUMAZENIL Vf Ra ICP
LOW[.0025MG/KG] 0 0 0
HIGH [.16MG/KG] 0 -- --
LOW[DOGS GETTING MIDAZOLAM] 0 +
HIGH[ “ ] 0 0
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OPIOIDS
FENTANYL Vf Ra ICP
LOW DOSE 0 -- --
HIGH DOSE -- 0/+ --/?
SUFENTANIL Vf Ra ICP
LOW DOSE 0 -- --
HIGH DOSE 0 0/+ 0/+
ALFENTANIL Vf Ra ICP
LOW DOSE 0 -- --
HIGH DOSE 0 0 0
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I.V. DRUGS
LIDOCAINE Vf Ra ICP
.5MG/KG1μG/KG/MIN -- 0 0/--
1.5 3
4.5 9
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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
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DIURETICS
Vf MECHANISMS
ACETAZOLAMIDE -- BY 50% INHIBITION OF CARBONIC ANHYDRASE
METHAZOLAMIDE INDIRECT ACTION ON ION TRANSPORT [VIA HCO3]
CONSTRICT CP ARTERIOLES & ↓ CPBF
OTHERS
DRUG L Vf MECHANISM
DIURETICS
Vf MECHANISMS
MUSCLE RELAXANTS
RELAXANTS Vf Ra
STEROIDS
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]
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REGULATION OF Vf /Ra
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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
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Adrenergic system
α constriction βdilatation
Decrease carbonic anhydrase activity
Norepinephrine:↓ Vf
high α mediated vasoconstriction
Low β1 mediated inhibitory action on CP
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Cholinergic system
Also ↓ Vf
Receptors presumably muscarinic
Act on CP epithelium, rather than on
vasculature
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METABOLIC REGULATION
HYPOTHERMIA: ↓ Vf – By decreasing
secretory and transport process and by ↓ing
CBF
between 41310 C: each 10 C↓in
temperature, ↓ Vf by 11%
METABOLIC REGULATION
↓osmolarity of
ventricular CSF
.
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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
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INTRACRANIAL MASS
ANIMAL STUDY IN 3 GROUPS OF DOGS
GROUP 1 HYPOCAPNIA
GROUP2 I.C. MASS
GROUP3 I.C.MASS + HYPOCAPNIA
EFFECT OF ANESTHETICS
FIVE GROUP OF DOGS
Vf Ra ICP REASON
HALOTHANE ↑ ↑ ↑
ACUTE SAH
Itrathecal injection: W.Blood / plasma
/dialysate of plasma/serum/saline
Bacterial meningitis
Animal study with 1.S pneumoniae 2.E coli
↓ is increased
Even with antibiotics it remained high for 2
weeks post Rx
Methyl prednisolone ↓ed Ra to a value
between control and infected
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PSEUDOTUMOR CEREBRI
Head Injury
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
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So……
HEAD INJURY
THANK YOU