Physiology of CSF dynamics with an anaesthesia eye!

1. PHYSIOLOGY OF CSF PRODUCTION
AND CIRCULATION, ALTERATIONS IN
VARIOUS PATHOLOGY
Dr Unnikrishnan P

2. 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

3. OUTLINE
CSF SPACES
CSF FORMATION-CIRCULATION-REABSORPTION
METHODS OF DETERMINING Vf and Ra
EFFECTS OF DRUGS
REGULATION
ALTERATION IN CSF DYNAMICS IN PATHOLOGIES

4. 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

5. 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

6. 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.

7. CHOROID PLEXUS BLOOD SUPPLY
. of lateral ventricle
Body Posterior choroidal artery
Body of third ventricle Anterior choroidal artery
Temporal horns Superior cerebellar artery
Fourth ventricles Posterior inferior cerebellar
artery
NERVE SUPPLY:IX,X, Sympathetic
nerves

8. MACROSCOPIC SPACES
 Two lateral ventricles
Third ventricle
Aqueduct of sylvius
Fourth ventricle
Central canal of spinal cord
Subarachnoid spaces

9. 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 ?

10. COMPOSITION
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

11. COMPOSITION
Vary according to sampling site
Altered during neuroendoscopy

12. CSF FORMATION

13. 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

14. @ CHOROID PLEXUS
L

15. @ CHOROID PLEXUS
Blood filtered protein rich
fluid similar to ISF
Hydrostatic pressure & bulk
flow-> enter cleft between
cells
Ultra filtration & secretion

16. @EXTRA CHOROIDAL SITES
Oxidation of glucose by brain [60%]
Ultra filtration from cerebral capillaries [40%]
TIGHT JUNCTIONS 
Glucose/electrolyte/water
Large polar/protein

17. MOVEMENT OF GLUCOSE
Glucose concentration is 60% that of plasma
Remains constant, unless blood glucose
>270-360
Enters CSF quickly by facilitated transport
Rate ∝ Serum glucose [not on gradient]

18. 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

19. Vƒ & ICP/CPP
Vƒ
↑ ICP
Vƒ
↓CPP

20. 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]

21. CIRCULATION OF CSF
Hydrostatic pressure of CSF formation
Cilia of ependymal cells
Respiratory variations
Vascular pulsations of cerebral arteries,CP

22. Site of formation
Choroid plexus of the
lateral ventricle
1. Lateral ventricle
Superiorly Interventricular foramina Superiorly
2. Third ventricle
Cerebral aqueduct Absorbed
Absorbed
3. Fourth ventricle
3.2 Lateral 3.2 Lateral
foramina foramina
(Luschka) (Luschka)
3.1 Median
foramen
(Magendie)
4. Subarachnoid space
Inferiorly

23. 5
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

24. Circulation of CSF in subarachnoid space :
Superior
cistern
Chiasmatic
cistern
Median
Interpeduncular foramen of
cistern 4th ventricle
Pontine Cerebellomedullary
cistern cistern
Median sagittal section to show the subarachnoid cisterns
& circulation of CSF

25. REABSORPTION
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%]

26. 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…

27. Arachnoid villus
L

28. ‘Traced’ journey
Radio labelled CSF enters
Low Cx-High Tx @ 10-20’
Tx-lumbar @ 30-40’
L-S cul de sac @60-90’
Basal cisterns @ 2-2.5 hrs
SSS @12-24 hrs

29. 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

30. Determinants of reabsorption
Rate of rebsorption of CSF (Va)
Resistance to reabsorption (Ra)
(Va) increase as the pressure gradient increase
(Ra) remains normal upto a CSF pressure of 30
cm of H2O; above this it decreases

31. CSF drainage & cerebral edema
vasogenic edema resolves partly by drainage
of fluid into ventricular CSF
Factors influencing:
(1) pressure gradient between brain tissue and CSF
(2) sink action of CSF
Brain ECF proteins cleared by glial uptake

32. 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

33. Control of the chemical environment
Exchange between neural tissue & CSF is easy
diffusion distance 15mm (max) & ISF space and
CSF spaces are continuous
CBF
CMR
CSF CBF-AR
Respiration

34. Control of the chemical environment

35. Control of the chemical environment
L

36. Excretion
Removes metabolic products,unwanted
drugs
BBB excludes out toxic large,polar and lipid
insoluble drugs, humoral agents etc

37. Intracerebral transport
MEDIAN
CSF EMINENCE
Neurohormone releasing factors formed in
hypothalamus

38. METHODS OF DETERMINING
CSF FORMATION RATE &
RESISTANCE TO CSF
ABSORPTION
• Plasm
• CSF

39. 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

40. 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

41. 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
Va= ViCi - V0C0/C0
V0=outflow rate of CSF from cisternal cannula
Ra= reciprocal measure of the slope relating
Va to CSF pressure

42. 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; Vf and Ra are
derived from this plot; compliance also can be
derived

43. 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 & Vf
and Ra from it.

44. METHODS OF DETERMINING
CSF FORMATION RATE &
RESISTANCE TO CSF
ABSORPTION
• Plasm
• CSF

45. 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

46. 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

47. 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

48. .
ANESTHETIC AND DRUG INDUCED CHANGES IN CSF
FORMATION RATE AND RESISTANCE TO CSF
ABSORPTION AND TRANSPORT OF VARIOUS
MOLECULES INTO CSF AND THE CNS

49. INHALED ANESTHETICS
ENFLURANE Vf Ra ICP
LOW [0.9% &1.8%] 0 + +
HIGH [2.65 &3.5 end + 0 +
expired]
ENFLURANE INDUCE INCREASED CP METABOLISM

50. INHALED ANESTHETICS
HALOTHANE Vf Ra ICP
1 MAC -- + +
INCREASE GLUCOSE TRANSPORT INTO BRAIN
INCREASE Na/Cl/H2O/Albumin TRANSPORT INTO CSF
HALOTHANE INDUCED STIMULATION OF VASOPRESSIN RECEPTORSDECREASE Vf

51. INHALED ANESTHETICS
ISOFLURANE Vf Ra ICP
LOW[0.6] 0 0 0
LOW[1.1%] 0 + +
HIGH[1.7,2.2%] 0 -- --
GLUTAMATE CONCENTRATION IN CSF IS MORE WHEN
ISOFLURANE IS USED THAN IN PROPOFOL BASED ANESTHESIA

52. INHALED ANESTHETICS
SEVOFLURANE Vf Ra ICP
1MAC -- + ?

53. INHALED ANESTHETICS
DESFLURANE Vf Ra ICP
HYPOCAPNIA & ↑CSF + + +
PRESSURE
OTHER SITUATIONS 0 0 0
ONLY FRUSEMIDE 2MG/KG DECREASED Vf IN THE FIRST
SITUATION.

54. INHALED ANESTHETICS
NITROUS OXIDE Vf Ra ICP
66% 0 0 0
DECREASE BRAIN GLUCOSE INFLUX AND EFFLUX

55. I.V. ANESTHETICS
KETAMINE Vf Ra ICP
40MG/KG/HR 0 + +
DECREASE TRANSPORT OF SMALL HYDROPHILIC MOLECULES
ACROSS BBB

56. I.V. ANESTHETICS
ETOMIDATE Vf Ra ICP
LOW [.86MG/KG.86MG/KG/HR] 0 0 0
HIGH[2.58MG/KG/HR] -- -- --

57. I.V. ANESTHETICS
PROPOFOL Vf Ra ICP
6MG/KG12,24 & 48 MG/KG/HR 0 0 0
PENTOBARBITAL Vf Ra ICP
40MG/KG 0 0 0
CSF CONCENTRATION OF PROPOFOL IS APPROX 60% OF THAT OF PLASMA
CONCENTRATION

58. 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

59. 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

60. 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

61. I.V. DRUGS
LIDOCAINE Vf Ra ICP
.5MG/KG1μG/KG/MIN -- 0 0/--
1.5 3
4.5 9

62. 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

63. DIURETICS
Vf MECHANISMS
ACETAZOLAMIDE -- BY 50% INHIBITION OF CARBONIC ANHYDRASE
METHAZOLAMIDE INDIRECT ACTION ON ION TRANSPORT [VIA HCO3]
CONSTRICT CP ARTERIOLES & ↓ CPBF
ACETAZOLAMIDE +OUABAIN↓Vf BY 95% = ADDITIVE

64. OTHERS
DRUG L Vf MECHANISM
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
ANP -- ↑cGMP

65. DIURETICS
Vf MECHANISMS
FUROSEMIDE -- DECREASE Na+ OR Cl- TRANSPORT
MANNITOL -- DECREASED CP OUTPUT AND ECF
FLOW FROM BRAIN TO CSF
COMPARTMENT

66. MUSCLE RELAXANTS
RELAXANTS Vf Ra
SCOLINE, VECURONIUM INFUSIONS 0 0

67. 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]

68. REGULATION OF Vf /Ra

69. 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

70. Adrenergic system
α  constriction βdilatation
Decrease carbonic anhydrase activity
Norepinephrine:↓ Vf
high α mediated vasoconstriction
Low β1 mediated inhibitory action on CP

71. Cholinergic system
Also ↓ Vf
Receptors presumably muscarinic
Act on CP epithelium, rather than on
vasculature

72. METABOLIC REGULATION
HYPOTHERMIA: ↓ Vf – By decreasing
secretory and transport process and by ↓ing
CBF
between 41310 C: each 10 C↓in
temperature, ↓ Vf by 11%
HYPOCAPNIA: acutely ↓ Vf [mechanism :
↓ CBF, ↓ H+ for exchange with Na]

73. METABOLIC REGULATION
Metabolic alkalosis ↓ Vf due to pH effect
Metabolic acidosis: no change

74. ↓ Vf in change of osmolarity/
Wald & associates
↑osmolarity of
serum
↓osmolarity of
ventricular CSF
↓/↑ in Vf caused by change in serum
osmolarity 4 times higher

75. ALTERATIONS IN VARIOUS
PATHOLOGIES
.

76. Intracranial volume change
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

77. 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

78. 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↑

79. INTRACRANIAL MASS
ANIMAL STUDY IN 3 GROUPS OF DOGS
GROUP 1 HYPOCAPNIA
GROUP2 I.C. MASS
GROUP3 I.C.MASS + HYPOCAPNIA
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

80. EFFECT OF ANESTHETICS
FIVE GROUP OF DOGS
Vf Ra ICP REASON
ENFLURANE ↑ ↑ ↑ CSF VOL DIDN’T↓TO THE EXTENT OF CBV
REEXPANSION
HALOTHANE ↑ ↑ ↑
ISOFLURANE N N N CSF VOL CONTRACTION= CBV REEXPANSION
FENTANYL N N N REEXPANSION MINIMAL
THIOPENTAL N N N CSF VOL CONTRACTION= CBV REEXPANSION

81. 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

82. C/C CHANGES AFTER SAH
Extensive fibrosis leptomeningeal
scarring functional narrowing or blockage
of CSF outflow tracts [Ra is increased]
hydrocephalus

83. 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

84. PSEUDOTUMOR CEREBRI
Increased Ra , Vf ,water movement into brain,
CBF & CBV
increased ICP
Impaired reabsorption is the principal cause
Prednisone decreased Ra

85. Head Injury
20% of the raised ICP derived from changes
in Ra &Vf

86. 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

87. So……
We demand more attention from you..

88. HEAD INJURY
THANK YOU