PHYSIOLOGY OF CSF PRODUCTIONAND CIRCULATION, ALTERATIONS IN      VARIOUS PATHOLOGY            Dr Unnikrishnan P
First few drops… Emanuel Swedenborg who discovered CSF,referred to it as “highly gifted juice” that isdispensed from the r...
OUTLINECSF SPACESCSF FORMATION-CIRCULATION-REABSORPTIONMETHODS OF DETERMINING Vf and RaEFFECTS OF DRUGSREGULATIONALTERATIO...
IntroductionCSF  flows via macroscopic & ECF spacesPRESSURES AND VOLUMESCSF PRESSURE [mm of Hg]CHILDREN                  ...
CHOROID PLEXUSInvagination of blood vessels & leptomeningescovered by a layer of modified ependymaEpithelium is the blood-...
Anatomy•   Choroid plexus projects into•   The temporal horn of each lateral ventricle,•   the posterior portion of the th...
CHOROID PLEXUS BLOOD SUPPLY . of lateral ventricleBody                             Posterior choroidal arteryBody of third...
MACROSCOPIC SPACES Two lateral ventriclesThird ventricleAqueduct of sylviusFourth ventricleCentral canal of spinal co...
MICROSCOPIC SPACES- BRAIN &  SPINAL CORD ECF SPACES are small Capillary – ECF exchange is l i m i t e d Blood brain barrie...
COMPOSITION                            Plasma    CSFNa+(mM)                      140      141K+(mM)          L            ...
COMPOSITIONVary according to sampling siteAltered during neuroendoscopy
CSF FORMATION
CSF FORMATIONRate [Vƒ] 0.35-0.40 mL/min OR             500-600 mL/day0.25% of total vol replaced each minuteTurn over tim...
@ CHOROID PLEXUSL
@ CHOROID PLEXUSBlood filtered protein richfluid similar to ISF   Hydrostatic pressure & bulk   flow-> enter cleft betwee...
@EXTRA CHOROIDAL SITESOxidation of glucose by brain [60%]Ultra filtration from cerebral capillaries [40%]TIGHT JUNCTIONS ...
MOVEMENT OF GLUCOSEGlucose concentration is 60% that of plasmaRemains constant, unless blood glucose>270-360Enters CSF qui...
MOVEMENT OF PROTEINCSF protein concentrations are 0.5% or lessthan that of plasma protein concentration[60% @ CP / 40%@ ex...
Vƒ & ICP/CPP               Vƒ↑ ICP Vƒ                ↓CPP
Vƒ and ICP/CPPAs long as CPP remains >70 mm of Hg,increase of ICP [upto 20 mm of Hg] has nomajor impact on VƒWhen CPP is s...
CIRCULATION OF CSFHydrostatic pressure of CSF formationCilia of ependymal cellsRespiratory variationsVascular pulsations o...
Site of formation                                  Choroid plexus of the                                  lateral ventricl...
5  Superiorly =  lateral aspect                         Choroid plexus of  of each                     1          the late...
Circulation of CSF in subarachnoid space :                                                     Superior                   ...
REABSORPTIONSubarachnoid spaceArachnoid villi &granulation venous bloodare protrusion of the arachnoid matter throughper...
ReabsorptionHigh velocity of blood flow through the fixeddiameter of the sinuses & the lowintraluminal pressure that devel...
Arachnoid villusL
‘Traced’ journeyRadio labelled CSF enters        Low Cx-High Tx @ 10-20’          Tx-lumbar @ 30-40’            L-S cul de...
Determinants of reabsorptionEndothelium covering the villus acts as a CSF-blood barrierTrans villous hydrostatic pressure ...
Determinants of reabsorptionRate of rebsorption of CSF (Va)Resistance to reabsorption (Ra)(Va) increase as the pressure gr...
CSF drainage & cerebral edema vasogenic edema resolves partly by drainageof fluid into ventricular CSFFactors influencing:...
FUNCTIONS OF CSF-support,nutrition  The low specific gravity of CSF (1.007) relative  to that of the brain(1.040) reduces ...
Control of the chemical environmentExchange between neural tissue & CSF is easydiffusion distance 15mm (max) & ISF space a...
Control of the chemical environment
Control of the chemical environment  L
ExcretionRemoves metabolic products,unwanteddrugsBBB excludes out toxic large,polar and lipidinsoluble drugs, humoral agen...
Intracerebral transport                                     MEDIAN                             CSF    EMINENCENeurohormone...
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 v...
VENTRICULO CISTERNAL PERFUSION Vf = Vi {Ci –C0/C0} Vi= mock CSF inflow rate Ci= concentration of label in mock CSF C0=conc...
VENTRICULO CISTERNAL PERFUSION Vf = Vi {Ci –C0/C0} Vi= mock CSF inflow rate Ci= concentration of label in mock CSF C0=conc...
MANOMETRIC INFUSIONMaffeo and colleagues & Mann and associatesManometric infusion device inserted into thespinal/supracort...
VOLUME INJECTION OR WITHDRAWAL  Marmarou and colleagues and Miller  Ventricular or spinal subarachnoid catheter  for injec...
METHODS OF DETERMINING          CSF FORMATION RATE &          RESISTANCE TO CSF          ABSORPTION• Plasm• CSF
VENTRICULOCISTERNAL PERFUSION Outflow catheter in lumbar subarachnoid space Ventricular & spinal CSF pressures are closely...
MANOMETRIC INFUSIONNumber of infusions are reducedInfusion rate 1.5-15 times Vf [.01-.1mL/sec]Infusions restricted to20-60...
VOLUME INJECTION OR WITHDRAWAL  No hazard associated with mock CSF  Hence more commonly used  CSF withdrawal can be therap...
.ANESTHETIC AND DRUG INDUCED CHANGES IN CSF FORMATION RATE AND RESISTANCE TO CSF ABSORPTION AND TRANSPORT OF VARIOUS MOLEC...
INHALED ANESTHETICSENFLURANE             Vf    Ra     ICPLOW [0.9% &1.8%]      0     +      +HIGH [2.65 &3.5 end   +     0...
INHALED ANESTHETICSHALOTHANE                Vf        Ra      ICP1 MAC                    --        +       +INCREASE GLUC...
INHALED ANESTHETICSISOFLURANE            Vf    Ra    ICPLOW[0.6]              0     0     0LOW[1.1%]             0     +  ...
INHALED ANESTHETICSSEVOFLURANE   Vf   Ra   ICP1MAC          --   +    ?
INHALED ANESTHETICSDESFLURANE          Vf      Ra    ICPHYPOCAPNIA & ↑CSF   +       +     +PRESSUREOTHER SITUATIONS    0  ...
INHALED ANESTHETICSNITROUS OXIDE      Vf       Ra    ICP66%                0        0     0DECREASE BRAIN GLUCOSE INFLUX A...
I.V. ANESTHETICSKETAMINE          Vf      Ra     ICP40MG/KG/HR        0       +      +DECREASE TRANSPORT OF SMALL HYDROPHI...
I.V. ANESTHETICSETOMIDATE                    Vf   Ra   ICPLOW [.86MG/KG.86MG/KG/HR]   0    0    0HIGH[2.58MG/KG/HR]      ...
I.V. ANESTHETICSPROPOFOL                                 Vf     Ra     ICP6MG/KG12,24 & 48 MG/KG/HR               0      ...
I.V. ANESTHETICSTHIOPENTAL                          Vf   Ra    ICPLOW DOSE[6MG/KG F/B 6-12MG/KG/HR]   0    +/0   +/0HIGH D...
I.V. ANESTHETICSMIDAZOLAM                     Vf   Ra   ICPLOW[1.6MG/KG.5MG/KG/HR]      0    +    +INTERMEDIATE[1-1.5MG/K...
OPIOIDSFENTANYL     Vf      Ra     ICPLOW DOSE     0       --     --HIGH DOSE    --      0/+    --/?SUFENTANIL   Vf      R...
I.V. DRUGSLIDOCAINE            Vf   Ra   ICP.5MG/KG1μG/KG/MIN   --   0    0/--1.5    34.5    9
I.V. DRUGS IV acetaminophen permeate readilyand attain peak concentration in 1 hourin CSF rapid central analgesia andanti...
DIURETICS                Vf          MECHANISMSACETAZOLAMIDE   -- BY 50%   INHIBITION OF CARBONIC ANHYDRASEMETHAZOLAMIDE  ...
OTHERSDRUG   L               Vf    MECHANISMDIGOXIN , OUABAIN      --    INHIBIT Na-K PUMP OF CPTHEOPHYLLIN            +  ...
DIURETICS             Vf   MECHANISMSFUROSEMIDE   --   DECREASE Na+ OR Cl- TRANSPORTMANNITOL     --   DECREASED CP OUTPUT ...
MUSCLE RELAXANTSRELAXANTS                       Vf   RaSCOLINE, VECURONIUM INFUSIONS   0    0
STEROIDS Decrease RaM.prednisolone/prednisone/cortisone/dexaProbable mechanisms postulated:Improved CSF flow in subarachno...
REGULATION OF Vf /Ra
NEUROGENIC REGULATIONAdrenergic nerves from superior and lowercervical ganglia innervate CPLateral ventricle– U/LMidline v...
Adrenergic systemα  constriction βdilatationDecrease carbonic anhydrase activityNorepinephrine:↓ Vfhigh α mediated vaso...
Cholinergic systemAlso ↓ VfReceptors presumably muscarinicAct on CP epithelium, rather than onvasculature
METABOLIC REGULATIONHYPOTHERMIA: ↓ Vf – By decreasingsecretory and transport process and by ↓ingCBF between 41310 C: each...
METABOLIC REGULATIONMetabolic alkalosis ↓ Vf due to pH effectMetabolic acidosis: no change
↓ Vf in change of osmolarity/      Wald & associates                          ↑osmolarity of                             s...
ALTERATIONS IN VARIOUS         PATHOLOGIES.
Intracranial volume changeVolume of intracranial blood/gas/tissue ↑ CSF volume ↓MECHANISM: >TRANSLOCATION INTO SPINAL SPA...
SUBDURAL HEMATOMAAdds volume  ↑ ICP  driving force forreabsorption  Va > Vf  CSF volumecontracts  ICP↓ Va starts ret...
SURGICAL REMOVAL OF TUMORSx ↓ intracranial volume ↓ed ICP a weakdriving force for reabsorption Va ↓, Vfsame CSF accumu...
INTRACRANIAL MASSANIMAL STUDY IN 3 GROUPS OF DOGS GROUP 1           HYPOCAPNIA GROUP2            I.C. MASS GROUP3         ...
EFFECT OF ANESTHETICS       FIVE GROUP OF DOGS              Vf   Ra   ICP   REASONENFLURANE     ↑    ↑    ↑     CSF VOL DI...
ACUTE SAHItrathecal injection: W.Blood / plasma/dialysate of plasma/serum/salineWhole blood and plasma raised ICP andcause...
C/C CHANGES AFTER SAHExtensive fibrosis leptomeningealscarring functional narrowing or blockageof CSF outflow tracts [R...
Bacterial meningitisAnimal study with 1.S pneumoniae 2.E coli↓ is increasedEven with antibiotics it remained high for 2wee...
PSEUDOTUMOR CEREBRIIncreased Ra , Vf ,water movement into brain,CBF & CBVincreased ICPImpaired reabsorption is the princi...
Head Injury20% of the raised ICP derived from changesin Ra &Vf
It means…Vf changes: changes ICPRa changes: changes ICP, alters pressurebuffering capacity of brainAnesthetics induced cha...
So……We demand more attention from you..
HEAD INJURYTHANK YOU
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PHYSIOLOGY OF CSF PRODUCTION AND CIRCULATION, ALTERATIONS IN VARIOUS PATHOLOGY

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PHYSIOLOGY OF CSF PRODUCTION AND CIRCULATION, ALTERATIONS IN VARIOUS PATHOLOGY

  1. 1. PHYSIOLOGY OF CSF PRODUCTIONAND CIRCULATION, ALTERATIONS IN VARIOUS PATHOLOGY Dr Unnikrishnan P
  2. 2. First few drops… Emanuel Swedenborg who discovered CSF,referred to it as “highly gifted juice” that isdispensed from the roof of the fourthventricle to the medulla oblongata, and thespinal cord.Albrecht von Haller found that that the“water” in the brain, in case of excesssecretion, descends to the base of the skullresulting in hydrocephalus
  3. 3. OUTLINECSF SPACESCSF FORMATION-CIRCULATION-REABSORPTIONMETHODS OF DETERMINING Vf and RaEFFECTS OF DRUGSREGULATIONALTERATION IN CSF DYNAMICS IN PATHOLOGIES
  4. 4. IntroductionCSF  flows via macroscopic & ECF spacesPRESSURES AND VOLUMESCSF PRESSURE [mm of Hg]CHILDREN 3.0-7.5ADULTS 4.5-13.5CSF VOLUME [mL]INFANTS 40-60YOUNG CHILDREN 60-100OLDER CHILDREN 80-120ADULTS 100-160
  5. 5. CHOROID PLEXUSInvagination of blood vessels & leptomeningescovered by a layer of modified ependymaEpithelium is the blood-CSF barrierCarbonic anhydrase present in the epithelium& Na-K pump in luminal plasma membraneplay major role in CSF formation
  6. 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. 7. CHOROID PLEXUS BLOOD SUPPLY . of lateral ventricleBody Posterior choroidal arteryBody of third ventricle Anterior choroidal arteryTemporal horns Superior cerebellar arteryFourth ventricles Posterior inferior cerebellar arteryNERVE SUPPLY:IX,X, Sympatheticnerves
  8. 8. MACROSCOPIC SPACES Two lateral ventriclesThird ventricleAqueduct of sylviusFourth ventricleCentral canal of spinal cordSubarachnoid spaces
  9. 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. 10. COMPOSITION Plasma CSFNa+(mM) 140 141K+(mM) L 4.6 2.9Mg2+(mM) 1.7 2.4Ca2+(mM) 5.0 2.5Cl-(mM) 101 124HCO3-(mM) 23 21Glucose (mM) 92 61Amino acids (mM) 2.3 0.8pH 7.41 7.31Osmolality (mosmol.Kg 289 289H2O-1)Protein (mg 100 g-1) 7000 28Specific gravity 1.025 1.007
  11. 11. COMPOSITIONVary according to sampling siteAltered during neuroendoscopy
  12. 12. CSF FORMATION
  13. 13. CSF FORMATIONRate [Vƒ] 0.35-0.40 mL/min OR 500-600 mL/day0.25% of total vol replaced each minuteTurn over time for total CSF vol  5-7 hours= 4 times / day40%-70% enters macroscopic spaces via CP30%-60% enters across ependyma and pia
  14. 14. @ CHOROID PLEXUSL
  15. 15. @ CHOROID PLEXUSBlood filtered protein richfluid similar to ISF Hydrostatic pressure & bulk flow-> enter cleft between cells Ultra filtration & secretion
  16. 16. @EXTRA CHOROIDAL SITESOxidation of glucose by brain [60%]Ultra filtration from cerebral capillaries [40%]TIGHT JUNCTIONS Glucose/electrolyte/waterLarge polar/protein
  17. 17. MOVEMENT OF GLUCOSEGlucose concentration is 60% that of plasmaRemains constant, unless blood glucose>270-360Enters CSF quickly by facilitated transportRate ∝ Serum glucose [not on gradient]
  18. 18. MOVEMENT OF PROTEINCSF protein concentrations are 0.5% or lessthan that of plasma protein concentration[60% @ CP / 40%@ extrachoroidal sites]If structural barrier between ECF & CSFspaces are not intact, it enters, but then alsocleared 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. 19. Vƒ & ICP/CPP Vƒ↑ ICP Vƒ ↓CPP
  20. 20. Vƒ and ICP/CPPAs long as CPP remains >70 mm of Hg,increase of ICP [upto 20 mm of Hg] has nomajor impact on VƒWhen CPP is significantly lowered  CBF↓CPBF↓, Vƒ↓But Rate of reabsorption(Va); @ ICPs > 7 cmsof H2O, Va ↑ directly as ICP ↑[relationlinear upto ICP of 30 cms of H2O]
  21. 21. CIRCULATION OF CSFHydrostatic pressure of CSF formationCilia of ependymal cellsRespiratory variationsVascular pulsations of cerebral arteries,CP
  22. 22. Site of formation Choroid plexus of the lateral ventricle 1. Lateral ventricleSuperiorly 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. 23. 5 Superiorly = lateral aspect Choroid plexus of of each 1 the lateral cerebral 2 ventricle hemisphere 3Choroid plexus of 3.2the 3rd ventricle 3.1 Choroid plexus of the 4th Inferiorly = ventricle subarachnoid 4 space around the brain & spinal cord
  24. 24. Circulation of CSF in subarachnoid space : Superior cisternChiasmaticcistern Median Interpeduncular foramen of cistern 4th ventricle Pontine Cerebellomedullary cistern cistern Median sagittal section to show the subarachnoid cisterns & circulation of CSF
  25. 25. REABSORPTIONSubarachnoid spaceArachnoid villi &granulation venous bloodare protrusion of the arachnoid matter throughperforations in the dura into the lumina ofvenous sinusesIntracranial-Superior sagittal sinus[85%-90%]Spinal-dural sinusoids on dorsal nerve roots[15%]
  26. 26. ReabsorptionHigh velocity of blood flow through the fixeddiameter of the sinuses & the lowintraluminal pressure that develops @ thecircumference of the sinus wall where thearachnoid villi enter, cause a suction –pumpaction circulation continues over a widerange of postural pressures…
  27. 27. Arachnoid villusL
  28. 28. ‘Traced’ journeyRadio 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. 29. Determinants of reabsorptionEndothelium covering the villus acts as a CSF-blood barrierTrans villous hydrostatic pressure gradient [CSF pressure-Venous sinus pressure]Pressure sensitive resistance to CSF outflow atthe arachnoid villusIf through endothelium:(1)pinocytic vesicles (2)transcellular openings
  30. 30. Determinants of reabsorptionRate of rebsorption of CSF (Va)Resistance to reabsorption (Ra)(Va) increase as the pressure gradient increase(Ra) remains normal upto a CSF pressure of 30cm of H2O; above this it decreases
  31. 31. CSF drainage & cerebral edema vasogenic edema resolves partly by drainageof fluid into ventricular CSFFactors influencing:(1) pressure gradient between brain tissue and CSF (2) sink action of CSFBrain ECF proteins cleared by glial uptake
  32. 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. 33. Control of the chemical environmentExchange between neural tissue & CSF is easydiffusion distance 15mm (max) & ISF space andCSF spaces are continuous CBF CMR CSF CBF-AR Respiration
  34. 34. Control of the chemical environment
  35. 35. Control of the chemical environment L
  36. 36. ExcretionRemoves metabolic products,unwanteddrugsBBB excludes out toxic large,polar and lipidinsoluble drugs, humoral agents etc
  37. 37. Intracerebral transport MEDIAN CSF EMINENCENeurohormone releasing factors formed inhypothalamus
  38. 38. METHODS OF DETERMINING CSF FORMATION RATE & RESISTANCE TO CSF ABSORPTION• Plasm• CSF
  39. 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. 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. 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. 42. MANOMETRIC INFUSIONMaffeo and colleagues & Mann and associatesManometric infusion device inserted into thespinal/supracortical SubArachnoid Space[SAS]Mock CSF into the SASCSF pressure measured @ same site of infusionEach steady state CSF pressure[Ps] is pairedwith its associated ViVi vs Ps semilog plot is made; Vf and Ra arederived from this plot; compliance also can bederived
  43. 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. 44. METHODS OF DETERMINING CSF FORMATION RATE & RESISTANCE TO CSF ABSORPTION• Plasm• CSF
  45. 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. 46. MANOMETRIC INFUSIONNumber of infusions are reducedInfusion rate 1.5-15 times Vf [.01-.1mL/sec]Infusions restricted to20-60 secDiscontinued @ CSF pressures of 60-70 cmH2O/ rapid riseNeeds multiple infusionsMock CSF
  47. 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. 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. 49. INHALED ANESTHETICSENFLURANE Vf Ra ICPLOW [0.9% &1.8%] 0 + +HIGH [2.65 &3.5 end + 0 +expired] ENFLURANE INDUCE INCREASED CP METABOLISM
  50. 50. INHALED ANESTHETICSHALOTHANE Vf Ra ICP1 MAC -- + +INCREASE GLUCOSE TRANSPORT INTO BRAININCREASE Na/Cl/H2O/Albumin TRANSPORT INTO CSFHALOTHANE INDUCED STIMULATION OF VASOPRESSIN RECEPTORSDECREASE Vf
  51. 51. INHALED ANESTHETICSISOFLURANE Vf Ra ICPLOW[0.6] 0 0 0LOW[1.1%] 0 + +HIGH[1.7,2.2%] 0 -- --GLUTAMATE CONCENTRATION IN CSF IS MORE WHENISOFLURANE IS USED THAN IN PROPOFOL BASED ANESTHESIA
  52. 52. INHALED ANESTHETICSSEVOFLURANE Vf Ra ICP1MAC -- + ?
  53. 53. INHALED ANESTHETICSDESFLURANE Vf Ra ICPHYPOCAPNIA & ↑CSF + + +PRESSUREOTHER SITUATIONS 0 0 0ONLY FRUSEMIDE 2MG/KG DECREASED Vf IN THE FIRSTSITUATION.
  54. 54. INHALED ANESTHETICSNITROUS OXIDE Vf Ra ICP66% 0 0 0DECREASE BRAIN GLUCOSE INFLUX AND EFFLUX
  55. 55. I.V. ANESTHETICSKETAMINE Vf Ra ICP40MG/KG/HR 0 + +DECREASE TRANSPORT OF SMALL HYDROPHILIC MOLECULESACROSS BBB
  56. 56. I.V. ANESTHETICSETOMIDATE Vf Ra ICPLOW [.86MG/KG.86MG/KG/HR] 0 0 0HIGH[2.58MG/KG/HR] -- -- --
  57. 57. I.V. ANESTHETICSPROPOFOL Vf Ra ICP6MG/KG12,24 & 48 MG/KG/HR 0 0 0PENTOBARBITAL Vf Ra ICP40MG/KG 0 0 0 CSF CONCENTRATION OF PROPOFOL IS APPROX 60% OF THAT OF PLASMA CONCENTRATION
  58. 58. I.V. ANESTHETICSTHIOPENTAL Vf Ra ICPLOW DOSE[6MG/KG F/B 6-12MG/KG/HR] 0 +/0 +/0HIGH DOSE[18-24MG/KG/HR] -- -- --INCREASE
  59. 59. I.V. ANESTHETICSMIDAZOLAM Vf Ra ICPLOW[1.6MG/KG.5MG/KG/HR] 0 + +INTERMEDIATE[1-1.5MG/KG/HR] 0 0 0HIGH [2MG/KG/HR] -- + --/?FLUMAZENIL Vf Ra ICPLOW[.0025MG/KG] 0 0 0HIGH [.16MG/KG] 0 -- --LOW[DOGS GETTING MIDAZOLAM] 0 +HIGH[ “ ] 0 0
  60. 60. OPIOIDSFENTANYL Vf Ra ICPLOW DOSE 0 -- --HIGH DOSE -- 0/+ --/?SUFENTANIL Vf Ra ICPLOW DOSE 0 -- --HIGH DOSE 0 0/+ 0/+ALFENTANIL Vf Ra ICPLOW DOSE 0 -- --HIGH DOSE 0 0 0
  61. 61. I.V. DRUGSLIDOCAINE Vf Ra ICP.5MG/KG1μG/KG/MIN -- 0 0/--1.5 34.5 9
  62. 62. I.V. DRUGS IV acetaminophen permeate readilyand attain peak concentration in 1 hourin CSF rapid central analgesia andantipyretic effectsIbuprofen :peak @ 30-40 mins
  63. 63. DIURETICS Vf MECHANISMSACETAZOLAMIDE -- BY 50% INHIBITION OF CARBONIC ANHYDRASEMETHAZOLAMIDE INDIRECT ACTION ON ION TRANSPORT [VIA HCO3] CONSTRICT CP ARTERIOLES & ↓ CPBFACETAZOLAMIDE +OUABAIN↓Vf BY 95% = ADDITIVE
  64. 64. OTHERSDRUG L Vf MECHANISMDIGOXIN , OUABAIN -- INHIBIT Na-K PUMP OF CPTHEOPHYLLIN + PHOSPHODIESTERASE INHIBITION↑cAMP  STIMULATE CP Na-K PUMPVASOPRESSIN -- CONSTRICT CP BLOOD VESSELS3% HYPERTONIC SALINE -- ↓OSMOLALITY GRADIENT FOR MOVEMENT OF FLUID PLASMACP OR BRAIN TISSUECSFDINITROPHENOL -- UNCOUPLE OXIDATIVE PHOSPHORYLATION DECREASE ENERGY AVAILABLE FOR MEMBRANE PUMPANP -- ↑cGMP
  65. 65. DIURETICS Vf MECHANISMSFUROSEMIDE -- DECREASE Na+ OR Cl- TRANSPORTMANNITOL -- DECREASED CP OUTPUT AND ECF FLOW FROM BRAIN TO CSF COMPARTMENT
  66. 66. MUSCLE RELAXANTSRELAXANTS Vf RaSCOLINE, VECURONIUM INFUSIONS 0 0
  67. 67. STEROIDS Decrease RaM.prednisolone/prednisone/cortisone/dexaProbable mechanisms postulated:Improved CSF flow in subarachnoid spaces/A. villiReversal of metabolically induced changes inthe structure of the villi, action @ CPDexamethasone ↓Vf by 50% [inhibition of Na-KATPase]
  68. 68. REGULATION OF Vf /Ra
  69. 69. NEUROGENIC REGULATIONAdrenergic nerves from superior and lowercervical ganglia innervate CPLateral ventricle– U/LMidline ventricle– B/L3rd ventricle rich in cholinergicinnervation, whereas 4th ventricle devoid ofitPeptidergic nerves contain VIP andsubstance-P : both are potent vasodilators
  70. 70. Adrenergic systemα  constriction βdilatationDecrease carbonic anhydrase activityNorepinephrine:↓ Vfhigh α mediated vasoconstrictionLow β1 mediated inhibitory action on CP
  71. 71. Cholinergic systemAlso ↓ VfReceptors presumably muscarinicAct on CP epithelium, rather than onvasculature
  72. 72. METABOLIC REGULATIONHYPOTHERMIA: ↓ Vf – By decreasingsecretory and transport process and by ↓ingCBF between 41310 C: each 10 C↓intemperature, ↓ Vf by 11%HYPOCAPNIA: acutely ↓ Vf [mechanism :↓ CBF, ↓ H+ for exchange with Na]
  73. 73. METABOLIC REGULATIONMetabolic alkalosis ↓ Vf due to pH effectMetabolic acidosis: no change
  74. 74. ↓ Vf in change of osmolarity/ Wald & associates ↑osmolarity of serum ↓osmolarity of ventricular CSF↓/↑ in Vf caused by change in serumosmolarity 4 times higher
  75. 75. ALTERATIONS IN VARIOUS PATHOLOGIES.
  76. 76. Intracranial volume changeVolume of intracranial blood/gas/tissue ↑ CSF volume ↓MECHANISM: >TRANSLOCATION INTO SPINAL SPACES >INCREASED REABSORPTIONVolume of intracranial blood/gas/tissue ↓ CSF volume ↑MECHANISM: >CEPHALAD TRANSLOCATION >DECREASED REABSORPTION
  77. 77. SUBDURAL HEMATOMAAdds volume  ↑ ICP  driving force forreabsorption  Va > Vf  CSF volumecontracts  ICP↓ Va starts returning tonormal Va & Vf in a new equillibrium–Here ICP & total intracranial volume are sameas before SDH, but CBV is ↑ed and CSFvolume ↓ed
  78. 78. SURGICAL REMOVAL OF TUMORSx ↓ intracranial volume ↓ed ICP a weakdriving force for reabsorption Va ↓, Vfsame CSF accumulates and volumeexpand ICP↑ and reach pre surgicalvaluesstimulate Va  Va ↑ Va = Vf here,ICP same; brain volume ↓; CSF volume↑
  79. 79. INTRACRANIAL MASSANIMAL STUDY IN 3 GROUPS OF DOGS GROUP 1 HYPOCAPNIA GROUP2 I.C. MASS GROUP3 I.C.MASS + HYPOCAPNIAHypocapnia ↓ed an increased ICP initially bydecreasing CBV but with sustainedhypocapnia,CBV reexpanded but H.C.improved access of I.C CSF to spinal sites ofreabsorption so CSF vol ↓ed ICPremained lower than initial values
  80. 80. EFFECT OF ANESTHETICS FIVE GROUP OF DOGS Vf Ra ICP REASONENFLURANE ↑ ↑ ↑ CSF VOL DIDN’T↓TO THE EXTENT OF CBV REEXPANSIONHALOTHANE ↑ ↑ ↑ISOFLURANE N N N CSF VOL CONTRACTION= CBV REEXPANSIONFENTANYL N N N REEXPANSION MINIMALTHIOPENTAL N N N CSF VOL CONTRACTION= CBV REEXPANSION
  81. 81. ACUTE SAHItrathecal injection: W.Blood / plasma/dialysate of plasma/serum/salineWhole blood and plasma raised ICP andcaused a 3 to 10 fold rise in Ra respectively
  82. 82. C/C CHANGES AFTER SAHExtensive fibrosis leptomeningealscarring functional narrowing or blockageof CSF outflow tracts [Ra is increased]hydrocephalus
  83. 83. Bacterial meningitisAnimal study with 1.S pneumoniae 2.E coli↓ is increasedEven with antibiotics it remained high for 2weeks post RxMethyl prednisolone ↓ed Ra to a valuebetween control and infected
  84. 84. PSEUDOTUMOR CEREBRIIncreased Ra , Vf ,water movement into brain,CBF & CBVincreased ICPImpaired reabsorption is the principal causePrednisone decreased Ra
  85. 85. Head Injury20% of the raised ICP derived from changesin Ra &Vf
  86. 86. It means…Vf changes: changes ICPRa changes: changes ICP, alters pressurebuffering capacity of brainAnesthetics induced changes in both,significantly alters Rx to reduce ICP
  87. 87. So……We demand more attention from you..
  88. 88. HEAD INJURYTHANK YOU
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