Neurosurgery notes/CSF

CSF

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Sub-item
Hydrocephalus (HCP)
Intracranial hypotension
Others CSF
CSF and ICP

General

Basic brain specs

  • Volume of intracranial contents
    • 1700 ml
    • Can be divided into three physiologic compartments
        • Adults
        • Brain parenchyma ≈ 1400 ml (80%)
          • 10% is solid material
          • 70% is tissue water
        • Cerebral blood volume (CBV) ≈ 150 ml (10%)
        • CSF ≈ 150 ml (10%)
          • 75ml 50% in cranium
            • Ventricular CSF 25 ml
          • 75ml 50% in spine
          • CSF production
            • 600mls/day
            • 30mls/hr
            • 0.5ml/min
        Infant
        • CSF production
          • 400ml/day
        Neonates
        • CSF = 50 ml
          • Ventricular CSF 25 ml
        • CSF production
          • 25ml/day
          • 1ml/hr
          • 0.01ml/min
  • About 2% of total body mass (1.4 kg)
  • The high metabolic activity of the brain
    • 20% of basal oxygen consumption
    • 25% of basal glucose consumption
      • Resting energy expenditure by organ
        • Brain 22%,
        • Liver 21%,
        • Heart 9%
        • Kidneys 8%
      • Cellular function
        • Maintenance of transmembrane electrical and ionic gradients (≈ 60%)
        • Maintenance of membrane structure and integrity and the synthesis and release of neurotransmitters (≈ 40%)
    • 20% of cardiac output (750 ml/min in adults) at rest,
      • Equates to an average CBF of about 50 ml/100 g/min.
      • Correlates to CBF
          • CBF (ml per 100 gm tissue/min)
          Condition
          >60 (approx)
          Hyperemia (CBF > tissue demand)
          45–60
          Normal brain at rest
          75–80
          Gray matter
          20–30
          White matter
          <20: Ischemia
          ㅤ
          16–18
          EEG becomes flatline
          15
          Physiologic paralysis
          12
          Brainstem auditory evoked response (BAER) changes
          10
          Alterations in cell membrane transport (cell death; stroke)
      • Cerebral blood flow and Ischaemia
          • CBF
          Cell state
          Time to infarction
          Consequences
          50 (20-80)
          Normal
          –
          Normal
          <23
          Oligemia
          >6 h
          EEG slowing
          10-17
          Penumbra
          Several hours
          Flatline EEG, absent evoked potentials
          <10
          Death
          Several minutes
          Membrane pump failure

Function

  • Shock absorber for the CNS.
  • Immunological function analogous to the lymphatic system (“glymphatics” a portmanteau word from glia and lymphatic).

Location

  • Within the subarachnoid space, between the arachnoid and the pial membranes

Normal CSF

  • Clear colourless fluid
  • Specific gravity of 1.007
  • pH of ≈ 7.33–7.35

CSF production

  • Location
    • At choroid plexus
      • 70-90% of total production
      • Found in all 4 ventricles except anterior horn of lateral
      • Choroid plexectomy reduces but do not stop CSF production
      • Occurs at the basolateral (blood facing) and apical (CSF facing) membrane
          • CSF secretion by the mammalian choroid plexus. The model includes recently obtained immunocytochemical and patch clamp data on the expression of ion transport proteins and ion channels in choroid plexus epithelial cells. C.A. = carbonic anhydrase.
          notion image
      • In 2 stages
          1. Ultrafiltration of plasma occurs across the fenestrated capillary wall into the ECF beneath the basolateral membrane of the choroid epithelial cells.
          1. Choroid epithelial cells secrete fluid into the ventricles
      • Histopathology
          • Left: The highly branched structure of the choroid plexus with villi projecting in to the ventricle.
          • Right: The choroid plexuses consist of network of capillaries and connective tissue which is covered by a single layer of cuboidal epithelial cells.
          notion image
    • At interstitial fluid
      • 10-30%
    • TAW baby: 0.5-1ml/min/kg
  • Active process
    • With the main ions being
      • Na
      • Cl
      • HCO₃-
    • Through Na/K ATPase
        • K is actively pump out of the CSF
        Ion channel
        Effect
        Sodium Potassium ATPase
        3 Na⁺ leave cell, 2 K⁺ enter cell; Uses 1 ATP molecule
        Cation chloride transporter
        Mixed effect: potassium and chloride may pass together out of cell; sodium and chloride may pass together into cell
        HCO₃⁻ transporters
        Chloride/bicarbonate exchange; Bicarbonate and sodium cotransporters
        Sodium Hydrogen exchange
        Move hydrogen out of cell
        Aquaporins
        Allow water to pass
        Potassium channels
        Potassium passes into cell creating the membrane potential
        Anion channels
        Mixed actions
    • Acetazolamide
      • Carbonic anhydrase inhibitor
      • H₂O + CO₂ → H₂CO₃ → H⁺ + HCO₃⁻
  • Independent of ICP
  • Inc. by
    • Volatile anaesthetic agents
    • NO
    • High CO₂
  • Dec. by
    • Remifentanyl
    • Noradrenaline

Models of CSF flow

Bulk flow model

  • There are discrete sites of CSF production, absorption, as well as circulation routes.
  • Short comings
    • It is inadequate to explain many of the different diseases
      • Other parts not taken into account by the bulk flow model
        • Pulsatile flow
        • Lymphatic channels (glymphatics) and
        • Distributed sites of production and absorption all appear to participate in CSF dynamics
  • Production
      • Location
      • 80% of CSF is produced by the choroid plexuses,
        • Both lateral ventricles (95%)
        • 4th ventricle (5%)
      • Remaining production in the
        • Interstitial space
        • Ependymal lining of the ventricles,
        • Dura of the nerve root sleeves.
      Production rate
      • In the adult, CSF is produced at a rate of about 0.3 ml/min. (450ml/day)
      • CSF is “turned over” ≈ 3 times every day.
      • The rate of formation is independent of the intracranial pressure
        • Except in the limiting case when ICP becomes so high that cerebral blood flow is reduced
      • Normal CSF production, volumes, and pressure (bulk flow model)
          • Property
          Newborn
          1–10 yrs
          Adult
          Total volume (ml)
          5
          ㅤ
          150 (50% intracranial, 50% spinal)
          Formation rate
          25 ml/d
          ㅤ
          ≈0.3–0.35 ml/min (≈450–750 ml/d)
          Pressureᵃ (cm of fluid)
          9–12
          Mean: 10, normal: <15
          Adult: 7–15 (>18 usually abnormal), young adult: <18–20
        • ᵃas measured in lumbar subarachnoid space, with the patient relaxed in lateral decubitus position
      Absorption
      • Mainly: arachnoid villi (granulations) that extend into the dural venous sinuses
      • Others
        • Choroid plexuses and glymphatics
      • Rate of absorption is pressure-dependent

Pulsatile flow

  • Intraventricular pressure is not constant but is constantly changing
  • Pulsatile pressure in CSF is transferred from arterial pulsation

Glymphatics

Constituents

  • CSF solutes. For CEA, AFP, & hCG, see tumor markers
      • Constituent
      Units
      CSF
      Plasma
      CSF:plasma ratio
      Osmolarity
      mOsm/L
      295
      295
      1.0
      H₂O content
      ㅤ
      99%
      93%
      ㅤ
      Sodium
      mEq/L
      138
      138
      1.0
      Potassium
      mEq/L
      2.8
      4.5
      0.6
      Chloride
      mEq/L
      119
      102
      1.2
      Calcium
      mEq/L
      2.1
      4.8
      0.4
      pCO₂
      mm Hg
      47
      41ᵃ
      1.1
      pH
      ㅤ
      7.33
      7.41
      ㅤ
      pO₂
      mm Hg
      43
      104ᵃ
      0.4
      Glucose
      mg/dl
      60
      90
      0.67
      Lactate
      mEq/L
      1.6
      1.0ᵃ
      1.6
      Pyruvate
      mEq/L
      0.08
      0.11ᵃ
      0.73
      Lactate:pyruvate
      ㅤ
      26
      17.6ᵃ
      ㅤ
      Total proteinᵇ
      mg/dl
      35
      7000
      0.005
      Albumin
      mg/L
      155
      36600
      0.004
      IgG
      mg/L
      12.3
      9870
      0.001
    • ᵃarterial plasma
    • ᵇCSF protein is lower in ventricular fluid than in lumbar subarachnoid space
  • Variations with age
      • Age group
      WBC/mm³
      RBC/mm³
      Protein (mg/dl)
      Glucose (mg/dl)
      Glucose ratio (CSF:plasma)
      Newborn (preemie)
      10
      Many
      150
      20–65
      0.5–1.6
      Newborn (term)
      7–8
      Mod
      80
      30–120
      0.4–2.5
      Infants (1–12 mos)
      5–6
      0
      15–80
      ㅤ
      ㅤ
      Infants (1–2 yrs)
      2–3
      0
      15
      ㅤ
      ㅤ
      Young child
      2–3
      0
      20
      ㅤ
      ㅤ
      Child (5–15 yrs)
      2–3
      0
      25
      ㅤ
      ㅤ
      Adolescent & adult
      3
      0
      30
      40–80
      0.5
      Senile
      5
      0
      40ᵃ
      ㅤ
      ㅤ
    • ᵃnormal CSF protein rises ≈ 1 mg/dl per year of age in the adult

“Davson’s equation”

  • A fundamental equation in the description of CSF hydrodynamics in physiological individuals.
  • It relates baseline intracranial pressure (ICP) to resistance to cerebrospinal fluid outflow (Rout), formation of cerebrospinal fluid (If) and sagittal sinus pressure (PSS), as shown below
    • ICP = Rout * If + PSS
      • This equation is valid if ICP is greater than Pss.
      • Below Pss , ICP may have any value
  • Shunting manipulates Rout value

Windkessel phenomenon?

  • The Windkessel phenomenon is the ability of the cerebral vasculature to expand and the ability of the cerebrospinal fluid (CSF) and venous blood to translocate to accommodate arterial pulsations and provide a smooth capillary flow in the brain.

Water channel proteins of the central nervous system (CNS)

  • Provide a major pathway for osmotically driven water movement across plasma membranes?
    • Aquaporins
      • Are the water channel proteins of the brain.
      • Could be a therapeutic target for pharmacologic treatment of hydrocephalus.
      • Aquaporin 1
        • In normal brain is expressed on the ventricle surface by the choroid plexus.
      • Aquaporin 4
        • The predominant water channel in normal brain
        • Strongly expressed in the plasma membranes of astrocytes.