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SOE 074: Cerebrospinal Fluid

Introduction

Regarding cerebrospinal fluid (CSF)…

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Question No. 2

Q: What is cerebrospinal fluid (CSF)?

Answer No. 2

  • Specialized transcellular fluid that surrounds the brain and spinal cord
  • Circulates within the cerebral ventricular system and the subarachnoid space

Question No. 3

Q: What are the functions of cerebrospinal fluid (CSF)?

Answer No. 3

Mechanical Protection
  • Provides buoyancy and cushioning
  • Reduces the effective weight of the brain
  • Protects against deformation caused by acceleration and deceleration
Maintenance of Constant Environment
  • Maintains a constant ionic and osmotic environment for neuronal cells
  • Essential for the functioning of normal neuronal activity
Regulation of ICP
  • Displacement of CSF into spinal canal provides important, though limited, compensation for increases in ICP ('Spatial compensation')
Control of Respiration
  • Central chemoreceptors detect changes in CSF pH caused by variations in CO2 levels resulting in the respiratory centre adjusting respiratory rate and tidal volumes
  • CO2 freely dissolves in CSF from blood given its lipid solubility and low molecular weight
  • Comparatively low protein levels in CSF reduce buffering capacity making CSF pH very sensitive to changes in blood pCO2
Clearance of Waste Products
  • The brain lacks a lymphatic system to cleat waste products (extracellular proteins excess fluid and metabolic waste)
  • A specialised 'glymphatic system' circulates CSF in paravascular channels where waste products are removed

Question No. 4

Q: How much CSF is normally produced?

Answer No. 4

  • Normal rate of production is 0.3-0.4ml/min or 20ml/hour or 500ml/day
  • Results in effective replacement of CSF volume 3x daily
  • Production is largely independent of ICP:
    • Raised ICP is compensated by increased absorption of CSF reducing total volume
    • Decreased when CPP <70 mmHg due to reduction in choroid plexus blood flow

Question No. 5

Q: How is CSF produced?

Answer No. 5

  • Produced by the four choroid plexuses:
    • Located in the two lateral, third, and fourth ventricles
    • Highly vascular invaginations of pia mater
    • Covered by specialised ciliated ependymal cells
Location of the choroid plexuses
  • Produced by a combination of:
    • Filtration of plasma through the fenestrated capillaries
    • Active transport of solutes
  • Control of substances entering is regulated by the blood-CSF barrier (distinct from the BBB)
Structure of the choroid plexus

Question No. 6

Q: Describe the circulation of CSF?

Answer No. 6

  • Cerebrospinal fluid (CSF) is produced by the choroid plexuses of the lateral, third and fourth ventricles
  • Passes from the lateral ventricles to the third ventricle through the two interventricular foramina (foramen of Monro)
  • passes from the third ventricle to the fourth ventricle via the Sylvian aqueduct
  • Escapes into the cerebellar subarachnoid space through the:
    • Foramen of Magendie (Medial)
    • Foramen of Lushka (Lateral)
  • CSF then flows around the cerebral hemispheres and spinal cord
    • Flow is aided by the ciliary movement of ependymal cells
  • Reabsorbed primarily by the arachnoid villi of the dural venous sinuses
Circulation of CSF between the ventricles and foramina

Question No. 7

Q: How and where is CSF reabsorbed?

Answer No. 7

  • Reabsorbed by the arachnoid granulations:
    • Villi arising from the arachnoid mater
    • Project into venous sinuses and veins
  • Reabsorption occurs throughout the brain and spine
    • 90% by villi of the sagittal and sigmoid Dural sinuses
    • 10% by spinal villi
  • Reabsorption due to differences in pressure between CSF and veins
    • Pressure of CSF typically 15 cm H2O and venous blood typical 8cm H2O
    • Removal of CSF increases with rising intracranial pressure.
Structure of the arachnoid granulations

Question No. 8

Q: Can you suggest any conditions that may cause hydrocephalus?

Answer No. 8

Obstructive Hydrocephalus
Obstructive Hydrocephalus
Foramina of Monro
  • Neoplasm
  • Haemorrhage
Third Ventricle
  • Neoplasm
  • Aneurysm
  • Arachnoid cyst
  • Infection
  • Haemorrhage
Aqueduct of Sylvius
  • Aqueductal stenosis
  • Arnold-Chiari malformation
  • Neoplasm
  • Infection
  • Haemorrhage
Fourth ventricle
  • Arnold-Chiari malformation
  • Neoplasm
  • Dandy-Walker cyst
  • Haemorrhage
Basilar
  • Arnold-Chiari malformation
Communicating Hydrocephalus
Communicating Hydrocephalus
  • Arachnoid granuloma dysfunction:
    • Post-infectious (meningitis / ventriculitis)
    • Post-haemorrhagic
  • Normal pressure hydrocephalus
  • Arachnoid granuloma dysfunction:
    • Post-infectious (meningitis / ventriculitis)
    • Post-haemorrhagic
  • Normal pressure hydrocephalus

Question No. 9

Q: What are the normal volumes of CSF?

Answer No. 9

  • Overall volume is between 100-150ml
    • 2⁄3 within the ventricles
    • 1⁄3 within the subarachnoid space around the spinal cord (35ml)
  • Equates to ~10% of intracranial volume

Question No. 10

Q: What is the normal pressure of CSF?

Answer No. 10

  • CSF pressure is gravitational and varies with position
    • In the lateral position normal pressure is 5-20 cm of H2O
    • In the sitting position:
      • Pressure in the lumbar region rises to 20-50 cmH20
      • Pressure in the cervical region may be sub-atmospheric

Question No. 11

Q: Compare the constituents of CSF and plasma?

Answer No. 11

CSF
Normal
Sodium
(mmol/L)
140
140
Calcium
(mmol/L)
1.2
(∼50% that of plasma)
2.2-2.6
Potassium
(mmol/L)
3.0
4.0-5.0
Chloride
(mmol/L)
120
96-106
Bicarbonate
(mmol/L)
24
Equal
24
Glucose
(mmol/L)
4
(∼60% that of plasma)
6
pCO2 (kPa)
6.6
5.2
pH
7.32
(0.08 lower than plasm)
7.40
Protein
(g/L)
0.2-0.4
(<1% that of plasma)
70
Specific Gravity
1.004-1.007
1.010
WCC
(per mm3)
0-5
(usually lymphocytes and monocytes)
4,000-11,000

Question No. 12

Q: What is the significance of low levels of protein?

Answer No. 12

  • Protein is <1% of plasma resulting in reduced buffering capability and a lower pH

Question No. 13

Q: For which disorders is analysis of CSF useful?

Answer No. 13

  • Meningoencephalitis
  • Neurological disorders:
    • Multiple Sclerosis
    • Guillain Barre
    • Mitochondrial Disorders
    • Paraneoplastic Syndromes
  • Subarachnoid haemorrhage
  • Disorders of intracranial pressure

Question No. 14

Q: What tests can be performed on CSF?

Answer No. 14

Routinely Performed
  • Opening pressure
  • Total Cell count (WBC & RBC)
  • Cell differential count
  • Glucose (CSF/plasma ratio)
  • Total protein
Useful in Specific Situations
  • Microbiological stains:
    • Gram stain
    • Acid-Fast stain
  • Microbiological cultures:
    • Bacterial culture
    • Fungal culture
    • TB culture
  • Microbiological Antigens:
    • VDRL
    • Pneumococcus / meningococcus
    • Cryptococcus
    • Aspergillus
    • Toxoplasmosis
  • Viral PCR
  • Electrophoresis
  • Cytologic examination
  • Specific proteins (CRP, Tau, B-amyloid)

Question No. 15

Q: What findings in CSF would suggest bacterial meningitis?

Answer No. 15

Normal
Bacterial Meningitis
Opening Pressure (cm/H2O)
5-20
>30
Appearance
Clear, colourless
Turbid
RBC
(per mm3)
<3
Normal
WCC
(per mm3)
<5
>500
(Up to 100,000)
Cell Differential
Usually lymphocytes and monocytes
Neutrophilic (polymorphonuclear) pleocytosis
Protein
(g/L)
0.2-0.4
>1
(High)
Glucose-Serum Ratio
0.5-0.66
(2.5-3.5 mmol/L)
<0.4
Lactate
(mmol/L)
<2.8–3.5
Elevated
Microscopy and Gram Stain
-
60-80% positive Gram Stain
Culture
-
Up to 80% positive
PCR
-
-
Other
-
-

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