Cerebrospinal Fluid System

1. Classic Concepts
a. CSF is formed by the choroid plexus
b. Circulates by bulk flow in the lateral ventricles, the foramen of Monroe, the
third ventricle, the aqueduct of Sylvius, and the fourth ventricle
c. Flows via the foramina of Magendie and Luschka to the cisterna magna
and subarachnoid spaces.
d. Finally absorbed through the arachnoid granulations is the superior
sagittal sinus into the venous circulation.
2. Current Concepts
- Formation
- Mechanism of formation
- Circulation
- Resorption
- Function
- Composition
- Physical properties
a. Formation
- CSF production can me maintained in the absence of the choroid
plexus:
o Ventricular source choroid plexus
o Extraventricular sites of producton cerebral pial surface,
cerebral extracellular space, etc.
- Approximately 60% of CSF is formed in the ventricles
- About half of the CSF formed in the ventricles comes from the choroid
plexus; the rest comes from the ependymal lining.
- In humans:
o CSF is formed at the rate of 0.35 mL/min (about 15-20 mL/hr,
500 mL/day) by the choroid plexus and to a much lesser degree
by the ependymal
- Average CSF volume in the adult is about 140mL, with most of the fluid
filling the cranial subarachnoid spaces.
- Approximately 30 mL of CSF is located in the ventricles and about 30
mL is in the spinal subarachnoidal space
- Turnover rate of CSF is estimate to be 4-5 times per day
- The rate of CSF formation is rather constant and not generally affected
by alteration in CSF pressure below 280mm of CSF.
- Decrease in CSF formation in:
o Chronic, experimentally produced, or human hydrocephalus in
which CSF pressure is very high
o Local arteriolar vasoconstriction or hypotension

o Almost total cessation of CSF formation from the choroi plexus

may result following vasoconstriction induced by low PCO2
during hyperventilation.
o Drugs:
Carbonic anhydrase inhibitor (acetazolamide)
Ouabain (an ATPase inhibitor)
Glucocorticoids
Diuretics
Increase in CSF Formation:
o Vasodilation induced by carbon dioxide inhalation
o Maturation

b. Mechanism of formation
- Diffusion
o Rate of diffusion depends on particle size and the lipid solubility
of the compound
o Diffusion is the primary mechanism of transport for respiratory
gases and some central nervous system active drugs such as
diazepam, phenobarbital and phenytoin.
o Ethanol is also transported by diffusion
o Water enters CSF readily by diffusion
- Active Transport
o Major cations that pass through the choroid plexus into the CSF
are sodium and potassium.
o The concentration of sodium is higher in CSF than in Plasma,
whereas that of potassium is lower
o Of all the cations in CSF, sodium is found in the greatest amount
and is used to stabilize the pH and total cation concentration in
CSF
o Most of the sodium in CSF enters via the choroid plexus, and
only a very small fraction traverses the brain capillaries and
brain substance
o The concentration of potassium in CSF is very stable and is not
affected by fluctuations in blood or CSF pH
o A proper balance between intracellular and extracellular
potassium is critical to nerve cell function
o Excess CSF potassium is quickly incorporated by neural tissue,
whereas reduction in CSF potassium is compensated by
movement of potassium from neural tissue to CSF
o Chloride constitutes the major anion in CSF and seems to
diffuse passively through the choroid plexus, although this
passage is closely regulated by sodium and potassium transport

o Certain metabolic substances of low lipid solubility, such as

glucose and some amino acids, reach CSF by means of specific
carrier-mediated transport systems
o The carrier systems for amino acids are independent of the
glucose carriers
o Glucose is the major energy substrate for the brain. Entry into
the CSF is facilitated by an insulin-dependent GLUT-1 glucose
transporter
o Reduced GLUT-1 transport may be associated with seizure,
impaired brain development, and mental retardation.
o Large molecules, such as plasma proteins, are almost
completely blocked by thee choroid plexus from entering CSF
o Albumin transfer from blood to CSF is only partially dependent
on bulk flow
o The major mechanism for protein entry into the CSF is receptormediated transcytosis. In this mechanism, protein binds to a
receptor on the luminal surface of brain capillaries, is then
internalized and forms intracellular vesicles similar to pinocytotic
vesicles similar to pinocytotic vesicles
o The protein then reaches the albuminal surface of the blood
brain barrier
o Immunoglobulins enter the CNS by this mechanism
c. Flow
- Lateral ventricle foramen of Monroe third ventricle aqueduct of
Sylvius fourth ventricle foramen of Magendie and Luschka
subarachnoid space of brain and spinal cord
- CSF resorbed in the superior sagittal sinus
- CSF in the lumbar subarachnoid space reach the basal cisterns within
1 hour
d. Circulation
- 3 factors that facilitate CSF circulation:
o Drift
CSF will drift from area of positive balance to those of
negative balance
o Oscillation
CSF is in continuous state of oscillation, increasing in
amplitude as it reaches the fourth ventricle, therefore
facilitating CSF flow into the cisterna magna
o Pulsatile Movement
CSF pulsations are synchronous with arterial pulse; the
pulsations originate from the expansion of the cerebrum

and its arteries during systole rather than choroid plexus

pulsations, as previously assumed
CSF pulsations occur roughly simultaneously with
intracranial arterial pulsations, and both begin about 150
ms into the cardiac cycle.

e. Resorption
- Arachnoid granulations and lacunae lateralis
o Constitute the major resorption sites for CSF
- Arachnoid granulations are:
o Not discernible in the newborn
o Become evident by the 18th month and become numerous and
widely disseminated by the 3rd or 4th year of life
o Most common along the superior sagittal sinus but occur at or
near other sinuses as well
o Other alternative sites:
Arachnoid membrane
Adventitia of leptomeningeal blood vessels
Cranial and spinal nerve rot sleeves
Capillary endothelium
Choroid plexus
Leptomeningeal vessels
Perineural sheaths of cranial and spinal nerves
Ependymal of the ventricles
f. Function: 3 principal functions
- It supports the weight of the brain within the skull. The buoyancy
function is disturbed when CSF is withdrawn, resulting in headache
because of more traction on vessels and nerves
- It acts as a buffer or cushion between the brain and adjacent dura and
skull; it protects the brain from physical trauma during injury to the skull
by dampening the effects of trauma
- It provides a stable chemical environment for the CNS. The chemical
composition of CSF is rather stable even in the presence of major
changes in the chemical composition of plasma
g. Composition- CSF is a clear colorless fluid composed of the following
substances and elements:
- Water
o major component of CSF
- Protein
o 15-45 mg/dL in normal CSF; lower value reflects protein value in
ventricular CSF, the higher value reflects protein value in the
lumbar subarachnoidal space.

o Three proteins account for the bulk of CSF protein content:

Albumin: most abundant
Beta globulins
Gamma globulins
Sugar
o Amount of glucose in normal CSF is approximately 2/3 that of
the blood
o Glucose value is slightly higher (75mg/dL) in ventricular fluid
than in lumbar subarachnoid space fluid (60mg/dL)
o Ratio of CSF glucose to blood glucose is higher in newborn and
premature infants, probably because of the immaturity of the
blood- CSF barrier
Cells
o Normal sample of CSF contains up to 3 lymphocytes per mm3
o Normal CSF contains no red blood cells
Electrolytes
o CSF contains sodium, potassium, chloride, magnesium and
calcium
o Concentration of sodium, chloride, and magnesium ions is
higher in CSF than in plasma, whereas the concentration of
potassium and calcium ions is lower
Peptides
o Luteinizing hormone releasing factor
o Cholecystokinin
o Angiotensin II
o Substance P
o Somatostatin
o Thyroid hormone- releasing hormone
o Oxytocin
o Vasopressin
Comparison of Serum and CSF

h. Physical properties
- Specific gravity
o Normal CSF varies between 1.006 and 1.009
o Increase in protein content of the CSF raises its specific gravity
o Mean CSF density is significantly lower in women than men
- Pressure
o Normal CSF pressure measured in the lumbar subarachnoid
space varies between 50-200 mm of CSF (up to 8mmHg),
measured with the patient in the lateral recumbent position and
relaxed
o Normal pressure range is higher (200-300mm of CSF) when
measures in the upright seated position
3. Pathologic states
a. Protein
- Increases in various disease states of the nervous system (infection,
tumor, hemorrhage) as well as after obstruction of CSF pathways
- Presence of oligoclonal bands (electrophoretic bands in the
immunoglobulin G region) and myelin basic proteins in the CSF
suggest a demyelinating process such as multiple sclerosis
b. Sugar
- Decreases in meningitis and after meningeal infiltration by tumors
c. Cells
- Increase in the number of WBC in CSF occurs in infectious processes

In general, leukocytes predominate in bacterial infections and

lymphocytes in viral infections
- The presence of RBCs in the CSF occurs as a result of trauma during
its collection or secondary to hemorrhage into the CSF
o Traumatic RBCs are usually present in samples of CSF
obtained early in the process of CSF collection and disappear in
samples collected subsequently
o RBCs from pathologic bleeding (subarachnoid hemorrhage)
render the CSF grossly bloody and xanthochromic (yellow). The
xanthochromia is due to release of bilirubin from the RBCs
- Neoplastic cells may occur in some types of central nervous system
neoplasms, particularly those associated with leptomeningeal
dissemination
d. Pressure
- Increased in CNS infections (meningitis), tumors, hemorrhage,
thrombosis, and hydrocephalus
4. Spinal Tap
- Also known as Lumbar Pucnture
- This is the procedure that is being done to do CSF analysis
- The needle usually inserts between L2-L3 or L4-L5
- Once inserted remove the stylus slowly to prevent herniation
- Avoid hitting the conus medullaris (L1-L2)
- Patient may experience slight headache afterward.