CEREBROSPINAL FLUID
FORMATION AND CIRCULATION
Dr ZIKRULLAH
DEFINITION
CSF is a modified tissue fluid present in the cerebral
ventricles, spinal canal & subarachnoid spaces thus
bathing the entire nervous system. The CNS is
devoid of lymphatics & the CSF replaces lymph here.
FORMATION OF CSF
Site of formation
•About two thirds of CSF originates from the choroid
plexusesin the four ventricles, mainly in the two
lateral ventricles .
•Additional small amounts of fluid are secreted by all
the ependymal surfaces of the ventricles and the
arachnoidal membranes, & a small amount comes
from the brain itself through the perivascular spaces
that surround the blood vessels entering the brain.
Choroid Plexus
•The ventricles contain capillaries which are derived
from internal carotid & posterior cerebral arteries.
•A choroid plexusis essentially, a tuft of such
capillaries projecting in the cavities of the ventricle,
which is covered by cubical epithelium of ependyma.
•The endothelial cells of the capillaries are not flat as
elsewhere,but are granular & cubical with
mitochondria & vacuoles thus indicating active
metabolic processes in the cells.
•This choroid plexus projects into the temporal horn of
each lateral ventricle, the posterior portion of third
ventricle & the roof of the fourth ventricle.
Choroid Plexus
Mechanism of formation
Two theories
1.Filtration –plays a minor role
2.Secretion –is the main process
•The secretion of fluid by the choroid plexus
depends mainly on active transportof sodium ions
through the epithelial cells that line the outsides of
the plexus.
•The sodium ions in turn pull along large amounts of
chlorideions as well because the positive charge of
the sodium ion attracts the chloride ion’s negative
charge.
•The two of these together increase the quantity of
osmotically active sodium chloride in the CSF, which
then causes almost immediate osmosis of water
through the membrane ,thus providing the fluid of the
secretion.
•Less important transport processes move small
amount of glucose intothe CSF & both potassium &
bicarbonate ions out of the CSF into the capillaries.
Rate of formation
•As seen with lumbar puncture, the rate of formation in
adults is about 0.35ml per minute or 20ml per hour or
500ml per day.
Volume and composition of CSF
•The total volume of CSF is about 100 to 150ml.
•The specific gravity of CSF varies between 1.002 to
1.009.
•CSF is not merely an ultra filtrate of plasma & its
composition therefore differs from plasma.
•CSF has lowerconcentrations of protein, calcium,
potassium, bicarbonate,urea,glucose,& phosphate but
higherconcentrations of sodium & chloride.
Composition of normal CSF
Colour–clear as water
Microscopic examination
Cells-1 to 5 cells per cu mm ( lymphocytes)
Chemical examination
Proteins-20 to 40 mg/dl
Glucose-50 to 80mg/dl
Chloride-700 to 750mg/dl
Sodium-330mg/dl
Calcium-5.3mg/dl(all in ionic form)
Phosphate-1.8 mg /dl (inorganic)
Bicarbonate-40 to 60 mg/dl
Urea-10 to 30 mg /dl
Potassium-12mg/dl
•The chemical composition of a sample of CSF,drawn
from a normal subject,depends on the site of
withdrawal of the fluid.
•Also the composition of the ventricular CSFis very
different from that of cisternal and spinal fluid,
indicating that some components are added to the
fluid across the spinal arachnoid.
Lumbar CSF Ventricular CSF
Total protein10 –40 5 -75 mg/100 ml
Glucose 50 -80 60 -100 mg/100 ml
Chloride 710 -750 710 -750 mg /100 ml
CEREBROSPINAL FLUID PRESSURE
•The normalpressure of CSF when one is lying in a
horizontal position averages 130 mm of water (10
mm Hg).
•It is regulated by a balance between daily production
& absorption of CSF.
•The CSF pressure is affected by several factors:
1.Rateof CSF formation & resistance to absorption
through the arachnoid villi. Under normal
circumstances the rate of formation is around 500 ml
per day.
2.Cerebral blood flow; If cerebral blood flow increases
(e.g. during halothane administration), CSF pressure
rises because of the concomitant increase in
cerebral blood volume.
3.Arterial blood pressure; This does not affect CSF
pressure within the normal range of autoregulation.
However, it does produce a systolic-diastolic
fluctuation in CSF pressure.
2.Venous pressure; The pressure in the intracranial
venous sinuses should be lower than the CSF
pressure to allow continuous reabsorption at the
arachnoid villi. In certain pathologic conditions, this
pressure relationship can easily be disturbed,
resulting in increased CSF pressure.
CIRCULATION OF CSF
•Movement of CSF is aided by the cilia on the
ependymal cells lining the ventricles.
•The fluid secreted in the lateral ventricles passes first
into the third ventricle through interventricular
foramina,and then after addition of small amounts of
additional fluid from the III ventricle, it flows downward
along the aqueduct of sylviusin the midbrain into the
fourth ventricle.
•It then passes out of the IV ventricle into the
subarachnoid space through three small openings -
central one, the foramen of Magendieending directly
into the cisterna magna & two lateral ones ,the
foramina of Luschkaending into the cisterna pontis on
the basal aspect of the brainstem.
•The SASis deepest at the base of the brain; its
expansions constitute the various cisterns, the largest
of which is the cerebello-medullary cistern or cisterna
magna which lies between the cerebellum and
medulla and extends downwards below the foramen
magnum behind the spinal cord.
•Almost all the CSF then flows upward from the
cisterna magna through the subarachnoid space
surrounding the cerebrum.
•From here the fluid flows into multiple arachnoidal villi
that project into the large sagittal venous sinus& other
venous sinuses of the cerebrum.
•Finally, the fluid empties into the venous blood through
the surfaces of these villi.
•The movement of CSF is rather sluggish within the
vertebral canal.
•It is assisted by the pulsation of arteriesin the SAS or
the alterations of posture.
•CSF is also drained back to vertebral venous plexuses
& the segmental veins.
ABSORPTION OF CSF
•After bathing the surface of the spinal cord and the
base of the brain, CSF passes upward over the
convexity of the hemispheres to be absorbed into the
intracranial venous sinuses via the arachnoid villi.
•Small amounts are absorbed by the perivascular
spaces & the spinal veins.
•Arachnoid villiare small finger like projections of the
arachnoidal membrane through the wall of the venous
sinuses. Conglomerates of these villi form
macroscopic structures called arachnoidal
granulationsthat can be seen protruding into the
sinuses.
•The endothelial cells covering the villi have been
shown by electron microscopy to have vesicular holes
passing directly through the bodies of the cells.
•It has been proposed that these are large enough to
allow relatively free flow of CSF and dissolved protein
molecules into the venous blood.
•When the pressure of the CSF (within the arachnoid
villi) is high, the pores open up and the fluid escapes
into the venous blood.
•But venous blood cannot enter the villi,because (i)
pressure within these sinuses are normally very low
(ii) if there be any rise of venous pressure within these
sinuses, the pores mentioned above close down.
•Further, the colloidal osmotic tension of venous blood
plasma ishigh (owing to high concentration of plasma
protein) whereas that in the CSF (of the villi) is very
low(owing very low protein concentration of CSF); this
also helps the transfer of CSF to the venous blood.
•Thus the CSF is absorbed, via the arachnoid villi, into
the venous blood of cranium and spinal cord.
BLOOD-CSF& BLOOD BRAIN BARRIER
•It has been seen that many large molecular
substances hardly pass at all from the blood into the
CSF or into the interstitial fluids of the brain,even
though these same substances pass readily into the
usual interstitial fluids of the body.
•It is because of the presence of barriers called the
blood –CSF& the blood –brain barrier,which exist
between the blood & the CSF and brain fluid ,
respectively.
•These barriers exist in essentially all areas of the
brain except in some areas of the
hypothalamus,pineal gland & area postrema.
•In general these barriers are highly permeableto
water, CO2,O2 & most lipid soluble substances such
as alcohol & anaesthetics; slightly permeableto the
electrolytes like Na, Cl & K and almosttotally
impermeableto plasma proteins & most non lipid
soluble large organic molecules.
•The cause of the low permeability of these barriers is
the manner in which the membranes of the adjacent
endothelial cells of the capillaries in the barrier are
joined to one another by so called tight junctions
rather than having slit like pores between them as is
the case in most other capillaries of the body.
FUNCTIONS OF CSF
1) Mechanical buffer
Remaining inside and outside the CNS it equalizes
mechanical pressure, thus acts as cushionbetween
the soft and delicate brain substance and the rigid
cranium. Any change of pressure is equally
distributed and thus mechanical injury is prevented
2)It regulates intracranial pressureby changing its
normal amount in response to changes in blood and
brain volume.
3)Drainage of metabolites
There is no lymphaticsin the brain parenchyma,
CSF maintains a fluid pathwayto enable chemical
substances to reach the brain and neural
metabolites to be returned to the blood stream.
4)To a small extent it may carry nutrientsto the brain.
5)Gives buoyancy to the brain reducing its effective
weight by 97%.
HYDROCEPHALUS
•It is a condition of excess accumulation of fluid within
the cavities of brain.
•It can be communicating or noncommunicating.
•In communicatingtype, there is blockage of fluid
flow in the subarachnoid spaces around the basal
regions of the brain or blockage of the arachnoidal
villi where the fluid is normally absorbed into the
venous sinuses. Fluid therefore collects both inside
the ventricles & outside the brain.
•Noncommunicating typeof hydrocephalus is caused
by block in the aqueduct of sylvius, resulting from
atresia before birth in many babies or from blockage
by a brain tumor at any age. The CSF therefore
accumulates within lateral & the III ventricles.
•Both these conditions causes the ICP to rise,
however in neonates this will also cause the head to
swell because the skull bones have not fused.
•The most effective therapy for many types of
hydrocephalus is surgical placementof a silicone
rubber tubeshuntall the way from one of the
ventricles to the peritoneal cavity,into an intestine,or
elsewhere in the abdominal cavity, wherethe fluid
can be absorbed into the blood.
Some important characteristics of CSF
related to diseased states
1)Inspection of CSF
•Raised pressureis seen in meningitis, hamorrhage,
space occupying lesions, hydrocephalus etc.
•Diminished pressureis seen in obstruction of CSF
flow due to any reason.
•Normally CSF is clear and colorless, but may be
turbid in meningitis. In TB meningitis characteristic
cobwebclot may form.
•CSF is blood stainedin intracerebral and
subarachnoid hamorrhages from any source (tumor,
vascular etc.)
•Yellow tinting or xanthochromiais seen in cases of
protein concentration secondary to block of CSF
circulation, in SDH etc.
2) Biochemical tests:
•Protein concentration increases (from normal 20 –
40 mg/dl) in cases of meningitis, encephalitis,
multiple sclerosis and other inflammatory and
neoplastic conditions.
•Chloride concentrationdecreasesin tubercular and
pyogenic meningitis.
•Glucose is reducedmarkedly in pyogenic meningitis,
moderately in TBM, but remains normal in syphilis
and aseptic meningitis.
Cytological tests
• Normally lymphocytes upto 5 /cmm are found. In
pyogenic meningitis, polymorphonuclear
leukocytosisis observed. Lymphocytosisis also
seen in cases of TBM, multiple sclerosis,
lymphocytic meningitis etc. In some cases of chronic
infections(e.g. brain abscess, syphilis) mixed type of
proliferation is seen.