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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
plexuses in 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 plexus is 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 transport of sodium ions
through the epithelial cells that line the outsides of
the plexus.
• The sodium ions in turn pull along large amounts of
chloride ions 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 into the 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 lower concentrations of protein, calcium,
potassium, bicarbonate,urea,glucose,& phosphate but
higher concentrations 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 CSF is 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 protein 10 – 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 normal pressure 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. Rate of 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 sylvius in 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 Magendie ending directly
into the cisterna magna & two lateral ones ,the
foramina of Luschka ending into the cisterna pontis on
the basal aspect of the brainstem.
• The SAS is 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 arteries in the SAS or
the alterations of posture.
• CSF is also drained back to vertebral venous plexuses
& the segmental veins.
CSF formation & circulation
CSF formation & circulation
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 villi are small finger like projections of the
arachnoidal membrane through the wall of the venous
sinuses. Conglomerates of these villi form
macroscopic structures called arachnoidal
granulations that 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 is high (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.
CSF formation & circulation
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 permeable to
water, CO2,O2 & most lipid soluble substances such
as alcohol & anaesthetics; slightly permeable to the
electrolytes like Na, Cl & K and almost totally
impermeable to 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 cushion between
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 pressure by changing its
normal amount in response to changes in blood and
brain volume.
3) Drainage of metabolites
There is no lymphatics in the brain parenchyma,
CSF maintains a fluid pathway to 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 nutrients to 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 communicating type, 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 type of 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 placement of a silicone
rubber tube shunt all 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 pressure is seen in meningitis, hamorrhage,
space occupying lesions, hydrocephalus etc.
• Diminished pressure is 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
cobweb clot may form.
• CSF is blood stained in intracerebral and
subarachnoid hamorrhages from any source (tumor,
vascular etc.)
• Yellow tinting or xanthochromia is 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 concentration decreases in tubercular and
pyogenic meningitis.
• Glucose is reduced markedly 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
leukocytosis is observed. Lymphocytosis is 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.
THANK YOU

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CSF formation & circulation

  • 1. CEREBROSPINAL FLUID FORMATION AND CIRCULATION Dr ZIKRULLAH
  • 2. 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.
  • 3. FORMATION OF CSF Site of formation • About two thirds of CSF originates from the choroid plexuses in 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.
  • 4. Choroid Plexus • The ventricles contain capillaries which are derived from internal carotid & posterior cerebral arteries. • A choroid plexus is 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.
  • 6. 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 transport of sodium ions through the epithelial cells that line the outsides of the plexus. • The sodium ions in turn pull along large amounts of chloride ions as well because the positive charge of the sodium ion attracts the chloride ion’s negative charge.
  • 7. • 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 into the 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.
  • 8. 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 lower concentrations of protein, calcium, potassium, bicarbonate,urea,glucose,& phosphate but higher concentrations of sodium & chloride.
  • 9. 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
  • 10. • 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 CSF is 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 protein 10 – 40 5 -75 mg/100 ml Glucose 50 -80 60 -100 mg/100 ml Chloride 710 -750 710 -750 mg /100 ml
  • 11. CEREBROSPINAL FLUID PRESSURE • The normal pressure 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. Rate of CSF formation & resistance to absorption through the arachnoid villi. Under normal circumstances the rate of formation is around 500 ml per day.
  • 12. 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.
  • 13. 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 sylvius in 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 Magendie ending directly into the cisterna magna & two lateral ones ,the foramina of Luschka ending into the cisterna pontis on the basal aspect of the brainstem.
  • 14. • The SAS is 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.
  • 15. • 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 arteries in the SAS or the alterations of posture. • CSF is also drained back to vertebral venous plexuses & the segmental veins.
  • 18. 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 villi are small finger like projections of the arachnoidal membrane through the wall of the venous sinuses. Conglomerates of these villi form macroscopic structures called arachnoidal granulations that can be seen protruding into the sinuses.
  • 19. • 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.
  • 20. • 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 is high (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.
  • 22. 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 .
  • 23. • In general these barriers are highly permeable to water, CO2,O2 & most lipid soluble substances such as alcohol & anaesthetics; slightly permeable to the electrolytes like Na, Cl & K and almost totally impermeable to 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.
  • 24. FUNCTIONS OF CSF 1) Mechanical buffer Remaining inside and outside the CNS it equalizes mechanical pressure, thus acts as cushion between 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 pressure by changing its normal amount in response to changes in blood and brain volume.
  • 25. 3) Drainage of metabolites There is no lymphatics in the brain parenchyma, CSF maintains a fluid pathway to 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 nutrients to the brain. 5)Gives buoyancy to the brain reducing its effective weight by 97%.
  • 26. HYDROCEPHALUS • It is a condition of excess accumulation of fluid within the cavities of brain. • It can be communicating or noncommunicating. • In communicating type, 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.
  • 27. • Noncommunicating type of 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 placement of a silicone rubber tube shunt all 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.
  • 28. Some important characteristics of CSF related to diseased states 1) Inspection of CSF • Raised pressure is seen in meningitis, hamorrhage, space occupying lesions, hydrocephalus etc. • Diminished pressure is 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 cobweb clot may form. • CSF is blood stained in intracerebral and subarachnoid hamorrhages from any source (tumor, vascular etc.)
  • 29. • Yellow tinting or xanthochromia is 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 concentration decreases in tubercular and pyogenic meningitis. • Glucose is reduced markedly in pyogenic meningitis, moderately in TBM, but remains normal in syphilis and aseptic meningitis.
  • 30. Cytological tests • Normally lymphocytes upto 5 /cmm are found. In pyogenic meningitis, polymorphonuclear leukocytosis is observed. Lymphocytosis is 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.