Cerebrospinal fluid (CSF)

PG-Ophthalmology
22 7 2018
 Meninges
• The brain is enclosed within the cranial cavity by
three concentric connective tissue layers
• Pia mater, arachnoid mater and dura mater, which
constitute the meninges of the brain
• Pia mater, covers the external surface of the brain,
and is a thin and highly vascular membrane.
• Folds of pia mater enclose tufts of capillaries
forming choroid plexuses
Meninges
 Cerebrospinal fluid (CSF)
• Subarachnoid space is the space between
arachnoid mater and pia mater
• Subarachnoid space is filled with cerebrospinal fluid
(CSF).
• The arachnoid mater has minute protrusions
(arachnoid villi), which pass through fenestrae in
the dura mater and project into the venous sinuses
to allow escape of CSF into the venous sinuses
• CSF also fill the cavities within the bran (ventricular
system) and central canal of the spinal cord
 Formation of CSF
- Formation Choroid plexes = 50%
Around Blood Vessels
Along Ventricular Walls
 COMPOSITION OF CSF

-Similar to brain ECF

-Formed as plasma ultrafiltrate
and through active secretions of
solutes
-Aquaporins provide for water
movement to balance osmotic
gradients
CSF formation & absorption at
varying CSF pressure
 Ventricular system in the brain and central canal of the spinal
cord
• The ventricles are four fluid-filled cavities located
within the brain; these are the two lateral ventricles,
the third ventricle, and the fourth ventricle
• The two lateral ventricles communicate through the
interventricular foramina with the third ventricle. The
third ventricle is connected to the fourth ventricle by
the narrow cerebral aqueduct (aqueduct of Sylvius).
• The fourth ventricle, in turn, is continuous with the
narrow central canal of the spinal cord and, through
the three foramina in its roof, with the subarachnoid
space..
• The ventricles are lined throughout with ependyma and
are filled with cerebrospinal fluid.
Ventricular system in the brain and central canal
of the spinal cord
Ventricular system in the brain and central canal
of the spinal cord

Cast of the ventricular cavities of the brain. A: Lateral

view. B: Anterior view.
Ventricular system in the brain and central canal
of the spinal cord

Cast of the ventricular cavities of the brain. A: Lateral

view. B: Anterior view.
 Cerebrospinal fluid (CSF)-Circulation
• The circulation begins with its secretion
from the choroid plexuses in the ventricles.
• The fluid passes from the lateral ventricles
into the third ventricle through the
interventricular foramina.
• It then passes into the fourth ventricle
through the narrow cerebral aqueduct. The
circulation is aided by the arterial
pulsations of the choroid plexuses and by the
cilia on the ependymal cells lining the
ventricles.
• From the fourth ventricle, the fluid passes
slowly through the median aperture (Foramen of
Magendie) and two the lateral foramina of the
lateral recesses of the fourth ventricle
(Foramen of Luschka) and enters the
subarachnoid space.
• Some of the cerebrospinal fluid moves
 Cerebrospinal fluid (CSF)-Absorption
• The CSF absorb into venous sinuses in the dural
space
• The absorption of cerebrospinal fluid into the
venous sinuses occurs when the cerebrospinal fluid
pressure exceeds the venous pressure in the sinus.
 Cerebrospinal fluid (CSF)-Absorption cont’

• Because the production of cerebrospinal fluid from

the choroid plexuses is constant, the rate of
absorption of cerebrospinal fluid through the
arachnoid villi controls the cerebrospinal fluid
pressure.
 FLOW OF CSF
Foramen of Magendie
Foramen of Luschka
Subarachnoid space
Ventricles
Arachnoid Villi

CSF formation Veins

in choroid plexus Cerebral venous sinuses
Production, circulation and resorption of CSF.
When ICP is raised, the pressure is transmitted along
the optic nerve causing papilloedema.
 Functions of the Cerebrospinal Fluid

1. Cushions and protects the central nervous system

from trauma
2. Provides mechanical buoyancy and support for the
brain
3. Serves as a reservoir and assists in the regulation of
the contents of the skull
4. Nourishes the central nervous system
5. Removes metabolites from the central nervous system
6. CSF is important for acid-base regulation for control of
respiration
 CSF has a protective function in the brain

• In air brain weighs about 1400 g, but in the "water

bath" of CSF - net weight of 50 g.
• - buoyancy of brain in CSF permits relatively flimsy
attachments to suspend it
• When the head receives a blow, - the arachnoid
slides on the dura and the brain moves, motion is
checked by - CSF cushion & the arachnoid
trabeculae.
 CEREBROSPINAL FLUID

• Fills -within Ventricles

-in Subarchnoid space.
- Volume - 150 ml
- Rate of production - 550 ml / day
 Cerebrospinal fluid (CSF)-compostion

• It is a clear, colorless fluid and possesses, in solution,

inorganic salts similar to those in the blood plasma.
• The glucose content is about half to two third of
blood, and there is only a trace of protein.
• Only are lymphocytes are present.
• The normal lymphocyte count is 0 to 4 cells per cubic
millimeter.
• Lumbar CSF pressure is 70 -180 mm H2O
• Pressure may be raised by straining, coughing, or
compressing the internal jugular veins in the neck
 CSF Pressure & variations in CSF formation

• Lumbar CSF pressure is 70 -180 mm H2O

• Pressures well above this range, the rate of CSF
formation is independent of intraventricular
pressure.
• absorption is proportional to the pressure
• At 112 mm H2O, (average normal CSF pressure) ,
filtration & absorption are equal
• Pressure < 68 mm H2O - absorption stops.
Cerebrospinal Fluid Pressure and Composition in Disease
• The examination of cerebrospinal fluid is of
great assistance in making a neurologic
diagnosis.
• An increase in pressure can be due to
– Infection (meningitis)
– Cerebral oedema
– Space occupying lesions (brain tumour, abscess or
haematoma).
• The appearance of a specimen of cerebrospinal
fluid is of great value.
• Normally, it is clear and colorless.
Cerebrospinal Fluid Pressure and Composition in Disease
• A cloudy fluid usually indicates the presence of
polymorphonuclear leukocytes or an excessive
quantity of protein.
• An increase in the white cells is seen in meningitis
(inflammation of the meninges) or encephalitis.
• An increase in protein content implies a change in
the vascular permeability, and protein escapes into
the cerebrospinal fluid.
• A raised protein content is seen in tuberculous,
meningitis and poliomyelitis.
 Cerebrospinal Fluid Pressure and Composition in Disease
• Normal CSF does not contain red blood cells.
• Gross blood in the cerebrospinal fluid is usually caused by
contamination brought about by puncture of a vertebral
vein by the spinal tap needle.
• Uniform blood staining is found in subarachnoid
hemorrhage.
• Yellow coloration or xanthochromia is caused by the
presence of oxyhemoglobin in the fluid some hours after
subarachnoid hemorrhage.
 Cerebrospinal Fluid Pressure and Composition in Disease
• Normal cerebrospinal fluid contains fewer than four white
cells.
• In bacterial infections, many thousands of cells may be
present per cubic millimeter.
• In viral infections of the nervous system, a moderate
lymphocyte reaction may occur.
• A slight rise in lymphocyte count may also occur in cerebral
tumors, cerebral infarction, and multiple sclerosis.
• The glucose level in the cerebrospinal fluid reduces in acute
bacterial meningitis but remains normal in viral infections.
 LUMBAR PUNCTURE
• This procedure is used to obtain samples of
cerebrospinal fluid (CSF)
• In this procedure lumbar meninges are punctured
using a long hollow needle inserted between the
spines of two lumbar vertebrae below the level of
the termination of the conus medullaris.
 LUMBAR PUNCTURE- TECHNIQUE
• First examine the fundi to exclude raised intracranial
pressure and, in the acute situation, consider CT
scanning of the brain.
• Except in acute bacterial meningitis, lumbar puncture is
almost always contraindicated in the presence of raised
intracranial pressure because of the risk of consequent
transtentorial or tonsillar herniation.
• Locate the third and fourth lumbar spines.
• The fourth lumbar spine usually lies in the transverse
plane of the iliac crests.
• The puncture may be made through either the L3/4 or
the L4/5 interspace.
 MENINGITIS
• Acute infection of the meninges is called meningitis
• This can be bacterial , viral protozoal and fungal
 CEREBROSPINAL FLUID INDICES IN MENINGITIS
Condition Cell type Cell count Glucose Protein Gram
stain
Normal Lymphocytes 0-4 ×106/l > 60% of Up to 0.45 -
blood g/l
glucose
Viral Lymphocytes 10-2000 Normal Normal -

Bacterial CEREBROSPINAL
Polymorphs FLUID INDICES
1000-5000 Low IN MENINGITIS*
Normal/elev +
ated
Tuberculous Polymorphs/l 50-5000 Low Elevated Often -
ymphocytes/
mixed

Fungal Lymphocytes 50-500 Low Elevated ±

 CSF analysis
• Normal CSF is clear and colourless, like water.
• Yellow coloration (xanthochromia)- is pathological
and is due to either old haemorrhage, jaundice or
an excess of protein.
• Turbidity. This may be due to the presence of white
blood cells, either as a result of infection or
following subarachnoid haemorrhage. If this does
not clear on standing it is due to microorganisms.
• Bloodstaining. The presence of blood may be due to
needle injury to a vessel or to subarachnoid
haemorrhage (see above).
 CSF analysis – Cytology
• A centrifugal deposit should be examined with
Leishman's stain in order to obtain an idea of the
character of the cells present, and by the Gram and
Ziehl-Neelsen methods for bacteria.
• Cell counts are performed in a counting chamber
and must be done immediately the fluid has been
collected.
• The normal white cell count is 0-4/mL.
 CSF analysis – Cytology
• An increased count may consist of
polymorphonuclear cells or lymphocytes.
• In a polymorphonuclear CSF more than 75% of the
cells are polymorphs;
• in a lymphocytic CSF more than 98% are
lymphocytes.
• syphilis with a lymphocytic CSF
• Tuberculous meningitis with either a lymphocytic or
a mixed type.
 CSF analysis -biochemistry
• Biochemistry. Normal CSF contains only a trace of albumin and
hardly any globulin
• In TB meningitis and in CSF obstruction the total protein is very
high.
• In some acute and subacute virus infections, the globulin
fractions in the CSF are increased.
• Glucose is present in normal CSF in a concentration of 2.5-
4.2mmol/L, which is about a half to two-thirds of the blood
glucose concentration.
• In bacterial, tuberculous or fungal meningitis and rarely in
carcinomatous meningitis the CSF sugar is reduced to less than
half of the blood glucose.
Blood brain Barrier
 Transport across capillary wall in brain
• Passive diffusion and vesicular transport is very
limited in cerebral capillaries
• But there are numerous carrier-mediated (
facilitated diffusion) and active transport systems in
the cerebral capillaries.
• Movement of molecules out of the brain is
generally more free than movement into it.
 PENETRATION OF SUBSTANCES INTO THE BRAIN
• Passive diffusion
– Water, CO2 , and O2 (but H+ and HCO3 – permeability is
less) and lipid-soluble free forms of steroid hormones
freely penetrate the brain
• Facilitated diffusion
– Glucose transport occurs through specific transporters (i.e
glucose transporter 1 (GLUT 1) in brain capillaries
– Infants with congenital GLUT 1 deficiency develop low CSF
glucose concentrations despite normal plasma glucose, leading
to seizures and delayed development.
– In addition, thyroid hormones, choline, nucleic acid precursors
and amino acids also transported through carried mediated
• Protein-bound molecules, all proteins and polypeptides
are impermeable
Transport across cerebral capillaries.
•Only free lipid-soluble substances can move passively across
the endothelial cells.
•Water-soluble solutes, such as glucose, require active
transport mechanisms.
•Proteins and protein-bound lipids are impermeable
 Blood–brain barrier
• The tight junctions between capillary endothelial
cells in the brain and between the epithelial cells in
the choroid plexus make a barrier that prevent
larger molecules (i.e.proteins) and limit smaller
molecules (i.e urea) entering into the brain in
adults.
• This is called as blood–brain barrier
• It is a barrier between blood and CSF .
FUNCTION OF THE BLOOD BRAIN BARRIER
• Maintain the consistancy of the environment of the
brain
• because of the sensitivity of the cortical neurons to
ionic change, it is not surprising that an additional
defense has evolved to protect them.
• Protection of the brain from endogenous and
exogenous toxins in the blood
• Prevents escape of neurotransmitters into the
general circulation.
 Kernicterus

• Severely jaundiced infants with high plasma levels

of free bilirubin due to immature hepatic bilirubin-
conjugating system, free bilirubin enters the brain
and, in the presence of asphyxia, damages the basal
ganglia
 Circumventricular organs (CVO)
• These are the brain areas that lies outside the blood
brain barrier
• These areas are
(1) the posterior pituitary (neurohypophysis) and the
adjacent ventral part of the median eminence of the
hypothalamus
(2) the area postrema
(3) the organum vasculosum of the lamina terminalis
(OVLT, supraoptic crest)
(4) the subfornical organ (SFO).
• All have fenestrated capillaries and permeable and
regarded as “outside the blood–brain barrier.”
 Significance of having circumventricular organs
outside the blood brain barrier
1. Functions as a neurohemal organs that
secrets polypeptides which enter the
circulation without penetrating the
bran
2. Contains receptors for many different
chemicals and function as chemoreceptor
zones in which substances in the
circulating blood can act to trigger
changes in brain function without
penetrating the blood–brain barrier.
• I.e.
– Area postrema is a chemoreceptor trigger zone that
initiates vomiting in response to chemical
changes in the plasma
– Circulating angiotensin II acts on the area
postrema to produce a neurally mediated increase
in blood pressure.
Circumventricular organs. Neuneurohypophysis (NH), organum
vasculosum of the lamina terminalis (OVLT, organum vasculosum of
the lamina terminalis), subfornical organ (SFO), and area postrema
(AP). PI, pineal; SCO, subcommissural organ.
Thank you