Cerebrospinal Fluid

&
Blood Brain
Barrier
 CSF - Cerebrospinal Fluid
• Cerebrospinal fluid is somewhat similar to
that of blood plasma and interstitial fluid

• It is present in ventricular system within CNS

& in subarachnoid space surrounding the CNS

• It bathes both the external and internal

surfaces of the brain and spinal cord and
provides a protective cushion between the CNS
and the surrounding bones
 In an Adult -

• Total volume of CSF is about

150 ml

 30 ml is in the ventricular
system
 120 ml in the subarachnoid
space
 Composition
• Cerebrospinal fluid is clear, colourless
and slightly alkaline fluid

• Specific gravity of 1005-1008

• Contains inorganic salts & traces of

protein and glucose similar to that
of blood plasma
Cerebrospinal Fluid-
• much lower protein content
• glucose content is about half
• chloride content is slightly
 Clinical Correlation
• Normally the CSF is clear and colourless

• almost cell free having 0-5 lymphocytes/mm3

 Analysis of CSF has diagnostic value in many

diseases of CNS

 Bacterial meningitis: the fluid is cloudy, with

raised protein content and vastly increased
number of cells
 Production
Choroid Plexuses-
– Lateral ventricles (80 to 90%)
– 3rd and 4th ventricles

CSF formed-
 per day is about 500 ml (Guyton)
 0.35-0.40 ml/min (GRAY’S Anatomy)
 550 ml/day (Ganong)
 Circulation and Absorption
• CSF is produced mainly in the lateral ventricles,
from where it passes through interventricular
foramina (of Monro) into the 3rd ventricle,
and then via cerebral aqueduct into the 4th
ventricle

• Here the fluid escapes via the median aperture

(foramen of Magendie) and lateral apertures
(foramina of Luschka) in the roof of fourth
ventricle, into the cerebellomedullary and
pontine cisterns respectively

• From these sites the fluid flows slowly in the

subarachnoid space over - brain & spinal cord
• Most of the CSF flows upwards through the
gap
in the tentorium cerebelli
• Then forwards and laterally over the inferior
surface of the cerebrum

• Finally, it ascends on the superolateral

aspect
of each cerebral hemisphere
• to reach Arachnoid Villi & Granulations which
penetrate into superior sagittal sinus

• CSF enters into the blood stream of the sinus

through the mesothelial cell lining of these villi
Coronal section
Sagittal section
• Some of the CSF moves inferiorly in the
subarachnoid space around the spinal cord
and cauda equina

• Small amount of absorption may also occur

into the pial veins

• The flow of CSF is facilitated by the

pulsations of cerebral and spinal
arteries present
 Functions of CSF
1. Cushion

2. Shock absorber

3. Supports the brain and spinal cord, and

maintains a uniform pressure upon them

4. The brain simply floats in the CSF, and

brain weighing 1500g in air, weighs 25-50g
in cerebrospinal fluid
 Functions of CSF
5. Change in the intracranial volume is
sometimes compensated by the
controlled production and absorption of
CSF
6. It nourishes the CNS
7. CSF removes the metabolites (waste
products) from the CNS
8. It serves as a pathway for pineal
secretions
 APPLIED
• Cerebrospinal fluid can be obtained by lumbar, cisternal or
ventricular puncture
• Lumbar puncture being the easiest, is commonly used by
the clinicians for taking out the CSF for various diagnostic
and therapeutic purposes
 Hydrocephalus
• Hydrocephalus is an abnormal increase in the
volume of cerebrospinal fluid within the skull

• Characterized by excessive accumulation of

CSF in cerebral ventricles/subarachnoid
space

Clinical features in infants and children :

1. Disproportionately large size of the head
(increased skull circumference)
2. Bossing of the forehead
3. Widely separated cranial sutures

4. Enlarged and tense Anterior

Fontanelle
Clinical features of hydrocephalus
in infants and children-
5. Thin scalp with dilated scalp veins
6. Eyes look downwards giving a typical
setting-sun appearance

7. Cracked-pot sound on skull percussion

8. Cranial nerve paralyses are common

9. Progressive loss of motor function

10. Dementia
 Types of Hydrocephalus
Internal (non- External
communicating) H. (communicating) H.

• CSF accumulates • CSF accumulates in the

within the subarachnoid space
ventricular system • No obstruction

• Occurs due to • Occurs due to blockage

obstruction of arachnoid villi and
granulations
at some point
• (e.g. adhesions after
meningitis)
 Obstruction
I. Inside the ventricular system :

1. Interventricular foramina of Monro

2. Aqueduct of Sylvius (commonest site)
3. Foramina of Magendie and Luschka
in the roof of fourth ventricle

 leads to distension of ventricles

 Obstruction
II.At the opening in the tentorium cerebelli:
• If the sub-arachnoid space surrounding
midbrain passing through the
tentorial notch is blocked due to
adhesions
• CSF cannot flow upwards through
the tentorial notch
Q. Explain, why CNS infections are
usually fatal?

Answer-
• CNS infections are usually fatal because
there are no antibodies in the CSF

• Further, a clinician has a limited choice

of antibiotics to give due to presence
of blood-CSF barrier
Q. Explain, why removal of CSF by lumbar
puncture or cisternal puncture may
cause severe headache afterwards?

Answer-
• Normally the brain floats freely in CSF but
when CSF is removed, the brain sags and
hangs on vessels and cranial nerve roots

• Traction of these structures

stimulate pain fibres producing
dragging pain
Q. What is Queckenstedt's test?

Answer-
• When the internal jugular veins are compressed
in the neck, there is rise in cerebral venous
pressure which inhibits the absorption of CSF
into the dural venous sinuses.
• Consequently there occurs a prompt rise in
manometric reading of the CSF pressure.

 If it does not happen, it indicates blockage

in the subarachnoid space (positive
Queckenstedt‘s test)
 CLINICAL CASE STUDY
• A 2-year and 6-month-old boy was taken by his
mother to a Paediatrician and complained that the
size of head of her son is unusually large and his
eyes look different from other children.

• On examination, the Paediatrician found :

– enlarged and tense anterior fontanelle
– widely separated cranial sutures
– typical setting-sun appearance of the
eyes.

 He made the diagnosis of

Q. What is hydrocephalus?

Answer-
• Abnormal increase in the volume of
cerebrospinal fluid (CSF) within
the skull
Q. Enumerate the openings through
which cavities within the brain
communicate with the subarachnoid
space around the brain

Answer-
• Foramen of Magendie (median
aperture)

• Foramina of Luschka (lateral

apertures)
Q.What is the difference between internal
and external hydrocephalus?

Answer-
• Internal hydrocephalus: Excessive
accumulation of CSF within the ventricular
system of brain

• External hydrocephalus: Excessive

accumulation of CSF in the subarachnoid
space around the brain
1. Cerebrospinal fluid (CSF) is formed
mainly by:

a) Choroid plexuses within the lateral

ventricles
b) Choroid plexus within the 3rd
ventricle
c) Choroid plexus within the 4th
ventricle
d) Ependyma of the ventricles
2. Which of the following
subarachnoid cisterns is largest?

a) Interpeduncular cistern
b) Cisterna ambiens
c) Pontine cistern
d) Cerebellomedullary cistern
3. Regarding cavities of brain, all of the
following statements are correct
except:

a) Right and left lateral ventricles are cavities

within the right and left cerebral
hemispheres, respectively
b) Third ventricle is the cavity within
diencephalon
c) Cerebral aqueduct is the cavity within the
pons
d) Fourth ventricle is the cavity within the
hindbrain
Blood-Brain Barrier (BBB)
 Blood-Brain Barrier (BBB)
• Brain and spinal cord need a stable
environment to function normally

• This is provided by the presence of a

semipermeable barrier, called blood-brain
barrier

• (the term blood-brain-spinal cord

barrier
would be more accurate)
 Blood-Brain Barrier (BBB)
• Protects - brain and spinal cord

• From potentially harmful substances

(toxic drugs and other exogenous
materials)

 While allowing the gases and

nutrients
to enter the nervous tissue
 Structure of Blood-Brain Barrier

1. Capillary endothelial cells and tight junctions

between them
2. Basement membrane on which the capillary
endothelial cells are arranged
3. Foot processes of the astrocytes that
adhere to the outer surface of the capillary
wall

 Tight junctions - most important component

Due to presence of blood-CSF barrier:
– Antibodies are not found in the CSF
hence infections of the CNS are often
fatal
– Bile is not found in CSF, even in
severe jaundice
– Most of the drugs cannot reach CSF
 No CSF-brain barrier
• Hence if drugs are injected into the
subarachnoid space (intrathecal injections)
they soon enter the extracellular spaces
around the neurons and neuroglia

 It has been shown that inflammation

increases the diffusion rate of penicillin
into the CSF
 Areas of the Brain devoid of BBB

Capillary endothelium has fenestrations

• Protein and small organic molecules may pass

• Neuronal receptors may sample the chemical
contents of the plasma directly

• The hypothalamus which is involved in the

regulation of the metabolic activities of the body
might react suitably and modify the activities
thereby protecting the nervous tissue
Areas of the Brain devoid of BBB
 Clinical Correlation

• Any injury to the brain

by trauma, chemical
toxins or inflammation
• causes a breakdown of
the blood-brain barrier
• allowing free diffusion
of larger molecules
into the nervous tissue
• For example, normally when penicillin
is administered systemically, only a
small amount of it enters the CNS and
penicillin in high concentration is
toxic to the nervous tissue

• In the presence of meningitis the

meninges become more permeable at
the site of inflammation thus
permitting sufficient antibiotic to
reach the site (to check the infection)
Drugs which pass Drugs which cannot
through Blood-Brain cross the Blood-
Barrier brain Barrier

• Chloramphenicol • Phenylbutazone
• Tetracyclines
• Sulphonamides • Neuro-transmitters
like exogenous
• Thiopental (lipid
– Epinephrine
soluble)
– Dopamine
• Atropine (lipid
soluble)
PARKINSON'S DISEASE
– there is deficiency of neurotransmitter
dopamine in the corpus striatum

• Unfortunately dopamine cannot be used for

the treatment, as it will not cross the blood-
brain barrier

• Instead levodopa (L-dopa) a precursor of

dopamine is used which readily crosses
the blood-brain barrier

• The L-dopa is converted into dopamine by

the neurons within CNS
 In infants, the blood-brain barrier is
not fully developed

• therefore if the serum bilirubin level is

high, the bilirubin readily enters the
brain tissue producing bilirubin
encephalopathy (syn. Kernicterus)

• a severe form of jaundice seen only

in newborn babies
 MCQs

1 – a
2 – d
3 – c
• Thank you