CEREBROSPINAL FLUID (CSF)
AND THE BLOOD-BRAIN
BARRIER (BBB)
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Student Preparation
Textbook of Medical Physiology,
Guyton and Hall, Ch. 61
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Cerebrospinal Fluid
• Cerebrospinal fluid (CSF) is a clear fluid
present in the ventricles of the brain, the
central canal of the spinal cord, and the
subarachnoid space.
• Normal content: almost no blood cells,
little protein.
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CSF Cont.
• Its rate of formation, flow, and
absorption is sufficiently high to cause
its replacement several times daily.
Measuring its pressure, performing cell
counts, and analyzing levels of various
biochemical constituents is
accomplished with a spinal tap.
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CSF Cont.
• Injecting radiopaque dyes into the
subarachnoid space is the basis of a
common neuroradiologic technique
called a myelogram.
• Obstruction of flow of CSF is a common
cause of hydrocephalus.
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CSF Cont.
• An understanding of the formation, flow,
and absorption of CSF is essential to an
understanding of these diagnostic
procedures and the pathophysiology of
hydrocephalus.
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Cerebrospinal Fluid
• A clear, colorless fluid that surrounds and
permeates the CNS. Offers support, protection
and nourishment.
• Functions:
– Protection of cranial contents
– Modulates pressure changes (has the same specific
gravity as brain tissues)
– Serves as a chemical buffer to maintain constant ionic
environment
– Serves as a transport medium for nutrients and
metabolites, endocrine substances and even
neurotransmitters
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Location of CSF
• Two lateral ventricles
• Third ventricle
• Fourth ventricle
• Spinal cord central
canal
• Subarachnoid space
• Continuous with
extracellular fluid of
brain parenchyma
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Formation of CSF
• Choroid plexuses of
lateral, third and
fourth ventricles
• Ependymal lining of
ventricular system
• Pia-glial membrane
• Blood vessels
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Formation of CSF
• Cells are believed to actively secrete
Na+ into the ventricular system in
exchange for K+. Sodium ions
electrically attract Cl- and osmotically
draw water from the blood vascular
system to constitute the CSF.
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Composition of CSF
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Circulation of CSF
• Due to
– Pulsation of blood in choroid plexus
– Due to pulsation of ependymal cells
• Lateral ventricles interventricular foramen
of Monroe third ventricle
mesencephalic aqueduct (aqueduct of Sylvius)
fourth ventricle
– Spinal cord central canal;
– Also, out the lateral apertures to the subarachnoid
space to the venous system
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Absorption of CSF
1. Through the arachnoid
villi, a protrusion of
arachnoid membrane
into the central venous
sinus and other sinuses
• Valves open when CSF
pressure exceeds
venous pressure
2. Absorption by veins and
capillaries of CNS
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CSF Pressure
• Dog - 170 mm H2O • Regulated by rate of
• Cow - 200 mm H2O absorption and rate of
• Horse - 400 mm H2O formation.
• Brain tumors lower
absorption & raise
• Subarachnoid
hemorrhage blocks pressure
absorption, raises • Inflamed meninges can
pressure cause excessive
• Congenital excessive formation & raise
formation or blockage to pressure
flow raises pressure
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Jugular compression maneuver
(Queckenstedt maneuver)
• Compress jugular veins in neck -
increases CSF pressure at the
cerebellomedullary cistern and the
lumbar cistern (normal)
• Decreased pressure at lumbar cistern
indicates blockage of spinal central
canal
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Cerebrospinal fluid
collection
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Cerebrospinal fluid
collection
• Small animals:
atlanto-occipital
(cerebellomedullary)
cistern
neck
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Cerebrospinal fluid
collection
• Large animals
– Cerebellomedullary
cistern
– Lumbar cistern
(L5-L6)
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CSF collection
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Dog Lumbar Myelogram
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Hydrocephalus
(water on the brain)
• An abnormal increase in the volume of
CSF
• Symptoms: depression, sleep, spastic
paresis, papilledema, bulging of the
skull in young, behavioral changes,
pacing, head pressing, seizures, cranial
nerve deficits, vestibular signs
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Types of Hydrocephalus
• Communicating – • Non-communicating –
due to excessive due to obstruction of
formation of CSF flow through ventricle
or lack of system
absorption
(nothing blocking
flow)
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Ventriculoperitoneal Shunt
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Coup – Coup-Contrecoup
Closed Head Injuries
With a blow to the
back of the
head, the forehead
strikes the surface
(coup), then the
brain bounces
back against
rear skull
(contrecoup)
Coup Coup-contrecoup
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Blood-Brain Barrier (BBB)
• Direct injection of large molecules (e.g.,
a dye) into the venous system will often
penetrate all tissues except the brain.
This observation led to the notion of a
physiological barrier to flow of
substances from blood to brain tissue –
the blood brain barrier.
• The BBB functions to preserve a stable
environment for neurons and glia of the
CNS
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• The human brain consists of 2% of total
body weight, but receives 16% of the
cardiac output and 25% of the oxygen
consumed by the body.
• The CNS requires both protection as well as
a sustained energy supply.
• The BBB provides the protection, and
special nutrient transporters (i.e. for
glucose) provide the energy sources.
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Differences between brain
and general capillaries
• General capillary • Brain capillary
– small solutes can – tight junctions
diffuse through – reduced
intercellular clefts pinocytosis
– pinocytosis – no fenestra
independent of – astrocyte foot
molecular size (pass
processes
large molecules)
– fenestrated 30
General vs. Brain Capillaries
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Brain capillary
• Tight junctions
• Surrounded by
astrocytes
• Few vesicles
• Carrier mediated
transport of glucose
and amino acids
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Blood-Brain Barrier
• Lipid soluble molecules will cross
• Negatively charged molecules cross more
freely than positively charged ones
• High CO2/low O2 produces vasodilation and
decreases resistance of BBB
• Injury or inflammation decreases resistance
of BBB (allows some antibiotics to be used for
treatment)
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Blood-Brain Barrier (BBB)
• Selected brain areas are not protected by the
BBB – the circumventricular organs (CVO)
bordering on the 3rd and 4th ventricles
– parts of the hypothalamus - median eminence
– neurohypophysis (posterior pituitary)
– pineal gland
– area postrema
– subfornical organ
– subcommissural organ
• Allows the brain to monitor humoral signals
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Blood – CSF Barrier
• Barrier from blood to the CSF
• Similar structural mechanism to the BBB
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Brain Edema
• Vasogenic edema – an increase in brain
volume resulting from a breakdown in
the BBB. Interstitial volume increases,
intracranial pressure (ICP) increases,
ventricles shrink.
• Cytotoxic edema – intracellular swelling
of neurons, glia, endothelia due to drug
poisoning.
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