Cerebrospinal Fluid

CSF
Prof. Dr. Rashid Mahmood
TRIGGER:
A 5 yrs. old child was brought to the hospital with complaints of photophobia,
fever and vomiting. On examination it was found that he has neck rigidity and
Brudzinski's sign positive. His CSF examination showed increased white blood
cells.
1.What is the likely diagnosis?
2.Why does brain edema develops rapidly?
3.What may be the mechanism of increased white blood cells in CSF?
Cerebrospinal Fluid (C.S.F)
Cerebral blood flow (C.B.F)
Blood Brain Barrier (B.B.B)
Brain Metabolism
Part-I & Part-II

CSF
Objectives
• Goal/Aim: To give the understanding of the physiology
of cerebrospinal fluid, its functions and blood brain
barrier.
• Specific Objectives: At the end of the lesson student
will be able to:
• Describe the secretion, composition, circulation,
reabsorption and functions of CSF.
• Describe the mechanism of brain edema.
• Describe the regulation of cerebral blood flow.
• Explain the functions of blood brain barrier.
2©Prof.Dr.Rashid Mahmood

CSF
Cerebrospinal Fluid
(C.S.F)
And
Cerebral blood flow

CSF
4
Lesson Plan
• Physiological
Anatomy
• Location
• Composition
• Functions
• Formation
• Circulation
• Reabsorption
• CSF Pressure
• Diseases
• Cerebral blood flow
• Perivascular Space
 Lymphatic system
• Cerebral Vascular
Resistance
• Cerebral
Microcirculation
• Protective
mechanisms of brain
• Blood-CSF and
Blood- Brain Barriers
• Brain metabolism©Prof.Dr.Rashid Mahmood

CSF
5
C.S.F Location
• Ventricles of brain
• Cisterns around outside of brain
• Subarachnoid around
Brain
Spinal cord
• All these chambers are connected with
one another
• Constant pressure
©Prof.Dr.Rashid Mahmood

CSF
6
Ventricles of Brain
(Right Lateral aspect)

CSF
7
Ventricles of Brain
(Anterior aspect)

CSF
8
VentriclesofBrain
(SuperiorLateralaspect)

CSF
9
Characteristics of CSF
1.Specific gravity = 1005
2.Clear, colorless,
transparent
3.Osmotic pressure is equal
to that of plasma
4.Reaction: Alkaline

CSF
10
Composition of CSF
• Water: 99.13%
• Solids: 0.87 %
Organic
Inorganic
Cells
Contd…….

CSF
11
Composition of CSF
• Inorganic substances
1. Sodium
2. Calcium
3. Potassium
4. Magnesium
5. Chlorides
6. Phosphates
7. Bicarbonates
8. Sulfates
• Organic substances
1. Proteins
2. Amino acids
3. Sugar
4. Cholesterol
5. Urea
6. Uric acid
7. Creatinine
8. Lactic acid
Contd…….

CSF
12
Composition of CSF
1. [Na+] is nearly equal to that of plasma
2. [Cl-
] ≈ 15% greater than plasma
3. [K+
] is ≈ 40% less
4. Ca++
is also less
5. GLUCOSE is 30% less (64mg%)
6. Protein. Only 20-25mg% as compared
to 7500mg% in plasma
7. Cells. Very few lymphocytes (1-5
cell/mm3
)

CSF
13
Functions of C.S.F
1. Acts as fluid buffer (cushioning the CNS
against injury)
2. Acts as reservoir to regulate the
contents of the cranium
3. May act as a medium of nutrient
exchange in the CNS; However brain
carries out its metabolic exchanges
directly with blood.
4. Clinical - DIAGNOSTIC
Therapeutic ©Prof.Dr.Rashid Mahmood

CSF
14
Cushioning Function of C.S.F
Specific gravity of brain and CSF is
about same
so a blow to head
(if not too severe)
moves the entire brain
simultaneously with skull

CSF
Assessment Question No. 1
• Write the functions of CSF.
©Prof.Dr.Rashid Mahmood 15

CSF
16
Formation of CSF
Sites:
>2/3 by Choroid plexus in 4 ventricles
mainly in two lateral ventricles
<1/3 by Ependymal surfaces of all the
ventricles and by the arachnoidal
membranes
(A small amount also comes from brain
itself)
Choroid plexus: Cauliflower like growth
of blood vessels covered by thin
epithelium, projecting into all
ventricles

CSF
17
Choroid
Plexus in a
lateral
Ventricle

CSF
18
Mechanisms involved in the formation
1. Active transport
2. Filtration (ultra-filtration)
3. Facilitated diffusion
4. Diffusion

CSF
19
Mechanism of secretion of CSF
Mechanism of secretion:
Active transport of Na →Passive
transport of Chloride →Osmosis of
water
• 500 – 700 ml/day (0.2 ml/min)
• Total 100 – 160 ml

CSF
20
Flow of CSF
1
2
3
4
5
6
7
8

CSF
21
Flow of CSF
1
2
3
4
5
6

CSF
22
Pathway of CSF

CSF
23
Circulation of C.S.F
Lateral Ventricles
Monro
3rd
Ventricle
Aqueduct of
Sylvius
(Mesencephalic Aqueduct)
4th
VentricleSubarachnoid
Space
2 – Luschka (lat.)
1 – Magendie

CSF
24
Flow of
CSF

CSF
25
Absorption
• To the venous system by bulk fluid
through arachnoid granulations, located in
the superior sagital sinus by pressure
gradient.
• Arachnoid granulations :
Projections of arachnoidal membrane in
venous sinuses:- Arachnoid villi (Microscopic)
Collection of Arachnoid villi:- Arachnoidal
Granulations (Macroscopic)
Endothelial cells cover the villi and absorb
through vesicular passages
• CSF
• Dissolved protein molecules
• RBC, WBC ©Prof.Dr.Rashid Mahmood

CSF
26
Drainage of a PERIVASCULAR
SPACE into the subarachnoid space
Lymphatic system

CSF
27
CSF Pressure
• 130 mm H2O (10 mmHg) in lateral
recumbent position
• Range: 65-195 mm H2O
• 200 – 300 mm H2O in sitting position
• C.S.F absorption stops below 68 mm
H2O
• Arachnoid villi function like Valves
and allow one-way flow

CSF
28
Regulation of CSF Pressure
• Balance between formation and
reabsorption
• Formation
Almost constant rate
• Reabsorption
Due to pressure gradient
Normally pressure does not rise due to
↑production in case of increased pressure
Abnormally high amount of cells or proteins
may block the reabsorption
Diseases of villi result in ↓ reabsorption
• Number of villi
• Quality of villi

CSF
29
Cerebral Blood Flow
(CBF)

CSF
30
Cerebral Blood Flow (CBF)
Normal CBF = 50 – 65 ml/100Gm/min
(750-900 ml/min) (15% of Cardiac Output)
Variation in CBF in various parts of brain
Determination of C.B.F
Fick Principle
P1 – P2
R
Mean arterial P – Internal Jugular P
Cerebral vascular resistance
Blood Flow ∝
C.B.F = k

CSF
31
Cerebral Vascular Resistance
1. Intracranial pressure
2. Viscosity of blood
3. Vascular diameter
i. Autoregulation
• Myogenic
• O2 demand
• Vasodilator substances
i. Cerebral Metabolism (Humoral factors)
ii. Vasomotor nerves

CSF
32
Regulation of CBF
1. Carbon dioxide concentration
 CO2+H2O=HCO3→H+
→ Vasodilatation
1. Hydrogen ion concentration
 ↑H+
→Vasodilatation
• Causes:
 Acidosis, ↑lactic acid, ↑ pyruvic acid
1. Oxygen concentration
 ↓O2→Vasodilatation
1. ↑ Mental activity → Vasodilatation
• PROTECTIVE MECHANISM
• ↓Oxygen, ↓blood supply to brain→
 Unconsciousness/ Coma
5. Substances released from Astrocytes

CSF
33
Relationship between arterial
PCO2 and cerebral blood flow

CSF
34
Relationship between brain activity
and cerebral blood flow

CSF
35
Substances released from
Astrocytes
• Astrocytes: (Astroglial cells)
Non-Neuronal cells
Surround blood vessels
Protect neurons
Nutrition
Foot processes

CSF
36
Substances released by Astrocytes
cause vasodilation
Vasoactive Metabolites:
1. Nitric Oxide
2. Metabolites of arachidonic acid
3. Potassium ions
4. Adenosine

CSF
37
Autoregulation of CBF
• Definition of Autoregulation:
• The process by which blood flow to the tissues is
maintained at relatively constant level despite
changes in perfusion pressure
• Extremely well autoregulated between arterial
pressure limits of 60 and 140 mmHg
• In hypertensives, upto 160-180 mmHg
• Roll of Sympathetic Nervous System in exercise
Very high mean arterial pressure
Sympathetic stimulation causes vasoconstriction of
brain arteries to prevent vascular hemorrhage

CSF
38
Autoregulation of CBF

CSF
39
Cerebral Microcirculation
• Capillaries are much less “leaky”
• No fenestrations (few exceptions)
• Mechanism: Glial feet by the surrounding
Glial cells surround the capillaries

CSF
40
Protective mechanisms of brain
1. Trauma
 Skull bones
 CSF
2. Blood flow in case of high arterial
pressure
 Autoregulation
 Sympathetic nervous system e.g. in
exercise
 Walls of small arterioles become
thickened to prevent transmission of
high blood pressure to capillaries
Contd…..

CSF
41
Protective mechanisms of brain
3. Blood flow in case of low blood
pressure and metabolic disorders
 Autoregulation
 Roll of CO2, H+
and O2
4. Edema
 Tight capillary junctions
5. Protection of brain from endogenous
and exogenous toxins
 Blood-CSF and Blood- Brain Barriers

CSF
42
Diseases related to CSF and
Cerebral Blood Flow
• Cerebral stroke
• Brain injury
• Brain edema
• ↑CSF Pressure

CSF
• List the factors that prevent the rupture of
cerebral arteries in strenuous exercise and
in hypertensives.

CSF
44
cerebral blood flow
(Cerebral stroke)
• Blockage of cerebral arteries
• Rupture of cerebral arteries
Contd……..

CSF
45
cerebral blood flow
(Cerebral stroke)
Blockage of cerebral arteries
Old age
Arteriosclerotic plaques
• Activation of clotting mechanism
Contd……..

CSF
46
Diseases related to CSF and cerebral blood flow
(Cerebral stroke)
Rupture of cerebral arteries
• Rupture of cerebral arteries
High blood pressure
• Middle cerebral artery
Loss of function in Wernich’s speech comprehension area
» Dementia
Loss of function in Broca’s area
» Unable to speak
• Posterior cerebral artery
Infarction in occipital lobe
» Loss of vision on both sides in the half of retina on the same
side of stroke lesion
• Damage to blood supply of midbrain
Blockage of nerve conduction in major pathways between brain
and spinal cord
» Sensory and motor abnormalities

CSF
47
cerebral blood flow
(Brain edema)
• When systems for protecting against
transudation of fluid into the brain break down
e.g.
Brain concussion
• Blow to head
High blood pressure
• Mechanism
↑Capillary Pressure
↑ Damage to capillary walls
• Coma and death ©Prof.Dr.Rashid Mahmood

CSF
48
Effects of Brain Edema
• Brain encased in solid cranial vault
• Brain compression
Brain damage
• Compression of blood vessels
• Initiation of two vicious cycles (+ve
feedbacks)
Leading to
• ↑Capillary Permeability
• ↑Capillary Pressure

CSF
49
Two vicious cycles due to Brain
Edema
EDEMA
Compression of
blood vessels
↓Blood flow
Brain
ischemia
Arteriolar
Dilatation
↑Capillary
Pressure
Contd……

CSF
50
Two vicious cycles due to Brain
Edema Contd……
EDEMA
Compression
of blood vessels
↓Cerebral
Blood
flow
↓O2 Delivery
↑Capillary Permeability
Turn off Na+ pump
→edema of cells

CSF
51
Treatment of Brain Edema
• Emergency
• Osmotic diuretics
Mannitol
• Ventricular needle puncture

CSF
• Why does brain edema develop?

CSF
53
cerebral blood flow
(Brain injury)
• Coupe
Damage/injury to the brain on the same side of
trauma
• Countercoup
Damage/injury to the brain on the opposite side
of trauma

CSF
54
Diseases related to CSF and cerebral blood
flow
(↑CSF Pressure)
• Causes
↑ formation (rare)
• ↑ number of blood cells or plasma proteins
Hemorrhage
Infection
» Blockage of reabsorption
↓reabsorption (Obstruction to outflow)
• Fibrosis of villi
• Brain tumors
• Congenital
Hydrocephalus ©Prof.Dr.Rashid Mahmood

CSF
55
Effects of ↑CSF Pressure
1. Papilledema
2. Hydrocephalus

CSF
56
• Papilledema : Edema of the Optic Disc
• Retinal edema
• Mechanism:
1. Fluid pushed into
• Optic nerve sheath
• Spaces between optic nerve fibers
1. ↓outward flow of fluid in optic nerves
2. ↓outward flow of blood in retinal veins
 Significance of Papilledema
 Clinical diagnosis of ↑CSF Pressure by
ophthalmoscope
• Effects of Papilledema
 Blindness/ blurred vision

CSF
57
• Hydrocephalus
Excess water in cranial vault
Types
• Communicating
• Non-Communicating
Swelling of head in children
Brain damage

CSF
58
Hydrocephalus
• Non-Communicating Hydrocephalus
Block in Aqueduct of Sylvius
• Atresia (Closure)
• Brain tumors
• Communicating Hydrocephalus
Blockage of fluid flow in subarachnoid space
Blockage of Arachnoid villi
Fluid collects outside and inside brain

CSF
59
Measurement of CSF pressure
• Person lying horizontally on his/ her side
so that pressure in spinal canal = pressure
in cranial vault
• Spinal needle is inserted in lumber spinal
canal
• Same procedure for composition of CSF

CSF
60
Blood-CSF and
Blood- Brain Barriers
• Blood- Brain Barrier
Tight junctions between adjacent Endothelial cells
• Blood-CSF Barrier
Tight junctions between adjacent Choroid Epithelial
cells
• Many large molecular weight substances hardly
pass into CSF or interstitial fluids of brain
• These barriers are similar, therefore
• Blood-CSF and Blood- Brain
Barriers= Blood- Brain Barrier

CSF
61
Blood- Brain Barrier
• All areas of brain parenchyma
except
Some areas of hypothalamus, pineal
gland, area postrema, pituitary gland
• Sensory receptors
Osmolarity, glucose, angiotensin II, etc
• Secretions
Oxytocin, vasopressin
• Fenestrated capillaries
• “outside blood-brain barrier”

CSF
62
(Controlled permeability)
Highly permeable to
•Water, CO2, O2, most lipid-soluble
substances (e.g. steroid hormones)
Slightly permeable to
•Electrolytes e.g. Na+
, Cl-
, K+
Impermeable to
(Slide ½)

CSF
63
Facilitated diffusion (Carrier protein)
•Glucose (GLUT1, GLUT 1 55 K)
•Thyroid hormones
•Amino acids
•Leptin
(Slide 2/2)Blood- Brain Barrier
(Controlled permeability)

CSF
64
Therapeutic drugs and
• Lipid-soluble and small size drugs cross
easily
• Water- soluble large size cross with
difficulty
• A few drugs cross but transported back by
transporter proteins (P-glycoprotein) in
apical membranes of endothelial cells

CSF
65
Functions of Blood- Brain Barrier
1. Maintain constant environment of
neurons
• Brain neurons highly sensitive to changes in
ionic concentration
1. Protection of brain from endogenous and
exogenous toxins
2. Prevention of escape of
neurotransmitters into general circulation

CSF
66
Clinical implications of
1. Immature at birth → Kernicterus (Entry of free
bilirubin in brain)
2. Some amines (e.g. dopamine and serotonin do not
penetrate brain tissue, so their precursors are
given, i.e. L-Dopa and 5-Hydroxytryptophane)
3. Breakdown of Blood- Brain Barrier in infection or
injury
4. Tumors may develop new capillaries and blood
vessels without fenestrations,→ no Blood- Brain
Barrier, →Diagnosis (radioactive iodine-labeled
albumin)
5. Temporary disruption of Blood- Brain Barrier in
marked ↑ in BP or injection of hypertonic fluids

CSF
• Write functions of blood brain barrier.

CSF
68
Brain metabolism
• Brain weight= 2% of body weight
• Brain metabolism= 15% of body
metabolism (resting, awake)
• Most of excess metabolism in neurons
Pumps
Transport
• ↑neuronal activity → ↑ metabolism

CSF
69
Special requirements of brain for Oxygen
Lack of significant Anaerobic metabolism
• Most tissues of body can live without
Oxygen for many minutes
Anaerobic metabolism
• Excessive amounts of glucose and glycogen are
used
• Brain is not capable of significant
anaerobic metabolism
Reason:-
• High metabolic rate of neurons
• Sudden cessation of brain blood flow/ or
total lack of oxygen:-
Unconsciousness within 5-10 minutes

CSF
70
Brain utilizes GLUCOSE as energy
• Brain needs continuous supply of Glucose
Only about 2 minute supply of glucose
normally stored in brain as Glycogen
Almost all energy is derived from glucose
derived from blood
• Glucose delivery to brain not dependent
on insulin
Advantage: preventing loss of function in
Diabetes (↓Insulin)
Disadvantage: over-treatment with insulin→
unconsciousness ©Prof.Dr.Rashid Mahmood

CSF
Take home points (1/2)
• CSF acts as fluid buffer (it cushions the CNS against
injury)
• Most of it is formed in Choroid Plexus of two Lateral
ventricles
• After circulating through all brain ventricles &
subarachnoid space of the brain & spinal cord, it is
reabsorbed through arachnoid granulations located in
the superior sagittal sinus by pressure gradient
• Cerebral blood flow is extremely well autoregulated
between arterial pressure limits of 60 and 140 mmHg
• When system far protecting against transudation of
fluid into the brain break down, brain edema develops
71©Prof.Dr.Rashid Mahmood

CSF
Take home points (2/2)
• Brain edema once initiated, rapidly develops through
vicious cycles, and is an acute emergency.
• Increased CSF pressure results in Papilledema and
Hydrocephalus
• Tight junctions between adjacent Endothelial Cells
are called Blood –Brain Barrier
• Tight junctions between adjacent Choroid Epithelial
Cells are called Blood –CSF Barrier
• These barriers protect the brain from toxins and
prevent escape of neurotransmitters into circulation
• Brain utilizes GLUCOSE as energy. Entry of glucose
in brain is not dependent on insulin
• Brain lacks significant anaerobic metabolism
72

CSF
The End
Thank You
Questions ?
Comments
drrashid62@gmail.com
rashid.mahmood@rmi.edu.pk

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