This document discusses cerebral blood flow and its regulation. It begins by outlining the clinical importance of abnormalities in blood flow, metabolism, fluids, composition, pressure and how they profoundly affect brain function. It then covers the vascular anatomy of the brain, control of cerebral blood flow, determinants of cerebral perfusion pressure, local and neurohumoral regulation of cerebral blood flow. Specific topics discussed in more detail include autoregulation of cerebral blood flow, effects of intracranial pressure, humoral control including catecholamines and neuropeptides, neural innervation, cerebrospinal fluid system, brain barriers, and circumventricular organs.

2. Clinical importance
 Abnormalities of
 Blood flow
 Metabolism
 Fluids
 Composition
 Pressure
 Affect brain function profoundly
 Decrease blood flow for 5-19sec
 loss of consciousness
 Increase in H+ ions
 depresses neuronal activity
 decreases brain activity

3. Outline
 Vascular anatomy of brain
 Control of cerebral blood flow
 Determinants of cerebral perfusion pressure
 Local regulation of cerebral blood flow
 Regulation of CBF by arterial pO2 and pCO2
 Neurohumoral regulation
 Cushing reflex
 Control by neuropeptides
 Conditions related to altered cerebral blood flow

4. Vascular Anatomy
(From E. Gardner, Fundamentals of Neurology. W.B. Saunders, 1963)
Circle
of Willis

5. Cerebral blood flow
 Normal blood flow 50-65mls/100gr/min
 Entire brain=750-900 mls/min
 15 % of resting cardiac ou put

6. Regulation of cerebral circulation
 Constant total cerebral blood flow is maintained
under varying conditions.
1. ABP at brain level.
2. Venous pressure at brain level.
3. Intracranial pressure.
4. Blood viscosity.
5. Degree of active constriction or dilation of cerebral
vessels.

7. Regulation of blood flow
 Highly related to tissue metabolism
1. Concentration of carbondioxide
2. Hydrogen ions concentration
3. Oxygen concentration
 Excess CO2 or H+
 Increase cerebral blood flow
 Vasodilator effect
 Indirect effect of CO2
 CO2 + H2O= H+ + HCO3-
 Others
 Metabolic acids
 Lactic acid & Pyruvic acid

8. Importance of cerebral blood flow
 Increased H+ conc greatly depresses neuronal activity
 Increased H+ leads to increased blood flow
 In turn carries H+ , CO2 and other acids forming
substances from the brain tissue
 Decreased H+ conc
 Achieves normal neuronal activity
 Oxygen deficiency
 Normal oxygen utilization 3.5+/- 0.2 mls O/100gr/min
 Decreased oxygen supply below normal
 Vasodilatation
 increased blood flow and O2 transport to the tissue

9.  Normal PO2 in cerebral blood is 35-40mmHg
 Decreased in cerebral tissue PO2 below 30mmHg
increase blood flow
 Below 20mmHg comma ensues

10. Measurement of blood flow
 Inject radio active substance in carotid artery
 Record radioactivity of each cerebral segment
 Press detectors against the surface of the cortex
 Detect rapidity of rise and decay of radioactivity in
each tissue segment
 Record increased blood flow where there is activity

11. 2. Autoregulation of cerebral blood flow
Autoregulation:
 Ability of tissue to regulate their blood flow according
to their activity.
 When the arterial pressure changes
 CBF is auto regulated extremely well
 Between arterial pressure limits
 60-140mmHg
 there is no significant changes in cerebral blood flow

12. Cerebral Autoregulation (Description)
Cerebral
Blood
Flow
Mean Arterial Pressure (mmHg)
0 200
100
Autoregulatory
Range
Cerebral
Hypoxia
Headaches
BBB disruption
Edema

13. Cerebral Autoregulation (Autoregulatory
Shift)
Cerebral
Blood
Flow
Mean Arterial Pressure (mmHg)
0 200
100
Normal
Chronic Hypertension
Acute Sympathetic Stimulation

14. Cerebral Autoregulation
(Possible Mechanisms)
 Metabolic
 Decreased perfusion pressure leads to:
  pO2 (decreased O2 delivery)
  pCO2 (decreased CO2 washout)
  H+ (decreased H+ washout plus lactic acid)
  adenosine (hypoxia resulting in net loss of ATP)
 Each of the above changes produces vasodilation
 Myogenic
 Decreased perfusion pressure decreases stretching of
arteriolar smooth muscle which causes relaxation

15. 3. Autonomic Control
 Sympathetic
 Innervation from superior cervical ganglion primarily
to larger cerebral arteries on brain surface
 Very weak sympathetic vascular tone
 Sympathetic blockade has little effect on flow
 Maximal sympathetic stimulation increases resistance
by 20-30% (cp >500% in muscle)
 Shifts autoregulatory curve to right
 Parasympathetic
 Innervation from facial nerve (VII)
 Weak dilator effect on pial vessels
 Baroreceptor reflexes
 Very weak

16. Sympathetic Control
Cerebral
Blood
Flow
(ml/min•100g)
Level of Sympathetic Activity
0
50
100
None Maximal
(From Lassen, N.A., Brain. In: Peripheral Circulation, P.C. Johnson, ed. Wiley, 1978)

17. Role of sympathetic NS in controlling CBF
 There is strong sympathetic innervations in the brain
 Inhibition or mild to moderate sympathetic
stimulation has mild or no effect in CBF changes
 Auto regulation overrides the nervous effect
 Important in preventing stroke
 Cerebral vascular accidents
 Incase of acute increase of Arterial pressure
 Strenuous exercise
 Excessive circulatory activity
 Constrict large and intermediate sized brain arteries
 High pressure is prevented reaching smaller brain vessels
 Prevent vascular hemorrhages

18. 4. Effects of Intracranial Pressure
(CNS Ischemic Reflex)
 Increased intracranial pressure leads to
mechanical compression of cerebral vasculature
and decreased flow
 Increased intracranial pressure elicits arterial
hypertension (“Cushing reflex”)
 May be caused by bulbar ischemia, which in turn
stimulates medullary cardiovascular centers and
increases sympathetic outflow to systemic
vasculature
 Bradycardia often accompanies the hypertension
because of baroreceptor activation of vagal efferents
to the heart

19. 5. Humoral Control
 Catecholamines
 Weak alpha-adrenergic vasoconstriction is masked by
autoregulation although very high doses of
epinephrine can decrease flow
 Beta-adrenoceptors cause vasodilation; however, this
is masked by autoregulation
 Angiotensin II
 Very little or no effect

20. Neuropeptides and Other Vascular
Control Mechanisms
 Vasodilation
 Calcitonin gene-related peptide (CGRP)
 Substance-P
 Vasoactive intestinal peptide (VIP)
 Vasoconstriction
 Neuropeptide-Y (NPY)
 Endothelin (vascular and neuronal ET-1 and neuronal ET-3
acting primarily on ETA receptors)

21. Neural Innervation of Cerebral
Vasculature

22. Cerebrospinal Fluid system
 Capacity of entire cerebral
cavity enclosing the brain
and spinal cord
 1600-1700 mls
 150mls is CSF
 1450-1550 mls Brain & spinal
cord
 Areas CSF formed
 Chambers in the brain
 Ventricles
 Cisterns around the outside
of the brain
 Subarachnoid space around
both & spinal cord
 Chambers are
interconnected
 Pressure of the fluid is
maintained at a constant
level

23. Function of Cerebrospinal Fluid
 The purpose of this fluid is
to protect the brain and
spinal cord
 acting as a shock absorber.
 It also carries away
disposed materials.


24. Functions of CSF, continued,…
2. Facilitation of pulsatile cerebral blood flow,
3. Distribution of peptides, hormones, neuroendocrine
factors and other nutrients and essential substances to
cells of the body,
4. Wash away waste products.

25. Formation, flow and absorption
 Rate per day
 500mls/day
 3-4 times its volume
 2/3rds secreted by choroid
plexus in ventricles
 Mainly 2 lateral ventricles
 Ependymal surface of all
ventricles
 Arachnoid membranes
 Brain itself

26. Composition of the CSF
 The composition of CSF is essentially the same as
brain ECF
Substance CSF Plasma
Na+ 147 150
K+ 2.9 4.6
HCO3- 25 24.8
PCO2 50 39.5
pH 7.33 7.4
Osmolality
Glucose
289
64
289
100

27. flow
1. From lateral ventricles
2. to 3rd ventricles
3. to Aqueduct of sylvius
4. to 4th ventricle
5. then passes through the three small openings
1. Two lateral foramina of lushka
2. Foramen magandie on the middle
3. And then enters cisterna magna
6. Then upwards through the subarachnoid space
surrounding the cerebrum
7. Finally to large sagital venous sinuses

29. Choroid plexus
 Is a cauliflower like growth of blood vessels covered by
a thin layer of epithelial cells
 Mechanism of CSF formation
 Na+ actively pumped outside the epithelial cells
 Pulls along with it Cl- ions
 Creates osmotically active environment
 Water flows by osmosis

30. Absorption of CSF
 Through arachnoidal villi
 Are microscopic fingerlike inward projections of
arachnoidal membrane
 Have vesicular passages in them that allows the
passage of
 CSF
 Dissolved protein molecules
 Particles as large as RBC & WBC
 into the venous blood

31. Perivascular space
 Space existing between pia matter and blood vessels in the
brain
 Act as a specialized lymphatic system for the brain
 Excess protein in the brain tissue leaves the tissue
flowing with fluid through perivascular spaces into
subarachnoid space
 Also transport extraneous particulate matter of the brain
 such as dead WBC and other debris after brain
infection

32. Cerebrospinal fluid pressure
 Normal average 10 mm Hg
 Regulated by arachnoidal villi
 Mechanism
 Arachnoidal villi function as a valve system
 Allows CFS and its contents to flow readily in the blood
of the venous sinuses
 while not allowing blood to flow backwards in the opposite
direction
 Operate when CSF pressure is about 1.5 mmHg greater
than the pressure in the venous sinuses

33. Disorders of CSF circulation
 Disease states
 Blocks the system
 Increase CSF pressure
1. Large brain tumors-
 decrease reabsorbption of CSF into the blood
 Increase 4x above normal
2. Haemorhage
3. Infection
 In cranial vault
 Release Large number of RBC+/- WBC in CSF
 block the system

34. Disorders of CSF circulation
4. Abnormal villi system
 Few arachnoid villi
 Or abnormal absorptive properties
 Hydrocephallus
 Excess water in the cranial vault
 Cause
 Obstruction of CSF flow
 Types
 Communicating
 Non communicating

35. Disorders of CSF circulation
 Communicating
 Fluid flow normal from ventricular system to arachnoid
spaces
 Non communicating
 There is blockage in fluid flow from one or two
ventricles
 Blockage of aqueduct of sylvius secondary top atresia
(closure) before birth
 Brain tumor at any age
 Communicating
 Blockage of arachnoid villi or subarachnoid spaces
 Fluids collects outside the brain

36. Brain barriers
1. Blood cerebral spinal fluid barrier
 Barrier formed between blood and cerebral spinal fluid
2. Blood brain barrier
 Barrier formed between blood and brain fluid
 Permeability Characteristics
 Highly permeable to H2O,CO2,O2, and most lipid
soluble substances e.g alcoholic & anaesthetics
 Slightly permeable to electrolytes Na+, Cl- and K+
 Glucose : its passive penetration is slow, but is
transported across brain capillaries by GLUT1
 totally impermeable to placenta proteins and non lipid
soluble large organic molecules

37. Cause of barrier
 Manner in which the endothelial cells of the brain
tissue capillaries are joined to one another
 Joined by tightly junctions
 Membranes of adjacent endothelial cells are tightly
fused rather than having large slit spores between
them
 Unlike other capillaries which have large pores

38. Functions of BBB
 Maintanins the constancy of the environment of the
neurons in the CNS.
 Protection of the brain from endogenous and
exogenous toxins.
 Prevent escape of the neurotransmitters into the
general circulation.

39. Development of BBB
 Premature infants with hyperbilirubinemia, free
bilirubin pass BBB, and may stain basal ganglia
causing damage (Kernicterus).

40. Clinical implications
 Some drugs penetrate BBB with difficulty e.g.
antibiotics and dopamine.
 BBB breaks down in areas of infection, injury, tumors,
sudden increase in blood pressure, and I.V injection of
hypertonic fluids.
 Injection of radiolabeled materials help diagnose
tumors as BBB is broken down at tumor site because of
increased vascularity by abnormal vessels.

41. Circumventricular organs
• Posterior pituitary.
• Area postrema.
• Organum vasculosum of the lamina terminalis (OVLT).
• Subfornical organ (SFO).
These areas are outside the blood brain barrier. They have
fenestrated capillaries .
Functions:
- Chemoreceptor trigger zone. As area postrema that trigger
vomiting & cardiovascular control.
- Ang II acts on SFO and OVLT to increase H2O intake.
- IL2 induce fever by (+) circumventricular organs.