1. Cerebral circulation & CSF formation

2. Clinical importance Abnormalities of Affect brain function profoundly
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 Circle of Willis
(From E. Gardner, Fundamentals of Neurology. W.B. Saunders, 1963)

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

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

7. Regulation of blood flow
Highly related to tissue metabolism
Concentration of carbondioxide
Hydrogen ions concentration
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
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)
Headaches
BBB disruption
Edema
Cerebral
Hypoxia
Cerebral
Blood
Flow
Autoregulatory
Range
100
200
Mean Arterial Pressure (mmHg)

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

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 Parasympathetic Baroreceptor reflexes
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 Level of Sympathetic Activity 100
Cerebral Blood Flow
(ml/min•100g) 50
None
Maximal
Level of Sympathetic Activity
(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 Angiotensin II
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)
CGRP and VIP are released during headache. The 5-HT1B/D agonist, sumatriptan, can reverse the vasodilation caused by these substances.

21. Neural Innervation of Cerebral Vasculature

22. Cerebrospinal Fluid system
Capacity of entire cerebral cavity enclosing the brain and spinal cord
mls
150mls is CSF
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,
Distribution of peptides, hormones, neuroendocrine factors and other nutrients and essential substances to cells of the body,
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
100

27. flow From lateral ventricles to 3rd ventricles to Aqueduct of sylvius
to 4th ventricle
then passes through the three small openings
Two lateral foramina of lushka
Foramen magandie on the middle
And then enters cisterna magna
Then upwards through the subarachnoid space surrounding the cerebrum
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
Large brain tumors-
decrease reabsorbption of CSF into the blood
Increase 4x above normal
Haemorhage
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
Blockage of arachnoid villi or subarachnoid spaces
Fluids collects outside the brain

36. Brain barriers Blood cerebral spinal fluid barrier Blood brain barrier
Barrier formed between blood and cerebral spinal fluid
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.