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Cerebral Blood FlowCerebral Blood Flow
Richard Klabunde, Ph.D.
September 11, 2003
OutlineOutline
• 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
Vascular AnatomyVascular Anatomy
(From E. Gardner, Fundamentals of Neurology. W.B. Saunders, 1963)
Circleof Willis
Cerebral Blood FlowCerebral Blood Flow(Basic Facts)(Basic Facts)
• ~15% of cardiac output to only 2% of body weight
• Blood flow supports an O2 consumption that is almost 20% of whole body O2 consumption at rest in adults (higher in infants)
• Cerebral blood flow is relatively high on a tissue weight basis: 50-60 ml/min/100g (cp. 80 ml/min/100g in heart)
• A-V O2 extraction is about 6 ml O2/100 ml blood
• Because of the rigid cranium, blood volume is nearly constant – this has important implications when hemorrhagic strokes occur and when intracranial pressures rise
Cerebral Perfusion PressureCerebral Perfusion Pressure
(normally 0-10 mmHg)
Coupling Between Cerebral Coupling Between Cerebral Blood Flow and Brain ActivityBlood Flow and Brain Activity
• The brain has an absolute requirement for O2 (for glucose oxidation) and has little anaerobic capacity– Reduction in blood flow (relative ischemia) impairs O2
delivery and causes cerebral hypoxia• Recall, O2 delivery = Flow x Arterial O2 Content• Recall, O2 consumption = Flow x (AO2-VO2 )
– Unconsciousness results after only a few seconds of oxygen deprivation
• Therefore, blood flow and metabolism need to be tightly coupled
Functional HyperemiaFunctional Hyperemia
• Total brain blood flow is tightly coupled to cerebral oxygen consumption– Changes in mental activity alter oxygen
consumption, which then either increases or decreases blood flow
– Changes in activity in specific brain regions leads to parallel changes in blood flow to those regions
Functional Hyperemia Functional Hyperemia cont.cont.
Coma Awake Seizure
CerebralBloodFlow
Increasing Oxygen Consumption
Mechanisms of Functional Mechanisms of Functional HyperemiaHyperemia
VOVO22 pOpO22
pCOpCO22
HH++
KK++
AdenosineAdenosineArteriolar
Vasodilation ??
NONO
Cerebral Autoregulation Cerebral Autoregulation (Description)(Description)
CerebralBloodFlow
Mean Arterial Pressure (mmHg)
0 200100
Autoregulatory
Range
CerebralHypoxia
HeadachesBBB disruption
Edema
Cerebral Autoregulation Cerebral Autoregulation (Autoregulatory Shift)(Autoregulatory Shift)
CerebralBloodFlow
Mean Arterial Pressure (mmHg)
0 200100
Normal
Chronic HypertensionAcute Sympathetic Stimulation
Cerebral AutoregulationCerebral Autoregulation(Possible Mechanisms)(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
Effects of Arterial pOEffects of Arterial pO22
• Systemic arterial hypoxia (pO2 < 50 mmHg) causes cerebral vasodilation and increased flow– Similar to the coronary circulation, although
coronaries are more sensitive to decreased pO2
– Unlike renal, splanchnic, and muscle circulations where systemic hypoxia causes sympathetic-mediated vasoconstriction
Effects of Arterial pOEffects of Arterial pO22C
ereb
ral B
lood
Flo
w(m
l/min
•100
g)
Arterial pO2 (mmHg)
0 2001000
50
100
(From Lassen, N.A., Brain. In: Peripheral Circulation, P.C. Johnson, ed. Wiley, 1978)
Effects of Arterial pCOEffects of Arterial pCO22
• Increased arterial pCO2 (hypercapnea) causes cerebral dilation– CO2 diffuses through blood-brain barrier
into the CSF to form H+ (via carbonic acid) which then causes the vasodilation
• Decreased arterial pCO2 as occurs during hyperventilation causes cerebral vasoconstriction, decreased blood flow, and cerebral hypoxia
Effects of Arterial pCOEffects of Arterial pCO22C
ereb
ral B
lood
Flo
w(m
l/min
•100
g)
Arterial pCO2 (mmHg)
0 80400
50
100
6020
(From Lassen, N.A., Brain. In: Peripheral Circulation, P.C. Johnson, ed. Wiley, 1978)
Autonomic ControlAutonomic 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
Sympathetic ControlSympathetic ControlC
ereb
ral B
lood
Flo
w(m
l/min
•100
g)
Level of Sympathetic Activity
0
50
100
None Maximal
(From Lassen, N.A., Brain. In: Peripheral Circulation, P.C. Johnson, ed. Wiley, 1978)
Effects of Intracranial PressureEffects of Intracranial Pressure(CNS Ischemic Reflex)(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
Humoral ControlHumoral 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
Neuropeptides and Other Neuropeptides and Other Vascular Control MechanismsVascular 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)
Neural Innervation of Neural Innervation of Cerebral VasculatureCerebral Vasculature
Conditions Related to Altered Conditions Related to Altered Cerebral CirculationCerebral Circulation
• Syncope– Hypotension
• Orthostatic• Vaso-vagal reflex
• Stroke– Hemorrhagic
• Ruptured aneurism• Vascular weakening due to chronic
hypertension
– Ischemic• Thrombus formation or embolism• Vasospasm (ET-1?) associated with
subarachnoid hemorrhage
• Headache– Associated with (not caused by)
neurovascular-mediated vasodilation in migraine and cluster headaches
– Possible roles for CGRP and VIP