clinical importance abnormalities of blood flow metabolism fluids composition pressure affect brain...
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Clinical importanceAbnormalities of
Blood flowMetabolismFluids
Composition Pressure
Affect brain function profoundlyDecrease blood flow for 5-19sec
loss of consciousnessIncrease in H+ ions
depresses neuronal activity decreases brain activity
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OutlineVascular anatomy of brainControl of cerebral blood flow
Determinants of cerebral perfusion pressureLocal regulation of cerebral blood flowRegulation of CBF by arterial pO2 and pCO2
Neurohumoral regulationCushing reflexControl by neuropeptides
Conditions related to altered cerebral blood flow
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(From E. Gardner, Fundamentals of Neurology. W.B. Saunders, 1963)
Circleof Willis
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Cerebral blood flowNormal blood flow 50-65mls/100gr/minEntire brain=750-900 mls/min
15 % of resting cardiac ou put
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Regulation of cerebral circulationConstant 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.
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Regulation of blood flowHighly related to tissue metabolism
1. Concentration of carbondioxide2. Hydrogen ions concentration3. 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
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Importance of cerebral blood flowIncreased H+ conc greatly depresses neuronal
activityIncreased 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 deficiencyNormal 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
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Normal PO2 in cerebral blood is 35-40mmHgDecreased in cerebral tissue PO2 below
30mmHg increase blood flowBelow 20mmHg comma ensues
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Measurement of blood flowInject radio active substance in carotid arteryRecord radioactivity of each cerebral
segmentPress detectors against the surface of the
cortexDetect rapidity of rise and decay of
radioactivity in each tissue segmentRecord increased blood flow where there is
activity
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2. Autoregulation of cerebral blood flowAutoregulation:Ability of tissue to regulate their blood flow
according to their activity.When the arterial pressure changesCBF is auto regulated extremely wellBetween arterial pressure limits60-140mmHgthere is no significant changes in cerebral
blood flow
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CerebralBloodFlow
Mean Arterial Pressure (mmHg)
0 200100
Autoregulatory
Range
CerebralHypoxia
HeadachesBBB disruptionEdema
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CerebralBloodFlow
Mean Arterial Pressure (mmHg)
0 200100
Normal
Chronic HypertensionAcute Sympathetic Stimulation
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Cerebral Autoregulation(Possible Mechanisms)
MetabolicDecreased 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
MyogenicDecreased perfusion pressure decreases
stretching of arteriolar smooth muscle which causes relaxation
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3. Autonomic ControlSympathetic
Innervation from superior cervical ganglion primarily to larger cerebral arteries on brain surface
Very weak sympathetic vascular toneSympathetic blockade has little effect on flowMaximal sympathetic stimulation increases
resistance by 20-30% (cp >500% in muscle)Shifts autoregulatory curve to right
ParasympatheticInnervation from facial nerve (VII)Weak dilator effect on pial vessels
Baroreceptor reflexesVery weak
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Cer
ebra
l Blo
od F
low
(ml/m
in•1
00g)
Level of Sympathetic Activity
0
50
100
None Maximal
(From Lassen, N.A., Brain. In: Peripheral Circulation, P.C. Johnson, ed. Wiley, 1978)
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Role of sympathetic NS in controlling CBFThere is strong sympathetic innervations in the
brainInhibition or mild to moderate sympathetic
stimulation has mild or no effect in CBF changesAuto regulation overrides the nervous effect
Important in preventing stroke Cerebral vascular accidentsIncase 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
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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
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5. Humoral ControlCatecholamines
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 IIVery little or no effect
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Neuropeptides and Other Vascular Control MechanismsVasodilation
Calcitonin gene-related peptide (CGRP)Substance-PVasoactive intestinal peptide (VIP)
VasoconstrictionNeuropeptide-Y (NPY)Endothelin (vascular and neuronal ET-1 and
neuronal ET-3 acting primarily on ETA receptors)
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Cerebrospinal Fluid systemCapacity of entire
cerebral cavity enclosing the brain and spinal cord1600-1700 mls
150mls is CSF 1450-1550 mls Brain &
spinal cordAreas 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
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Function of Cerebrospinal Fluid The purpose of this
fluid is to protect the brain and spinal cordacting as a shock
absorber.It also carries away
disposed materials.
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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.
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Formation, flow and absorptionRate per day
500mls/day 3-4 times its volume
2/3rds secreted by choroid plexus in ventriclesMainly 2 lateral
ventriclesEpendymal surface of
all ventriclesArachnoid membranesBrain itself
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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
OsmolalityGlucose
28964
289100
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flow1. From lateral ventricles 2. to 3rd ventricles3. to Aqueduct of sylvius4. to 4th ventricle5. then passes through the three small openings
1. Two lateral foramina of lushka2. Foramen magandie on the middle3. And then enters cisterna magna
6. Then upwards through the subarachnoid space surrounding the cerebrum
7. Finally to large sagital venous sinuses
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Choroid plexusIs a cauliflower like growth of blood vessels
covered by a thin layer of epithelial cellsMechanism of CSF formation
Na+ actively pumped outside the epithelial cells
Pulls along with it Cl- ionsCreates osmotically active environmentWater flows by osmosis
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Absorption of CSFThrough arachnoidal villiAre microscopic fingerlike inward projections
of arachnoidal membraneHave vesicular passages in them that allows
the passage of CSF Dissolved protein molecules Particles as large as RBC & WBC
into the venous blood
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Perivascular spaceSpace existing between pia matter and blood
vessels in the brainAct as a specialized lymphatic system for the
brainExcess protein in the brain tissue leaves the
tissue flowing with fluid through perivascular spaces into subarachnoid space
Also transport extraneous particulate matter of the brainsuch as dead WBC and other debris after
brain infection
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Cerebrospinal fluid pressureNormal average 10 mm HgRegulated by arachnoidal villiMechanism
Arachnoidal villi function as a valve systemAllows 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
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Disorders of CSF circulationDisease states
Blocks the system Increase CSF pressure
1.Large brain tumors- decrease reabsorbption of CSF into the blood
Increase 4x above normal
2.Haemorhage3.Infection
In cranial vault Release Large number of RBC+/- WBC in CSF block the system
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Disorders of CSF circulation4. Abnormal villi system
Few arachnoid villiOr abnormal absorptive properties
HydrocephallusExcess water in the cranial vaultCause
Obstruction of CSF flowTypes
Communicating Non communicating
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Disorders of CSF circulationCommunicating
Fluid flow normal from ventricular system to arachnoid spaces
Non communicatingThere 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
CommunicatingBlockage of arachnoid villi or subarachnoid spacesFluids collects outside the brain
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Brain barriers1. 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 CharacteristicsHighly permeable to H2O,CO2,O2, and most lipid
soluble substances e.g alcoholic & anaestheticsSlightly permeable to electrolytes Na+, Cl- and
K+Glucose : its passive penetration is slow, but is
transported across brain capillaries by GLUT1totally impermeable to placenta proteins and non
lipid soluble large organic molecules
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Cause of barrierManner in which the endothelial cells of the
brain tissue capillaries are joined to one another
Joined by tightly junctionsMembranes of adjacent endothelial cells are
tightly fused rather than having large slit spores between them
Unlike other capillaries which have large pores
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Functions of BBBMaintanins 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.
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Development of BBBPremature infants with hyperbilirubinemia,
free bilirubin pass BBB, and may stain basal ganglia causing damage (Kernicterus).
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Clinical implicationsSome 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.
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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.