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Phys Chapter 61
Cerebral Blood Flow
 Arteries arising from circle of Willis travel along brain surface and give rise to pial arteries, which branch out into
smaller vessels (penetrating arteries and arterioles)
o Penetrating vessels separated slightly from brain tissue by extension of subarachnoid space (VirchowRobin space)
o Penetrating vessels give rise to intracerebral arterioles, which eventually branch into capillaries where
exchange across BBB occurs
 Cerebral blood flow regulated by CO2 concentration, H+ concentration, O2 concentration, and substances
released from astrocytes
o Increase in CO2 increases blood flow; combines with H2O to form H2CO3, which dissociates H+, which
cause vasodilation of cerebral vessels
o Increased H+ greatly depresses neuronal activity
o Decrease in cerebral tissue PO2 increases blood flow through vasodilation
o Astrocytes have numerous projections that make contact with neurons and surrounding blood vessels,
providing mechanism for neurovascular communication
 Gray matter astrocytes (protoplasmic astrocytes) extend fine processes that cover most
synapses and large foot processes closely apposed to vascular wall
 Stimulation of excitatory glutaminergic neurons leads to increases in intracellular Ca2+ in
astrocyte foot processes and vasodilation of nearby arterioles
 NO, metabolites of arachidonic acid, K+, adenosine, and other substances generated by
astrocytes in response to stimulation of adjacent excitatory neurons important in mediating
local vasodilation
 Blood flow changes in response to changes in local neuronal activity (making fist causes increase in blood flow in
motor cortex of opposite side of brain, reading increases blood flow to occipital cortex and language areas of
temporal cortex, etc.)
 Cerebral blood flow autoregulated so not as effected by arterial blood pressure
 Cerebral circulatory system has strong SNS innervation that comes from superior cervical SNS ganglia along
cerebral arteries; supplies both large brain arteries and arteries that penetrate into substance of brain
o Transectino of SNS nerves or mild to moderate stimulation of them causes little change in cerebral blood
flow because blood flow autoregulation mechanism can override nervous effects
o When BP rises with stress, SNS normally constricts large and intermediate-sized brain arteries enough to
prevent high pressure from reaching smaller brain blood vessels; important for preventing vascular
hemorrhages (cerebral stroke)
 Number of capillaries and rate of blood flow greater in gray matter than white matter
 Capillaries less leaky because of glial feet that abut against all surfaces of capillaries and provide physical support
to prevent overstretching of capillaries in case of high capillary BP
 Walls of small arterioles leading to brain capillaries thicken in people who develop high BP; arterioles remain
constricted at all times to prevent transmission of high pressure to capillaries
 Most strokes caused by arteriosclerotic plaques that occur in one or more feeder arteries to brain
 In about ¼ of people who develop strokes, high BP makes one of blood vessels burst, hemorrhage occurs,
compressing local brain tissue and further compromising its function
o One of most common strokes is blockage of middle cerebral artery (leads to loss of function in
Wernicke’s speech comprehension area and loss of words because of loss of Broca’s area)
o Blockage of posterior cerebral artery can cause loss of vision in both eyes in half of retina on same side
as stroke lesion
Cerebrospinal Fluid System
 CSF present in ventricles of brain, cisterns around outside of brain, and subarachnoid space around both brain
and spinal cord
 Poles and inferior surface of frontal and temporal lobes (where brain comes into contact with bony
protuberances in base of skull) often sites of injury and contusions after severe blow to head
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CSF formed more than entire volume of fluid system every day; most comes from choroid plexuses in ventricles,
mainly lateral 2 ventricles; small amounts secreted by ependymal surfaces of all ventricles and arachnoidal
membranes; small amount comes from brain itself through perivascular spaces
o Fluid secreted in lateral ventricles passes to 3rd ventricle, then along aqueduct of Sylvius into 4th
ventricle, then through 2 lateral foramina of Luschka and midline foramen of Magendie, entering
cisterna magna (space behind medulla beneath cerebellum
o Cisterna magna continuous with subarachnoid space that surrounds entire brain and spinal cord
o CSF then flows up through arachnoid spaces into arachnoidal villi that project into sagittal sinus into
venous blood
Secretion of fluid into ventricles by choroid plexus depends mainly on active transport of Na+ through epithelial
cells lining outside of plexus; Na+ pull Cl-, and 2 ions combined increase osmotically active NaCl in CSF, which
causes osmosis of water through membrane, providing fluid of secretion
o Transport processes move small amounts of glucose into CSF and K+ and HCO3- out into capillaries
Conglomerates of arachnoidal villi form macroscopic structures (arachnoidal granulations); protrude into sinuses
o Endothelial cells covering villi have vesicular passages directly through bodies of cells large enough to
allow relatively free flow of CSF, dissolved protein molecules, RBCs and WBCs into venous blood
Perivascular space – space between pia mater and vessels penetrating brain
Because no true lymphatics present in brain, excess protein in brain tissue leaves flowing with fluid through
perivascular spaces into subarachnoid spaces; on reaching subarachnoid spaces, protein flows with CSF to be
absorbed through arachnoidal villi into cerebral veins
o Perivascular spaces transport extraneous particulate matter out of brain (dead WBCs, etc.)
Normal rate of CSF formation nearly constant, so changes in fluid formation seldom factor in pressure control
o Arachnoidal villi function like valves that allow CSF and contents to flow readily into blood of venous
sinuses while not allowing blood to flow backward
o In disease states, villi can become blocked, causing high CSF pressure
Large brain tumor elevates CSF pressure by decreasing reabsorption of CSF back into blood
CSF rises considerably with hemorrhage or infection; large numbers of RBCs and/or WBCs suddenly appear in
CSF and cause serious blockage of small absorption channels through arachnoidal villi
Dura of brain extends as sheath around optic nerve and connects with sclera of eye; when pressure rises in CSF
system, it also rises inside optic nerve sheath
o Retinal artery and vein pierce sheath behind eye and pass along with optic nerve fibers into eye
o High CSF pressure pushes fluid first into optic nerve sheath then along spaces between optic nerve fibers
to interior of eyeball
o High pressure decreases outward fluid flow in optic nerves, causing accumulation of excess fluid in optic
disc at center of retina
o Pressure in sheath impedes flow of blood in retinal vein, increasing retinal capillary pressure throughout
eye, resulting in more retinal edema
o Optic disc far more distensible than remainder of retina; papilledema develops
Noncommunicating hydrocephalus caused by block in aqueduct of Sylvius
Communicating hydrocephalus caused by blockage of fluid flow in subarachnoid spaces around basal regions of
brain or blockage of arachnoidal villi where fluid normally absorbed into venous sinuses
Barriers exist at choroid plexus and tissue capillary membranes in essentially all areas of brain parenchyma
except in some areas of hypothalamus, pineal gland, and area postrema, where substances diffuse with greater
ease into tissue spaces
o Ease of diffusion important because they have sensory receptors that respond to specific changes in
body fluids, such as changes in osmolality and glucose concentration, and receptors for peptide
hormones that regulate thirst (angiotensin II)
BBB has specific carrier molecules that facilitate transport of hormones (such as leptin) from blood into
hypothalamus where they bind to specific receptors that control functions such as appetite and SNS activity
In general, blood-CSF barrier and BBB highly permeable to water, CO2, O2, and most lipid-soluble substances
such as alcohol and anesthetics; slightly permeable to electrolytes; and almost totally impermeable to plasma
proteins and most non-lipid-soluble large organic molecules
o
Endothelial cells of brain tissue capillaries joined by tight junctions; membranes of adjacent endothelial
cells tightly fused rather than having large slit-pores between them, as is case for most other capillaries
of body
 Usual cause of brain edema either greatly increased capillary pressure or damage to capillary wall that makes
wall leaky to fluid; common cause is serious blow leading to brain concussion (brain tissues and capillaries
traumatized and capillary fluid leaks into traumatized tissues)
o Edema compresses vasculature, which decreases blood flow and causes brain ischemia; ischemia causes
arteriolar dilation with further increase in capillary pressure, which causes more edema fluid
o Decreased cerebral blood flow decreases O2 delivery, increasing permeability of capillaries, allowing
more fluid leakage; turns off Na+ pumps of neuronal tissue cells, allowing cells to swell in addition
o Once brain edema develops, treat with IV concentrated osmotic substances (mannitol), pulling fluid by
osmosis from brain tissue and breaking vicious cycles
o Can remove fluid quickly from lateral ventricles of brain by ventricular needle puncture
Brain Metabolism
 Most of excess metabolism of brain occurs in neurons; needed to pump ions through membranes
 Brain not capable of much anaerobic metabolism because of high metabolic rate of neurons, so most neuronal
activity depends on delivery of O2 from blood
 Under normal conditions, almost all energy used by brain cells supplied by glucose derived from blood; only 2minute supply normally stored in neurons at any given time
o Glucose transport to neurons not dependent on insulin
o Excess insulin causes almost all glucose in blood to be transported rapidly into vast numbers of insulinsensitive non-neural cells throughout body (muscle and liver); when this happens, not enough glucose
left in blood to supply neurons properly and mental function becomes seriously deranged