PHYSIOLOGY OF CEREBRAL CIRCULATION (February 1, 2010;  Volume of brain tissue, CSF, blood,

Dr. A. Pasco III) other fluids in cranium is relatively

constant
Cerebral Circulation  An increase in volume in any of the
contents increase ICP
Arterial Supply of the Brain
Regulation of Cerebral Blood Flow
 Internal carotid (2)
o Anterior cerebral  Metabolism, pH, CO2, O2, hormones
 Medial aspect (vasoconstrictors, vasodilators), neural
 Frontal, parietal  Role of effective perfusion pressure
o Middle cerebral o Effective perfusion pressure = systemic
 Almost all of cerebral cortex; arterial BP – intracranial venous pressure
supplies majority of cerebrum o Cerebral blood flow is proportional to
 Frontal, parietal, occipital effective perfusion pressure
 Vertebral artery o If venous pressure in the brain is zero or
o Basilar artery decreased, the most important factor in
 Posterior cerebral regulating CBF is arterial pressure
 Temporal, occipital o Increased arterial pressure increases CBF
 Communicating arteries connect anterior cerebral  But normally CBF nearly
and middle cerebral maintained at a constant flow at
 Circle of Willis – anastomosis of blood vessels; perfusion or arterial pressure of 60
superficial surface of brain; provides ample supply of to 150 mmHg…this is
blood to the brain AUTOREGULATION
 End arteries or end zones – deep arteries that do not  If patient is hypertensive,
connect with each other CBF remains normal
 If MAP > 160 mmHg, or <
Cerebral Blood Flow
60 mmHg, autoregulation
 15 – 16% of cardiac output (large amount of blood fails, CBF falters
supplied to small part of the body – contributes little  Mechanism involved is
to body weight) myogenic theory
 Importance o Increase in BP,
o Brain tissue needs continuous blood supply stretching of
(constant supply of glucose and oxygen) vessel walls,
o Brain is least tolerant to ischemia (loss of vasoconstriction,
blood supply for 5 secs = dizziness, for 5 decreases in CBF
mins – irreparable damage to brain cells) o Abolished by
 Characteristics hypercapnea and
o Cerebral blood flow is fairly constant potent
o Subjected to very controls vasodilator
o Little overlap in distribution of each  Despite changes in arterial
cerebral vessel ppressure between 60 to 150
o Cerebral vasculature is encased or within a mmHg, cerebral blood flow
rigid skull (follow Kellie-Monro doctrine) remains constant
 Constant volume  Role of cerebral vascular resistance
 Any change in components will be o IC venous pressure
reflected in the other components o IC or CSF pressure
 If not maintained, may reflect as o Viscosity of blood
increased intracranial pressure  Role of venous pressure
o Increased VP, dec in effective perfusion, dec
CBF
 o Inc VP, inc ICP, compression of blood
vessels, dec CBF
o Helps to compensate for changes in arterial
pressure at the level of the head
 +G (body accelerated upwards) =
blood pools at the feet, AP at the
head falls, venous pressure falls,
ICP falls, pressure in BV dec, no
compromise in blood flow
 -G (body accelerated downwards)
= inc in AP at the head, inc ICP, inc
compression of BV, support BP,
prevention of rupture (also during
straining of defecation and
delivery)
 Role of intracranial pressure
o Inc in ICP, compression of cerebral
vasculature, dec CBF
o Related to jugular venous pressure
 Applying pressure over the jugular
vein, inc ICP
 Queckenstedt’s sign
o Cushing’s reflex or phenomenon
 Inc in arterial BP in response to inc
ICP
 Reduction in CBF is only for a short
time
 Compression produces
ischemia, which activates
vasomotor center,
increasing sympathetic
discharge, peripheral
vasoconstriction, increase
in AP, restore blood flow
 Seen in head injury or brain tumor
 Role of blood viscosity
o Increase in blood viscosity, inc cerebral
vascular resistance, dec CBF
o Polycythemia dec CBF
o Anemia inc CBF
 Neural or nervous control
o Role of the sympathetic, parasympathetic
and sensory nerves (trigeminal)
o Weak control unless situation causes a
predominance of either sympathetic or
parasympathetic
 Chemical (metabolic) control
o Dec arterial oxygen, pH, and inc in CO2
(seen in increased metabolism),
Brain metabolism
vasodilation, inc in CBF
o pH
 arterial changes, indirectly affect
CBF through CO2
 Local changes in pH (brain ECF,
CSF) directly affect CBF
 increase in lactic acid,
pyruvic acid, increases
cerebral blood flow
 Decreased pH at constant pCO2
(metabolic acidosis), little effect on
CBF
 Dec pH bec of increased pCO2
(respiratory acidosis), inc CBF
 Hyperventilation, CO2 dec, dec CBF
due to vasoconstriction (dizziness
in panicking patients)
o pCO2
 Main chemical regulator
 Level greater than 45 mmHg inc
CBF
 Dec arterial pCO2,
vasoconstriction, dec CBF
o pO2
 Less pronounced response
o Potassium and adenosine inc CBF
 Hypoxia, electrical stimulation of
the brain, induced seizures,
hypotension, hypocapnia
 Role of Neuronal Activity
o Inc neuronal activity, inc metabolism, inc
CO2, dec O2, inc pH, vasodilation
o There is regional changes in dist of blood
flow in response to changing patterns of
neuronal activities
 region of the brain which is active
during a specific
o Mechanism
 Active neuron, inc metab, inc local
pCO2, vasodilation, inc BF
 Hypothesis by David Harper: role
of glutamate
o During these diseases, there are changes in
blood flow
 Epileptic foci, increase flow during
seizures
 Agnosia, dec flow in the
parietooccipital
 Alzheimer’s, dec flow in superior
parietal cortex
  Utilized by brain: oxygen, glucose, glutamate
o Glutamate – excitotoxic substance;
excitatory, toxic to neurons
o Glucose goes into brain independent of
insulin, but with GLUT-1 transporter (does
not need stimulation, only relies on
concentration gradient)
 Brain produces: carbon dioxide, glutamine
o Glutamine is nontoxic in the brain
Stroke or Cerebrovascular accident
 Neurologic signs and symptoms that result from
diseases involving blood vessels
 Middle cerebral artery usually affected
 Types
o Hemorrhagic
o Ischemic (occlusion)
Blood Brain Barrier
 Special property of the CNS blood vessels to exclude
certain substances
 Some blood borne substances are not allowed entry
into the brain
 Cerebral capillaries are not in contact with neurons
 Characteristics
o Comparison of systemic capillaries with
brain capillary
 Pericytes
 Astroglial process
 Arrangement of endothelium of
cerebral capillaries responsible for
blood brain barrier
 Zonula occludens / tight
junctions
 No fenestrations
 No intercellular clefts
 Thick basement
membrane
 Lack vesicular transport
(transcytosis)
o Selective permeability of the barrier
 Lipid soluble substances can
diffuse across barrier
 CO2, O2, H2O
 Ethanol, caffeine, heroine
 Water-soluble substances pass
very slowly
o Presence of ion channels and exchanges
o Facilitation and energy-dependent receptor
mediated transport of specific water soluble
substances
 GLUT1 for glucose
 L system
 A system
 ASC system – ala, ser, cys
 MDR transporter (P-glycoprotein) –
multidrug non-specific transporter
removes hydrophobic toxin from
cells
o Enzyme system (metabolic blood brain
barrier)
 Dopa decarboxylase, MAO
 Gamma glutamyl transpeptidase
 Acid hydrolases, peptidases
o Ionized substances at phyiosologic pH
attached to protein transporters not
transportable through BBB
 Functions of the BBB
o Maintains constancy or stability of the envt
o Protects neurons from circulation
neurotransmitters
o Removes waste products
o Selectively transport substances needed for
growth
 Deficient or weak BBB
o No significant BBB in some regions of the
brain
 Circumventricular organs
 Subfornical organ, pineal gland,
OVLT, post pituitary, median
eminence, area postrema
 These areas detect changes in the
blood and stimulate certain action;
required to act right away
o BBB during infancy
o During infection, brain tumor, brain injuries
 Infection causes deficient BBB, also
makes drugs (antibiotics) easily
penetrate BBB
o May be weakened temporarily by exposure
to hyperosmolar solutions (contraction of
epithelial cells, inc passage of substances
through BBB)
 Brain or cerebral edema
o Net accumulation of water in the brain
o Generalized or focal
o Headache, vomiting, altered consciousness,
etc.
o Types
  Vasogenic edema – most common o CSF pressure (ICP)
 Cytotoxic edema o CSF sample for visual, chemical and cells fro
o Vicious cycle in cerebral edema microscopic analysis
 Compressed vasculature, dec BF, o Between L3 and L4 or L4 and L5
ischemia, vasodilation, inc capillary o Lateral decubitus position
pressure, fluid transudation  CSF pressure (ICP)
 Dec oxygen, inc permeability o Papilledema – reflected at the optic disc
o Tx: mannitol o Increased in Tumors, obstruction, etc
o Queckenstedt’s test or sign
Cerebrospinal Fluid System o 130 cmH2O (60 to 200) or 10 mmHg (5 to
15 mmHg)
 Choroid plexus found in roof of lateral, third and
 Normal CSF
fourth ventricles produces CSF
o Clear and colorless
 Drained in superior sagittal sinus
 If turbid or cloudy, presence of
 Also from ependymal cells and brain tissue itself
leukocytes and proteins
 Mechanism of formation
 If bloody or yellow, blood pigments
o Substances transported, secretion,
(hemorrhage)
absorbed 3
o Has no RBS, WBC is less than 4/mm
o Dependent on presence of transporters
 Bacterial or viral meningitis
 CSF composition
 Proteins increased, meningitis,
o Osmolality and Na [ ] same as plasma, Cl is
tumors
higher
 Glucose decreased, acute bacterial
o K (40% less) and bicarbonate [ ] lower than
infection
plasma
 Hydrocephalus
o Glucose 30% lower than plasma
o Excess fluid in the cranial cavity
o Slightly acidic
o Inc CSF volume leading to ventricular
o One-way flow
enlargement
 Absorption of CSF from the subarachnoid space by
o Causes
arachnoid granulations and villi
 Oversecretion of ICF
 Bulk flow of CSF from subarachnoid space to venous
 Rare
sinus; more CSF formed, increase pressure, increases
 Tumor in choroid plexus
bulk flow
 Impaired absorption
 Driving force
 Communicating
o Colloid osmotic pressure of plasma is
hydrocephalus
25mmHg higher than CSF
 Impaired arachnoid villi
o Hydrostatic pressure……….
o Enlargement of
 Granulations function as one-way valve through bulk
entire ventricular
flow (vacuole formation…transcytosis)
system without
 Blood-CSF barrier (choroid epithelium
obstruction
 Functions of CSF
o From
o Provides optimum environment of neurons
subarachnoid
and glial cells
hemorrhage
o Homeostatic
 Thrombosis of cerebral
o Lymphatic system
veins and sinuses
o Protective function
 Fluid collects both inside
 Mechanical cushion
and outside brain
 Allows brain to float
 Obstruction of CSF pathway
o Conduit for hormones secreted by
 Tumors, congenital
hypothalamus
malformation, scarring
 Examination of CSF
o Lumbar puncture
  Block of aqueduct of
Sylvius (atresia or closed
at birth, tumors)
 Inc in size in area before
the obstruction
o Treatment
 Shunt from ventricles to peritoneal
cavity, right atrium