Regional circulations

Regional circulationsRegional circulations
Prof. VajiraProf. Vajira WeerasingheWeerasinghe
Dept of PhysiologyDept of Physiology
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Regional circulationsRegional circulations
nn CoronaryCoronary
nn CerebralCerebral
nn CutaneousCutaneous
nn MuscleMuscle
nn SplanchnicSplanchnic

Coronary circulationCoronary circulation

Coronary blood vesselsCoronary blood vessels
nn Heart receives blood supply from two coronaryHeart receives blood supply from two coronary
arteriesarteries
–– Left coronary arteryLeft coronary artery
§§ Anterior descending branchAnterior descending branch
§§ Circumflex branchCircumflex branch
–– Right coronary arteryRight coronary artery
nn DominanceDominance
–– Right in 50%Right in 50%
–– Left in 20%Left in 20%
–– Equal in 30%Equal in 30%

nn 4% of Cardiac Output4% of Cardiac Output
nn high resting blood flow of 70high resting blood flow of 70--80 ml/min/100g80 ml/min/100g
–– At maximal cardiac work: 300At maximal cardiac work: 300--400 ml/min/100 g400 ml/min/100 g
nn Has a high capillary density (3000Has a high capillary density (3000--5000 mm5000 mm2, about, about
one capillary perone capillary per myocytemyocyte))
nn large surface arealarge surface area
nn short diffusion distances (short diffusion distances (≤≤99µµm)m)

Coronary blood flowCoronary blood flow
nn Coronary blood flow occursCoronary blood flow occurs
during diastoleduring diastole
nn WhyWhy
–– During systole, contraction ofDuring systole, contraction of
heart musculature squeezesheart musculature squeezes
the coronary vesselsthe coronary vessels
–– This effect is more in deeperThis effect is more in deeper
layers (layers (subendocardialsubendocardial vessels)vessels)
than superficial layersthan superficial layers
((epicardialepicardial vessels)vessels)
–– This effect is maximal in theThis effect is maximal in the
left ventricleleft ventricle

nn myocardial blood flow is characterized bymyocardial blood flow is characterized by
almost complete oxygen extraction (70almost complete oxygen extraction (70--80%)80%)
from the blood across the coronary capillariesfrom the blood across the coronary capillaries
nn therefore, blood flow must increase to increasetherefore, blood flow must increase to increase
oxygen delivery to the heartoxygen delivery to the heart
nn myocardial oxygen delivery is FLOW LIMITEDmyocardial oxygen delivery is FLOW LIMITED
nn aortic pressure provides driving force foraortic pressure provides driving force for
coronary blood flowcoronary blood flow

Regulation of Coronary Blood FlowRegulation of Coronary Blood Flow
nn Metabolic (Functional) HyperemiaMetabolic (Functional) Hyperemia
nn Reactive HyperemiaReactive Hyperemia
nn AutoregulationAutoregulation

Metabolic (Functional) HyperemiaMetabolic (Functional) Hyperemia
nn primary determinant of coronary blood flow isprimary determinant of coronary blood flow is
myocardial oxygen consumptionmyocardial oxygen consumption
–– which is dependent on metabolic activitywhich is dependent on metabolic activity
nn myocardial oxygen consumption is influenced bymyocardial oxygen consumption is influenced by
–– cardiac pressure developmentcardiac pressure development
–– wall tensionwall tension
–– heart rateheart rate
–– cardiac outputcardiac output
–– inotropicinotropic statestate
–– AfterloadAfterload
–– preloadpreload

MechanismMechanism
nn The exact means by which increased oxygenThe exact means by which increased oxygen
consumption causes coronary circulation not knownconsumption causes coronary circulation not known
nn Possible mechanismPossible mechanism
–– HypoxiaHypoxia --> vasodilator substances to be released from> vasodilator substances to be released from
cardiac muscle cellscardiac muscle cells
–– AdenosineAdenosine is the main vasodilator substanceis the main vasodilator substance
–– adenosine produced inadenosine produced in myocytesmyocytes from the metabolism offrom the metabolism of
ATPATP
–– stimulates nitric oxide release from endotheliumstimulates nitric oxide release from endothelium
–– nitric oxide is a potent vasodilatornitric oxide is a potent vasodilator

Other factorsOther factors
nn K+ ionsK+ ions
nn H+ ionsH+ ions
nn CO2CO2
nn BradykininBradykinin
nn ProstaglandinsProstaglandins
nn LactateLactate

Reactive hyperemiaReactive hyperemia
nn brief occlusion of coronary vessel is followed bybrief occlusion of coronary vessel is followed by
a transient increase in coronary blood flowa transient increase in coronary blood flow
nn occlusion results in the accumulation ofocclusion results in the accumulation of
vasodilator metabolites in thevasodilator metabolites in the interstitiuminterstitium
nn magnitude and duration of extra flowmagnitude and duration of extra flow
dependent on the duration of the occlusiondependent on the duration of the occlusion

AutoregulationAutoregulation
nn blood flow is relatively constant at perfusionblood flow is relatively constant at perfusion
pressures from 60 mmHgpressures from 60 mmHg →→ 150 mmHg150 mmHg
nn metabolic andmetabolic and myogenicmyogenic mechanisms involvedmechanisms involved
nn curve resets upward at elevated O2 such ascurve resets upward at elevated O2 such as
during exerciseduring exercise
nn autoregulatoryautoregulatory capacity is important incapacity is important in
maintaining coronary flow when vessels aremaintaining coronary flow when vessels are
partially obstructedpartially obstructed

Neural controlNeural control
nn sympathetic vasoconstrictor fiberssympathetic vasoconstrictor fibers -- tonictonic
activityactivity
–– direct effect of SNS stimulation is vasoconstrictiondirect effect of SNS stimulation is vasoconstriction
viavia αα11--adrenergic receptorsadrenergic receptors
–– net effect of sympathetic stimulation of the heart isnet effect of sympathetic stimulation of the heart is
to increase coronary blood flow due to increase into increase coronary blood flow due to increase in
the production of metabolic vasodilators withthe production of metabolic vasodilators with
increased oxygen consumptionincreased oxygen consumption

nn parasympathetic cholinergic fibersparasympathetic cholinergic fibers
–– →→ direct effect todirect effect to vasodilatevasodilate coronary resistancecoronary resistance
vessels via endothelial release of NOvessels via endothelial release of NO
–– net effect of parasympathetic stimulation of thenet effect of parasympathetic stimulation of the
heart may actually be reduced coronary blood flowheart may actually be reduced coronary blood flow
resulting from decreased heart rate and oxygenresulting from decreased heart rate and oxygen
consumptionconsumption

nn When the systemic BP fallsWhen the systemic BP falls
nn The overall effect of increase in noradrenergicThe overall effect of increase in noradrenergic
discharge is increased coronary blood flow duedischarge is increased coronary blood flow due
toto
–– Metabolic changesMetabolic changes
–– On the contraryOn the contrary cutaneouscutaneous, renal and, renal and splanchnicsplanchnic
vessels are constrictedvessels are constricted
–– Protecting the heartProtecting the heart

Hormonal factorsHormonal factors
nn circulating epinephrinecirculating epinephrine
–– →→ ββ22--adrenergic receptoradrenergic receptor--mediatedmediated vasodilationvasodilation
nn vasopressin produces coronaryvasopressin produces coronary vasodilationvasodilation

Clinical conditionsClinical conditions
nn CAD (Coronary artery disease)CAD (Coronary artery disease)
–– Coronary artery disease (CAD) (or atheroscleroticCoronary artery disease (CAD) (or atherosclerotic
heart disease) is the end result of the accumulationheart disease) is the end result of the accumulation
ofof atheromatousatheromatous plaques within the walls of theplaques within the walls of the
coronary arteries that supply the myocardiumcoronary arteries that supply the myocardium
–– Is the leading cause of death worldwideIs the leading cause of death worldwide
WHO Data

Clinical conditionsClinical conditions
nn CAD causesCAD causes
–– Angina pectoris, commonlyAngina pectoris, commonly
known as anginaknown as angina
§§ is severe chest pain due tois severe chest pain due to
ischemia (a lack of blood andischemia (a lack of blood and
hence oxygen supply) of thehence oxygen supply) of the
heart muscle, generally due toheart muscle, generally due to
obstruction of the coronaryobstruction of the coronary
arteriesarteries
–– Myocardial infarction (MI)Myocardial infarction (MI)
commonly known as a heartcommonly known as a heart
attackattack
§§ is the interruption of bloodis the interruption of blood
supply to part of the heart,supply to part of the heart,
causing some heart cells to diecausing some heart cells to die

Cerebral circulationCerebral circulation

General CharacteristicsGeneral Characteristics
nn brain least tolerant of organs to ischemiabrain least tolerant of organs to ischemia
nn --↓↓blood flow for 5 secondsblood flow for 5 seconds →→loss ofloss of
consciousnessconsciousness
nn --↓↓blood flow for a few minutesblood flow for a few minutes →→irreversibleirreversible
damagedamage

Anatomical detailsAnatomical details
nn Two internal carotidsTwo internal carotids
nn Two vertebral arteriesTwo vertebral arteries
–– Basilar arteryBasilar artery
nn Circle of WillisCircle of Willis
nn No crossing over from R to L (because of equalNo crossing over from R to L (because of equal
pressure)pressure)
nn Occlusion of vessel producesOcclusion of vessel produces ischaemiaischaemia andand
infarctioninfarction

General CharacteristicsGeneral Characteristics
nn Rest: blood flowRest: blood flow
–– of 50of 50--60 ml/min/100 g (750 ml/min)60 ml/min/100 g (750 ml/min)
(in contrast Coronary: 70-80 ml/min/100g; 250ml/min)
nn 15% of cardiac output15% of cardiac output
– (in contrast Coronary: 4% of CO)4% of CO)
nn Exercise: blood flow of 750 ml/minExercise: blood flow of 750 ml/min
nn greatest flow goes to grey matter (100greatest flow goes to grey matter (100
ml/min/100 g)ml/min/100 g)
nn 35% O2 extraction at rest35% O2 extraction at rest

Notable Anatomic CharacteristicsNotable Anatomic Characteristics
nn circulation is enclosed in a rigid skullcirculation is enclosed in a rigid skull →→
constant volumeconstant volume
nn brain tissue is incompressiblebrain tissue is incompressible
nn brainbrain ““floatsfloats”” in a water bath of cerebrospinalin a water bath of cerebrospinal
fluidfluid
nn high capillary density (3000high capillary density (3000 -- 4000/mm2)4000/mm2)
→→large surface area, short diffusion distanceslarge surface area, short diffusion distances
nn bloodblood--brain barrierbrain barrier -- tight junctions betweentight junctions between
endothelial cellsendothelial cells →→prevents circulatingprevents circulating
vasoactivevasoactive substances from affecting cerebralsubstances from affecting cerebral
blood flowblood flow

cushioning functioncushioning function
nn brain is floating in the fluidbrain is floating in the fluid
nn this provides a protective functionthis provides a protective function

Normal FlowNormal Flow
nn Constant cerebral blood flow is maintainedConstant cerebral blood flow is maintained
under varying conditionsunder varying conditions
nn Factors affecting the total cerebral blood flowFactors affecting the total cerebral blood flow
–– Arterial pressure at brain levelArterial pressure at brain level
–– Venous pressure at brain levelVenous pressure at brain level
–– The intracranial pressureThe intracranial pressure
–– The viscosity of bloodThe viscosity of blood
–– The degree of active contraction/dilatation ofThe degree of active contraction/dilatation of
cerebral arteriolescerebral arterioles
§§ This is controlled by local vasodilator metabolitesThis is controlled by local vasodilator metabolites

Role of intracranial pressureRole of intracranial pressure
nn Since the brain is enclosed within the skull the volumeSince the brain is enclosed within the skull the volume
of blood, brain and CSF should remain constantof blood, brain and CSF should remain constant
((MonroMonro--Kellie hypothesis)Kellie hypothesis)
nn ICP is normally 0ICP is normally 0--10 mmHg10 mmHg
nn Whenever ICP increases, cerebral vessels areWhenever ICP increases, cerebral vessels are
compressedcompressed
nn Change in venous pressure cause a similar change inChange in venous pressure cause a similar change in
ICPICP
nn Rise in venous pressure decreases CBF byRise in venous pressure decreases CBF by
compressing the vessels thereby decreasing perfusioncompressing the vessels thereby decreasing perfusion
pressurepressure

AutoregulationAutoregulation
nn pronouncedpronounced autoregulatoryautoregulatory capacity from 50capacity from 50 --
170 mmHg170 mmHg
nn bothboth myogenicmyogenic and metabolic mechanismsand metabolic mechanisms
involvedinvolved
nn sympathetic nervous system activity can shiftsympathetic nervous system activity can shift
the curve to the rightthe curve to the right

ChemicalChemical
nn Arterial PCOArterial PCO22 (normal, 35(normal, 35--45 mmHg)45 mmHg)
–– hypercapniahypercapnia ((↑↑PCOPCO22 )) →→ dilatationdilatation →→ ↑↑blood flowblood flow
–– hypocapniahypocapnia ((↓↓PCOPCO22 )) →→ constrictionconstriction →↓→↓blood flowblood flow
–– COCO22 diffuses from blood into brain ECFdiffuses from blood into brain ECF
–– COCO22+H+H22OO →→ HH22COCO33 →→ HH+++HCO+HCO33
–– ↑↑ [H[H++]] →→ vasodilatationvasodilatation
–– blocks Cablocks Ca2+2+ entryentry
–– hyperpolarizes the membranehyperpolarizes the membrane
–– ↑↑NOS activityNOS activity

nn Arterial pH (acidosis)Arterial pH (acidosis)
–– has little effecthas little effect
–– HH++ does not cross the BBBdoes not cross the BBB
nn Arterial POArterial PO22 (normal, 80(normal, 80--100 mmHg)100 mmHg)
–– diffuses easily from blood to cerebral ECFdiffuses easily from blood to cerebral ECF
–– hypoxia (PO2<40hypoxia (PO2<40--50 mmHg)50 mmHg) →→dilatationdilatation
–– PO2 > 100 mmHgPO2 > 100 mmHg →→little effectlittle effect
–– dilatation adenosine mediated (?)dilatation adenosine mediated (?)

nn Sympathetic nervous systemSympathetic nervous system
–– rich innervation from superior cervical ganglionrich innervation from superior cervical ganglion
–– maximum sympathetic nervous system activitymaximum sympathetic nervous system activity
causes only small vasoconstrictor responsecauses only small vasoconstrictor response
–– baroreceptorbaroreceptor reflexes have little influence onreflexes have little influence on
cerebral blood flowcerebral blood flow
–– ↑↑sympathetic nervous system activity may preventsympathetic nervous system activity may prevent
hyperperfusionhyperperfusion during acuteduring acute ↑↑ in MAPin MAP

nn Parasympathetic nervous systemParasympathetic nervous system
–– innervation via facial and superficialinnervation via facial and superficial petrosalpetrosal nervesnerves
–– stimulation of nerves cause vasodilatation (stimulation of nerves cause vasodilatation (AChACh stimulatesstimulates
NO release)NO release)
–– cut nervescut nerves →→ no effectno effect
–– physiological importance is unknownphysiological importance is unknown
nn OtherOther
–– ↑↑nerve activitynerve activity →→ ↑↑NO releaseNO release →→ local vasodilatationlocal vasodilatation
–– PerivascularPerivascular neurons also contain 5HT (serotonin) aneurons also contain 5HT (serotonin) a
powerful vasoconstrictorpowerful vasoconstrictor -- may cause vasospasmmay cause vasospasm
egeg. in migraine. in migraine

MetabolicMetabolic
nn PotassiumPotassium
–– ↑↑K+ (i.e., seizures, hypoxia)K+ (i.e., seizures, hypoxia) →→ vasodilatationvasodilatation
–– ↑↑K+K+ →→ stimulation of Na+/stimulation of Na+/K+ATPaseK+ATPase →→ hyperpolarize membranehyperpolarize membrane
–– stable concentration instable concentration in autoregulatoryautoregulatory rangerange
nn AdenosineAdenosine
–– ↑↑ interstitial adenosine concentration with hypoxia, ischemia,interstitial adenosine concentration with hypoxia, ischemia, ↓↓ perfusionperfusion
pressure,pressure, ↑↑metabolic activity,metabolic activity, ↓↓supply/demandsupply/demand
–– vasodilatation occursvasodilatation occurs
nn Nitric OxideNitric Oxide
–– NONO synthasesynthase active under basal conditionsactive under basal conditions
–– tonic vasodilator effecttonic vasodilator effect
–– glialglial--derived (derived (astrocytesastrocytes)) -- NOS stimulated by NE,NOS stimulated by NE, bradykininbradykinin, glutamate, glutamate
→→ Role?Role?

Central Nervous System IschemicCentral Nervous System Ischemic
ResponseResponse
n When the blood flow to the brain has been sufficiently
interrupted to cause ischemia of the vasomotor center
n these vasomotor neurons become strongly excited
nn causing massive vasoconstriction as a means ofcausing massive vasoconstriction as a means of
raising the blood pressure to levels as high as theraising the blood pressure to levels as high as the
heart can pump againstheart can pump against
n This response can raise the blood pressure to levels as
high as 270 mm Hg for as long as 10 minutes

Central Nervous System IschemicCentral Nervous System Ischemic
ResponseResponse
n This response is a last ditch stand to preserve the
blood flow to vital brain centers
n it does not become activated until blood pressure has
fallen to at least 60 mm Hg, and it is most effective in
the range of 15 to 20 mm Hg
n If the cerebral circulation is not reestablished within 3
to 10 minutes, the neurons of the vasomotor center
cease to function
nn ↑↑sympathetic nervous system vasoconstrictor activitysympathetic nervous system vasoconstrictor activity
to systemic resistance vesselsto systemic resistance vessels →↑→↑TPRTPR →→ ↑↑MAPMAP →→ ↑∆↑∆PP
→→ ↑↑cerebral blood flowcerebral blood flow

CushingCushing’’s Reflexs Reflex
n The Cushing reflex is a special type of CNS reflex resulting from
an increase in intracranial pressure
nn spacespace--occupying lesion (i.e., tumor, hemorrhage) willoccupying lesion (i.e., tumor, hemorrhage) will ↑↑ICPICP
nn forces brainstem down into the foramen magnumforces brainstem down into the foramen magnum
nn brainstem becomes compressedbrainstem becomes compressed →→ ischemiaischemia
nn ↑↑sympathetic nervous system vasomotor drive to systemicsympathetic nervous system vasomotor drive to systemic
resistance vesselsresistance vessels →→ vasoconstrictionvasoconstriction →↑→↑TPRTPR →↑→↑MAPMAP →↑∆→↑∆PP →→
↑↑cerebral blood flowcerebral blood flow
nn baroreceptorbaroreceptor--mediated reflexmediated reflex bradycardiabradycardia
nn Main features: hypertension,Main features: hypertension, bradycardiabradycardia, respiratory, respiratory
depressiondepression
nn The Cushing reflex is usually seen in the terminal stages ofThe Cushing reflex is usually seen in the terminal stages of
acute head injuryacute head injury

HumoralHumoral
nn few hormones pass blood brain barrierfew hormones pass blood brain barrier
nn some PGs are lipid solublesome PGs are lipid soluble →→vasodilatevasodilate

Clinical conditionClinical condition
Stroke (Stroke (cerebrovascularcerebrovascular accidentaccident
or CVA)or CVA)

StrokeStroke
nn rapidly developing loss of brain function due torapidly developing loss of brain function due to
disturbance in the blood supply to the brain,disturbance in the blood supply to the brain,
caused by a blocked or burst blood vesselcaused by a blocked or burst blood vessel
nn This can be due to ischemia caused byThis can be due to ischemia caused by
thrombosis or embolismthrombosis or embolism
nn or due to a hemorrhageor due to a hemorrhage

CutaneousCutaneous blood flowblood flow

CUTANEOUS CIRCULATIONCUTANEOUS CIRCULATION
nn primary role is regulation of internalprimary role is regulation of internal
temperaturetemperature
nn protection against the environmentprotection against the environment
nn blood pressure controlblood pressure control
nn 6% of the CO at rest (106% of the CO at rest (10--20 ml/min/100g)20 ml/min/100g)→→
↓↓50% to retain heat,50% to retain heat, ↑↑77--fold to lose heatfold to lose heat

Resistance vesselsResistance vessels
nn Two typesTwo types
–– ArteriovenousArteriovenous anastomosesanastomoses ((AVAsAVAs))
–– ArteriolesArterioles

ArteriovenousArteriovenous anastomosesanastomoses
nn coiled, thickcoiled, thick--walled vesselswalled vessels
nn direct connections between dermal arterioles and veinsdirect connections between dermal arterioles and veins
nn provide low resistance shunt pathwaysprovide low resistance shunt pathways →→ feed dermal venousfeed dermal venous
plexusplexus
nn little basal tone (little basal tone (myogenicmyogenic))
nn little metabolic controllittle metabolic control -- nono autoregulationautoregulation or reactiveor reactive
hyperemiahyperemia
nn sympathetic nervous system vasoconstrictor innervation hassympathetic nervous system vasoconstrictor innervation has
almost exclusive controlalmost exclusive control
nn →→tonic activitytonic activity
nn located inlocated in ““acralacral skinskin””: areas of high SA/: areas of high SA/volvol.. -- fingers, toes,fingers, toes,
palms, soles, lips, nose, earspalms, soles, lips, nose, ears
nn passivepassive vasodilationvasodilation due todue to ↓↓sympathetic nervous systemsympathetic nervous system
activityactivity

ArteriolesArterioles
nn located in nonlocated in non--acralacral skinskin -- limbs, trunk, scalplimbs, trunk, scalp
nn high density ofhigh density of αα--adrenergic receptorsadrenergic receptors
nn lack oflack of ββ22--adrenergic receptorsadrenergic receptors
nn sympathetic nervous system vasoconstrictorsympathetic nervous system vasoconstrictor
innervationinnervation -- little activity at normal core temperaturelittle activity at normal core temperature
nn sympathetic nervous system cholinergic (vasodilator)sympathetic nervous system cholinergic (vasodilator)
innervation is prominent to sweat glandsinnervation is prominent to sweat glands →→
BRADYKININBRADYKININ
nn bradykininbradykinin mediatesmediates ““activeactive”” vasodilationvasodilation
nn arterioles exhibitarterioles exhibit autoregulationautoregulation, reactive hyperemia, reactive hyperemia
and basal tone (and basal tone (myogenicmyogenic))

Venous PlexusVenous Plexus
nn contains greatestcontains greatest cutaneouscutaneous blood volumeblood volume --
acts as a reservoiracts as a reservoir
nn important for heat transferimportant for heat transfer
nn sympathetic nervous system vasoconstrictorsympathetic nervous system vasoconstrictor
innervationinnervation

Control ofControl of CutaneousCutaneous Blood FlowBlood Flow
nn Sympathetic Nervous SystemSympathetic Nervous System
–– to conserve heat SNS activity increases causingto conserve heat SNS activity increases causing
vasoconstriction and reducing heat transfer to thevasoconstriction and reducing heat transfer to the
environmentenvironment
–– to lose heat SNS activity is reduced causingto lose heat SNS activity is reduced causing
vasodilationvasodilation and enhanced heat transfer to theand enhanced heat transfer to the
environmentenvironment

Local Skin ReflexesLocal Skin Reflexes
nn local warming will produce locallocal warming will produce local vasodilationvasodilation
and sweatingand sweating
nn local cooling will produce local vasoconstrictionlocal cooling will produce local vasoconstriction
due to increased affinity ofdue to increased affinity of αα22--adrenergicadrenergic
receptors forreceptors for norepinephrinenorepinephrine
nn intensity controlled by central brainintensity controlled by central brain
temperature centerstemperature centers
nn cutting spinal cord results in extremely poorcutting spinal cord results in extremely poor
temperature regulationtemperature regulation

nn ColdCold--InducedInduced VasodilationVasodilation
–– when temperature falls, smooth muscle becomeswhen temperature falls, smooth muscle becomes
paralyzed and vasodilatation occursparalyzed and vasodilatation occurs
nn Physical compression (e.g. sitting)Physical compression (e.g. sitting)
–– ischemiaischemia →→accumulation of metabolitesaccumulation of metabolites →→
stimulatesstimulates nociceptorsnociceptors →→ painpain →→ shift weightshift weight
–– →→ reactive hyperemia (substance P/CGRP?)reactive hyperemia (substance P/CGRP?)

nn HormonesHormones
–– epinephrineepinephrine →→ constrictionconstriction
–– angiotensinangiotensin IIII →→ constrictionconstriction
–– vasopressinvasopressin →→ constrictionconstriction
nn Role in Blood Pressure ControlRole in Blood Pressure Control
–– HypotensionHypotension →→ ↑↑sympathetic nervous systemsympathetic nervous system →→AVA,AVA,
arteriole and venous constrictionarteriole and venous constriction
–– →→ ↑↑TPR and mobilization of blood to support venousTPR and mobilization of blood to support venous
pressurepressure
–– During exercise enhanced blood flow to theDuring exercise enhanced blood flow to the cutaneouscutaneous
circulation is necessary forcirculation is necessary for
–– dissipating heatdissipating heat →→ reduces venous return to the heartreduces venous return to the heart →→
arterial pressure fallsarterial pressure falls

White reactionWhite reaction
nn When a pointed object is drawn across the skinWhen a pointed object is drawn across the skin
nn Stroke lines becomes paleStroke lines becomes pale
nn Called white reactionCalled white reaction
nn Due to mechanical stimulus initiatingDue to mechanical stimulus initiating
precapillaryprecapillary sphincter contractionsphincter contraction

Triple responseTriple response
nn When the skin is stroked more stronglyWhen the skin is stroked more strongly
nn Triple responseTriple response
–– 1. Red reaction1. Red reaction
§§ Capillary dilatationCapillary dilatation
–– 2. Wheal (swelling)2. Wheal (swelling)
§§ Increased capillary permeabilityIncreased capillary permeability
–– 3. Flare (redness spreading out from injury)3. Flare (redness spreading out from injury)
§§ Arteriolar dilatationArteriolar dilatation
§§ Due to axon reflexDue to axon reflex

Axon reflexAxon reflex
nn A response in which impulses initiated inA response in which impulses initiated in
sensory nerves by the injury are relayedsensory nerves by the injury are relayed
antidromicallyantidromically down other branches of thedown other branches of the
sensory nervesensory nerve fibresfibres
Skin
Arteriole

ReactiveReactive hyperaemiahyperaemia
–– brief occlusion of blood flow is followed by abrief occlusion of blood flow is followed by a
transient increase in flowtransient increase in flow

Skeletal MuscleSkeletal Muscle
CirculationCirculation

nn enormous range of blood flow in skeletalenormous range of blood flow in skeletal
muscle: 3.0 ml/min/100 g at rest (20% of CO)muscle: 3.0 ml/min/100 g at rest (20% of CO)
nn exercise: 100 ml/min/100g (80exercise: 100 ml/min/100g (80--85% of CO)85% of CO)
nn resistance vessels have high resting toneresistance vessels have high resting tone
((myogenicmyogenic))

Regulation of Skeletal Muscle BloodRegulation of Skeletal Muscle Blood
FlowFlow
nn NeuralNeural
–– neural control dominates at restneural control dominates at rest
–– tonic sympathetic nervous system vasoconstrictortonic sympathetic nervous system vasoconstrictor
activity (1 Hz)activity (1 Hz) -- αα11--adrenergic receptor mediatedadrenergic receptor mediated
–– an increase in sympathetic nervous system activityan increase in sympathetic nervous system activity
(4(4--5 Hz) can decrease flow by 70%5 Hz) can decrease flow by 70%
–– vasodilatation at rest is passive due to withdrawalvasodilatation at rest is passive due to withdrawal
of sympathetic nervous system activityof sympathetic nervous system activity
–– sympatheticsympathetic--cholinergic fibers are anatomicallycholinergic fibers are anatomically
presentpresent -- physiological role is uncertainphysiological role is uncertain

HormonalHormonal
–– circulating epinephrinecirculating epinephrine vasodilatesvasodilates at lowat low
concentration (concentration (ββ22--adrenergic receptor),adrenergic receptor),
–– constricts at high concentration (constricts at high concentration (αα1/1/αα22--adrenergicadrenergic
receptors)receptors)
–– vasopressinvasopressin →→ constrictsconstricts
–– angiotensinangiotensin IIII →→ constrictsconstricts

Metabolism (functional hyperemia)Metabolism (functional hyperemia)
nn with increased activity there is an increase inwith increased activity there is an increase in
the production of vasodilator metabolitesthe production of vasodilator metabolites
nn vasodilator metabolites are dominant duringvasodilator metabolites are dominant during
exercise although sympathetic nervous systemexercise although sympathetic nervous system
activity to the working muscle is also enhancedactivity to the working muscle is also enhanced

Metabolism (functional hyperemia)Metabolism (functional hyperemia)
nn Mediators ofMediators of VasodilationVasodilation
–– increased interstitial [K+]increased interstitial [K+] →→stimulatesstimulates
Na+/Na+/K+ATPaseK+ATPase →→ hyperpolarizes membranehyperpolarizes membrane
–– interstitial acidosis/hypoxiainterstitial acidosis/hypoxia →→ hyperpolarizeshyperpolarizes
membranemembrane
–– interstitialinterstitial hyperosmolarityhyperosmolarity
–– adenosine?adenosine?

Physical FactorsPhysical Factors
nn cyclical contraction and relaxation of activecyclical contraction and relaxation of active
skeletal muscle vesselsskeletal muscle vessels
nn vessels are compressed during the contractionvessels are compressed during the contraction
phasephase →→ blood flow becomes intermittentblood flow becomes intermittent
nn muscle perfusion is enhanced by the musclemuscle perfusion is enhanced by the muscle
pumppump
nn during activity muscle pump lowers the venousduring activity muscle pump lowers the venous
pressure which increases the pressure gradientpressure which increases the pressure gradient
driving flowdriving flow

–– blood flow is relatively constant from 60blood flow is relatively constant from 60 →→ 120120
mmHg (mainlymmHg (mainly myogenicmyogenic))
nn Reactive HyperemiaReactive Hyperemia
–– brief occlusion of blood flow is followed by abrief occlusion of blood flow is followed by a
transient increase in flowtransient increase in flow

nn Role of Skeletal Muscle Circulation in BloodRole of Skeletal Muscle Circulation in Blood
Pressure ControlPressure Control
–– large mass of tissue: 40large mass of tissue: 40 -- 45% of body weight45% of body weight
–– major site of resistance vesselsmajor site of resistance vessels
–– Peripheral resistance regulated by controllingPeripheral resistance regulated by controlling
muscle resistancemuscle resistance
–– resistance influenced byresistance influenced by
§§ tonic vasoconstrictor activitytonic vasoconstrictor activity
§§ metabolic vasodilatorsmetabolic vasodilators
§§ regulation by reflex mechanisms (regulation by reflex mechanisms (baroreceptorsbaroreceptors,,
cardiopulmonary receptors, etc.)cardiopulmonary receptors, etc.)

SplanchnicSplanchnic CirculationCirculation

nn blood flow 25% of resting COblood flow 25% of resting CO -- can increase bycan increase by
3030 --100% after a meal100% after a meal
nn blood flow is closely coupled to absorption ofblood flow is closely coupled to absorption of
water, electrolytes and nutrientswater, electrolytes and nutrients
nn Series/parallel configuration: the venousSeries/parallel configuration: the venous
drainage from the capillary bed of thedrainage from the capillary bed of the
gastrointestinal tract, spleen and pancreasgastrointestinal tract, spleen and pancreas
flows into the portal vein, which provides mostflows into the portal vein, which provides most
of the blood flow to the hepatic circulationof the blood flow to the hepatic circulation

nn the hepatic artery provides the remainder ofthe hepatic artery provides the remainder of
the blood flow into the liverthe blood flow into the liver
nn high compliance venous system (25high compliance venous system (25
ml/mmHg/kg)ml/mmHg/kg) →→ acts as a reservoir (especiallyacts as a reservoir (especially
the liver)the liver)
nn contains 20% of the blood volume at restcontains 20% of the blood volume at rest

NeuralNeural
nn Sympathetic nervous systemSympathetic nervous system
–– innervation of arterioles,innervation of arterioles, precapillaryprecapillary sphincters andsphincters and
venous capacitance vesselsvenous capacitance vessels
–– little or no basal sympathetic nervous system tonelittle or no basal sympathetic nervous system tone
–– ↑↑sympathetic nervous system activitysympathetic nervous system activity →→ strongstrong
vasovaso-- andand venoconstrictionvenoconstriction →→
–– redistributes BF, and increases functional circulatingredistributes BF, and increases functional circulating
blood volume (blood volume (““mobilizationmobilization””))

Parasympathetic nervous systemParasympathetic nervous system
nn no innervation of blood vesselsno innervation of blood vessels
nn ↑↑activityactivity →→ ↑↑motility,motility, ↑↑metabolismmetabolism→→
functional hyperemia due to local vasodilatorfunctional hyperemia due to local vasodilator
metabolites (NO?)metabolites (NO?)

HormonesHormones
nn GastrinGastrin,, cholecystokinincholecystokinin →→ functionalfunctional
hyperemiahyperemia
nn AngiotensinAngiotensin II, vasopressinII, vasopressin →→vasoconstrictionvasoconstriction

–– poorly developedpoorly developed →→ metabolic mechanismmetabolic mechanism
dominatesdominates
nn AutoregulatoryAutoregulatory escapeescape
–– ↑↑sympathetic nervous system activitysympathetic nervous system activity →→ transienttransient ↓↓
in BFin BF
–– after 2after 2 --4 minutes blood flow returns towards4 minutes blood flow returns towards
normal due to accumulation of metabolitesnormal due to accumulation of metabolites
(adenosine) and(adenosine) and vasodilationvasodilation of arteriolesof arterioles
–– veins remain constrictedveins remain constricted

Role in Blood Pressure ControlRole in Blood Pressure Control
nn HypotensionHypotension
–– vasoconstriction due tovasoconstriction due to ↑↑sympathetic nervoussympathetic nervous
system, AII and VPsystem, AII and VP→→ ↑↑TPRTPR
–– venoconstrictionvenoconstriction →→displaces blood centrallydisplaces blood centrally →→
↑↑CVPCVP →→ ↑↑SVSV

Hepatic, portal arterial and venousHepatic, portal arterial and venous
pressurespressures
90
10
5

Renal circulationRenal circulation
nn At rest 25% CO, 1.2At rest 25% CO, 1.2--1.3 l/min1.3 l/min
nn Pressure drop across thePressure drop across the glomerulusglomerulus is only 1is only 1--3 mmHg3 mmHg
nn Further drop at the efferent arterioleFurther drop at the efferent arteriole
nn RegulationRegulation
–– NorepinephrineNorepinephrine,, AngiotensinAngiotensin IIII -- vasoconstrictionvasoconstriction
–– DopamineDopamine –– vasodilatationvasodilatation
–– Sympathetic activity (alpha receptor)Sympathetic activity (alpha receptor) –– vasoconstrictionvasoconstriction
–– Stimulation of renal nervesStimulation of renal nerves -- increasesincreases reninrenin secretionsecretion
nn AutoregulationAutoregulation is presentis present
–– MyogenicMyogenic effect, NO may be involvedeffect, NO may be involved
nn Renal cortex high blood flow poor O2 extraction but in medullaRenal cortex high blood flow poor O2 extraction but in medulla
low blood flow but high O2 extractionlow blood flow but high O2 extraction

Regional circulations

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Regional circulations