regional circulations

Regional circulations Regional circulations

Prof. Vajira Prof. Vajira WeerasingheWeerasinghe

Dept of PhysiologyDept of Physiology

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Regional circulations Regional circulations

nn Coronary Coronary

nn CerebralCerebral

nn CutaneousCutaneous

nn Muscle Muscle

nn SplanchnicSplanchnic


Coronary circulation Coronary circulation


Coronary blood vessels Coronary blood vessels

nn Heart receives blood supply from two coronary Heart 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 Output 4% 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 g 400 ml/min/100 g

nn Has a high capillary density (3000Has a high capillary density (3000--5000 mm5000 mm2, about , about one capillary per one 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 occurs Coronary blood flow occurs during diastoleduring diastole

nn WhyWhy

–– During systole, contraction of During systole, contraction of heart musculature squeezes heart musculature squeezes the coronary vesselsthe coronary vessels

–– This effect is more in deeper This effect is more in deeper layers (layers (subendocardialsubendocardial vessels) vessels) than superficial layers than superficial layers ((epicardialepicardial vessels)vessels)

–– This effect is maximal in the This effect is maximal in the left ventricleleft ventricle



nn myocardial blood flow is characterized by myocardial blood flow is characterized by almost complete oxygen extraction (70almost complete oxygen extraction (70--80%) 80%) from the blood across the coronary capillaries from the blood across the coronary capillaries

nn therefore, blood flow must increase to increase therefore, blood flow must increase to increase oxygen delivery to the heartoxygen delivery to the heart

nn myocardial oxygen delivery is FLOW LIMITED myocardial oxygen delivery is FLOW LIMITED

nn aortic pressure provides driving force for aortic pressure provides driving force for coronary blood flowcoronary blood flow


Regulation of Coronary Blood Flow Regulation of Coronary Blood Flow

nn Metabolic (Functional) Hyperemia Metabolic (Functional) Hyperemia

nn Reactive HyperemiaReactive Hyperemia

nn AutoregulationAutoregulation


Metabolic (Functional) Hyperemia Metabolic (Functional) Hyperemia

nn primary determinant of coronary blood flow is primary determinant of coronary blood flow is myocardial oxygen consumptionmyocardial oxygen consumption

–– which is dependent on metabolic activity which is dependent on metabolic activity

nn myocardial oxygen consumption is influenced by myocardial oxygen consumption is influenced by

–– cardiac pressure developmentcardiac pressure development

–– wall tensionwall tension

–– heart rateheart rate

–– cardiac outputcardiac output

–– inotropicinotropic statestate

–– AfterloadAfterload

–– preload preload


MechanismMechanism

nn The exact means by which increased oxygen The exact means by which increased oxygen consumption causes coronary circulation not knownconsumption causes coronary circulation not known

nn Possible mechanismPossible mechanism

–– Hypoxia Hypoxia --> 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 in adenosine produced in myocytesmyocytes from the metabolism of from the metabolism of ATPATP

–– stimulates nitric oxide release from endothelium stimulates nitric oxide release from endothelium

–– nitric oxide is a potent vasodilatornitric oxide is a potent vasodilator


Other factors Other factors

nn K+ ionsK+ ions

nn H+ ionsH+ ions

nn CO2CO2

nn BradykininBradykinin

nn ProstaglandinsProstaglandins

nn LactateLactate


Reactive hyperemia Reactive hyperemia

nn brief occlusion of coronary vessel is followed by brief occlusion of coronary vessel is followed by a transient increase in coronary blood flow a transient increase in coronary blood flow

nn occlusion results in the accumulation of occlusion results in the accumulation of vasodilator metabolites in the vasodilator metabolites in the interstitiuminterstitium

nn magnitude and duration of extra flow magnitude and duration of extra flow dependent on the duration of the occlusion dependent on the duration of the occlusion


AutoregulationAutoregulation

nn blood flow is relatively constant at perfusion blood flow is relatively constant at perfusion pressures from 60 mmHg pressures from 60 mmHg →→ 150 mmHg 150 mmHg

nn metabolic and metabolic and myogenicmyogenic mechanisms involved mechanisms involved

nn curve resets upward at elevated O2 such as curve resets upward at elevated O2 such as during exercise during exercise

nn autoregulatoryautoregulatory capacity is important in capacity is important in maintaining coronary flow when vessels are maintaining coronary flow when vessels are partially obstructed partially obstructed


Neural controlNeural control

nn sympathetic vasoconstrictor fibers sympathetic vasoconstrictor fibers -- tonic tonic activity activity

–– direct effect of SNS stimulation is vasoconstriction direct effect of SNS stimulation is vasoconstriction via via αα11--adrenergic receptors adrenergic receptors

–– net effect of sympathetic stimulation of the heart is net effect of sympathetic stimulation of the heart is to increase coronary blood flow due to increase in to increase coronary blood flow due to increase in the production of metabolic vasodilators with the production of metabolic vasodilators with increased oxygen consumption increased oxygen consumption



nn parasympathetic cholinergic fibers parasympathetic cholinergic fibers

–– →→ direct effect to direct effect to vasodilatevasodilate coronary resistance coronary resistance vessels via endothelial release of NO vessels via endothelial release of NO

–– net effect of parasympathetic stimulation of the net effect of parasympathetic stimulation of the heart may actually be reduced coronary blood flow heart may actually be reduced coronary blood flow resulting from decreased heart rate and oxygen resulting from decreased heart rate and oxygen consumptionconsumption


nn When the systemic BP fallsWhen the systemic BP falls

nn The overall effect of increase in noradrenergic The overall effect of increase in noradrenergic discharge is increased coronary blood flow due discharge is increased coronary blood flow due toto

–– Metabolic changes Metabolic changes

–– On the contrary On the contrary cutaneouscutaneous, renal and , renal and splanchnicsplanchnicvessels are constrictedvessels are constricted

–– Protecting the heart Protecting the heart


Hormonal factors Hormonal factors

nn circulating epinephrine circulating epinephrine

–– →→ ββ22--adrenergic receptoradrenergic receptor--mediated mediated vasodilationvasodilation

nn vasopressin produces coronary vasopressin produces coronary vasodilationvasodilation


Clinical conditions Clinical conditions

nn CAD (Coronary artery disease)CAD (Coronary artery disease)

–– Coronary artery disease (CAD) (or atherosclerotic Coronary artery disease (CAD) (or atherosclerotic heart disease) is the end result of the accumulation heart disease) is the end result of the accumulation of of atheromatousatheromatous plaques within the walls of the plaques 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 conditions Clinical conditions

nn CAD causesCAD causes–– Angina pectoris, commonly Angina pectoris, commonly

known as anginaknown as angina§§ is severe chest pain due to is severe chest pain due to

ischemia (a lack of blood and ischemia (a lack of blood and hence oxygen supply) of the hence oxygen supply) of the heart muscle, generally due to heart muscle, generally due to obstruction of the coronary obstruction of the coronary arteriesarteries

–– Myocardial infarction (MI) Myocardial infarction (MI) commonly known as a heart commonly known as a heart attackattack§§ is the interruption of blood is the interruption of blood

supply to part of the heart, supply to part of the heart, causing some heart cells to die causing some heart cells to die


Cerebral circulationCerebral circulation


General CharacteristicsGeneral Characteristics

nn brain least tolerant of organs to ischemia brain least tolerant of organs to ischemia

nn --↓↓blood flow for 5 seconds blood flow for 5 seconds →→loss of loss of consciousness consciousness

nn --↓↓blood flow for a few minutes blood flow for a few minutes →→irreversible irreversible damage damage


Anatomical details Anatomical 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 equal No crossing over from R to L (because of equal pressure)pressure)

nn Occlusion of vessel produces Occlusion of vessel produces ischaemiaischaemia and and infarction infarction


General CharacteristicsGeneral Characteristics

nn Rest: blood flow Rest: 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 output 15% of cardiac output – (in contrast Coronary: 4% of CO) 4% of CO)

nn Exercise: blood flow of 750 ml/min Exercise: blood flow of 750 ml/min

nn greatest flow goes to grey matter (100 greatest 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 skull circulation is enclosed in a rigid skull →→constant volume constant volume

nn brain tissue is incompressible brain tissue is incompressible

nn brain brain ““floatsfloats”” in a water bath of cerebrospinal in a water bath of cerebrospinal fluid fluid

nn high capillary density (3000 high capillary density (3000 -- 4000/mm2) 4000/mm2) →→large surface area, short diffusion distances large surface area, short diffusion distances

nn bloodblood--brain barrier brain barrier -- tight junctions between tight junctions between endothelial cells endothelial cells →→prevents circulating prevents circulating vasoactivevasoactive substances from affecting cerebral substances from affecting cerebral blood flow blood 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 maintained Constant 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 of The 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 pressure Role of intracranial pressure

nn Since the brain is enclosed within the skull the volume Since the brain is enclosed within the skull the volume of blood, brain and CSF should remain constant of 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 are Whenever ICP increases, cerebral vessels are compressed compressed

nn Change in venous pressure cause a similar change in Change in venous pressure cause a similar change in ICPICP

nn Rise in venous pressure decreases CBF by Rise in venous pressure decreases CBF by compressing the vessels thereby decreasing perfusion compressing the vessels thereby decreasing perfusion pressure pressure


AutoregulationAutoregulation

nn pronounced pronounced autoregulatoryautoregulatory capacity from 50 capacity from 50 --170 mmHg 170 mmHg

nn both both myogenicmyogenic and metabolic mechanisms and metabolic mechanisms involved involved

nn sympathetic nervous system activity can shift sympathetic nervous system activity can shift the curve to the right the curve to the right


Chemical Chemical

nn Arterial PCOArterial PCO22 (normal, 35(normal, 35--45 mmHg)45 mmHg)

–– hypercapniahypercapnia ((↑↑PCOPCO22 ) ) →→ dilatation dilatation →→ ↑↑blood flow blood flow

–– hypocapniahypocapnia ((↓↓PCOPCO22 ) ) →→ constriction constriction →↓→↓blood flow blood flow

–– COCO22 diffuses from blood into brain ECF diffuses from blood into brain ECF

–– COCO22+H+H22O O →→ HH22COCO33 →→ HH+++HCO+HCO33

–– ↑↑ [H[H++] ] →→ vasodilatation vasodilatation

–– blocks Cablocks Ca2+2+ entryentry

–– hyperpolarizes the membrane hyperpolarizes the membrane

–– ↑↑NOS activity NOS activity


nn Arterial pH (acidosis) Arterial pH (acidosis)

–– has little effect has little effect

–– HH++ does not cross the BBB does not cross the BBB

nn Arterial POArterial PO22 (normal, 80(normal, 80--100 mmHg) 100 mmHg)

–– diffuses easily from blood to cerebral ECF diffuses easily from blood to cerebral ECF

–– hypoxia (PO2<40hypoxia (PO2<40--50 mmHg) 50 mmHg) →→dilatation dilatation

–– PO2 > 100 mmHg PO2 > 100 mmHg →→little effect little effect

–– dilatation adenosine mediated (?) dilatation adenosine mediated (?)



nn Sympathetic nervous system Sympathetic nervous system

–– rich innervation from superior cervical ganglion rich innervation from superior cervical ganglion

–– maximum sympathetic nervous system activity maximum sympathetic nervous system activity causes only small vasoconstrictor response causes only small vasoconstrictor response

–– baroreceptorbaroreceptor reflexes have little influence on reflexes have little influence on cerebral blood flow cerebral blood flow

–– ↑↑sympathetic nervous system activity may prevent sympathetic nervous system activity may prevent hyperperfusionhyperperfusion during acute during acute ↑↑ in MAPin MAP



nn Parasympathetic nervous system Parasympathetic nervous system

–– innervation via facial and superficial innervation via facial and superficial petrosalpetrosal nerves nerves

–– stimulation of nerves cause vasodilatation (stimulation of nerves cause vasodilatation (AChACh stimulates stimulates NO release) NO release)

–– cut nerves cut nerves →→ no effect no effect

–– physiological importance is unknownphysiological importance is unknown

nn OtherOther

–– ↑↑nerve activity nerve activity →→ ↑↑NO release NO release →→ local vasodilatation local vasodilatation

–– PerivascularPerivascular neurons also contain 5HT (serotonin) a neurons also contain 5HT (serotonin) a powerful vasoconstrictor powerful vasoconstrictor -- may cause vasospasm may cause vasospasm egeg. in migraine . in migraine


MetabolicMetabolic

nn Potassium Potassium –– ↑↑K+ (i.e., seizures, hypoxia) K+ (i.e., seizures, hypoxia) →→ vasodilatation vasodilatation

–– ↑↑K+ K+ →→ stimulation of Na+/stimulation of Na+/K+ATPaseK+ATPase →→ hyperpolarize membrane hyperpolarize membrane

–– stable concentration in stable concentration in autoregulatoryautoregulatory range range

nn Adenosine Adenosine –– ↑↑ interstitial adenosine concentration with hypoxia, ischemia, interstitial adenosine concentration with hypoxia, ischemia, ↓↓ perfusion perfusion

pressure, pressure, ↑↑metabolic activity, metabolic activity, ↓↓supply/demand supply/demand

–– vasodilatation occursvasodilatation occurs

nn Nitric Oxide Nitric Oxide –– NO NO synthasesynthase active under basal conditions active under basal conditions

–– tonic vasodilator effect tonic vasodilator effect

–– glialglial--derived (derived (astrocytesastrocytes) ) -- NOS stimulated by NE, NOS stimulated by NE, bradykininbradykinin, glutamate , glutamate →→ Role? Role?


Central Nervous System Ischemic Central 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 of causing massive vasoconstriction as a means of raising the blood pressure to levels as high as the raising 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 Ischemic Central 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 activity sympathetic nervous system vasoconstrictor activity to systemic resistance vessels to systemic resistance vessels →↑→↑TPR TPR →→ ↑↑MAP MAP →→ ↑∆↑∆P P →→ ↑↑cerebral blood flow cerebral 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) will occupying lesion (i.e., tumor, hemorrhage) will ↑↑ICP ICP

nn forces brainstem down into the foramen magnum forces brainstem down into the foramen magnum

nn brainstem becomes compressed brainstem becomes compressed →→ ischemia ischemia

nn ↑↑sympathetic nervous system vasomotor drive to systemic sympathetic nervous system vasomotor drive to systemic resistance vessels resistance vessels →→ vasoconstriction vasoconstriction →↑→↑TPR TPR →↑→↑MAP MAP →↑∆→↑∆P P →→↑↑cerebral blood flow cerebral blood flow

nn baroreceptorbaroreceptor--mediated reflex mediated reflex bradycardiabradycardia

nn Main features: hypertension, Main features: hypertension, bradycardiabradycardia, respiratory , respiratory depression depression

nn The Cushing reflex is usually seen in the terminal stages of The Cushing reflex is usually seen in the terminal stages of acute head injury acute head injury


HumoralHumoral

nn few hormones pass blood brain barrier few hormones pass blood brain barrier

nn some PGs are lipid soluble some PGs are lipid soluble →→vasodilatevasodilate


Clinical conditionClinical condition

Stroke (Stroke (cerebrovascularcerebrovascular accident accident or CVA)or CVA)


StrokeStroke

nn rapidly developing loss of brain function due to rapidly 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 by This can be due to ischemia caused by thrombosis or embolism thrombosis or embolism

nn or due to a hemorrhageor due to a hemorrhage


CutaneousCutaneous blood flow blood flow


CUTANEOUS CIRCULATIONCUTANEOUS CIRCULATION

nn primary role is regulation of internal primary role is regulation of internal temperature temperature

nn protection against the environment protection against the environment

nn blood pressure control blood 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 heat fold to lose heat


Resistance vesselsResistance vessels

nn Two types Two types

–– ArteriovenousArteriovenous anastomosesanastomoses ((AVAsAVAs) )

–– ArteriolesArterioles


ArteriovenousArteriovenous anastomosesanastomoses

nn coiled, thickcoiled, thick--walled vessels walled vessels

nn direct connections between dermal arterioles and veins direct connections between dermal arterioles and veins

nn provide low resistance shunt pathways provide low resistance shunt pathways →→ feed dermal venous feed dermal venous plexus plexus

nn little basal tone (little basal tone (myogenicmyogenic) )

nn little metabolic control little metabolic control -- no no autoregulationautoregulation or reactive or reactive hyperemia hyperemia

nn sympathetic nervous system vasoconstrictor innervation has sympathetic nervous system vasoconstrictor innervation has almost exclusive control almost exclusive control

nn →→tonic activity tonic activity

nn located in located in ““acralacral skinskin””: areas of high SA/: areas of high SA/volvol. . -- fingers, toes, fingers, toes, palms, soles, lips, nose, ears palms, soles, lips, nose, ears

nn passive passive vasodilationvasodilation due to due to ↓↓sympathetic nervous system sympathetic nervous system activity activity


Arterioles Arterioles

nn located in nonlocated in non--acralacral skin skin -- limbs, trunk, scalp limbs, trunk, scalp

nn high density of high density of αα--adrenergic receptors adrenergic receptors

nn lack of lack of ββ22--adrenergic receptors adrenergic receptors

nn sympathetic nervous system vasoconstrictor sympathetic nervous system vasoconstrictor innervation innervation -- little activity at normal core temperature little activity at normal core temperature

nn sympathetic nervous system cholinergic (vasodilator) sympathetic nervous system cholinergic (vasodilator) innervation is prominent to sweat glands innervation is prominent to sweat glands →→BRADYKININBRADYKININ

nn bradykininbradykinin mediates mediates ““activeactive”” vasodilationvasodilation

nn arterioles exhibit arterioles exhibit autoregulationautoregulation, reactive hyperemia , reactive hyperemia and basal tone (and basal tone (myogenicmyogenic))


Venous Plexus Venous Plexus

nn contains greatest contains greatest cutaneouscutaneous blood volume blood volume --acts as a reservoir acts as a reservoir

nn important for heat transfer important for heat transfer

nn sympathetic nervous system vasoconstrictor sympathetic nervous system vasoconstrictor innervation innervation


Control of Control of CutaneousCutaneous Blood Flow Blood Flow

nn Sympathetic Nervous System Sympathetic Nervous System

–– to conserve heat SNS activity increases causing to conserve heat SNS activity increases causing vasoconstriction and reducing heat transfer to the vasoconstriction and reducing heat transfer to the environment environment

–– to lose heat SNS activity is reduced causing to lose heat SNS activity is reduced causing vasodilationvasodilation and enhanced heat transfer to the and enhanced heat transfer to the environment environment


Local Skin ReflexesLocal Skin Reflexes

nn local warming will produce local local warming will produce local vasodilationvasodilationand sweating and sweating

nn local cooling will produce local vasoconstriction local cooling will produce local vasoconstriction due to increased affinity of due to increased affinity of αα22--adrenergic adrenergic receptors for receptors for norepinephrinenorepinephrine

nn intensity controlled by central brain intensity controlled by central brain temperature centers temperature centers

nn cutting spinal cord results in extremely poor cutting spinal cord results in extremely poor temperature regulation temperature regulation


nn ColdCold--Induced Induced VasodilationVasodilation

–– when temperature falls, smooth muscle becomes when temperature falls, smooth muscle becomes paralyzed and vasodilatation occurs paralyzed and vasodilatation occurs

nn Physical compression (e.g. sitting) Physical compression (e.g. sitting)

–– ischemia ischemia →→accumulation of metabolites accumulation of metabolites →→stimulates stimulates nociceptorsnociceptors →→ pain pain →→ shift weight shift weight

–– →→ reactive hyperemia (substance P/CGRP?) reactive hyperemia (substance P/CGRP?)


nn Hormones Hormones –– epinephrine epinephrine →→ constriction constriction

–– angiotensinangiotensin II II →→ constriction constriction

–– vasopressin vasopressin →→ constriction constriction

nn Role in Blood Pressure Control Role in Blood Pressure Control –– Hypotension Hypotension →→ ↑↑sympathetic nervous system sympathetic nervous system →→AVA, AVA,

arteriole and venous constriction arteriole and venous constriction

–– →→ ↑↑TPR and mobilization of blood to support venous TPR and mobilization of blood to support venous pressure pressure

–– During exercise enhanced blood flow to the During exercise enhanced blood flow to the cutaneouscutaneouscirculation is necessary for circulation is necessary for

–– dissipating heat dissipating heat →→ reduces venous return to the heart reduces venous return to the heart →→arterial pressure falls arterial pressure falls


White reaction White 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 initiating Due to mechanical stimulus initiating precapillaryprecapillary sphincter contractionsphincter contraction


Triple response Triple response

nn When the skin is stroked more strongly When the skin is stroked more strongly

nn Triple response Triple response

–– 1. Red reaction1. Red reaction

§§ Capillary dilatation Capillary 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 reflex Due to axon reflex


Axon reflexAxon reflex

nn A response in which impulses initiated in A response in which impulses initiated in sensory nerves by the injury are relayed sensory nerves by the injury are relayed antidromicallyantidromically down other branches of the down other branches of the sensory nerve sensory nerve fibresfibres

Skin

Arteriole


Reactive Reactive hyperaemiahyperaemia

–– brief occlusion of blood flow is followed by a brief occlusion of blood flow is followed by a transient increase in flow transient increase in flow


Skeletal Muscle Skeletal Muscle Circulation Circulation


nn enormous range of blood flow in skeletal enormous 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 tone resistance vessels have high resting tone ((myogenicmyogenic) )


Regulation of Skeletal Muscle Blood Regulation of Skeletal Muscle Blood FlowFlow

nn Neural Neural

–– neural control dominates at restneural control dominates at rest

–– tonic sympathetic nervous system vasoconstrictor tonic sympathetic nervous system vasoconstrictor activity (1 Hz) activity (1 Hz) -- αα11--adrenergic receptor mediated adrenergic receptor mediated

–– an increase in sympathetic nervous system activity an 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 withdrawal vasodilatation at rest is passive due to withdrawal of sympathetic nervous system activity of sympathetic nervous system activity

–– sympatheticsympathetic--cholinergic fibers are anatomically cholinergic fibers are anatomically present present -- physiological role is uncertain physiological role is uncertain


HormonalHormonal

–– circulating epinephrine circulating epinephrine vasodilatesvasodilates at low at low concentration (concentration (ββ22--adrenergic receptor), adrenergic receptor),

–– constricts at high concentration (constricts at high concentration (αα1/1/αα22--adrenergic adrenergic receptors) receptors)

–– vasopressin vasopressin →→ constricts constricts

–– angiotensinangiotensin II II →→ constricts constricts


Metabolism (functional hyperemia)Metabolism (functional hyperemia)

nn with increased activity there is an increase in with increased activity there is an increase in the production of vasodilator metabolites the production of vasodilator metabolites

nn vasodilator metabolites are dominant during vasodilator metabolites are dominant during exercise although sympathetic nervous system exercise although sympathetic nervous system activity to the working muscle is also enhanced activity to the working muscle is also enhanced


Metabolism (functional hyperemia)Metabolism (functional hyperemia)

nn Mediators of Mediators of VasodilationVasodilation

–– increased interstitial [K+] increased interstitial [K+] →→stimulates stimulates Na+/Na+/K+ATPaseK+ATPase →→ hyperpolarizes membrane hyperpolarizes membrane

–– interstitial acidosis/hypoxia interstitial acidosis/hypoxia →→ hyperpolarizes hyperpolarizes membrane membrane

–– interstitial interstitial hyperosmolarityhyperosmolarity

–– adenosine? adenosine?


Physical FactorsPhysical Factors

nn cyclical contraction and relaxation of active cyclical contraction and relaxation of active skeletal muscle vesselsskeletal muscle vessels

nn vessels are compressed during the contraction vessels are compressed during the contraction phase phase →→ blood flow becomes intermittent blood flow becomes intermittent

nn muscle perfusion is enhanced by the muscle muscle perfusion is enhanced by the muscle pump pump

nn during activity muscle pump lowers the venous during activity muscle pump lowers the venous pressure which increases the pressure gradient pressure which increases the pressure gradient driving flow driving flow



–– blood flow is relatively constant from 60 blood flow is relatively constant from 60 →→ 120 120 mmHg (mainly mmHg (mainly myogenicmyogenic) )

nn Reactive Hyperemia Reactive Hyperemia

–– brief occlusion of blood flow is followed by a brief occlusion of blood flow is followed by a transient increase in flow transient increase in flow


nn Role of Skeletal Muscle Circulation in Blood Role of Skeletal Muscle Circulation in Blood Pressure Control Pressure Control

–– large mass of tissue: 40 large mass of tissue: 40 -- 45% of body weight 45% of body weight

–– major site of resistance vessels major site of resistance vessels

–– Peripheral resistance regulated by controlling Peripheral resistance regulated by controlling muscle resistance muscle resistance

–– resistance influenced by resistance 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 Circulation Circulation


nn blood flow 25% of resting CO blood flow 25% of resting CO -- can increase by can increase by 30 30 --100% after a meal 100% after a meal

nn blood flow is closely coupled to absorption of blood flow is closely coupled to absorption of water, electrolytes and nutrients water, electrolytes and nutrients

nn Series/parallel configuration: the venous Series/parallel configuration: the venous drainage from the capillary bed of the drainage from the capillary bed of the gastrointestinal tract, spleen and pancreas gastrointestinal tract, spleen and pancreas flows into the portal vein, which provides most flows into the portal vein, which provides most of the blood flow to the hepatic circulation of the blood flow to the hepatic circulation


nn the hepatic artery provides the remainder of the hepatic artery provides the remainder of the blood flow into the liver the blood flow into the liver

nn high compliance venous system (25 high compliance venous system (25 ml/mmHg/kg) ml/mmHg/kg) →→ acts as a reservoir (especially acts as a reservoir (especially the liver) the liver)

nn contains 20% of the blood volume at restcontains 20% of the blood volume at rest


Neural Neural

nn Sympathetic nervous system Sympathetic nervous system

–– innervation of arterioles, innervation of arterioles, precapillaryprecapillary sphincters and sphincters and venous capacitance vessels venous capacitance vessels

–– little or no basal sympathetic nervous system tone little or no basal sympathetic nervous system tone

–– ↑↑sympathetic nervous system activity sympathetic nervous system activity →→ strong strong vasovaso-- and and venoconstrictionvenoconstriction →→

–– redistributes BF, and increases functional circulating redistributes BF, and increases functional circulating blood volume (blood volume (““mobilizationmobilization””) )


Parasympathetic nervous systemParasympathetic nervous system

nn no innervation of blood vessels no innervation of blood vessels

nn ↑↑activity activity →→ ↑↑motility, motility, ↑↑metabolismmetabolism→→functional hyperemia due to local vasodilator functional hyperemia due to local vasodilator metabolites (NO?) metabolites (NO?)


HormonesHormones

nn GastrinGastrin, , cholecystokinincholecystokinin →→ functional functional hyperemia hyperemia

nn AngiotensinAngiotensin II, vasopressin II, vasopressin →→vasoconstriction vasoconstriction



–– poorly developed poorly developed →→ metabolic mechanism metabolic mechanism dominates dominates

nn AutoregulatoryAutoregulatory escape escape

–– ↑↑sympathetic nervous system activity sympathetic nervous system activity →→ transient transient ↓↓in BF in BF

–– after 2 after 2 --4 minutes blood flow returns towards 4 minutes blood flow returns towards normal due to accumulation of metabolites normal due to accumulation of metabolites (adenosine) and (adenosine) and vasodilationvasodilation of arterioles of arterioles

–– veins remain constricted veins remain constricted


Role in Blood Pressure ControlRole in Blood Pressure Control

nn Hypotension Hypotension

–– vasoconstriction due to vasoconstriction due to ↑↑sympathetic nervous sympathetic nervous system, AII and VPsystem, AII and VP→→ ↑↑TPR TPR

–– venoconstrictionvenoconstriction →→displaces blood centrally displaces blood centrally →→↑↑CVP CVP →→ ↑↑SV SV


Hepatic, portal arterial and venous Hepatic, portal arterial and venous pressures pressures

90

10

5


Renal circulation Renal circulation

nn At rest 25% CO, 1.2At rest 25% CO, 1.2--1.3 l/min1.3 l/min

nn Pressure drop across the Pressure 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 Regulation Regulation –– NorepinephrineNorepinephrine, , AngiotensinAngiotensin II II -- vasoconstrictionvasoconstriction

–– Dopamine Dopamine –– vasodilatation vasodilatation

–– Sympathetic activity (alpha receptor) Sympathetic activity (alpha receptor) –– vasoconstrictionvasoconstriction

–– Stimulation of renal nerves Stimulation of renal nerves -- increases increases reninrenin secretion secretion

nn AutoregulationAutoregulation is present is present –– MyogenicMyogenic effect, NO may be involved effect, NO may be involved

nn Renal cortex high blood flow poor O2 extraction but in medulla Renal cortex high blood flow poor O2 extraction but in medulla low blood flow but high O2 extraction low blood flow but high O2 extraction


regional circulations

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