SECTON IV CIRCULATION

Physiology

SECTON IV CIRCULATION

Chapter 12~14

2008-09Cardiovescular system: B 2

CHAP 12 DYNAMICS OF BLOOD AND LYMPH FLOW

12.1 INTRODUCTION12.2 FUNCTIONAL MORPHOLOGY OF BLOOD

VESSELS12.3 BIOPHYSICAL CONSIDERATIONS12.4 ARTERIAL AND ARTERIOLAR

CIRCULATION12.5 CAPILLARY CIRCULATION12.6 LYMPHATIC CIRCULATION AND

INTERSTITIAL FLUID VOLUME12.7 VENOUS CIRCULATION

CHAP 12 DYNAMICS OF BLOOD AND LYMPH FLOW


12.1 INTRODUCTION

The blood vessels are a closed system of conduits

Blood flows: depended on different pressure Primarily because of the forward motion imparted to it by the pumping of the heart

Diastolic recoil of the walls of the arteriesCompression of the veins by skeletal musclesNegative pressure in the thorax during inspiration also move the blood forward

Resistance to flow Viscosity of the blood Diameter of the vessels, principally the arterioles


12.2 FUNCTIONAL MORPHOLOGY OF BLOOD VESSELS

Windkessel vessels ： large arteriesDistribution vessels: arterial systemic vesselsResistance vessels: arteriolesExchange vessels: capillariesCapacitance vessels: venous systemic vesselsShunt vessels: arteriovenous anastomosis


12.3 BIOPHYSICAL CONSIDERATIONS

12.3.1 Pressure, flow, and resistanceBasic concepts of hemodynamics F=P/R

F: blood flowP: blood pressure gradientR: blood flow resistance



Blood flow Flow rate=volume / second F (mL/s) ＝ P/R ＝ K(P1 － P2)r4/L ＝ (P1 － P2)r4/8L r: radius of blood vessels L: length of blood vessels : blood viscosity



Blood flow (F) is directly proportional to the pressure gradient (P, not P) and inversely to the resistance (R)

P=(100 － 10)mmHg =90mmHgFlow=10mL/min

P=(500 － 410)mmHg =90mmHgFlow=10mL/min

P1 P2

P1 P2



Blood flow resistance R ＝ F/P ＝ 8L/r4

Blood flow types and resistancer1=2F1=16

r2=1F2=1

P



Blood pressure Side pressure: force /area of vesselsP ＝ F·R F ： Cardiac Output R ： 8L/r4

1mmHg ＝ 0.133 kPa ＝ 1333 dyn·cm-2 1kPa ＝ 7.5mmHg



12.3.2 Average velocity V (cm/s) ＝ Q/A V:Velocity Q:flow A: the area of the conduit

Aorta: 40cm/sCapillaries: 0.07cm/s

the capillaries have 1000 times the total cross-sectional area of the aorta



12.3.3 Viscosity and resistanceThe resistance to blood flow is determined by the :

Radius of the blood vessels (vascular hindrance): resistance vessels Viscosity of the blood: dependent on the hematocrit



12.3.4 Law of Laplace


12.4 ARTERIAL AND ARTERIOLAR CIRCULATION

12.4.1 Arterial pressureFormation of arterial blood pressure: dependent on relationship of the blood volume/vessel capacity Blood filling in the systemCardiac output + recoil of arterial wallPeripheral resistance



12.4.2 Normal arterial pressureMeasurement of systemic arterial pressure: aortic pressure

Systolic pressure (SP): 120mmHgDiastolic pressure (DP): 70mmHgPulse pressureMean arterial pressure (MAP)

MAP=DP + 1/3(SP － DP)



12.4.3 Factors affecting arterial pressureStoke volumeHeart ratePeripheral resistanceCompliance of aorta and large arteryCirculatory blood volume/Capacity of vessels




12.5 CAPILLARY CIRCULATION

Micro-circulation Between arterioles and venules About capillary bed blood supply


12.5 CAPILLARY CIRCULATIONv

Microcirculation channels and theirs main functionsCircuitous channels

Exchange of metabolitesThoroughfare channel

Rapid return blood into circulationA-V shunt

Regulation of circulating blood volume and temperature


Structure of capillary




12.5.1 Capillary pressure and flowCapillary pressures vary considerablyTypical values capillaries ：

32 mm Hg at the arteriolar end15 mm Hg at the venous end

Blood flowThe capillaries are shortVelocity: about 0.07 cm/stransit time from the arteriolar to the venular end is 1-2 seconds



Exchange of substancesDiffusionConcentration gradientPermeability of capillary wallFiltration and osmosisHydrostatic pressure gradient and colloid osmotic pressure gradientVesicular transportEndocytosis and exocytosis



12.5.2 Equilibration with interstitial fluid

Capillary filtration and osmosisInterstitial fluid from filtrated plasma (0.3% plasma)


Formation and return of interstitial fluid


Arteriolar end Capillary Venular end

Capillary hydrostatic pressure

intestinal fluidhydrostatic pressure

Colloid osmotic pressureof plasma

Colloid osmotic pressure of intestinal fluid

Pc

i

fPi

f

p



V ＝ Kf [ (Pc ＋ if) － (p ＋ Pif) ]V: formatting volume of interstitial fluid Kf: filtration coefficient----permeability of capillaries, filtration areas(Pc ＋ if) － (p ＋ Pif): effective filtration pressure (EFP) or net filtration pressure (NFP)

At arteriolar end, EFP= ＋ 10mmHg, →net filtration net filtration≈~20L /d At venular end, EFP= － 8mmHg, →net return net return≈~18L/d Lymphatic return ≈~2L/d


12.6 LYMPHATIC CIRCULATION AND INTERSTITIAL FLUID VOLUME

12.6.1 Lymphatic circulationFrom extra fluid and to drain through them back into the blood Lymph flow is 2~4L/24hrLymphatic vessels

Initial lymphaticsCollecting lymphatics



Function of the lymphatic systemReclaiming protein and absorbing nourishment

Cleaning the RBC、 bacterium and foreign substance

Balancing the formation and absorption of interstitial fluid



12.6.2 Interstitial fluid volumeThe amount of fluid in the interstitial spaces depends on the:Capillary pressure: ratio of precapillary to postcapillary venular resistanceInterstitial fluid pressureColloid osmotic pressureCapillary filtration coefficientNumber of active capillaries,Lymph flowTotal ECF volume



EdemaIncreased filtration pressure: Arteriolar dilation; Venular constriction; Increased venous pressure (heart failure, incompetent valves, venous obstruction, increased total ECF volume, effect of gravity, etc)Decreased osmotic pressure gradient across capillary: Decreased plasma protein level; Accumulation of osmotically active substances in interstitial spaceIncreased capillary permeability: Substance P; Histamine and related substancesKinins, etcInadequate lymph flow


12.7 VENOUS CIRCULATION

12.7.1 Venous pressure and flow Venous pressure

Peripheral venous pressure (PVP)Venules: 12-18 mm Hglarger veins: 5.5 mm Hg Gravitational force ← postureCentral venous pressure (CVP)

4.6 mm Hg (4~12cmH2O)Dependent on cardiac ejection function and venous return volume



Venous blood flowFrom the venules to the large veins, its average velocity increases In the great veins, the velocity of blood is averaging about 10 cm/s (about 1/4 in the aorta)



12.7.2 Factors affecting venous flowCardiac contractionMuscle pumpThoracic Pump (respiratory “pump”)


CHAP 13 CARDIOVASCULAR REGULATORY MECHANISMS

13.1 INTRODUCTION13.2 SYSTEMIC REGULATION BY THE

NERVOUS SYSTEM13.3 SYSTEMIC REGULATION BY

HORMONES13.4 SUBSTANCES SECRETED BY THE

ENDOTHELIUM13.5 LOCAL REGULATION

CHAP 13 CARDIOVASCULAR REGULATORY MECHANISMS


13.1 INTRODUCTION

Regulatory mechanismsNeural regulation: cardiovascular reflexHumoral regulation: active substancesAutoregulation

Regulatory effectsAltering cardiac outputChanging the diameter of the resistance of vesselsAltering the amount of blood pooled in the capacitance vessels


13.1 INTRODUCTION

Regulatory significationsTo maintain homeostasis of blood pressure

To redistribute the blood supplyTo maintain blood volume adequately


13.2 SYSTEMIC REGULATION BY THE NERVOUS SYSTEM

13.2.1 Vessels innervation and vasomotor controlNoradrenergic fibers end on vessels in all parts of the body

Sympathetic vasoconstrictor fibers activitiesNA→-adrenergic receptor →vasoconstriction

→2-adrenergic receptor →vasodilationTransmitter released by varicositiesTonic discharge: vasodilation or vasoconstrictionTo increase flow resistance——determining the MAP and the organic blood flow



Distribution on the small vessels



Cholinergic fibers end on vessels in parts of the organsSympathetic and parasympathetic vasodilator fibers activities

ACh→M-receptor → vasodilationNo tonic dischargeTo increase blood flow of the special region

Noncholinergic, nonadrenergic fibersNO, peptide, purine,…



HormonesAd, Ang II, VP, ET-1, ANP, NO,…Local controls--flow autoregulation

Active hyperemia: chemical factorsO2↓, CO2, H+, adenosine, K+, PGs,… Metabolic productMyogenic response: intrinsic tone: Arteriolar smooth muscle possesses spontaneous activity (independent)Response to injury



13.2.2 Cardiac innervationCardiac sympathetic nerves: noradrenergic fibers

Tonic discharge To increase the cardiac rate (positive chronotropic effect), A-V conduction rate (positive dromotropic effect) and the force of cardiac contraction (positive inotropic effect)To inhibit the effects of vagal stimulation (probably by neuropeptide Y )



Cardiac vagal nerves: cholinergic fibersTonic discharge (vagal tone) To decrease the heart rate (negative chronotropic effect) and A-V conduction rate (negative dromotropic effect)



Medullar cardiovascular centerVasoconstrictor area: RVLMVasodilator area: CVLMCardioinhibitory area: ambiguous nucleusRelay station of afferent nerve: NTS

Cardiovascular center over the medullarBrain stemHypothalamus Cerebral cortex



The baroreceptor reflex activity



Physiological significance of baroreceptor reflex Monitoring the arterial pressureMaintaining the arterial pressure homeostasis

Baroreceptor resetting (in chronic hypertension)



13.2.4 Effects of chemoreceptor stimulation on the vasomotor areaChemoreceptors: carotid and aortic bodiesExert their main effect on respirationAlso converge on the vasomotor area: peripheral vasoconstriction and bradycardia


13.3 SYSTEMIC REGULATION BY HORMONES

13.3.1 KininsKinins: vasodilator peptides

BradykininLysylbradykinin (kallidin)



Kallikreins: proteases types of kallikreinsplasma kallikrein: kallikreinogen activation by factor XIIa

Acting on HMWK to form bradykininTissue kallikrein: sweat and salivary glands, pancreas, prostate, intestine, and kidneys

Acting on HMWK to form bradykinin and LMWK to form lysylbradykinin. When activated, plasma kallikrein



Actions of the kininsresemble those of histamineVisceral smooth muscle contraction Vascular smooth muscle relaxiton (via NO) ：↑ blood flow of exocrine glands Capillary permeability increase

Bradykinin receptors: G proteins coupling receptorsB1: to mediate the pain-producing effects B2: homology to the H2 receptor (arousal, sexual behavior, pituitary hormones secretion, blood pressure, drinking, and pain thresholds)



13.3.2 AdrenomedullinDepressor polypeptide: by increasing production of NO To inhibit aldosterone secretion in salt-depleted animals and appears to produce its depressor effect



13.3.3 Natriuretic hormonesANP, BNP and CNPThe atrial natriuretic peptide (ANP) secreted by the myocardium Antagonizes the action of various vasoconstrictor agents and lowers blood pressureThe natriuretic Na+-K+ATPase inhibitor (endogenously produced ouabain)



13.3.4 Circulating vasoconstrictorsVasopressin (ADH) is a potent vasoconstrictorNorepinephrine has a generalized vasoconstrictor actionAngiotensin II has a generalized vasoconstrictor action


13.4 SUBSTANCES SECRETED BY THE ENDOTHELIUM

Endothelial cells make up a large and important organSecretes many growth factors and vasoactive substancesVasoactive substances: prostaglandins and thromboxanes, nitric oxide, and endothelins



13.4.1 Prostacyclin and thromboxane A2Prostacyclin

Produced by endothelial cellsTo promote platelet aggregation and vasoconstriction

Thromboxane A2Produced by plateletsTo inhibit platelet aggregation and promote vasodilation



13.4.2 Nitric oxideNO synthase

NOS 1 & NOS 3 are activated by [Ca2+]iNOS 2 is activated by cytokin

NO diffuse to smooth muscle cells, activate soluble guanylyl cyclase, producing cGMP, which in turn mediates the relaxation of vascular smooth muscleNO is inactivated by hemoglobin



Physiologic role of NOVasodilationVascular remodeling and angiogenesisPenile erection



13.4.3 Carbon monoxideFrom heme As well as NO produces local dilation in blood vessels



13.4.4 EndothelinsPotent vasoconstrictor agents Endothelin: ET-1, ET-2, and ET-3Endothelin receptors: coupled via G proteins to phospholipase C

ETA receptor: to mediate the vasoconstriction produced by endothelin-1ETB receptor is coupled to Gi, may mediate vasodilation, and it appears to mediate the developmental effects of the endothelins


13.5 LOCAL REGULATION

13.5.1 AutoregulationBlood flow remains relatively constant

In the kidneys, mesentery, skeletal muscle, brain, liver, and myocardium Myogenic theory of autoregulation: intrinsic contractile response of smooth muscle to stretchMetabolic theory of autoregulation: vasodilator substances tend to accumulate



13.5.2 Vasodilator metabolitesRelaxation of the arterioles and precapillary sphincters etc

O2 tension and pH↓CO2 tension, osmolality, temperature, K+,lactate and histamine↑



13.5.3 Localized vasoconstrictionInjured arteries, arterioles and veins constrictlocal liberation of serotonin from platelets that stick to the vessel wall in the injured area Injured also constrict.


CHAP 14 CIRCULATION THROUGH SPECIAL REGION

14.1 INTRODUCTION14.2 CORONARY CIRCULATION14.3 CEREBRAL CIRCULATION14.4 PULMONARY CIRCULATION

CHAP 14 CIRCULATION THROUGH SPECIAL REGION


14.1 INTRODUCTION

The distribution of the cardiac output to various parts of the body at rest in a normal manOrganic blood flow dependent on:F∝(PA － PV)×R


14.1 INTRODUCTION


14.2 CORONARY CIRCULATION

14.2.1 Pressure gradients and flow in the coronary vesselsCoronary blood flow depend on

Pressure gradients: the difference between aortic pressure and coronary sinus The diastolic and systolic state of blood vessel in the heart


Pathway of coronary circulation



Characteristic of coronary blood flowRich flow: ~5%COGreatest Arteriovenous oxygen difference:

O2 A-V = 11~14ml/100ml Interrupted blood flow



14.2.2 Variations in coronary flow Chemical Factors

O2 lack: metabolic level → O2 →adenosine → coronary vasodilation → flow Increased concentrations of CO2, H+,K+, lactate, prostaglandins, adenine nucleotides, and adenosine

Neural Factors-adrenergic receptors mediate vasoconstriction-adrenergic receptors mediate vasodilation


14.3 CEREBRAL CIRCULATION

14.3.1 Cerebral blood flowCharacteristic of cerebral blood flowRich blood flow and great oxygen consumption: 15%COStabilized blood flow: controlled by a combination auto-regulationDependent on cerebral functionBlood brain barrier


14.3 CEREBRAL CIRCULATION

14.3.2 Cerebral blood flow regulationRole of intracranial pressureAutoregulation Role of Vasomotor & Sensory Nerves


14.4 PULMONARY CIRCULATION

Characteristic of pulmonary blood flowLow pressure & low resistance system: 1/6~1/5 of systemic circulation

Greater blood volume changeNo capillaries filtrationArterioles constrict by alveolar PO2 & PCO2

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SECTON IV CIRCULATION