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Circulatory system ( 循环系统 ) Circulatory system: heart + blood vessels Function: nutrient transportation and metabolites returning Blood: carrier Heart: pump Blood vessels: route, substance communications 2014-04-21 生理与病理生理学系 1

Bioelectrical phenomenon of heart Heart muscular organ Classification of cardiac muscle Working cardiac muscles: atrial & ventricular muscle Abilities: excitability, contractility, conduction Specialized cardiac muscle: Sinus node (sinoatrial node, SA node) Atrioventricular (AV) node AV bundles Purkinje cells Abilities: excitability, conduction, autorhythmicity Specialized excitatory-conductive system Internodal pathway atrial muscles (anterior, middle, posterior) 2014-04-21 生理与病理生理学系 2

Bioelectrical phenomenon of cardiac muscle Transmembrane potentials Resting potential Action potential Working and autorhythmic cardiac muscle cell 2014-04-21 生理与病理生理学系 3

RP of working cardiac muscle cell -90 mv Ion basis: Cardiac muscle K + equilibrium potential Slow leaking of Na + Activity of Na + -K + pump ACh activated potassium channel: hyperpolarization 2014-04-21 生理与病理生理学系 4

AP of working cardiac muscle cell Complex, longer Depolarization: Phase 0: -90 ~ +30mV, 1 ms Repolarization: Phase 1 (initial rapid repolarization): +30 ~ 0mV, 10 ms Phase 2 (plateau): 0 mv, 100~150 ms Phase 3 (final repolarization): 0 ~ -90 mv, 100 ~ 150 ms Phase 4 (resting potential): -90 mv 2014-04-21 生理与病理生理学系 5

Ion basis for AP of working cell Phase 0:Na + influx Phase 1:K + efflux Phase 2: Ca 2+ influx: L-Ca 2+ channels K + efflux Phase 3: K + efflux Phase 4: resting potential 2014-04-21 生理与病理生理学系 6

AP in atrial muscle cell Duration: shorter, 150ms Reason: permeability to K + is higher 2014-04-21 生理与病理生理学系 7

Transmembrane potential in Purkinje cells Characteristic: Phase 4 potential level not stable Maximal repolarizing potential maximal relaxation potential Working cell Purkinje cell 2014-04-21 生理与病理生理学系 8

Transmembrane potential in Purkinje cell Phase 0,1,2,3: same to working cell Phase 4: automatic depolarization Depolarization net inward current K + channel inactivation: begins at -60mV I f current (pacemaker current) Activated at -60 mv, full activation -100 mv Na + influx Blocker: Cs 2014-04-21 生理与病理生理学系 9

AP in pacemaker cell of SA node Maximal relaxation potential: -60 mv Threshold: -40 mv 0 Automatic depolarization: Fast Lack of phase 1, 2 Phase 0 depolarization: slow -40-60 2014-04-21 生理与病理生理学系 10

AP in pacemaker cell of SA node Characteristic: Lack of I k1 maximal relaxation potential -60 mv inactive Na + channels no Na + influx in phase 0 0 Phase 0: Ca 2+ influx from L- Ca 2+ channels, Phase 3: K + efflux Phase 4: K + channel inactive at -60mV -40-60 I f current: not fully activated, protective effect I Ca : activation of T- Ca 2+ channels at -50mV 2014-04-21 生理与病理生理学系 11

Fast response and slow response cell According to Phase 0 Fast Action P, fast Na + channels ( fast response cell) Slow Action P, slow Ca 2+ channels (slow response cell) Fast response cell: working cell, Purkinje cell Slow response cell: Pacemaker cell Autorhythmicity: Autorhythmic cell: P cell, Purkinje cell Non autorhythmic cell: working cell 2014-04-21 生理与病理生理学系 12

Electrical properties of cardiac muscle Electrical properties Excitability Autorhythmicity Conductance Mechanical property Contractility 2014-04-21 生理与病理生理学系 13

Excitability Difference between RP and Threshold ACh: hyperpolarization Quinidine: inhibits the activation of Na + Channels upshift threshold (myocarditis: arrhythmia) State of Na + channels Resting, activating, inactivating potential, temporal dependent Resting Activating Inactivating Reliving 2014-04-21 生理与病理生理学系 14

Excitability Working cell Effective refractory P: 0 ~ -60 mv Absolute refractory P: 0 ~ -55 mv Local response P: -55 ~ -60 mv Relative refractory P: -60 ~ -80 mv Supranormal P -80 ~ -90 mv Pacemaker cell Slow recovery: postrepolarization refractoriness 2014-04-21 生理与病理生理学系 15

Significance of long-lasting refractory period No tetanus Premature contraction Compensatory pause (CP) Premature C Cardiac contraction CP SA node rhythm Extra stimuli 2014-04-21 生理与病理生理学系 16

Autorhythmicity of specialized muscles Definition: generates impulses automatically Number of impulse/min 2014-04-21 生理与病理生理学系 17

Normal rhythm of heart All conductive tissues: intrinsic autorhythmicity Ranks of autorhythmicity: SA node >AV node >AV bundle >Purkinje cell Normal Pacemaker SA node (sinus rhythm) Others potential pacemakers (ectopic rhythm) Significances of potential pacemakers Dangerous : myocarditis Protective: AV block 2014-04-21 生理与病理生理学系 18

SA node controls the heart beat 1. Capture 2. Overdrive suppression Reasons: over activity of Na + -K + pumps Hyperpolarization Counterbalancing inward current Suppression: Frequency difference Clinical significances No arrhythmia with sudden lose of SA rhythm (Sick sinus syndrome, SSS) Artificial cardiac pacemaker 2014-04-21 生理与病理生理学系 19

Factors influence autorhythmicity Speed of depolarization NE increase I f and I Ca ACh increases I + K Difference between TP and Max relaxation potential ACh hyperpolarization 2014-04-21 生理与病理生理学系 20

Conductance of AP in heart Normal conductance: Speed Route Abnormal: Arrhythmia ( 心律失常 ) 2014-04-21 生理与病理生理学系 21

Conductance of AP in heart Route: SA node atrial muscles AV node AV bundles Purkinje cells ventricular muscles Electrical conductance Gap junctions MW < 1000 functional syncycium (atrial, ventricular) 2014-04-21 生理与病理生理学系 22

Characters of AP conductance in heart Speed Fast in A and V, slow at AV node Atria: 1.0 ~ 1.2 m/s; Ventricles: 2 ~ 4 m/s AV node: 0.02 m/s Significance: Fast in A and V synchronization Slow at AV node AV delay: Atria systole just before ventricular systole AV block 2014-04-21 生理与病理生理学系 23

Characters of AP conductance in heart High frequency filtration AP in atrial muscle: shorter duration HR increase refractory P decrease AV node postrepolarization refractoriness High frequency filtration: atrial fibrillation 2014-04-21 生理与病理生理学系 24

Factors influence AP conductance Diameter current resistance Purkinje cell > ventricular muscle > atrial muscle >AV node 2014-04-21 生理与病理生理学系 25

Factors influence AP conductance Speed and amplitude of depolarization: Amplitude: resting P Velocity: number of activated Na + channel potential, temporal dependent State of channels in adjacent membrane 2014-04-21 生理与病理生理学系 26

Electrocardiogram (ECG) Each cardiac cycle, AP from P cell precisely spreads throughout the heart according to exact route, sequence Electrocardiogram (ECG) 2014-04-21 生理与病理生理学系 27

Waves in electrocardiogram Set of electrocardiogram: 0.1mV/mm, 0.04 s/mm Waves: P wave: atrial depolarization, 0.08-0.11s QRS complex: ventricle depolarization, 0.06-0.10s T wave: ventricle repolarization, 0.05-0.25s U wave: unclear, 0.1-0.3s 2014-04-21 生理与病理生理学系 28

Waves in electrocardiogram Others: P-R interval: AP spreads to ventricle from SA node, 0.12 ~ 0.20 s Q-T interval: beginning of ventricular depolarization to completeness of repolarization S-T segment: all ventricular muscle stay at phase 2 2014-04-21 生理与病理生理学系 29

Relationship between ECG and AP AP is the origin of ECG Difference: Recording technique AP intracellular, single cell ECG extracellular, summation 2014-04-21 生理与病理生理学系 30

ECG and cardiac contraction ECG: Electrical activity Cardiac muscle contraction: Mechanical property 2014-04-21 生理与病理生理学系 31

Blood pumping process Cardiac cycle & heart rate: 60~90/min Systole Diastole Heart rat increase cardiac cycle decrease Time (S) Atria S D Ventricle D S D 2014-04-21 生理与病理生理学系 32

Heart pumping process Ventricular Systole Isovolumic contraction Ejection Rapid ejection Slow ejection 2014-04-21 生理与病理生理学系 33

Heart pumping process Ventricular Diastole Isovolumic diastole Ventricular filling Rapid filling Slow filling Atrial systole 2014-04-21 生理与病理生理学系 34

Role of atrial contraction Primary pump Increase ventricular filling: 10-30% Arial pressure A wave: atrial systole C wave: ventricular systole V wave: venous retuning a c v 2014-04-21 生理与病理生理学系 35

Functional evaluation of the heart pump Cardiac output Stroke volume ( 每搏输出量 ): 70 ml Cardiac output ( 每分输出量, 心输出量 ): 5L Cardiac index ( 心指数 ) Cardiac output / body surface area Ejection fraction ( 射血分数 ) Stroke volume / End diastolic volume 2014-04-21 生理与病理生理学系 36

Functional evaluation of heart Work output of heart Stroke work output ( 每搏功 ) = internal (stroke output pressure difference)+ external work (stenosis): external work increase Minute work output ( 每分功 ) = Stroke work output heart rate Efficiency of cardiac work output = work output / energy consumption Normal value: 20~25 % Heart failure: 5~10 % Increase in artery pressure: decrease in efficiency 2014-04-21 生理与病理生理学系 37

Cardiac reservation ( 心脏功能贮备 ) Resting state: 5L/min Heavy excises: 30L/min Cardiac reservation: Stroke volume reservation: End diastolic volume: 15ml End systolic volume: 35~40ml HR reservation: 2~2.5 times Hear diseases (heart failure) mobilization of cardiac reservation 2014-04-21 生理与病理生理学系 38

Factors that influence cardiac output Cardiac output = Stroke volume HR 1. Stroke volume Preload ( 前负荷 ) Afterload ( 后负荷 ) Contractility of cardiac muscle 2. Heart rate 2014-04-21 生理与病理生理学系 39

Influence of CO by preload Preload initial length end diastolic volume end diastolic pressure Compliance ( 顺应性 )of ventricle Intraventricular pressure (mmhg) Low C Normal C High C Ventricular volume Compliance curve 2014-04-21 生理与病理生理学系 40

Influence of CO by preload Ventricular functional curve Normal state: 5 ~ 6 mmhg 12 ~ 15 mmhg: optimal preload 15 ~ 20 mmhg: flat on work output >20 mmhg: no obvious decline Frank-Starling mechanism intrinsic ability increase following inflow increase Stroke work of LV LV end diastolic P (mm H2O) NE group Normal C Heart failure Ventricular functional curve 2014-04-21 生理与病理生理学系 41

Factors that influence preload End diastolic volume = remained blood + inflowing blood Filling time Venous returning speed Compliance of ventricle Stroke work of LV NE group Normal C Heart failure LV end diastolic P (cm H2O) Ventricular functional curve 2014-04-21 生理与病理生理学系 42

Influence of cardiac out by afterload Afterload artery pressure Afterload isometric contraction stroke volume (Recovered in 30 s) Mechanism: Frank-Starling mechanism Longtime increase in afterload pathological remodeling 2014-04-21 生理与病理生理学系 43

Influence of cardiac output by contractility Contractility: Isometric regulation Factors that influence excitation-contraction coupling NE β receptor L-Ca 2+ channel opening Stroke work of LV NE group Normal C Heart failur Caffeine: affinity of troponin to Ca 2+ Thyroid hormone: ATPase activity on cross bridge LV end diastolic P (cm H2O) Ventricular functional curve 2014-04-21 生理与病理生理学系 44

Influence of cardiac output by HR HR Cardiac Output >170 CO (too short filling time) <40 maximal EDV Staircase phenomenon: Cardiac output (L/min) Brady~ Normal HR tachycardia HR contractility 150-180: maximal Heart rate (beats/min) 2014-04-21 生理与病理生理学系 45

Heart sounds Originally from: closure of valves, vibrations of atrial or ventricular wall, or arteriole wall, fluid vibration Phonocardiogram: First sound low pith and long lasting, symbol of systole, closure of AV valves, vibration of arteriole wall and blood Second sound high pith and short lasting, symbol of diastole, the aortic and pulmonary valves close Third sound rapid filling, oscillation of blood, vibration of valves, ventricular wall and papillary muscle Fourth sound-atrial sound, inrush of blood into the ventricles during atrial systole 2014-04-21 生理与病理生理学系 46