1. CHAPTER 4 CIRCULATION血液循环 Prof. Wang Ting huai Department of Physiology

2. 根据WHO 的统计结果，全球心血管疾病的流行情况 • 2002年全球因罹患心血管疾病而死亡的人数约为1700万，其中 • 冠心病（coronary heart disease）：700万 • 中风（stroke）：600万 • 高冠心病发病率的前三位国家 • 印度（India） ： 153万 • 中国（China） ： 70万 • 俄罗斯（Russian federation ）： 67万 （数字为2002年死于冠心病的人数）http://www.who.int/cardiovascular_diseases/en/

3. 2003年居民前十种慢性疾病患病率(‰)Morbidity Rate of 10 Main Chronic Diseases (‰) • 高血压 Hypertension26.2 ‰ 第一位 • 脑血管病 Cerebrovascular Disease6.6‰第五位 • 糖尿病 Diabetes Mellitus5.6 ‰第七位 • 缺血性心脏病 Ischaemic Heart Disease4.6 ‰第九位 中华人民共和国卫生部——2004年中国卫生统计提要

5. The composition of circulation system循环系统的组成 systemic circulation 体循环 left ventricle the aorta organs left ventricle right atrium 左心室 主动脉 全身器官 右心房 pulmonary circulation 肺循环 right ventricle pulmonary artery gas exchange in the lung left atrium 右心室 肺动脉 肺内气体交换 左心房

6. Blood circulation: circulation system is made up of the heart and vessels in which blood is flowing in certain direction ,going round and begin again.血液循环：心脏和血管组成机体的循环系统，血液在其中按一定方向流动，周而复始。The function of blood circulation血液循环的功能：

7. Transport oxygen and nutriment necessary for metabolism to the body and send off the metabolic products. 运送机体代谢活动所必须的氧气和营养物质，运走代谢产物。 • Maintain the stable state of the internal environment, deliver hormones and body fluid to the target organ to perform humoral regulation • 维持内环境的相对稳定，运送激素及体液因素到靶器官，实现体液调节。 • function to cease blooding and defending 止血及防卫功能 • body temperature regulation体温调节

8. Section1 . Electrical Activity of Myocardium • 第一节. 心肌细胞的电活动 • Section2 . The Pump Function of Heart • 第二节. 心脏的泵血功能 • Section3. Physiology of Blood Vessels • 第三节. 血管生理 • Section4. Regulation of Cardiovascular Activity • 第四节. 心血管活动的调节 • Section5. Organ Circulation • 第五节. 器官循环

9. SECTION 1 ELECTRICAL ACTIVITY OF HEART第一节 心脏的电活动

10. I. Bioelectrical Phenomena of Myocardium心肌的生物电现象

11. Four physiological properties of cardiac muscle • 兴奋性(excitability) • 自律性(autorhythmicity) • 传导性(conductivity) • 收缩性(contractivity) 心肌的四种生理特性： 电特性

12. types of cardiomuscular cells 心肌细胞的类型 special conducting system 心脏特殊转导系统 • autorhythmic cells 自律性细胞 sinoatrial node窦房结 atrioventricular area 房室交界区atrioventricular bundle 房室束 left and right bundle 左右束 purkinje fiber 浦肯野纤维 • unautorhymic cells非自律细胞 ventricular muscle 心室肌 atrial muscle 心房肌 working cells 工作细胞

13. Basic concepts基本概念 • Depolarization –– cations influx ---- Na+、 Ca2+ inward current 去极化－阳离子内流－Na+, Ca2+内向电流 • Repolarization –– cations efflux ---- K+ outward current 复极化－阳离子外流－ K+外向电流

14. Hyperpolarization: Vm → more negative than RMP 超极化：Vm → 比静息膜电位更负 Net current:电流趋势 inward ＜ outward repolarization 内向电流<外向电流 复极化 inward ＞ outwarddepolarization 内向电流>外向电流 去极化 inward ＝ outwardno change in Vm 内向电流＝外向电流 膜电位固定

15. Concentration and balanced potential of major ions in cadiomuscular cells 心肌细胞主要离子浓度及其平衡电位

16. Electrical Activity of Myocardium 心肌细胞的电活动

17. （a）心脏传导系统示意图（窦房结，结间束，房室结，His束，浦肯野纤维）（b）窦房结去极化（c）兴奋从结间束迅速扩布到房室结（d）去极化沿心房传播，兴奋传递在窦房结处延搁（e）去极化通过心室传导系统快速传导至心尖部（f）去极化由心尖部扩布到整个心室（a）心脏传导系统示意图（窦房结，结间束，房室结，His束，浦肯野纤维）（b）窦房结去极化（c）兴奋从结间束迅速扩布到房室结（d）去极化沿心房传播，兴奋传递在窦房结处延搁（e）去极化通过心室传导系统快速传导至心尖部（f）去极化由心尖部扩布到整个心室

18. The configurations of AP in different regions of the heart are different，according to depolarization rate, AP can be classified into two groups： 不同心肌细胞动作电位形成原理不同。根据去极化速率的不同，心肌细胞的动作电位可以分为两类： • Fast response action potential快反应动作电位 Fast response cells: atrium cell and ventricle cells – working myocardium 快反应细胞：心房和心室肌细胞－工作心肌

19. Fast response automatic cells: Purkinje fiber and bundle of His 快反应自律细胞：浦肯野纤维和His束（希氏束） • Slow response action potential慢反应动作电位 Slow response cells: S–A node and A–V node 慢反应细胞：窦房结和房室结细胞

20. TRANSMEMBRANE POTENTIAL OF MYOCARDIAL CELL AND THEIR IONIC BASIS心肌细胞的跨膜电位及其离子基础

21. A . Electrical Activity of Myocardium 心肌细胞的电活动 1. Typical feature典型特征 complex pattern形态复杂 long lasting持续时间长 unsymmetrical AP rising branch and descending branch 动作电位的升支与降支不对称

22. ⒉ Ionic basis for RMP and AP of working myocardium工作心肌的静息电位和动作电位的离子基础 a. Ionic concentration differences cross membrane膜内外的离子浓度差异 b. Permeability to ions (conductance) 离子的通透性(传导性)

23. TRANSMEMBRANE POTENTIAL OFVENTRICULARMUSCLE AND THEIR IONIC BASIS心室肌细胞的跨膜电位及其离子基础

24. ⑴ Ionic basis for RMP静息膜电位的离子基础 K+ permeability ↑, [K+]i ＞ [K+]o K+通透性↑, [K+]i ＞ [K+]o RMP ≌ K+ equilibrium potential 静息膜电位（RMP） ≌ K+平衡电位(-90mv)

25. ⑵ Ionic basis for AP动作电位的离子基础 Phase 0 (depolarization)0期（去极化） Stimulation → partial depolarization → threshold potential (-70mV) → Na+ Ch. opening →Na+ influx into cell down electrochemical gradient →Vm less negative→0 mV → +30 mV (overshoot). 刺激→部分去极化→达到阈电位(－70mV)→快Na+通道 开放→Na+内流，电化学浓度梯度降低→膜电位负值 降低→0mV→+30mV(超射)

26. Phase 0 (0期) • Character:Intracellular potential rapidly depolarize from -90mv to +30mv,the phase lasts about 1~2ms, the largest velocity of depolarization is 200~300 V/s. • 特征：膜电位由静息状态的－90mv迅速上升到＋30mv左右。去极相延续1-2ms。最大除极速率为 200-300V/s。 • Mechanism:opening of voltage –sensitive fast sodium channels , the regenerative process of sodium channels entering the cell quickly. • 机制：电压依赖性钠通道(INa)开放，快速Na+内 流的再生性除极过程。

27. Regenerative process: depolarization 再生性除极过程 Na+ influx induces more Na+ Ch. to open and Na+ influx increases. At the same time, K+ conductance falls and keeps Vm at depolarization state. Na+内流引发更多的Na+通道开放，加速Na+内流， 形成再生性除极。同时,K+通透性降低，膜电位保持 在去极化水平。

28. The fast Na+ channel (INa) 快钠通道 (INa) ①Activated and inactivated激活和失活状态 very fast Speed of depolarization: 快速去极化 (800-1000 V/s) Fast response potential快反应电位 Fast response cell快反应细胞 Fast channel快通道

29. ②Voltage dependent电压依赖性 Activation（激活）： -70mV Inactivation （失活）：＋30 mV Recovery to reopen：from -60mV 自－60mV复活 ③Blocked by TTX 能被河豚毒所阻断

30. Phase 1 （1期）1期（快速复极化） Character:Intracellular potential rapidly recovers from +30mv to 0mv ,the phase lasts about 10 ms. 特征：膜内电位迅速从＋30mv恢复到0mv左右，历时 约10ms。 Mechanism:The occurrence phase 1 is caused by the transient outward current （Ito ) , K+flows outward through the membrane. Na+ channel inactivating, the inward flowing of Na+ stops 。 机制：1期复极是由瞬时性外向K+离子流（Ito)引起， Na+通道失活，Na+内流终止。

31. ①Na+ Ch. is inactivated at +30mV Na + 通道在+30mV 失活 ② Transient outward current (Ito)--- K+ outward current, blocked by TEA. 快速外向电流(Ito)---K+外向电流，能被TEA阻断。 The quick repolarization of phase 0 and phase 1 form into a sharp peak in the graph which is called spike. 0期的快速去极和1期的快速复极构成一个尖锋状图形，称为锋电位(spike) 。

32. Phase 2 (plateau) 2期（平台期） • Character:the membrane potential keeps about 0mv,lasts 100-150ms,which is the cause of the whole AP lasts a long period of time and The main difference between the AP of the myocardial contraction cell and that of a skeletal muscle fiber or a neuron is a lengthening of the AP . 特征：膜电位基本停滞于0mv左右，持续约100－150ms，平台期是整个动作电位持续长的主要原因,也是心室肌细胞动作电位区别于骨骼肌细胞、神经纤维动作电位的主要特征。

33. Mechanism: Phase 2 is the integration of inward Ca2+ current and outward K+ current. The formation of phase 2 is connected with L type Ca2+ channel、k channel 和IK1channel. 机制：平台期是内向Ca2+电流和外向 K+电流整合的结果。平台期涉及的离子通道包括L型Ca2+通道、k通道和IK1通道。

34. Ca2+ inward－ Long-lasting Ca2+ Ch. • Ca2内流－L型钙通道 L Ca2+ Ch. activated at –40mV → Ca 2+ influx→ Ca2+ inward current L型Ca2+通道在–40mV被激活→Ca2+内流→ Ca2+内向电流 • K+ outward －delayed rectifier K+ channel（k）and inward integration potassium channel （k1） • K+外流 － 延迟整流钾通道（k） 内向整流钾通道（k1）

35. k channel : the growing k current during plateau is activated from +20mv and closes until the potential reaches -50mv. • k通道：在平台期逐渐增大的k电流在＋20mv激活，至复极到-50mV左右关闭。 • IK1 channel：IK1channels closes during the process of degeneration and reopens till the membrane repolarize into –60mv. The K+ permeability keeps slow and so the membrane can’t repolarize quickly. • IK1通道:0期去极化过程中关闭，复极化至－60mv 恢复开放。平台期K+通透性较低，不能迅速复极化。

36. Early state（早期）： Ca2+ inward current = outward K+ current Ca2+内向电流＝ K+外向电流 Late state（晚期）： Ca2+ Inward current ＜ outward K+ current → Vm more negative → repolarization Ca2+内向电流 ＜ K+外向电流 →Vm 更负 →复极化

37. The features of Long-lasting Ca2+ channelL型Ca2+通道的特征 ① Slow channel, slow inward current, Slow activation and inactivation and reactivation. 慢通道，慢速内向电流，慢速激活、失活和再激活。 ② Voltage dependent: Activated at –40mV, inactivated at 0mV 电压依赖性: 在–40mV被激活，0mV失活。

38. ③ Blocked by Mn2+ and VERAPAMIL 能够被Mn2+和维拉帕米所阻断。 ④ Low specialty: permeability to Na+ also. 特异性低：也可对Na+开放。

39. Phase 3 (late repolarization) 3期（复极晚期） • Character:the membrane potential repolarize quickly from 0mv to –90mv ,which lasts 100-150ms.There is no distinct margin between phase 2 and phase 3. • 特征：膜电位迅速从0mv复极到－90mv，历时100－150ms。2期和3期之间没有明显界限。 • Mechanism: Phase 3 is the result of Ca2+ current closing and increasing outward K+ current. • 机制：3期复极是由于L型钙通道关闭，内流停止，而K+外流进行性增加所致。

40. L type Ca2+ channel is inactivated： L型Ca2+通道失活 • K+ outward －k and k1 K+外流－ 延迟整流钾通道（k） 内向整流钾通道（k1） K+ channel opening→K+efflux↑→outward K+current↑ →Vm more and more negative → RMP. K+ 通道开放→K+外流趋势↑→外向 K+电流↑ →Vm负值更低 → 静息膜电位.

41. k channel : the growing k current during plateau is activated from +20mv and closes until the potential reaches -50mvduring the repolarization of phase 3. k通道：在平台期逐渐增大的k电流在至3期复极到-50mV左右关闭。 • IK1 channel：IK1channels reopens till the membrane repolarize into –60mv.The K+ permeability increases in a regenerative positive feedback process ,which makes the membrane repolarize quickly. IK1通道: IK1通道复极化至－60mv恢复开放，膜对K+通透性进行性增大，K+外流不断增强，为再生性正反馈过程，导致膜快速复极化。

42. Phase 4 (resting stage) 4期（静息水平） • Character:the membrane potential keeps around –90mv, but the exchange of ions continues . 特征：膜电位稳定于－90mv，但膜内外持续进行离子交换。 • Mechanism: During Phase 4, Na+、Ca2+ efflux against concentration gradient; K+ influx against concentration gradient to rebalance the concentration of ions outside and inside cell. 机制：在4期，Na+,Ca2+逆浓度梯度外流; K+逆浓度梯度内流，以恢复细胞膜内外的离子浓度。

43. Na+-K+ pump activity:Na+-K+泵的活动: 3 Na+ out and 2 K+ in Na+-Ca2+ exchange – antiport 逆向转运–3 个Na+外流和2个 K+内流 1 Ca2+ out and 3 Na+ in dependent of Na+ concentration difference inside and outside cell. Ca2+ pump on SR Ca2+ is pumped into SR Na+-Ca2+交换： 1 个Ca2+外流，3 个Na+内流 其驱动力是细胞膜内外的 Na+浓度差。 SR（肌浆网）上的Ca2+泵：将 Ca2+泵入SR内。

44. Ca2+的主动转运是依靠Na+_ K+泵提供的能量。此外，有部分 Ca2+是通过Ca2+泵主动转运至细胞外。(如图示)

45. 3. Electrical phenomena of automatic cells 自律细胞的生物电现象 Automatic fast response cell –– Purkinje cell 快反应自律细胞－浦肯野细胞 Automatic slow response cell： S-A node and A-V node 慢反应自律细胞：窦房结细胞和房室结细胞

46. a. Spontaneous, phase 4 depolarization –– the cause of automaticity pacemaker potential 4期自动除极－起搏细胞的自动节律性电活动 ⑴ Maximal repolarization potential at the end of phase 3. 3期末到达最大舒张复极电位。 ⑵ Phase 4, depolarizes automatically . 4期自动除极。 ⑶ When depolarization reaches threshold level excitation (AP) appears. 当去极化到达阈电位水平，兴奋性动作电位产生。

47. b. Ionic basis for phase 4 automatic depolarization4期自动除极的离子基础 ⑴ Fast response cell-Purkinje cell快反应细胞－浦肯野细胞 Ionic mechanisms of AP of rapid response automatic cells as the same as that of AP of working cells except phase 4. 除4期外，快反应自律细胞动作电位的离子基础和 工作心肌细胞一致。

49. The main pacing ionic current of Purkinje cell is If ,a special inward current.But the decreasing of IK is not important. • 浦肯野细胞的主要起搏离子流是一种特殊的内向电流If ，而IK衰减在自律活动发生原理中不重要。

50. The features of If:内向电流If的特征 ①Carried by Na+, blocked by Cs, but not by TTX 由Na+负载，能够被Cs阻断，但不能被TTX阻断。 Diminish outward K+ current (IK), If ＞ IK , depolarization → threshold potential → a new AP 外向K+电流IK减弱，If ＞ IK ，去极化→到达阈电位 → 产生新的 AP