1、Pathogenic Mechanism of Pulmonary Hypertension Role of Ca2+ and Ion Channels and NO,Certain problems related to distribution of blood flow and other hemodynamics are special to the pulmonary circulation and are especially important for gas ex-change in the lungs. The present discussion is concerned
2、specially with these special features of the pulmonary circu1ation,PHYSIOLOGIC ANATOMY OF THE PULMONARYCIRCULATORY SYSTEM,Pulmonary vessels,The pulmonary artery extends only 5 centimeters beyond the apex of the right ventricle and then divides into the right and left main branches, which supply bloo
3、d to the two respective lungs.,The pulmonary artery is also thin, with a wall thickness about twice that of the venae cavae and one third that of the aorta. The pulmonary arterial branches are very short, and all the pulmonary ateries, even the smaller arteries and arterioles, have larger diameters
4、than their counterpart systemic arteries.,This,combined with the fact that the vessels are very thin and distensible,gives the pulmonary arterial tree a large compliance, averaging almost 7ml/mm Hg, which is similar to that of the entire systemic arterial tree. This large compliance allows the pulmo
5、nary arteries to accommodate about two thirds of the stroke volume output of the right ventricle.The pulmonary veins, like the pulmonary arteries, are short, but their distensibility characteristics are similar to those of the veins in the systemic circulation,Bronchial Vessels,Blood also flows to t
6、he lungs through small bronchial arteries that originate from the systemic circulation, amounting to about l to 2 percent of the total cardiac output. This bronchial arterial blood is oxygenated blood, in contrast to the partially deoxygenated blood in the pulmonary arteries.It supplies the supporti
7、ng tssues of the lungs, including the connective tissue, septa, and large and small bronchi.,PRESSURES IN THE PULMONARY SYSTEM,Pulmonary arterial pressure averages about 25mm Hg in the normal human being; the diastolic pulmonary arterial pressure, about 8mm Hg; and the mean pulmonary arterial pressu
8、re,15mm Hg.,Pulmonary arterial pressure,Pulmonary Capillary Pressure,The mean pulmonary capillary pressure, has been estimated by indirect means to be about 7mm Hg. The importance of this low capillary pressure is related to fluid exchange functions of the pulmonary capillaries.,Left Atrial and Pulm
9、onary Venous Pressures.,The mean pressure in the left atrium and the major pulmonary veins averages about 2mm Hg in the recumbent human being,varying from as low as l mm Hg to as high as 5mm Hg.,BLOOD VOLUME OF THE LUNGS,The blood volume of the lungs is about 450 ml, about 9 percent of the total blo
10、od volume of the circulation system. Approximately 70 milliliters of this is in the pulmonary capillaries, and the remainder is divided about equally between the arteries and the veins,Lungs as a blood reservoir of normal to 2 times of normal,Shift of blood between the pulmonary and systemic circula
11、tory system as a result of cardiac pathology.,BLOOD FLOW THROUGH THE LUNGS AND ITS DISTRIBUTION,Factors that control cardiac output-mainlyperipheral factors also control pulmonary blood.For adequate aeration of the blood to occur,it is important for the blood to be distributed to those segments of t
12、he lungs where the alveoli are best oxygenated,Mechanism,Effect of Diminished Alveolar Oxygen on Local Alveolar Blood Flow-Automatic Control of Pulmonary Blood Flow Distribution.,When the concentration of oxygen in the alveoli decreases below normal-especially when it falls below 70 per cent of norm
13、al (below 73mm Hg Po2)-the adjacent blood vessels constrict during the ensuing 3 to10minutes, with the vascular resistance increasing more than five fold at extremely :low oxygen levels.,Hypoxia Pulmonary Vasoconstriction, HPV,This is opposite to the effect observed in systemic vessels, which dilate
14、 rather than constrict in response to low oxygen.,Significance,Providing an automatic control system for distributing blood now to the pulmonary areas in proportion to their degrees of ventilation.,Pulmonary Microcirculation,组成,Composition,由肺毛细血管、肺毛细血管前终末微动脉、微动脉,以及毛细管后的终末微静脉和微静脉所组成的灌流系统,Morphology C
15、haracteristics,在体循环，根据口径、结构和管壁的厚度，将血管 分为动脉、静脉、小动脉、小静脉、微动脉、微静脉和毛细血管。其中小动脉和小静脉是体循环阻力形成的主要部位。而在肺循环中则不存在相当于体循环中的小动脉和小静脉的结构。肺的大血管直接移行为毛细血管。,(一) Difference from systematic system,对于同样口径的血管，肺循环，血管管壁薄、管腔大, 管壁平滑肌少，其中层平滑肌层要比体循环血管薄许多。,肺动脉与肺静脉之间的组织结构差异不如体循环动脉和静脉的差异明显,肺的毛细血管前微动脉多以直角形式自母支发出。此种解剖学排列特点, 使供应肺泡的血流不致因
16、呼吸运动的牵张和回缩作用而受影响,肺泡壁毛细血管网和体循环毛细血管网的形态也存在差 异.肺毛细血管则是互相吻合成为一个六边形的毛细血管网，没有明显的起点和终点，而且并非所有的毛细血管都在同一个平面,肺微循环的血流动力学特征,肺泡毛细血管血压肺微循环的血管阻力 肺毛细血管血流及其分布,气体交换的原理气体交换的过程气体交换的影响因素,肺微循环的功能,-组织液的生成与回流功能,肺泡组织液的生成与回流肺水肿的发生与微循环,膜片钳技术的基本原理,离子通道研究的基本方法之一：,Part two,一、细胞膜离子的转运方式,主动转运： 钠-钾泵、钙泵继发性主动转运：钠-钙交换被动转运：各种离子通道,离子通道简
17、介,细胞膜或细胞器膜上的特殊蛋白质 通道分子构型变化表现开放和关闭两种基本状态； 通道分子的随机运动：开放和关闭状态是随机的；,单个通道电流 （随机量） 大量同类通道的电流（统计量）,通道开放时，特定离子顺电化学梯度被动 转运形成单通道电流。,细胞膜离子通道分类,电压门控通道 （voltage-gated channel)Na, K , Ca, Cl敏感元件：带电荷基团受体激活通道 (ligand-gated channel)第二信使激活通道（Second-messenger gated channel)Ca, cAMP, cGMP, IP3,G protein,（一）、激活方式,机械门控通道,KATP KACh,
