Local hemodynamic disorders 局部血液循环障碍 白求恩医学院病理学系 李 伟 2010.9.27

A clinical case

病例摘要 1、该患者的死亡原因是什么？ 2、其死因是否与之前的骨科手术有关？ 死者熊卓为，49岁，北大医院心血管研究所研究员。2006年初，因腰腿疼痛，到北大医院门诊接受保守治疗。1月18日，其X光检查结果显示：腰椎骨关节病、腰4-5椎间盘病变、腰4Ⅰ度滑脱伴峡部裂。于2006年1月23日入住北大医院。次日，熊接受了“L4/5椎管减压，椎弓根钉内固定，后外侧植骨融合术”手术。术后第六天，即1月30日，熊在下地行走时忽感头晕，摔倒于地，恶心呕吐，血压、脉搏测不出。经抢救无效，于31日死亡。 状告北京大学第一医院(以下简称北大医院)“非法行医” 3年多后，2009年11月3日，经由央视《经济半小时》报道 2010年4月28日，对于熊卓为的丈夫王建国状告北大医院 “非法行医”一案，北京市高级人民法院作出终审(二审)判决。 1、该患者的死亡原因是什么？ 2、其死因是否与之前的骨科手术有关？

Intact Circulation --- Proper function of Heart and lung Integrity of the vasculature maintenance of balance between the coagulation and fibrinolytic systems stability of normal fluid homeostasis

Local hemodynamic disorders Water extravasation Edema 水肿/积液 Hyperemia充血 Blood contents Congestion /淤血 Ischemia 缺血 Thrombus 血栓 Abnormal substances Embolism 栓塞 --- Infarction 梗死 vascular injury Hemorrhage 出血

Section 1 Hyperemia or congestion A local increased volume of blood in a particular tissue 局部组织血管内血液含量的增多

Hyperemia 动脉性充血 An active process resulting from augmented blood flow due to arteriolar dilation 器官或组织因动脉输入血量的增多而发生的充血

Hyperemia 动脉性充血 Physiologic， Types: Pathologic (inflammation) Morphology: 组织器官体积轻度增大 ，颜色鲜红，温度增高 细动脉和毛细血管扩张充血 Consequence:

Hyperemia 动脉性充血 常见类型： 生理性充血Physiologic ： 病理性充血Pathologic：炎症反应的早期 减压后充血：受压的组织或器官→突然解除压力→细动脉反射性扩张充血,如一次性大量抽取胸水或腹水→血压下降 肉眼：组织器官体积轻度肿胀，颜色鲜红，温度升高，代谢功能亢进 镜下：动脉和毛细血管扩张、充满血液 后果：暂时性变化，去除原因即可恢复正常，因而影响小 但血管本身有病变时，充血可以是血管破裂的诱因

Congestion 淤血 A passive process resulting from impaired venous return from a tissue 器官或组织静脉血流回流受阻，血液淤积于小静脉 和毛细血管内，称淤血

Congestion 淤血 Causes Systemically, in cardiac failure Local--venous obstruction -- venous compressed

Morphology and Consequences Congestion 淤血 Morphology and Consequences Swollen, cyanosis (Blue-red color), low temperature 肿胀，发绀(蓝紫色），体表温度下降 Dilatation of local venules and capillaries 局部静脉和毛细血管扩张 Congestive edema 淤血性水肿 Congestive hemorrhage，hemosiderin–laden macrophage 淤血性出血 Parenchyma cell: atrophy, reversible injury, necrosis 实质细胞萎缩、变性、坏死 Interstitial hyperplasia: fibrosis, congestive sclerosis 间质纤维组织增生

Dilatation of local venules and capillaries Congestion 淤血 Morphology Dilatation of local venules and capillaries

Parenchyma cell: atrophy, reversible injury and necrosis Interstitial hyperplasia: fibrosis, congestive sclerosis

Chronic pulmonary congestion Acute pulmonary congestion Lung congestion 肺淤血 Left heart failure Chronic pulmonary congestion Acute pulmonary congestion

Congestion 淤血 Acute pulmonary congestion

Congestion 淤血 Acute pulmonary congestion Alveolar capillaries engorged with blood Alveolar septal edema Intra-alveolar edema fluid and hemorrhage

Congestion 淤血 Chronic pulmonary congestion normal lung The septa become thickened and fibrotic The alveolar spaces contain hemosiderin–laden macrophages normal lung

Congestion 淤血 Chronic pulmonary congestion Heart failure cells The septa become thickened and fibrotic The alveolar spaces contain hemosiderin–laden macrophages Heart failure cells

Congestion 淤血 Chronic pulmonary congestion Brown duration （肺褐色硬化）

---肝淤血 Liver congestion Right-sided heart failure Acute hepatic congestion: Gross: dusky red, tense, slightly heavy; LM: central vein and sinusoids are distended with blood There may be central hepatocyte necrosis Chronic hepatic congestion: Gross: nutmeg liver LM: centrilobular necrosis and peri-lobular fatty change; hemorrhage; atrophy long standing congestion—hepatic fibrosis

Congestion 淤血 Chronic hepatic congestion nutmeg liver —in chronic hepatic congestion, the central regions of the hepatic lobules are grossly red-brown, accentuated against the surrounding zones of uncongested tan. 在慢性肝淤血时，肝小叶中央区因严重淤血呈暗红色，两个或多个肝小叶中央淤血区可相连，而肝小叶周边部肝细胞则因脂肪变性呈黄色，致使在肝的切面上出现红（淤血区）黄（肝脂肪变区）相间的状似槟榔切面的条纹，称为槟榔肝

Congestion 淤血 Chronic hepatic congestion nutmeg liver

---肝淤血 Liver congestion central vein and sinusoids are distended with blood centrilobular necrosis, peri-lobular fatty change hemorrhage and hemosiderin

Congestion 淤血 congestion of liver

Centrilobular necrosis with hemorrhage and hemosiderin Congestion 淤血 congestion of liver Centrilobular necrosis with hemorrhage and hemosiderin

Centrilobular necrosis Congestion 淤血 congestion of liver Centrilobular necrosis

Chronic congestion of the liver fibrosis

淤血性肝硬变(Congestive cirrhosis) Congestion 淤血 淤血性肝硬变(Congestive cirrhosis)

Morphology and Consequences of congestion Dilatation of local venules and capillaries Congestive edema Congestive hemorrhage Parenchyma cell: atrophy,degeneration, necrosis Interstitial hyperplasia: fibrosis, congestive sclerosis

出血 (Hemorrhage) Loss of blood from the vascular compartment, usually as a result of trauma or disease of the vessel wall. This can involve large vessels, e.g, aorta or small vessels, e.g., capillaries. 血液从血管或心腔逸出,称出血. 破裂性出血 漏出性出血

出血 (Hemorrhage) 外出血-- 鼻出血，咯血，呕血，血便，血尿 内出血 体腔积血: (心包腔,胸腔,腹腔,关节腔) 淤点，紫癜，淤斑 内出血 体腔积血: (心包腔,胸腔,腹腔,关节腔) 软组织血肿: (硬脑膜下血肿，腹膜后血肿，皮下血肿) petechia 淤点(1-2mm) purpura 紫癜(3-5mm), ecchymosis 淤斑(大于1-2cm) hematoma 血肿

皮下出血 脑出血 心脏破裂及心包积血 hemorrhages 硬膜下血肿

petechia 淤点 ecchymosis 淤斑

Thrombosis 血栓形成 The formation of a clotted mass of blood in the noninterrupted cardiovascular system is known as thrombosis, and the mass itself is termed a thrombus. 在活体的心脏和血管内，血液发生凝固或血液中某些有形成 分凝集形成固体质块的过程称为血栓形成(thrombosis)。 所形成的固体质块称为血栓(thrombus)

Pathogenesis of thrombosis Three important elements in thrombosis virchow triad: 心血管内皮细胞的损伤 血流状态的改变 血液凝固性增加 Virchow’s triad in thrombosis. Endothelial integrity is the single most important factor. Injury to endothelial cells can affect local blood flow and/or coagulability. Abnormal blood flow (stasis or turbulence can cause endothelial injury. The factors may act independently or may combine to cause thrombus formation.

血栓形成条件 1.心血管内皮细胞的损伤 endothelial injury：dominant influence 正常心血管内膜的内皮细胞具有抗凝和促凝两种功能，生理情况下以抗凝作用为主，使血液保持流动状态。 是血栓形成的最重要条件 内膜损伤，内皮下胶原暴露，活化XⅡ因子，启动内源性凝血系统 损伤内皮能释放组织因子，激活因子VII，启动外源性凝血系统 血小板的活化在触发凝血过程中起核心作用（凝血酶激活血小板）

血栓形成条件 血小板活化表现为： 粘附反应(adhesion) 血小板粘附于局部内皮下胶原 分泌和释放反应(secretion and release reaction) 血小板被激活，释出ADP等，使血小板互相粘集 粘集反应(aggregation) 血小板活化时生成的血栓素A2，可促成血小板不可复性粘集

血栓形成条件 心血管内膜损伤常见于： 动脉粥样硬化溃疡 风湿性或细菌性内膜炎 心肌梗死 结节性多动脉炎 同一静脉经过多次注射 缺氧、休克、败血症等，全身广泛内皮损伤，弥散性血管内凝血

血栓形成条件 2.血流状态的改变 changes in the pattern of blood flow 血流缓慢、停滞或涡流形成。 正常轴流消失，血小板与内膜接触机会增加，促进血小板粘集 局部凝血因子和凝血酶浓度增加，达到凝血所需浓度 内皮细胞缺氧，受损 血流缓慢—静脉血栓 涡流—动脉和心脏血栓

血栓形成条件 为什么静脉比动脉更易发生血栓？ 常见于：夜间熟睡，心力衰竭，久病卧床者 部 位：静脉瓣，血管分叉处，曲张的静脉 部 位：静脉瓣，血管分叉处，曲张的静脉 二尖瓣狭窄的左心房，动脉粥样硬化斑块，动脉瘤内 静脉血栓 ：动脉血栓=4 ：1 下肢血栓 ：上肢血栓=3 ：1 为什么静脉比动脉更易发生血栓？ 静脉血栓常见于心衰、久病和术后卧床患者 原因：静脉瓣，不搏动，壁薄易受压，血液粘滞性增加

血栓形成条件 3.血液凝固性增加 changes in the blood constituents 指血液的高凝状态。血小板数量或粘度增加，凝血因子增多 遗传性高凝状态：第V因子基因突变 获得性的高凝状态 恶性肿瘤时癌细胞释放出促凝因子 DIC及游走性血栓性脉管炎 妊娠，手术后、大面积烧伤、产后

Pathogenesis of thrombosis Three important elements in thrombosis 心血管内皮细胞的损伤 血流状态的改变 血液凝固性增加 Virchow’s triad in thrombosis. Endothelial integrity is the single most important factor. Injury to endothelial cells can affect local blood flow and/or coagulability. Abnormal blood flow (stasis or turbulence can cause endothelial injury. The factors may act independently or may combine to cause thrombus formation.

Process of thrombogenesis Thrombosis 血栓形成 Process of thrombogenesis 血栓形成的过程

Thrombosis 血栓形成 静 脉 内 血 栓 的 形 成

Morphology and types of thrombi 白色血栓pale thrombi 混合血栓mixed thrombi 红色血栓red thrombi 透明血栓hyaline thrombi 按形态分类：

Morphology and types of thrombi 按发生部位分类 发生于心血管系统的任何部位 心脏或主动脉壁上血栓 --层状血栓（lines of Zahn),为混合血栓（mixed thrombi) ：由灰白色的血小板和纤维素层以及暗红色的红细胞层相间而成，并混有变性的白细胞 --附壁血栓（mural thrombi)—底部与心壁、血管壁相连 -- 球形血栓（ball thrombi)—左心房内血栓 静脉—红色血栓

Morphology and types of thrombi 层状血栓（lines of Zahn 混合血栓（mixed thrombi)

Morphology of thrombi 左心房附壁血栓（mural thrombi) 球形血栓

Morphology and types of thrombi 按发生部位分类 动脉血栓（arterial thrombi) 静脉血栓(venous thrombi, phlebothrombi) 微循环内血栓(fibrin thrombi, microthrombi) 心脏瓣膜血栓(cardiac valve thrombi)

Morphology and types of thrombi 动脉血栓（arterial thrombi) 动脉粥样硬化斑块基础上 血管损伤 白色或混合血栓 pale thrombus mixed thrombus

Morphology and types of thrombi 静脉血栓(venous thrombi, phlebothrombi) 阻塞性血栓 常见于下肢深静脉 头部--白色血栓 体部--混合血栓 尾部--红色血栓

Morphology and types of thrombi 微循环内血栓(fibrin thrombi, microthrombi)

Morphology and types of thrombi 心脏瓣膜血栓(cardiac valve thrombi) 常见于急性风湿性心脏病，二尖瓣和主动脉瓣 肉眼：灰白色小结节或赘生物状，表面粗糙，质实，与血管壁紧密粘着不易脱落 镜下：主要由血小板及少量纤维蛋白构成，为白色血栓，又称血小板血栓

Morphology and types of thrombi 心脏瓣膜血栓(cardiac valve thrombi)

Fate of the thrombus Dissolution 软化、溶解、吸收: complete dissolution, embolism Organization 机化: granulation tissue Recanalization 再通: 在血栓机化过程中，由于水分被吸收，血栓干燥收缩或部分溶解而出现裂隙，周围新生的内皮细胞长入并被覆于裂隙表面形成新的血管，并相互吻合沟通，使被阻塞的血管部分地重建血流。 Calcification 钙化

Fate of the thrombus organization recanalization

Calcification of thrombus Fate of the thrombus Calcification of thrombus

Fate of the thrombus

Consequence of thrombus Hemostasia 自行止血 obstruct vessel 阻塞血管 Embolism 栓塞 deformed valves 心瓣膜变形 disseminated intravascular coagulation 广泛性出血