弥散性血管内凝血 Chapter 11,中山医学院病理生理教研室 邓宇斌,DIC 一、DIC原因和发病机制 二、促进DIC发生发展的因素（诱发困素） 三、DIC的分期和分型 四、DIC的功能代谢变化（病理生理变化） 五、DIC防治的病理生理基础,第一节 概述,1.血液的凝固与抗凝流动性血液运输载体方向性内（）凝血系统 凝血 外（）血小板 ： 粘 聚 释,凝抗凝 栓塞 失衡凝抗凝 出血倾向2.DIC的概念出血 病因 微血栓 后 休克 致凝 继发纤溶亢进 果 栓塞溶血 120种病：感染、肿瘤、产科意外,Introduction,DIC is characterized by the activation of the coagulation system with resultant consumption of a variety of coagulation proteins and platelets, which results in hemorrhagic diathesis and ischemic injury to various tissues.,1.Blood Coagulation It is propagated by an enzymatic events termedcoagulation cascade.Contact factors and the intrinsic pathway Tissue factor and extrinsic pathway,2.FibrinolysisIt is the result of the action of plasmin, a proteolytic enzyme produced from an inert plasma precursor (plasminogen) by the action of various substances termed plasminogen activators.,Humoral plasminogen activators Tissue plasminogen activators Fibrin or fibrinogen degradation products FDP (Significant biological activity) Fragments X, Y and E (potent antithrombins) Fragments Y and D( inhibit fibrin polymerization),a a aPC APCTM+ 灭 活 PS(+)C4bC4b PS(-),酶纤溶 FDP酶 AT PC抗 APC TM+a凝 PSPGI2VECTM,第二节 DIC的病因发病学,一、发病原因及机理 1.VEC广泛受损原因感染炎症、免疫损伤（抗磷脂综合征）高低温、放射损伤缺血缺氧酸中毒,Etiology of DIC,1.acute DIC (1)septicemia (2)severe trauma(3)obstetric accidents (4)shock 2.subacute DIC (1)malignant tumors (2)retained dead fetus 3.chronic DIC (1)giant hemangioma (2)systemic lupus erythematosus (SLE),机理胶原暴露凝 VEC 释放 受损 合成PGI2TXA2抗凝 表达TM APC,2.血细胞大量受损 RBC受损感染：疟疾原因：溶血 G6PDase：蚕豆病免疫损伤：异型输血红细胞素（）机理： 释ADP P聚集,WBC激活或受损坏死白血病细胞 释 原因 化疗受损 机理炎症激活 合成 、释（内毒素、补体、LC、P、AgAb）,P激活或受损原发性：免疫损伤（抗P抗体抗磷脂抗体）继发性：DIC 粘（GPb胶原）聚（GPba fg）TXA2等 P聚、血管收缩机理PF111 提供“反应面” aCa2+a aCa2+aPF3 PF3,3.大量致凝物质入血肿瘤细胞 坏死（包括产科意外）组织细胞带负电颗粒物质（内毒素）a胰蛋白酶其它丝氨酸蛋白水解酶 a蝰蛇毒,Pathogenesis of DIC,1.extensive damage of vascular endothelial cells Intrinsic clotting cascade 2.severe tissue injuryExtrinsic clotting reaction,3.excessive destruction of the circulating blood cellsGeneration of procoagulant-active substancesIntravascular coagulation 4.other thromboplastic materials entering the bloodActivation of clotting system through the contact of blood with an abnormal surface,the net effects are summarized as follows: 1.loss of plasma fibrinogen as it is consumed by the clotting process and by the action of plasma. 2.loss of other clotting factors notably , and , as they are used up during the operation of the clotting cascade. 3.fall in the platelet count, as the platelets aggregate and leave the circulation. 4.appearance of fibrin degradation products, as plasmin acts on its substrates.,二、诱因与发生机理消除致凝物质功能血液凝血活性抗凝活性 1.单核吞噬细胞系统功能内毒素血症、糖皮质激素、脾消除功能 ：致凝物、a 、凝纤产物,2.肝功能严重障碍灭活活化凝血因子合成AT、PC枯否细胞吞噬功能3.血液的高凝状态凝血活性 凝血物质：怀孕、肿瘤、应激抗纤溶：胎盘、药抗凝活性 抗肝素：HAT、PC、TM等4.血流郁滞,Predisposing factors to DIC,1.impairment of the clearance mechanism. 2.hypercoagulable state. 3.disorder of microcirculation.,第三节 DIC的分期及分型,高凝期分期 消耗性低凝期继发性纤溶亢进期急性按发病速度 亚急性分 慢性型 代偿型按代偿情况 失代偿型过度代偿型,Types of DIC 1.acute DIC Multiside bleeding diathesis Thrombotic complications usually Severe bleeding lead to shock and severe ischemic change in organs 2.subacute DIC Rarely bleeding The evidence of DIC can be detected by laboratory examinations 3.chronic DIC,Stage of DIC,1.hypercoagulable stage2.hypocoagulable stage3.secondary fibrinolytic stage,第四节 临床表现,1.出血 凝血物质消耗性酶：破坏凝血因子 继发性纤溶亢进 aFDP抗凝：竞争性抑制 aP聚 血管壁受损及溶栓,Consequences of DIC,1.disturbance of coagulation-bleeding(1)the consumption of clotting factors and platelets(2)the activation of fibrinolytic system(3)the production of fibrin degradation products (FDPs),2.休克 出血回心血量 微血栓阻断通路CO 心泵功能 :心肌DIC BP 右心后负荷 : 肺DIC外周阻力: 四个酶系统激活 A、B肽扩血管物质 FDP(通透性) 激肽C3a、C5a,2.disturbance of circulation-shock Microthromobus in capillariesand venules Blood returning decrease Cardiac muscle damage Cardiac output and blood volume reduce Effective circulating blood volume decrease Hypotension,3.栓塞微血栓 器官 功能BP 供血 障碍4.溶血：微血管病性溶血性贫血,3.ischemic tissue damage-dysfunction of multiple organs Renal insufficiency Acute adrenal failure Pituitary necrosis Adult or acute respiratory distress syndrome (ARDS) Convulsion and coma,4.microangiopathic hemolytic anemia (MHA) characteristic morphologic abnormality of the red blood cells Twisted cells, crenated cells, triangular cells, helmet-shaped cells, and microspherocytes are seen on the blood smear.,