血栓性微血管病ppt课件.ppt

血栓性微血管病Thromboticmicroangiopathy*血栓性微血管病溶血性尿毒症综合征血栓性血小板减少性紫癜恶性高血压硬皮病肾危象妊娠肾病药物性内皮细胞损伤*背景A16yearoldgirlanemia,petechiae,feverandrenalinvolvement“hrombosisofterminalarteriolesandcapillaries” MoschowitzArchInternMed1925;36:89-93FoursimilarcasesAnemiaandthrombocytopenicpurpuraThrombi---agglutinatingplatelets ;51:43-58*Thromboticthrombocytopenicpurpura(TTP)HemorrhagicdiathesisGeneralizedplateletthrombosis ;2:542-554Thromboticmicroangiopathy(TMA) ;2:897-903Hemolyticuremicsyndrome(HUS)ThrombocytopeniaCoombsnegativehemolyticanemiaRenalfailure ;85-905-909*HUS血栓性微血管病TMATTPH因子突变硬皮病妊娠恶性高血压血管炎肿瘤/化疗其它移植*发病机制TriggersofvascularinjuryViruses(HIV)Bacterialverotoxins/plexesDrugsCongenitalpredisposingconditionsDecreasedC3levelsDecreasedfactorHbioavailability/activityAbnormalvWFcleavingproteaseactivitiesvWFgenemutations(?)plementconsumptionEnhancedvascularshearstressAbnormalvWFfragmentation血栓性微血管病(TMA)*一、内皮细胞损伤致病微生物大肠杆菌肺炎链球菌vWF剪切蛋白酶ADAMTS13缺乏抗体及免疫复合物药物*大肠杆菌Verotoxin-(VTEC)---O157:H7有腹泻、出血性结肠炎的HUS(D+HUS)90%为VTEC感染其中70%为O157:H7*VTECVerotoxin与粘膜细胞受体结合细胞死亡腹泻粘膜血管网O157:H7出血性结肠炎Verotoxin进入肠道血循环与粒细胞结合血管内皮系统HUS*产神经氨酸酶(neuraminidase)肺炎链球菌RBC、PLT和内皮细胞膜均有TF(Thomsen-Friedenreich)抗原TF抗原被N-乙酰神经氨酸酶所覆盖正常人存在IgM抗TF抗原的抗体神经氨酸酶降解N-乙酰神经氨酸酶使TF抗原裸露神经氨酸酶RBCPLT内皮细胞病HUS*