弥散性血管内凝血课件整理.ppt

1、disseminated or diffuse intravascular coagulation1.DIC的概念的概念2.DIC的病因的病因3.凝血与抗凝凝血与抗凝4.DIC的发病机制的发病机制5.影响影响DIC发生发展的因素发生发展的因素6.DIC时机体功能代谢的变化时机体功能代谢的变化7.DIC防治的病理生理基础防治的病理生理基础病人病人,女女,岁岁,因停经周因停经周,胎儿肢体脱出阴道口胎儿肢体脱出阴道口外小时入院，检查发现子宫破裂外小时入院，检查发现子宫破裂,立即行全子宫切除。立即行全子宫切除。术中出血术中出血,病人出现心率加快、血压下降病人出现心率加快、血压下降即输血、输液即输血、输

2、液,强心等抗休克强心等抗休克治疗治疗,待血压回升至正常，查待血压回升至正常，查3试验试验(+)、测凝血时间测凝血时间超过分不凝超过分不凝、血小板减少血小板减少，凝血时间延长凝血时间延长,结合病史结合病史,诊断成立诊断成立,立即在输大量新鲜血同时输入立即在输大量新鲜血同时输入肝素、肝素、凝血酶原复合物凝血酶原复合物,并给予支持、对症治疗并给予支持、对症治疗,病情逐渐好转病情逐渐好转,各项检查指标转正常各项检查指标转正常,术后天出院。术后天出院。DIC是一种以是一种以凝血功能失常凝血功能失常为主要特征的病为主要特征的病理过程。由于某些致病因子的作用，凝血因子和理过程。由于某些致病因子的作用，凝血因

3、子和血小板被激活，大量促凝物质入血，血小板被激活，大量促凝物质入血，凝血酶增加凝血酶增加，进而微循环中形成广泛的微血栓。微血栓形成中进而微循环中形成广泛的微血栓。微血栓形成中消耗了大量凝血因子和血小板，继发性纤维蛋白消耗了大量凝血因子和血小板，继发性纤维蛋白溶解功能增强，导致患者出现明显的出血、休克、溶解功能增强，导致患者出现明显的出血、休克、器官功能障碍和溶血性贫血等临床表现。（器官功能障碍和溶血性贫血等临床表现。（从高从高凝状态转变到低凝状态凝状态转变到低凝状态）各种病因 激活凝血系统 凝血酶增多大量微血栓形成 凝血因子、血小板消耗纤溶系统激活 产生纤溶酶 FDP形成纤溶、抗凝作用增强 1

4、32 妇产科疾病妇产科疾病 感染性疾病感染性疾病 肿瘤性疾病肿瘤性疾病 创伤及手术创伤及手术凝血凝血抗凝抗凝纤溶纤溶凝血因子凝血因子血小板血小板血管痉挛血管痉挛纤溶系统纤溶系统AT-，TM-PC系统系统TFPI，肝素，肝素细胞抗凝细胞抗凝凝血酶凝血酶TFTFCaCa2+2+a aa aPL+CaPL+Ca2+2+a aa aPL+CaPL+Ca2+2+选择通路选择通路传统通路传统通路a a a a等等外凝系统外凝系统CaCa2+2+a aa a胶原胶原HKK KPKPK内凝系统内凝系统凝血酶原凝血酶原纤维蛋白原纤维蛋白原纤维蛋白纤维蛋白 单体单体稳定的稳定的纤维蛋白纤维蛋白CaCa2+2+a

5、aCaCa2+2+少量凝血酶少量凝血酶激活激活因子因子血小板活化血小板活化激活激活和和因子因子大量凝血酶大量凝血酶激活纤溶系统激活纤溶系统激活抗凝物质激活抗凝物质a fa 血浆激肽血浆激肽释放酶原释放酶原血浆激肽血浆激肽释放酶释放酶纤溶酶纤溶酶补体系补体系统统C3aC5aC3b5-HT组胺组胺TF红细胞溶解红细胞溶解血小板释放血小板释放PF3 血小板激活剂与血小板膜受体结合，通过G蛋白作用产生第二信使激活血小板发挥其黏附、聚集、释放功能 致密颗粒释放ADP等，颗粒释放黏附蛋白 GPb/a(b）与纤维蛋白原结合，血小板扁平伸展、聚集、黏附 活化血小板表面出现负电荷磷脂，结合凝血因子，形成纤维蛋白

6、网，血小板以伪足伸入网中，使血块回缩，形成坚固血栓TXA2TXA2TX合成酶合成酶PGG2/PGH2AAPEPCPLA2弱激活剂弱激活剂强激活剂强激活剂（胶原（胶原 PAF）GPPLCPIP2IP3DGPKC肌浆网肌浆网Ca2钙调蛋白钙调蛋白肌动球蛋白肌动球蛋白分泌分泌ADP 肾上腺肾上腺素素 5羟羟色胺等色胺等纤溶酶纤溶酶纤溶酶原纤溶酶原凝血酶凝血酶纤溶酶原激活物纤溶酶原激活物激肽释放酶激肽释放酶纤维蛋白（原）纤维蛋白（原）FDP水解凝血因子水解凝血因子内内外外内内 抗凝血酶抗凝血酶v 丝氨酸蛋白酶抑制物丝氨酸蛋白酶抑制物v抑制抑制a a a av由肝和内皮细胞合成由肝和内皮细胞合成v 与肝

7、素结合后活力大增与肝素结合后活力大增 血栓调节蛋白血栓调节蛋白凝血酶凝血酶凝血活性降低凝血活性降低凝血酶原凝血酶原蛋白蛋白C由肝合成由肝合成活化蛋白活化蛋白C灭活灭活a a、a a蛋白蛋白S内皮细胞表面内皮细胞表面 组织因子释放，启动凝血系统组织因子释放，启动凝血系统 血管内皮细胞损伤，凝血、抗凝调血管内皮细胞损伤，凝血、抗凝调控失调控失调 血细胞大量破坏，血小板被激活血细胞大量破坏，血小板被激活 促凝物质进入血液促凝物质进入血液 组织因子组织因子（TFTF）263Aa 263Aa 跨膜糖蛋白跨膜糖蛋白 组织细胞破坏，大量组织因子入血组织细胞破坏，大量组织因子入血 内皮细胞、单核细胞、中性粒细

8、胞及巨噬细胞在内毒内皮细胞、单核细胞、中性粒细胞及巨噬细胞在内毒素刺激下可诱导素刺激下可诱导TFTF表达表达 组织因子组织因子与凝血因子与凝血因子结合，启动外源性凝血系统结合，启动外源性凝血系统 a a-TF-TF复合物激活复合物激活、因子，产生的凝血酶反馈因子，产生的凝血酶反馈激活激活、等，扩大凝血反应等，扩大凝血反应TFTFCaCa2+2+a aa aPL+CaPL+Ca2+2+a aa aPL+CaPL+Ca2+2+选择通路选择通路传统通路传统通路a a a a等等外凝系统外凝系统CaCa2+2+a aa a胶原胶原 HKHKK KPKPK内凝系统内凝系统凝血酶原凝血酶原 凝血酶凝血酶纤

9、维蛋白原纤维蛋白原纤维蛋白纤维蛋白 单体单体稳定的稳定的纤维蛋白纤维蛋白CaCa2+2+a aCaCa2+2+释放组织因子，启动凝血系统 暴露胶原、激活因子，启动凝血反应，血小板激活，同时激活激肽系统、补体系统和纤溶系统 内皮细胞抗凝作用减低：TM/PC和HS/AT-系统功能降低，TFPI减少 内皮细胞tPA产生减少，PAI-产生增多，纤溶活性降低 NO、PGI2、ADP酶等减少，抑制血小板黏附聚集功能降低抑制血小板聚集抑制血小板聚集抑制抑制a a、a a、TFTF蛋白蛋白S外伤外伤肾上腺素肾上腺素凝血酶凝血酶ADPNO PGIPGI2 2、ADPADPaseaseTFPI灭活灭活a aa a

10、TMPCAPC凝血酶凝血酶肝素肝素AT抑制抑制a a、a a 纤溶酶原激活物纤溶酶原激活物（tPA、uPA）纤溶酶纤溶酶纤维蛋白溶解纤维蛋白溶解阻止血液凝固阻止血液凝固 红细胞破坏红细胞破坏 释放磷脂释放磷脂 促凝促凝 促血小板释放反应促血小板释放反应 释放释放ADPADP 使血小板聚集使血小板聚集 促血小板释放反应促血小板释放反应PF3 白细胞破坏白细胞破坏释放释放TF样物质样物质 白细胞激活白细胞激活内毒素、内毒素、ILIL1 1、TNFTNF使中性粒细胞合成和释使中性粒细胞合成和释放放TFTF组织损伤组织损伤白细胞白细胞组织因子组织因子血小板血小板激活激活红细胞红细胞破坏破坏羊水、转移羊

11、水、转移瘤细胞瘤细胞细胞膜磷脂细胞膜磷脂血管内皮血管内皮损伤损伤凝血酶原凝血酶原凝血酶凝血酶内凝系统激活内凝系统激活外凝系统激活外凝系统激活纤维蛋白原纤维蛋白原纤维蛋白纤维蛋白纤溶酶纤溶酶纤溶酶纤溶酶原原 CaCa2+2+LPS TNFLPS TNFa aFDPFDP聚集聚集血栓血栓胶原胶原K KPKPK其他促其他促凝物质凝物质HKHK 单核吞噬细胞系统功能受损单核吞噬细胞系统功能受损 肝功能严重障碍肝功能严重障碍 血液高凝状态血液高凝状态 微循环障碍微循环障碍 合成抗凝物不足 灭活凝血因子障碍 肝细胞坏死释放TF 病毒、药物损肝并激活凝血因子为什么孕妇易并发为什么孕妇易并发DICDIC孕孕3

12、周周妊娠末期妊娠末期 血液高凝状态血小板增多血小板增多凝血因子增多凝血因子增多、抗凝物质减少抗凝物质减少AT3、tPA、uPA胎盘产生纤溶酶原激活物抑制物增多胎盘产生纤溶酶原激活物抑制物增多为什么酸中毒易引起为什么酸中毒易引起DICv 损伤内皮，启动凝血损伤内皮，启动凝血v 凝血因子的酶活性升高凝血因子的酶活性升高v 肝素抗凝活性减弱肝素抗凝活性减弱v 血小板聚集性加强血小板聚集性加强分期：分期：1.高凝期：高凝期：2.消耗性低凝期消耗性低凝期 3.继发性纤溶亢进期继发性纤溶亢进期分型：分型：急性型急性型 慢性型慢性型 亚急性型亚急性型 失代偿型失代偿型 代偿型代偿型 过度代偿型过度代偿型 出

13、血出血：最初的表现最初的表现 器官功能障碍：器官功能障碍：休克休克：DICDIC和休克可互为因果和休克可互为因果 贫血贫血:即微血管病性溶血性贫血即微血管病性溶血性贫血l 凝血物质被消耗而减少凝血物质被消耗而减少l 纤溶系统激活纤溶系统激活l FDPFDP的形成的形成FDP抗凝作用抗凝作用 X X、Y Y碎片可与纤维蛋白单体聚碎片可与纤维蛋白单体聚合，抑制纤维蛋白多聚体形成合，抑制纤维蛋白多聚体形成 Y Y、E E碎片有抗凝血酶作用碎片有抗凝血酶作用 D D碎片抑制纤维蛋白单体聚合碎片抑制纤维蛋白单体聚合 抑制血小板的黏附和聚集抑制血小板的黏附和聚集 “3P”“3P”试验（鱼精蛋白副凝试验）试

14、验（鱼精蛋白副凝试验）检测检测X X片断的存在片断的存在 D D二聚体检查二聚体检查 凝血酶凝血酶 纤溶酶纤溶酶纤维蛋白原纤维蛋白原 纤维蛋白多聚体纤维蛋白多聚体 D D二聚体二聚体 广泛微血栓形成广泛微血栓形成 血管床容量增加血管床容量增加 血容量减少血容量减少 心泵功能障碍心泵功能障碍 概念概念 出现红细胞出现红细胞碎片的的贫碎片的的贫血血 机制机制1.纤维蛋白性微血栓网纤维蛋白性微血栓网2.缺氧、酸中毒使红细胞变形缺氧、酸中毒使红细胞变形能力降低能力降低3.红细胞游出红细胞游出4.获得性球形红细胞增多症获得性球形红细胞增多症5.内毒素对红细胞的损害作用内毒素对红细胞的损害作用 1.防治原

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20、%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%r%u(y+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5

21、G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkV

22、nYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y

23、0C3F6IaLdPgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNf

24、QiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*

25、x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaM

26、dPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp

27、#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5

28、H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkV

29、nZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbMeQhTlWoZr%u(x+B+B2E6H9KcOfRiUmXp!s&v)z

30、0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+A2E5H9KcNf

31、RiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhSkWnZr$u*

32、x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z0C4F7JaM

33、dPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUiUlXo#s%v)y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp

34、!s&v)z0C4F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5

35、H9KcNfRiUmXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkW

36、nZr$u*x+A2E5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z

37、1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOf

38、RjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$

39、u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7J

40、aMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9LcOgRjUm

41、Yp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2

42、E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G8JbMeQ

43、hTkWoZr%u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjUmYp!t&w)z1C4F7J7JaMePhSkWnZq$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t

44、&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp!s&v)z0C3F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#r%u(y+B3E6H9LcOfRjUmYp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A2D5G8KbNeQiTlXo#r%v(y+B3E6I9

45、LcOgRjUmYp!t&w)z1C4F7JaMePhSkWnZq$u*x+A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhTkWnZr$u*x+A2E5H8KcNfQiUlXp#s%v)y0B3F6IaLdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#

46、r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPhSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#s%v(y0B3E6I9LdOgRjVmYp!t&w-z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWoZr$u(x+A2E5H9KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D

47、4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRjUmXp!s&v)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z0C4F7JaMdPhSkVnZq$u*x-A2D5G8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KbNfQiUlXo#s%v(y0B3F6I9LdOgRjVmYq!t&w-z1C4G7JbMePhTkWnZr$u(x+A2E5H8KcNfRiUlXp#s%v)y0C3F6IaLdOgSjVnYq!t*w-z1D4G7JbMeQhTkWoZr$u(x+B2E5H9KcNfRiUmXp#s&v)y0C3F7IaLdPgSjVnYq$t*w-A1D4G8JbNeQhTlWoZr%u(y+B2E6H9KcOfRiUmUmXp!s&v)z0C4F7IaMdPgSkVnYq$t*x-A1D5G8JbNeQiTlWo#