第八章北醫(yī)病理學課件-dic

1、彌散性血管內(nèi)凝血Disseminated Intravascular Coagulation (DIC),病理生理學系Department of Pathophysiology高遠生,,概念(Concept),DIC 是在多種病因作用下凝血過程強烈激活，廣泛微血栓形成,導致凝血因子與血小板大量消耗，繼發(fā)纖溶功能增強，出現(xiàn)凝血功能障礙并以出血為特征的臨床綜合征。,,Common Causes of DIC,,,機體的凝血系統(tǒng)Bl

2、ood Clotting Mechanisms,內(nèi)源性凝血系統(tǒng) 外源性凝血系統(tǒng),,,,,,內(nèi)源性凝血系統(tǒng)(Intrinsic Pathway for Blood Clotting),高分子激肽原前激肽釋放酶,纖維蛋白,交聯(lián)纖維蛋白凝塊,,,,,Ⅹa,Ⅹ,,,Ⅻa,Ⅻ,Ⅺa,Ⅺ,,,,,Ca2+,Ⅷa,Ⅷ,,Ca2+,,,凝血酶原,凝血酶,凝血酶原激活物,,,,Ⅴ,Ⅴa,,Ca2+,血管內(nèi)皮損傷接觸膠原,,Ca2+,,纖維蛋白原,,

3、Ca2+,ⅩⅢa,,,,,,,ⅩⅢ,,,,,,外源性凝血系統(tǒng)(Extrinsic Pathway for Blood Clotting),組織因子,Ⅹ,,凝血酶原激活物,凝血酶原,凝血酶,,Ⅶa,Ⅶ,,,Ⅹa,,,Ca2+,,,組織損傷,,Ca2+,,,Ⅴa,,Ca2+,,纖維蛋白原,纖維蛋白,交聯(lián)纖維蛋白凝塊,,,,ⅩⅢa,ⅩⅢ,,,,,Ca2+,,Ⅷa,,,,Ⅴ,,Ⅷ,,,抗凝血系統(tǒng)Anticoagulation System,

4、體液抗凝 （組織因子途徑抑制物，抗凝血酶Ⅲ,蛋白C系統(tǒng)，纖維蛋白溶解系統(tǒng)）細胞抗凝（單核巨噬細胞，肝細胞）,,,組織因子途徑抑制物Tissue Factor Pathway Inhibitor(TFPI),,,抗凝血酶Ⅲ和肝素Antithrombin Ⅲ & Heparin,,,蛋白C系統(tǒng)Protein C System,,受損組織，內(nèi)皮細胞,纖溶酶,纖溶酶原,纖維蛋白(原),纖維蛋白降解產(chǎn)物,激肽釋放酶,尿激酶原

5、,尿激酶,組織纖溶酶原激活物,,,,,,,,纖溶酶原激活物抑制物,,,纖維蛋白溶解(Fibrinolysis),,Ⅻa,前激肽釋放酶,,,,纖溶酶 (Plasmin)具有廣泛的絲氨酸水解酶活性，能水解凝血終產(chǎn)物纖維蛋白(fibrin)生成可溶性的纖維蛋白降解產(chǎn)物，也能水解纖維蛋白原(fibrinogen)和其他多種凝血因子、血漿蛋白與組織蛋白。,纖維蛋白降解產(chǎn)物（Fibrin Degradation Products, FDP）,,

6、血小板在微血管損傷部位adhesion、aggregation，形成血小板栓子血小板膜內(nèi)側(cè)面的磷脂在活化中外翻,是凝血因子X和凝血酶原活化的反應(yīng)場血小板活化釋放出纖維蛋白原、凝血因子XIII, XI和ADP等，促進凝血血小板受膠原刺激可直接活化凝血因子Ⅺ，受ADP刺激可直接活化Ⅻ血小板釋放的5-HT、ADP、組胺、陽離子蛋白等能損傷內(nèi)皮細胞，促進凝血過程,血小板在抗凝血中的作用Effect of Platelets o

7、n Blood Coagulation,,血管內(nèi)皮細胞在凝血中的作用Vascular Endothelial Cells & Blood Clotting,,,其它機體抗凝機制Some Other Clot-inhibiting Mechanisms,單核巨噬細胞和肝細胞清除內(nèi)毒素、免疫復合物等促凝物質(zhì)，清除激活的凝血因子。血流稀釋、運走促凝物質(zhì)和活化的凝血因子。,問題：DIC的概念?主要的體液抗凝因素?,,體液

8、抗凝Humoral Anticoagulation,組織因子途徑抑制物抗凝血酶Ⅲ蛋白C系統(tǒng)纖維蛋白溶解系統(tǒng),,,,,,,,,,凝血因子與血小板耗竭,,,,,,纖維蛋白溶解,,,凝血因子水解,,纖維蛋白降解產(chǎn)物,,凝血酶血小板聚集纖維蛋白交聯(lián),,,,,,,引起大量組織因子釋放的一些疾病Causes of Release of Tissue Factor,,,嚴重感染和內(nèi)毒素血癥強烈免疫反應(yīng)生成過量抗原-抗體復合物持續(xù)

9、廣泛的組織缺血缺氧嚴重酸中毒等,廣泛血管內(nèi)皮細胞損傷原因Causes of Extensive Damage of Vascular Endothelial Cells,,,單核吞噬系統(tǒng)功能受損肝功能障礙(體內(nèi)單核吞噬系統(tǒng)的主要臟器,制造凝血因子,抗凝血酶Ⅲ,蛋白C,蛋白S)血液高凝狀態(tài)(妊娠后期:凝血因子含量↑; 酸中毒:肝素活性↓,凝血因子活性↑,血小板聚集性↑) 微循環(huán)障礙 (血液淤滯,血小板聚集,酸中毒:內(nèi)皮細胞損傷)

10、纖溶功能降低(高齡、吸煙、糖尿病和妊娠后期，體內(nèi)的纖溶功能常明顯降低),影響DIC發(fā)生發(fā)展的因素Predisposing Factors for DIC,問題：DIC的形成機制?,DIC的功能代謝變化Functional & Metabolic Changes of DIC,,1. 出血2. 器官功能障礙3. 休克4. 微血管病性溶血性貧血,凝血因子、血小板過度消耗纖溶系統(tǒng)激活(子宮，前列腺，肺富含纖溶酶原激活

11、物；應(yīng)急，缺氧→內(nèi)皮細胞釋放纖溶酶原激活物↑)纖維蛋白降解產(chǎn)物(FDP)形成,對凝血酶，血小板聚集及纖維蛋白交聯(lián)抑制,,1. 出血 (Bleeding),,2. 器官功能障礙Organ Disorders,華-佛綜合征(Waterhouse-Friderichsen syndrome)微血栓導致腎上腺皮質(zhì)出血壞死產(chǎn)生的腎上腺皮質(zhì)功能障礙。席-漢綜合征(Sheehan syndrome)微血栓導致垂體出血壞死產(chǎn)生的功能障礙。,,,

12、,,,,3. 休克（Shock）,,缺血,缺氧酸中毒,回心血量,微栓塞,心肌功能障礙,,,凝血,激活補體及激肽系統(tǒng),血管擴張,,,毛細血管通透性,,,,血粘度,血液流動阻力,,器官功能障礙,,,,,,,,,,,,4. 微血管病性溶血性貧血Microangiopathic Hemolytic Anemia,裂體細胞(schistocyte),在慢性DIC和有些亞急性DIC外周血涂片可發(fā)現(xiàn)新月形、盔甲形、星形、三角形等變形紅細胞，

13、被稱為裂體細胞（schistocyte）。裂體細胞變形能力顯著降低，脆性增高，容易破裂，發(fā)生溶血。因微血管發(fā)生病理變化而導致紅細胞破裂引起的貧血，稱為微血管病性溶血性貧血。外周血涂片中發(fā)現(xiàn)較多schistocyte（超過紅細胞數(shù)2%），是診斷DIC的重要參考指標。,問題：華-佛綜合征、席漢綜合征?微血管病性溶血性貧血?,高凝期: 凝血酶增多，微血栓形成。消耗性低凝期: 凝血因子、血小板消耗，纖溶系統(tǒng)激活，出血。繼發(fā)性纖溶期

14、: 纖溶酶增多，纖維蛋白降解產(chǎn)物(FDP)形成。,DIC的分期及其特點（Stages of DIC and Their Characteristics）,,根據(jù)DIC發(fā)生快慢:1. 急性型 2. 慢性型3. 亞急型根據(jù)代償情況：1. 失代償型2. 代償型3. 過度代償型,DIC分型（Types of DIC）,,各型DIC的特征Characteristics of Different DIC Types,急性型：常在數(shù)

15、小時到一、二天內(nèi)發(fā)生，臨床表現(xiàn)以休克和出血為主，病情迅速惡化，分期不明顯。多見于嚴重感染、急性溶血、嚴重創(chuàng)傷、急性移植　排斥反應(yīng)等。慢性型：發(fā)病緩慢，病程可達數(shù)月或更長，臨床表現(xiàn)不明顯，出血輕微、休克少見，常表現(xiàn)為器官功能障礙。多見于惡性腫瘤、膠原病、慢性溶血性貧血。亞急性型：常在數(shù)日至幾周內(nèi)逐漸發(fā)病。多見于癌癥擴散、死胎滯留等，,,失代償型：凝血因子和血小板消耗占優(yōu)勢，數(shù)量減少；臨床表現(xiàn)：出血、休克；多見于急性型DIC。

16、代償型：凝血因子和血小板的生成和消耗基本平衡，臨床表現(xiàn)不明顯或輕微；多見于輕度DIC。過度代償型：凝血因子和血小板生成超過消耗；臨床表現(xiàn)不明顯；多見于慢性或恢復期DIC。,各型DIC的特征Characteristics of Different DIC Types,,Platelet count: Markedly decreasedProthrombin time: IncreasedActivated partia

17、l thromboplastin time: IncreasedFibrin degradation products: Markedly increasedFibrinogen: Normal or decreasedAntithrombin III: Markedly decreasedProtein C: Markedly decreased,Laboratory Findings in DIC,,問題：

18、DIC的分期與特點?DIC的分型?,A 56-year-old man was admitted to the emergency department after a car accident. He had several bone fractures, a cerebral contusion, and hemodynamic instability caused by a ruptured spleen. Emergen

19、cy splenectomy and aggressive administration of fluids restored hemodynamic stability, and the patient was transferred to the intensive care unit (ICU). A few hours later, profuse extravasation was noted from the abdomin

20、al drains, endotracheal tube, and puncture sites of all intravascular lines.,Clinical Case,,Laboratory tests showed a rapidly falling hemoglobin level and a platelet count of 25,000/µL (normal>150,000/µL). T

21、he activated partial thromboplastin time (aPTT) was 44 sec (normal, <28), prothrombin time (PT) was 29 sec (normal, <12.5). The level of fibrinogen degradation products was 360-520 g/L (normal, <40) and the pla

22、sma antithrombin III level was 28% (normal, 80-120).,Clinical Case,,Based on these findings, the diagnosis was DIC secondary to severe trauma. Surgical exploration revealed diffuse oozing of blood at the site of the oper

23、ation, but only partial surgical hemostasis could be achieved. The patient was given supportive treatment with large infusions of fresh plasma and platelet concentrates. The bleeding stopped 48 hours later. Coagulation p

24、arameters eventually returned to normal and the subsequent clinical course was uneventful.,Clinical Case,,DIC治療的病理生理基礎(chǔ) Pathophysiological Basis of DIC Treatment,,1. 積極防治原發(fā)病2. 早期發(fā)現(xiàn)、及時治療,保護重要臟器功能抗凝治療補充凝血物質(zhì)適當?shù)目估w溶治療,Voc

25、abulary,,disseminated intravascular coagulation (DIC;彌散性血管內(nèi)凝血)prothrombin (凝血酶原), thrombin (凝血酶)fibrinogen (纖維蛋白原)，fibrin (纖維蛋白)，tissue factor pathway inhibitor (組織因子途徑抑制物)protein C system (蛋白C系統(tǒng)) thrombinmodulin (血栓

26、調(diào)節(jié)蛋白)antithrombin Ⅲ (抗凝血酶Ⅲ),Vocabulary,,tissue plasminogen activator (t-PA；組織纖溶酶原激活物)plasminogen (纖溶酶原)，plasmin (纖溶酶), fibrinolysis (纖維蛋白溶解)fibrin degradation products(FDP, 纖維蛋白降解產(chǎn)物)Waterhouse syndrome (華-佛綜合征) Sheeh