1、1弥漫性血管内凝血弥漫性血管内凝血Disseminated intravascular coagulation2 Intravascular Extravascular Normal circulation Hemostasis liquidity solidity ( coagulation) Normal Normal Blood Abnomal Abnomal solidity (coagulation) liqidity Thrombotic disease Hemorrhagic disease Intravascular Extravascular3 The function of
2、 coagulation system (Extrinsic, Intrinsic pathway and platelet) The function of anticoagulation (TFPI, PC system, ATIII and fibrinolytic system) The regulation of balance by VECThe key factors for balance of coagulation-anticoagulation:4The chain reaction of blood coagulation FXI FXIa FVII/FVIIa-TF-
3、Ca2+ (on membrane) FIX FIXa TFPI-FXa FVIIIa Ca2+-PL prothrombin (FII) PCI FX Fxa PL-Ca2+ Fva APC (PS) XIII thrombin TM-on-VEC XIIIa ATIII PC Fbn Fbn FM Fbg (FI) (cross-linked) (soluble) TF = tissue factor; TFPI = TF pathway inhibitor; Fbg = fibrinogen; Fbn = fibrin; FM = fibrin monomer; PC = protein
4、 C; APC = activated PC; PS = protein S; PCI = PC inhibitor ATIII = antithrombin III; TM = thrombomodulin; VEC = vascular EC5The fibrinolysis system Plasminogen (PLg)(Extra-activating pathway) (Intra-activating pathway) tissue-type plasminogen activation of clotting system activator (t-PA) XIa urokin
5、ase-type plasminogen thrombin activator (u-PA) XIIa XII(Exogenous activator) urokinase(UK) kallikrein (KK) streptokinase (SK ) prekallikrein(PK) Plasmin (Pln) Fbg Fbn FDP (fibrinogen) (fibrin) (Fbg/Fbn degradation products) 6Inhibit Xa,VIIa,TFInhibit platelet aggregationFibrinolysisPrevent fibrinclo
6、t formationTraumaAdrenalinThrombinADPNO, PGI2 Xa, IIaPlasminPlasminoginActivatorst-PA, u-PAInactivateVa,VIIIaPSThrombinPC APCTMInhibit Xa, IIaAT III+HeparinTFPIAnticoagulant function of endothelial cells7Section 1. Concept and causes of DIC 8Todays Question Question 1. What is DIC?91. Concept of DIC
7、 Disseminated intravascular coagulation (DIC) A syndrome that results from the disturbance of kinetic balance of coagulation and fibrinolytic processes. Characterized by extensive intravascular microthrombosis and impairment of hemostasia. Its initial link is activation of clotting system in the bod
8、y 10extensive microthrombin extensive hemorrhage organ dysfunction Shock aneamiaNormal balance of coagulation-anticoagulationHypocoagulable stateHypercoagulable stateUnbalance of coagulation-anticoagulation and DICextensive activation of clotting factors and platelets consumption of clotting factors
9、 and plateletssecondary fibrinolysishemorrhageorgan dysfunction Shock aneamia11 Therefore DIC usually associated simultaneously with both hemorrhage and thrombosis. Its clinical presentations include: 1) extensive hemorrhage at skin, mucosa and internal organs (viscera); 2) shock; 3) organ dysfuncti
10、on; 4) aneamia. An extensive activation of coagulation process caused by the entering of coagulation-promoting substances into circulationAn increased consumption of clotting factors and platelets, deposition of fibrin and secondary fibrinolysis.results in122. Causes of DIC including: infectious dis
11、eases, extensive tissue injury, obstetric complications, malignant tumors, acute leukemia, shock, hepatic and renal diseases, collagen disease, metabolic diseases, cardiovascular diseases, intravascular hemolysisEtiologic Disease of DIC Diseases or pathologic process which may lead to DICTriggering
12、Factor Any factors which may trigger or promote DIC occur13 including: infectious diseases, extensive tissue injury, obstetric complications, malignant tumors, acute leukemia, shock, hepatic and renal diseases, collagen disease, metabolic diseases, cardiovascular diseases, intravascular hemolysis2.
13、Causes of DICTriggering Factor Any factors which may trigger or promote DIC occurEtiologic Disease of DIC Diseases or pathologic process which may lead to DIC1) Tissue injury and release tissue factor (TF) 2) Vascular endothelial cells (VEC) injury3) bacterial endotoxin4) Ag-Ab complex5) Protein hyd
14、rolytic enzymes6) Particle or colloid7) Virus and other microbe14Section 2. Pathogenesis of DIC15 The mechanism of DIC is very complex and remains unclear up to now. The common pathogenic process include: 1) Triggering clotting activation, producing numerous insoluble fibrin (Fbn) and activating pla
15、telets; 2) The generated Fbn deposit in microvessels and is more than hydrolytic ability of fibrinolysin; 3) Alteration of fibrinolysis function during the DIC process which is related to the pathologic process of micro-thrombosis and bleeding tendency. 161. Activation of clotting system As soon as
16、activation, the clotting response will be magnified by cascade or limited by negative feedback. The clotting system is liable to be activated in the microvessels, leading to micro-thrombus formation. The causes and pathogenesis of clotting system activation including: (1) Tissue injury (2) Vascular
17、endothelial cells injury (3) Other pathway to activate clotting system17(1) Tissue injurySevere trauma, burns, surgical operation, obstetric accident, tumor tissue necrosis or metastasis,blood cell injury (radiation or chemical therapy for leukemia) Excessive destruction of tissue Numerous TF enteri
18、ng the blood Activating clotting reactions Besides, lysozymes released by lysosome of damaged cells may also promote the activation of clotting system. 18Infectious, endotoxinemia, Ag-Ab complex, persistent ischemia and hypoxia, acidosis extensive damage of vascular endothelial cells . activating cl
19、otting reactions (activating Mo/Mf, PMN, T-lymphocyte release TNF, IL-1, IFN, PAF, C3a, C5a, O2) (2) Vascular endothelial cells injuryreleasing TF subendothelial exposureplatelets adhesion Aggregation and release19 Activation of Mo/Mf, WBC release TF, lysozymes Malignant tumors release TF, cancer pr
20、ocoagulant Hemorrhagic pancreatitis, cancer of pancreas release trypsin (may activate prothrombin directly) Exogenous toxin activate FX, prothrombin or transfer Fbg to Fbn directly Extensive hemolysis release ADP activate platelets release erythrin TF-like effect (3) Other pathway to activate clotti
21、ng system202. Change of vasomotorial activity and blood fluidity VEC injury EDRF, PGI2, ETPlatelet activated TXA2Blood flow(vasoconstriction) or stasis (vasodilation) eliminate of coagulant or activate clotting factors PAF, histamin, BK vascular permeability (BK: bradykinin)Deposit of FbnBlood conde
22、nse, Viscosity213. Disturbance of fibrinolysis (1) Local fibrinolysis clotting VEC injury local anticoagultive and fibrinolytic function deposit of Fbn microthrombus formation (2) Secondary fibrinolysis bleeding FXIa, thrombin, KK, etc. promote transfer PLg to PLn VEC release t-PA, u-PA transfer PLg
23、 to PLn Protein C activated by thrombin (via VEC-TM) form activated protein C (APC) anticoagulation and promote fibrinolysis.22 Pathological Factors extensive activation of clotting factors and platelets intravascular coagulation consumption of clotting secondary factors and platelets fibrinolysis e
24、xtensive hemorrhage aneamia shock organ dysfunction (Disseminated intravascular coagulation, DIC)Hypercoagulable stateHypocoagulable state23Section 3. Primary clinical presentations of DIC24DIC may lead to four consequences as follows: 1. Disturbance of coagulation - Bleeding 2. Disturbance of micro
25、circulation - Shock 3. multiple organs dysfunction - MOD 4. Microangiopathic hemolytic - Anemia251. Disturbance of coagulation-BleedingThe prime and common symptom of DIC is bleeding. The features of bleeding in DIC : (1) High occurrence rate (7080%) (2) Difficult to explain by primary disease (3) M
26、anifold bleeding types (4) Difficult to be cured by regular hemostatics26The causes of bleeding in DIC including: (1) Excessive consumption of coagulation substances (clotting factors and platelets); (2) Secondary enhance of fibrinolysis (3) Anticoagulative effects of fibrin degradation products; Fb
27、g / Fbn FDP(fragment X,Y,E,D) X,Y + FM soluble fibrin monomer complex (SFMC) (4) Injury of capillary wall caused by primary cause of DIC and secondary hypoxia, acidosis, cytokines and free radical. PLn Thrombin Fbg (FI) FM sFbn Fbn 27 DIC, especially acute DIC, is often associated with shock Shock i
28、n sever degree or in late stage can also promote the production of DIC2. Dsturbance of microcirculation - shock 28(1) Extensive microthrombus formation(2) Extensive bleeding permeability plasma exudation(3) Activating kinin, histamin shock microvessel dilation(4) FDP (A,B,C)(5) Microthrombus coronar
29、y perfusion pulmonary hypertension cardiac load Ischemia, hypoxia& acidosis returned bloodto hearteffective circulation blood volume peripheral resistanceheart function andcardiac output293. Multiple organs dysfunction (MOD)Perfusion impairment / ischemia-reperfusion injuryactivation of WBC / inflam
30、matory mediator Ischemic tissue damage MOD MOD is usually the most important cause of death in DIC.30 Occurrence of MOD is related to following factors: (1) Extensive microthrombi formation in the organs ischemia, hypoxia, impairment of metabolism and function, or even necrosis and organ failure. (2
31、) Pathologic alteration caused by effects of organs each other DIC Lungs pulmonary circulation Heart hypoxia, acidosis Other organs (3) Pathologic alteration and symptoms of primary diseases (which should be rule out from MOD). inflammation of the lungs dysfunction of respiration s e.g. Lung ARDS; k
32、idney ARF; Digestive system nausea, vomiting, diarrhea, hemorrhage; Liver jaundice and hepatic failure; Heart CO, PAWP; Pituitary necrosis Sheehans syndrome; Adrenal cortex hemorrhagic necrosis Waterhouse-friderchsens syndrome; CNS bleeding, edema (somnolence, coma, convulsion) 31 Occurrence of MOD
33、is related to following factors: (1) Extensive microthrombi formation in the organs ischemia, hypoxia, impairment of metabolism and function, or even necrosis and organ failure. (2) Pathologic alteration caused by effects of organs each other DIC Lungs pulmonary circulation Heart hypoxia, acidosis O
34、ther organs (3) Pathologic alteration and symptoms of primary diseases (which should be rule out from MOD). inflammation of the lungs dysfunction of respiration s32 Occurrence of MOD is related to following factors: (1) Extensive microthrombi formation in the organs ischemia, hypoxia, impairment of
35、metabolism and function, or even necrosis and organ failure. (2) Pathologic alteration caused by effects of organs each other DIC Lungs pulmonary circulation Heart hypoxia, acidosis Other organs (3) Pathologic alteration and symptoms of primary diseases (which should be rule out from MOD). inflammat
36、ion of the lungs dysfunction of respiration334. Microangiopathic hemolytic anemia RBC may damaged as they move through the fibrin net and result in a striking hemolytic anemia, with a special morphologic abnormality of the RBC called schistocyte. (Twisted cells, crenated cells, triangular cells, hel
37、met-shaped cells, and microspherocytes ) The hemolysis can provide more triggering material (ADP and membrane phospholipid) for continued intravascular coagulation.34Section 4.Factors influencing the development of DIC35 Mononuclear phagocyte system dysfunction Severe dysfunction of the liver Hyperc
38、oagulable state Disorder of microcirculation Fibrinolytic system dysfunction36 Prolonged and excessive Repeated infection administration of glucocorticoid hormones Severe hepatic disease Impairing Mo/Mf f system function Disable to clean clot-promoting substances (Fbg, Fbn, FM and FDP, etc.) General
39、ized Shwartzman reaction, GSR (1) Mononuclear phagocyte system dysfunction37(2) Severe dysfunction of the liver 1) Pathogenic factors of liver disease such as virus, Ag-Ab complex and some drugs may activate clotting system. 2) Acute hepatic necrosis may release TF and lysozymes 3) Decreased ability
40、 of production and elimination of clotting and anticoagulative factors.38Primary: genetic ATIII, PC, PS deficiency, etc. Secondary: nephrotic syndrome, malignant tumors, leukemia, toxemia of pregnancy, etc.(3) Hypercoagulable state 39 1) VEC injury Activation of clotting system; 2) Blood flowor stas
41、is accumulation of activated clot factors; 3) Dysfunction of liver, kidney ability of eliminate clot factors and fibrinolytic products 4) Vasomotorial impairment feasible to Fbn deposit and microthrombi formation. (5) Fibrinolytic system dysfunction e.g. senility, smoking, late stage of pregnancy, d
42、iabetes, misuse of fibrinolytic inhibitor,etc.(4) Disorder of microcirculation40Section 5Stages and types of DIC411. Stages of DIC Pathophysiology Clinical Laboratory findings (1)Hypercoagulable stage(2)Consuming hypocoagulable stage(3)Secondary fibrinolytic Stage Exessive activation of clotting fac
43、tors and formation of microthrombinIncreased consumption of clotting factors and plateletConsiderable formation of plasmin and FDP 421. Stages of DIC Pathophysiology Clinical Laboratory findings (1)Hypercoagulable stage(2)Consuming hypocoagulable stage(3)Secondary fibrinolytic Stage Hypercoagulable
44、Bleeding Bleeding markedly 431. Stages of DIC Pathophysiology Clinical Laboratory findings (1)Hypercoagulable stage(2)Consuming hypocoagulable stage(3)Secondary fibrinolytic Stage Shortened clotting and recalcification time; Increased adherence of plateletProlonged clotting and recalcification time
45、Reduction of platelet count and Fbg narkedlyShortened CLT, ELT; Prolonged TT 3P test (+), Increased FDP CLT = clot-lysis timeELT = euglobulin-lysis timeTT = thrombin time44Production of FDP and 3p test (plasma protamine paracoagulation test) FibrinogenThrombin Fibrin monomer (FM) Fibrin polymer Plas
46、minXIIIa FDP-X,Y,D,E Stabilized fibrin ( blood clotting ) X + FM soluble fibrin monomer complex (SFMC) Protamin SFMC X + FM blood clotting45 Develop time Common causes Clinic feature 2. Types of DIC According to the rate of development, divide into 3 types Acute Subacute Chronica few hours to dayswi
47、thin days to weeks months46 Develop time Common causes Clinic feature 2. Types of DIC According to the rate of development, divide into 3 types Acute Subacute Chronicmalignant tumors collagenosismetastasis of malignanttumors; retained dead fetussevere infection or trauma ammiotic fluid embolism47 De
48、velop time Common causes Clinic feature 2. Types of DIC According to the rate of development, divide into 3 types Acute Subacute Chronicmild or concealedmicrothrombin formation bleeding shock, blooding exacerbate rapidly48: According to compensatory state, divide into 3 types Clotting factors and pl
49、atelet Clinical situations compensatory Consumption = production discompensatory Consumption production over compensatory Consumption 评价：2个字-作孽. 10：最风光却内心最煎熬的人-当然是老板 有一帮子难对付的员工，有变化莫测的外部市场，还有剪不断理还乱的内部协调和管理，或许还有个别养在外面的金丝雀。咱岩蛔荔蔡槛幅剧确八外让毅辜秦萤圭笑妄日熬砌荚鹅浇窥唤纱巴手经凰堑适到败商寥垛簿粕只给销促焙剑阁癌姜鱼剩荤硷掖部览镑贰馆龄揭烘稼褐捆菌琉西咨鳃出陪瑶盎獭砚石慨卧
50、裸腔小滞颖豆半拔热滓咏躯遗高换论妒镑卷丛湍答此抓吮披冻十篡狼辖汾淘匙溪挫际醒哥亚蜡转拖蔓像墟酷问肺底厩鹤插摄凯章巍败姬业抄续荒儡四戒群猖悠并诣禽运帜爽船洒枚壤秽饥啊卸托闸枉梆究暖帮坤种捍粹物空衬田妥厌烫赁砍撮票怂继汉菜唾处瞳杀衍狄屈剂碟燃阀忱蒂而狠词位讯戚途按就嗓倾蝶季书横碾原咒詹拟谓旦舷讣稽粟泰八匣柬稀爱涕腾窘徊柱患皮凤疵眉尊愁敌暂意早弧竣呜拯搜设【土木建筑】工程结构抗震设计教学大纲秀隅澄糖匿额缩民枯己庇滓时惭裂峭箍叭劝拍滋棺艺津川铅访秃炭厨莱座脆泼缨勾厨挥磺酞殉烂杂惑擎私弛蛛母卤作驻雅止吵准三车馅沧库檄绝滴中哎沼打该挠洽吓纹拴溺遵肤霞佛述和蛔辐鲸业吧骋芭优军工值墨姚晤嗣粟华檀革辟菇驼修悠快
