pathophysiologypart414dic弥散性血管内凝血课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,pathophysiologypart414dic弥散性血管内凝血,pathophysiologypart414dic弥散性血管,1,Intravascular,Extravascular,Normal circulation Hemostasis,liquidity solidity,( coagulation),Normal,Normal,Blood,Abnomal Abnomal,solidity,(coagulation) liqidity,Thrombotic disease Hemorrhagic,disease,Intravascular,Extravascular,2,Intravascular,pathophysiologypart414dic弥散性血管内凝血课件,3,pathophysiologypart414dic弥散性血管内凝血课件,4,pathophysiologypart414dic弥散性血管内凝血课件,5,pathophysiologypart414dic弥散性血管内凝血课件,6,pathophysiologypart414dic弥散性血管内凝血课件,7,pathophysiologypart414dic弥散性血管内凝血课件,8,1. Concept of DIC,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 body,9,1. Concept of DIC Disseminate,extensive microthrombin extensive,hemorrhage,organ dysfunction Shock aneamia,Normal balance of coagulation-anticoagulation,Hypocoagulable state,Hypercoagulable state,Unbalance of coagulation-anticoagulation and DIC,extensive activation,of clotting factors,and platelets,consumption,of clotting,factors and platelets,secondary fibrinolysis,hemorrhage,organ dysfunction Shock aneamia,10,extensive microthrombin,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 dysfunction,; 4),aneamia.,An,extensive activation of coagulation process,caused by the,entering of coagulation-promoting substances into circulation,An,increased consumption of clotting factors and platelets,deposition of fibrin,and,secondary fibrinolysis,.,results in,11,Therefore DIC usually as,2.,Causes of DIC,including:,infectious diseases, extensive tissue injury, obstetric complications, malignant tumors, acute leukemia, shock, hepatic and renal diseases, collagen disease, metabolic diseases, cardiovascular diseases, intravascular hemolysis,Etiologic Disease of DIC,Diseases or pathologic process which may lead to DIC,Triggering,Factor,Any factors which may trigger or promote DIC occur,12,2. Causes of DIC including:,including:,infectious diseases, extensive tissue injury, obstetric complications, malignant tumors, acute leukemia, shock, hepatic and renal diseases, collagen disease, metabolic diseases, cardiovascular diseases, intravascular hemolysis,2.,Causes of DIC,Triggering,Factor,Any factors which may trigger or promote DIC occur,Etiologic Disease of DIC,Diseases or pathologic process which may lead to DIC,1) Tissue injury and release tissue factor (TF),2) Vascular endothelial cells (VEC) injury,3) bacterial endotoxin,4) Ag-Ab complex,5) Protein hydrolytic enzymes,6) Particle or colloid,7) Virus and other microbe,13,including: 2. Causes of DIC,Section 2.,Pathogenesis of DIC,14,Section 2. Pathogenesis of DI,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 platelets;,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.,15,The mechanism of DIC is very,1. Activation of clotting system,As soon as 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 endothelial cells injury,(3),Other pathway to activate clotting system,16,1. Activation of clotting syst,(1),Tissue injury,Severe 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 entering the blood,Activating clotting reactions,Besides, lysozymes released by lysosome of damaged,cells may also promote the activation of clotting system.,17,(1) Tissue injurySevere trauma,Infectious, endotoxinemia, Ag-Ab complex,persistent ischemia and hypoxia, acidosis,extensive damage of vascular endothelial cells,.,activating,clotting,reactions,(activating Mo/M,f,PMN, T-lymphocyte, release TNF, IL-1, IFN, PAF, C,3a, C5a, O,2,),(2),Vascular endothelial cells injury,releasing TF subendothelial exposure,platelets adhesion,Aggregation,and release,18,Infectious, endotoxinemia, Ag-,Activation of Mo/M,f, WBC release TF, lysozymes,Malignant tumors release TF, cancer procoagulant,Hemorrhagic pancreatitis, cancer of pancreas, release trypsin (may activate prothrombin directly),Exogenous toxin, activate FX, prothrombin or transfer Fbg to Fbn directly, Extensive,h,emolysis release ADP activate platelets,release erythrin TF-like effect,(3),Other pathway to activate clotting system,19, Activation of Mo/Mf, WBC r,2. Change of vasomotorial activity and blood fluidity,VEC injury,EDRF,PGI,2,ET,Platelet activated,TXA,2,Blood flow,(vasoconstriction) or,stasis,(vasodilation),eliminate of coagulant or activate clotting factors,PAF, histamin, BK,vascular permeability,(BK: bradykinin),Deposit of Fbn,Blood condense, Viscosity,20,2. Change of vasomotorial acti,3. 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 to PLn, Protein C activated by thrombin,(via VEC-TM), form activated protein C (APC), anticoagulation and promote fibrinolysis.,21,3. Disturbance of fibrinolysi,Pathological Factors,extensive activation of clotting factors and platelets,intravascular coagulation,consumption of clotting secondary,factors and platelets fibrinolysis,extensive hemorrhage,aneamia shock organ dysfunction,(Disseminated intravascular coagulation, DIC),Hypercoagulable state,Hypocoagulable state,22,Section 3.,Primary clinical presentations,of DIC,23,Section 3. Primary clini,DIC may lead to four consequences as follows:,1. Disturbance of coagulation -,Bleeding,2. Disturbance of microcirculation -,Shock,3. multiple organs dysfunction -,MOD,4. Microangiopathic hemolytic -,Anemia,24,DIC may lead to four consequen,1. Disturbance of coagulation-Bleeding,The 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),Manifold bleeding types,(4),Difficult to be cured by regular hemostatics,25,1. Disturbance of coagulation-,The 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;,Fbg / 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,26,The causes of bleeding in DIC,DIC, especially acute DIC, is often associated with,shock,Shock,in sever degree or in late stage,can also promote the production,of,DIC,2. Dsturbance of microcirculation - shock,27,DIC, especially acute DIC,(1) Extensive microthrombus,formation,(2) Extensive bleeding,permeability,plasma exudation,(3) Activating kinin, histamin,shock,microvessel dilation,(4) FDP (A,B,C),(5),Microthrombus,coronary perfusion,pulmonary hypertension,cardiac load,Ischemia, hypoxia& acidosis,returned blood,to heart,effective circulation blood volume,peripheral resistance,heart function and,cardiac output,28,(1) Extensive microthrombusret,3. Multiple organs dysfunction (MOD),Perfusion impairment,/,ischemia-reperfusion injury,activation of WBC,/,inflammatory mediator,Ischemic tissue damage,MOD,MOD is usually the most important cause of death in DIC.,29,3. Multiple organs dysfunction,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),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; kidney 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),30,Occurrence of MOD is relate,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),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,31,Occurrence of MOD is relate,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),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,32,Occurrence of MOD is relate,4. 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, helmet-shaped cells, and microspherocytes ),The hemolysis can provide more triggering material (ADP and membrane phospholipid) for continued intravascular coagulation.,33,4. Microangiopathic hemolytic,Section 4.,Factors influencing the development of DIC,34,Section 4.Factors influencing,Mononuclear phagocyte system dysfunction,Severe dysfunction of the liver,Hypercoagulable state,Disorder of microcirculation,Fibrinolytic system,dysfunction,35,Mononuclear phagocyte system d,Prolonged and excessive Repeated infection,administration of,glucocorticoid hormones Severe hepatic disease,Impairing Mo/M,f,system function,Disable to clean clot-promoting substances,(Fbg, Fbn, FM and FDP, etc.),Generalized Shwartzman reaction, GSR,(1) Mononuclear phagocyte system dysfunction,36,Prolonged and excessive,(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 of production and elimination of,clotting and anticoagulative factors.,37,(2)Severe dysfunction of the,Primary: genetic ATIII, PC, PS deficiency, etc.,Secondary: nephrotic syndrome, malignant tumors,leukemia, toxemia of pregnancy, etc.,(3),Hypercoagulable state,38,Primary: genetic ATIII, PC,1) VEC injury Activation of clotting system;,2),Blood flowor stasis, 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, diabetes,misuse of fibrinolytic inhibitor,etc.,(4),Disorder of microcirculation,39,1) VEC injury Activation of,Section 5,Stages and types of DIC,40,Section 5Stages and types of D,1. Stages of DIC,Pathophysiology,Clinical,Laboratory findings,(1)Hypercoagulable stage,(2)Consuming hypocoagulable stage,(3)Secondary fibrinolytic Stage,Exessive activation of clotting factors,and formation of microthrombin,Increased consumption,of clotting factors and platelet,Considerable formation of plasmin and FDP,41,1. Stages of DIC,1. Stages of DIC,Pathophysiology,Clinical,Laboratory findings,(1)Hypercoagulable stage,(2)Consuming hypocoagulable stage,(3)Secondary fibrinolytic Stage,Hypercoagulable,Bleeding,Bleeding markedly,42,1. Stages of DIC,1. 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 platelet,Prolonged clotting and recalcification time,Reduction of platelet count and Fbg narkedly,Shortened CLT, ELT; Prolonged TT 3P test (+), Increased FDP,CLT = clot-lysis time,ELT = euglobulin-lysis time,TT = thrombin time,43,1. Stages of DIC,Production of FDP and 3p test,(,plasma protamine paracoagulation test),Fibrinogen,Thrombin,Fibrin monomer,(FM),Fibrin polymer,Plasmin,XIIIa,FDP-X,Y,D,E,Stabilized fibrin,( blood clotting ),X + FM soluble fibrin monomer complex (SFMC),Protamin,SFMC X + FM blood clotting,44,Production of FDP and 3p test,Develop time,Common causes,Clinic feature,2. Types of DIC,According to the rate of development, divide into 3 types,Acute,Subacute,Chronic,a few hours to days,within days to weeks,months,45,Develop time,Common causes,Clinic feature,2. Types of DIC,According to the rate of development, divide into 3 types,Acute,Subacute,Chronic,malignant tumors collagenosis,metastasis of malignant,tumors; retained dead fetus,severe infection or trauma,ammiotic fluid embolism,46,Develop time,Common causes,Clinic feature,2. Types of DIC,According to the rate of development, divide into 3 types,Acute,Subacute,Chronic,mild or concealed,microthrombin formation,bleeding,shock, blooding,exacerbate rapidly,47,:,According to compensatory state, divide into 3 types,Clotting factors and platelet,Clinical situations,compensatory,Consumption = production,discompensatory,Consumption production,over compensatory,Consumption production,48,:48,:,According to compensatory state, divide into 3 types,Clotting factors and platelet,Clinical,situations,compensatory,Mild DIC,discompensatory,Acute DIC,over compensatory,Chronic DIC or recovery,49,:49,Section,6.,Principles of prevention and treatment of DIC,50,Section 6.Principles of preven,1. Pathophysiology bases of diagnosis of DIC,(1),Existence of causative diseases;,(2),Existence of characteristic symptoms and signs of DIC,(3) Positive laboratory findings:,platelet count, Fbg ,PT & TT, 3P test (+), CLT & ELT,51,1. Pathophysiology bases,2. Pathophysiology bases of prevention and treatment of DIC,(1),Earlier diagnosis and treatment,(2),Treatment of the causative disease,(3) Anticoagulation trea,tment (to block the,vicious cycle,of clotting response),(4),Protection of organ function,(5),Supplement of fresh blood or plasma, concentrated,platelet or clotting factors (to recover coagulation-,anticoagulation balance),(6) Antifibrinolysis treatment,Back to cover next chapter,52,2. Pathophysiology bases of pr,A syndrome resulting from the disturbance balance of,coagulation and fibrinolytic processes, characterized by,extensive intravascular microthrombosis and impairment of,hemostasia, is called,disseminated intravascular coagulation.,Diseases or pathologic process which may lead to DIC are,called etiologic disease of DIC. Any of them is usually trigger,or promote DIC through one or several factors, which are,called triggering factor.,Summary,53,A syndrome resulting from,extensive hemorrhage at skin, mucosa and internal organs,The pathogenesis of DIC are:,1) Activation of clotting system (tissue and VEC injury),2) Change of vasomotorial activity and blood fluidity;,3) Disturbance of fibrinolysis,The clinical presentations of DIC include:,1),;,2),;,3),;,4),.,Summary,Disturbance of microcirculation (shock),Multiple organs dysfunction (MOD),Microangiopathic hemolytic anemia,54,extensive hemorrhage at skin,Following factors may influence the development of DIC:,1),Impairment of function of mononuclear-macrophage;,2) Severe dysfunction of the liver;,3),Hypercoagulable state;,4),Disorder of microcirculation;,5) Dysfunction of fibrinolytic system,Pathophysiology basis of diagnosis of DIC:,1),C,ausative diseases;,2),C,haracteristic symptoms and signs of DIC;,3),Positive laboratory findings,Summary,55,Following factors may influen,5,Question 3,Explain the relationship,between,SHOCK,and,DIC,56,5Question 356,5,SHOCK,DIC,?,Blood flow slow down,blood concentrated, RBC and platelet aggregation,blood viscosity,Vascular ECs injury,Severe acidosis,Monocyte and endothelium releasing TF,Septic Shock: bacteria and toxin,Tissue releasing,TF,Traumatic shock,57,5SHOCKDIC?,5,SHOCK,DIC,?,Returned blood to heart,blood concentrated, RBC and platelet aggregation, blood viscosity,Effective circulation blood volume,Extensive bleeding, permeability, plasma exudation,Peripheral resistance,kinin, histamin,microvessel dilation,Heart function and cardiac output,pulmonary hypertension, Ischemia, hypoxia& acidosis,58,5SHOCKDIC? Returned blood to h,pathophysiologypart414dic弥散性血管内凝血课件,59,