1、Chapter 11 Shock,Department of Pathophysiology Cheng Yang,Whats shock？,sick or unconsciousness？,Introduction,hypotension？,Introduction,vasoconstrictive treatment vasodilative treatment,Introduction,LartinGeneral Critical Reaction: strike and vibration1731, Henri Francois Le Dranapply to medicine for
2、 the first time,I. Concept of Shock,pale face cyanosis cold and clammy limbs oliguria faint consciousness hypotension,1.Description of symptoms & signs “shock syndrome”,I. Concept of Shock,2.Acute circulatory disorder,I. Concept of Shock,blood volumeECBV microcirculation disturbancessympathetic acti
3、vation,3.Microcirculation theory,I. Concept of Shock,systemic inflammatory response syndrome, SIRS全身炎症反应综合征pro-inflammatory & anti-inflammatory humeral factors,4.Cellular and molecular level,I. Concept of Shock,Regardless of causes, shock is defined as a clinical condition and pathophysiologic proce
4、ss characterized by microcirculation dysfunction inadequate blood flow vital organs and inability of cell body mass to metabolize normally.causes acute circulatory failure microcirculation disturbance ECBV(effective circulatory blood volume) “low flow state” in vital organs abnormal cellular metabol
5、ism and function, tissue injury, dysfunction of vital organs shock,I. Concept of Shock,1.Loss of blood or fluid:Blood loss: peptic ulcer, varices due to portal hypertension Fluid loss: severe vomiting, diarrhea, intestinal obstruction(collapse) 2.Burn:early stage: loss of body fluid, pain later stag
6、e: loss of body fluid, infection 3.Trauma:hemorrhage, severe pain 4.Infection:G- infection release of endotoxinssepsis,II. Etiology of Shock,5.Anaphylaxis:,allergen combination of IgE and mast cells release of histamine and bradykinin vasodilation and capillary permeabilityperipheral resistance bloo
7、d flow back to the heartcardiac output Bp, plasma exosmosis,allergen,II. Etiology of Shock,6.Strong stimulation on nerve system: brain injury, the depressant action of drugs, general anesthesia, hypoxia, or lack of glucose, spinal anesthesia or spinal cord injury decreased sympathetic control,7.Hear
8、t & large blood vessels diseases: acute massive myocardial infarction, acute myocarditis, perimyocarditis, cardiac tamponade, serious arrhythmias, myocardial diseases, cardiovalvular problems, etc. pumping function of the heart is impaired “cardiogenic shock” coronary artery disease, pulmonary embol
9、ism, etc. “extracardiac obstructive shock”,II. Etiology of Shock,According to Etiology:,1、Hemorrhagic Shock 2、Dehydration Shock 3、Traumatic Shock4、Burn Shock5、Infectious Shock: endotoxic, septic6、Cardiogenic Shock7 、Extracardiac Obstructive Shock8 、Anaphylactic Shock9 、Neurogenic Shock,III. Classifi
10、cation of Shock,blood volumecardiac outputblood vessels capacity,According to the pathogenesis of shock :,III. Classification of Shock,marked vasodilation,“Hypovolemic Shock”,“Cardiogenic Shock”,“Vasogenic Shock”,Conditions necessary for effective perfusion Initial event Shock type Clinical examples
11、Sufficient blood volume Decreased Hypovolemic Hemorrhageshock SurgeryBurns or traumaVomiting or diarrhea Adequate capacity Increased Vasogenic Anaphylaxis of vascular bed shock SepsisNormal function Impaired Cardiogenic Myocardial infarction of heart pump shock Congestive heartArrhythmias,According
12、to the Hemodynamics,III. Classification of Shock,Microcirculation(MC): The capillaries, venules, and metarterioles of the circulatory system are collectively referred to as the microcirculation. 1.Function of microcirculation: It is here that exchange of gases, nutrients, and metabolites move betwee
13、n the tissues and the circulating blood. transport of nutrients to the tissues and removal of cellular excreta,IV. Pathogenesis and Mechanisms of Shock,微动脉Arteriole 后微动脉Metarteriole 毛细血管前括约肌Precapillary Sphincters 真毛细血管True capillary 通血毛细血管（直捷通路） Preferential channels 微静脉Venule 动静脉短路Arteriovenous an
14、astomosis,后微动脉,2.Structure of microcirculation:,IV. Pathogenesis and Mechanisms of Shock,Arteriole MetarterioleArteriovenous anastomosisPrecapillary Sphincters True capillary Preferential channels Venule,IV. Pathogenesis and Mechanisms of Shock,(1)precapillary & postcapillary vessels (resistance) (2
15、)true capillary: extremely thin structures with tubular walls of single-layer, highly permeable endothelial cells (3)three channels for blood flow, 直捷通路（） thoroughfare channel, 动静脉短路（） arteriovenous shunt, 迂回通路 (营养通路 ) nutrient flow,后微动脉,“microcirculation disturbance”,IV. Pathogenesis and Mechanisms
16、 of Shock,compensatory stage,progressive stage,refractory stage,Stage I: compensatory stage,IV. Pathogenesis and Mechanisms of Shock,Alterations of Microcirculation and Tissue Perfusion:,Stage I: compensatory stage,vasoconstrictionarteriolar and pre-capillary sphincter constrictionpre- capillary res
17、istance low perfusionpostcapillary resistancelow flow arteriovenous shunt openingtissue perfusiontissue ischemia and hypoxia *degree of vasoconstriction is different,Stage I: compensatory stage: “ischemic hypoxia stage”,Mechanisms of Microcirculation Disturbance:,vasoconstriction,arteriovenous shunt
18、 opening,causes(hemorrage,etc),-receptor: skin, skeletal m., kidneys, abdominal organs,release of catecholamine,-receptor: arteriovenous shunt,SAMS(+) (sympathetic-adrenal-medulla system),“initial link”,“result”,Stage I: compensatory stage,Stage I: compensatory stage,Mechanisms of Microcirculation D
19、isturbance:,ischemia & hypoxia in pancreas MDF (myocardial depressant factor,心肌抑制因子),vasoconstriction,catecholamine,(2) several humoral factors: catecholamine, AngII (angiotensin II), vasopressin, TXA2, ET(endothelin) ,etc.,Stage I: compensatory stage,Mechanisms of Microcirculation Disturbance:,(3)
20、production of PGI2,(1) activation of SAMS: vasoconstriction,(4) production of MDF,A summary for mechanism of stage I of shock:,(1) self-blood transfusion: 肝脾储血库、静脉收缩、动静脉短路开放 “first defense line”venous constriction blood return to the heart cardiac outputaldosterone(ADS) & vasopressin(ADH) (2) self-f
21、luid infusion: “second defense line”precapillary resistance postcapillary resistance capillary pressure fluid transfer from interstitial fluid to circulation(3) blood redistribution:-adrenoceptor:brain, coronary A.-adrenoceptor:skin, skeletal m., kidneys, abdominal organs(4) activation of SAMS: cate
22、cholamine myocardial contractility,Stage I: compensatory stage,Effects on Body:,Stage I: compensatory stage,Main Clinical Manifestations:,“reversible compensatory stage”eliminating pathogenic factors & restoring blood volume and tissue perfusion尽早消除休克的动因，补充血容量，防止向休克期发展。,Stage I: compensatory stage,T
23、reatment Principle:,Stage II: progressive stage,IV. Pathogenesis and Mechanisms of Shock,Alterations of Microcirculation and Tissue Perfusion:,Stage II: progressive stage,Stage II: progressive stage: “stagnant hypoxia stage”,precapillary resistancehigh perfusion postcapillary resistancelow flow tiss
24、ue congestion and hypoxia,1.Acidosis:anaerobic glycolysisproduction of lactic acidmetabolic acidosisresponse of arteriole and metarteriole to catecholamine vasodilation,Stage II: progressive stage,Mechanisms of Microcirculation Disturbance:,2.Local accumulation of metabolic products:histamine, adeno
25、sine, Kinin,3.Endotoxin: myocardial contractilityactivate mononuclear cells production of IL-1, TNF, and NO vasodilation, Bp,5. Alteration of hemorheology: RBC aggregation and adhesion, WBC rolling and block, platelet aggregation and adhesion blood concentration & increased blood viscosity,4.Effects
26、 of humoral factors: endorphin(内啡肽)vasomotor center(-)vasodilation,WBC penetrate capillary,Blockage of WBC,白细胞附壁、滚动、嵌塞,组织间胶体,venous stasis vasodilation cap permeability,“self-blood transfusion” stop,blood vessels capacity blood return,Stage II: progressive stage (decompensated stage),Decompensated c
27、hanges:,self-blood transfusion and self-fluid infusion stop,cap static pressure plasma exudation,“self-fluid transfusion” stop,formation of vicious cycle,cap static pressure cap permeability,plasma exudation blood concentration,vasodilation,blood stasis,blood return,C.O.,Bp,sympathetic N.(+),tissue
28、perfusion,ischemia,hypoxia,acidosis,Stage II: progressive stage (decompensated stage),Decompensated changes:,Heart heart failure,Kidneysoligura or anuria,Skincyanosis,Bp,Brain dull or coma,80/50mmHg,Stage II: progressive stage,Main Clinical Manifestations:,Stage III: refractory stage,Microcirculatio
29、n changes and mechanism,2. Effects on body,3. Mechanism of refractory shock,IV. Pathogenesis and Mechanisms of Shock,Alterations of Microcirculation and Tissue Perfusion and its Mechanism:,Stage III: refractory stage,Stage III: refractory stage: “microcirculation failure stage”,后微动脉,no any response
30、to vasoactive drugs:blood flow stop no perfusion and no flow,血细胞聚集成团块，似淤泥状，在血管内摆动,Stage III: refractory stage,DIC (disseminated intravascular coagulation),（1） alteration of hemorheology:blood stasis, concentration, viscosity, blood cells aggregation “hypercoagulable state” （2）acidosis （3）impairment
31、of mono-macrophages system （4）imbalance of TXA2 and PGI2,(3) MODS (multiple organs dysfunction syndrome, 多器官功能障碍),“circulatory failure”,(1) DIC,shock,(2) capillary no-reflow phenomenon(无复流现象),(4) SIRS（systemic inflammatory response syndrome,全身炎症反应综合征）,Effects on Body:,Stage III: refractory stage,毛细血
32、管无复流现象(capillary no-reflow phenomenon),Concept: large amount of blood transfusion and fluid infusion Bp but capillary blood flow has no recovery 休克晚期即使大量输血补液，血压回升，有时仍不能恢复毛细血管血流，称为无复流现象。Mechanism：（1） WBC adhesion and aggregation （2）capillary endothelial cells swelling（3）formation of extensive microth
33、rombiblockage of capillaries,SIRS (systmic inflammatory response syndrome，全身炎症反应综合征) Concept：SIRS is a hard-controlling systemic inflammatory cascade caused by infectious or non-infectious factors. 因感染或非感染因素作用于机体而引起的一种全身性炎症反应临床综合征。机体失控的自我持续放大和自我破坏的炎症。Mechanisms of SIRS in shock:severe ischemia, hypo
34、xia of intestinal tractimmunity and barrier function entergenic bacterial and endotoxins enter blood flowact on mono-macrophages systemSIRS,Stage III: refractory stage,Mechanism of refractory shock: DIC, SIRS,后微动脉,后微动脉,后微动脉,后微动脉,A,B,C,D,Summary for the Mechanism of Shock,neural-humeral,cellular,micr
35、ocirculation theory,SAMS(+) microcirculation disturbances cell injuries, organ dysfunction“concept”,proinflammatory & antiinflammatory factors imbalance“SIRS”,causes cell injuries (structure, metabolism & function changes)“cellular level”,Neural-humeral mechanism:,SAMS,Hypothalamus-pituitary-adrenoc
36、ortical system(下丘脑-垂体-肾上腺皮质系统),RAAS,endothelin（ ET ，内皮素 ）,vasoconstrictors,catecholamine (CA),include：epinephrine (EP) and norepinephrine (NE),angiotensin （Ang ，血管紧张素）,vasopressin（ADH，血管升压素）,TXA2（thromboxane,血栓素A2）,Neural-humeral mechanism:,CGRP （calcitonin gene-related peptide,降钙素基 因相关肽）,atrial nat
37、riuretic peptide （ANP ,心房钠尿肽）,endogenous opioid peptide （内源性阿片肽）,kinin,NO,vasodilators,histamine,-endorphin,vasoactive intestinal peptide（VIP,血管活性肠肽）,early: improve ischemia；myocardial contractility; C.O. later: hypotension; I-RI.,7,Neural-humeral mechanism:,Cell injury:,Cellular and molecular mecha
38、nism:,glycolysis,ATP,lactic acid ,impaired Na+-K+ pump ,cell edema hyperkalemia,metabolic acidosis,hypoxia,Mit injury,ATP,lysosome injury,protease release,Cell injury:,Cellular and molecular mechanism:,Metabolism disturbances:,Cellular and molecular mechanism:,V. Organ Dysfunction,1.Causes:renal per
39、fusionendoxinsrenal damage 2.Main clinical manifestations: oliguria, metabolic acidosis, hyperkalemia, azotemia,(I) Effects on Kidneys: “shock kidney”,休克时最易损害的脏器之一,early stage:,later stage:,renal tubular dilation upper: microthrombilower: macrophages,(II) Effects on Lungs: “shock lung”,1. pulmonary
40、edema:histamine, kinin, adenosine, etc capillary permeabilityvasodilation fluid transude from capillaries to tissue2. pulmonary atelectasis:pulmonary perfusion production of surfactant(DPL) by type II alveolar cell alveolar collapse,3. pulmonary hemorrhage:DIC continuous bleeding4. alveolar hyaline
41、membrane formation:capillary permeability plasma proteins deposit in alveolar cavity,ALI （acute lung injury） ARDS（acute respiratory distress syndrome）,lung edema,vasodilation upper: normal lung tissuelower: lung edema,diffused lung edema,alveolar hyaline membrane,1. coronary blood volume: SAMS(+) HR
42、, myocardial contractility oxygen consumption deterioration of myocardial hypoxia2. water, electrolytes and acid-base disturbance:hyperkalemia, acidosis HR, myocardial contractility3. production of MDF:ischemic pancreas production of MDF myocardial contractility4. myocardial DIC myocardial contracti
43、lity5. endotoxins damage myocardium6. ATP myocardial contractility,(III) Effects on Heart:,hypoxia, acidosisATP impaired Na+-K+ pump cytotoxic brain edemalysosome injury brain cell injuryactivation of complement (C3a,C5a) histamine, bradykinin capillary permeability vasogenic brain edema,(IV) Effect
44、s on Brain:,(V) Effects on Digestive System:,enterogenous endotoxemia （肠源性内毒素血症),ischemia stasis,barrier function,endotoxin enter blood,stress ulcer,jaundice & hepatic encephalopathy,Definition:,Dysfunctions of more than two organs occur successively in patients without pre-exist organ dysfunction d
45、efined as MODS.,(VI) MODS(multiple organ dysfunction syndrome,多器官功能障碍综合征):,MSOF ( Multiple System Organ Failure,多系统器官衰竭 )high incidence； great expense； high mortality,Causes:,1.infectious causes:70 septicemia 2.non-infectious causes: big operationsevere trauma,Clinical classification:,1.速发单相型 (immed
46、iate monophase MODS, rapid single-phase type),2.迟发双相型(delayed dual phase MODS,delayed two-phases type),速发单相型(rapid single-phase) “原发型（primary type）”“一次打击型（one hit type）”caused by shock,trauma,etc directly由损伤因子直接引起organs injury occur at the same time or simultaneously器官损害同时或者相继develop rapidly, only o
47、ne phase, only one peak病情发展快，只有一个时相，损伤只有一个高峰,This kind of MODS often takes place rapidly after the occurrence of shock and trauma. This kind of MODS is only one phase, i.e., there is only one peak of organ failure during the pathological processes.,迟发双相型(delayed two-phase) “继发型（secondary type）”“二次打击
48、型（double hit type）”remssion after the first hit 第一次打击后出现一个缓解期second hit 其后13周又受到第二次打击发生MODSdual-phase, two peaks病情发展呈双相，出现两个损伤高峰,The first peak of organ failure of patients with trauma, shock or hemorrhage usually appears in a short time. If the condition of those patients could not be effectively controlled, a second organ failure peak will appear in 3 to 5 days due to a rapidly happened septicemia. The course of the MODS described above shows a dual-phase progression with two peaks of organ failures.,
