1、Hemodynamic Disorders王漱阳王漱阳Department of PathologyAn Anatomical Study of the Motion of the Heart and of the Blood in Animals,1628Containing Heart,artery,Vein General circulation Pulmonary circulationFunctionsDeliver oxygen and nutrientsCarry away metabolic wastesA Healthy circulatory system Normal b
2、lood volume HomeostasisNormal homeostasis vessel wall integrity intravascular pressure osmolarity normal hemostasis Edema Hyperemia&congestion Thrombosis&Embolism Infarction Hemorrhage ShockThree Major Causes of morbidity and mortality Myocardial infarction Pulmonary embolism Cerebral vascular accid
3、entCirculation Disturbance General(systemic)Some severe situation affecting all over the body:cardiac dysfunction,shock Local1.Abnormal blood volume and the velocity of blood flow:hyperemia and ischemia2.Abnormality of vascular integrity and permeability:edema and hemorrhage 3.Occlusion of the vesse
4、l lumen:thrombosis,embolism and infarction EDEMA(水肿)Increased fluid in the interstitial tissue spaces General&local Pathogenesis Vascular hydrostatic pressure Plasma colloid osmotic pressure Lymphatic drainageEDEMAIncreased hydrostatic pressure(cardiac edema,etc.)Reduced plasma osmotic pressure(neph
5、rotic,hepatic,malnutrient edema,etc.)Lymphatic obstruction(filariasis infection elephantiasis，breast surgery,etc)Sodium and water retention(ARF,etc)Minimal Change DiseaseelephantiasisPitting edemaEDEMAMost common typesSubcutaneous edemaPulmonary edemaEdema of the brain MorphologyLight Microscope（LM）
6、:Clearing and separation of the extracellular matrix elements Cell swelling hydrothorax hydropericardium hydroperitoneum(ascites)anasarcaEDEMAClinical correlationu from annoying to fatalu indicate subtle diseaseu benefit or harmfulHYPEREMIA&CONGESTIONA local increased volume of blood in a particular
7、 tissue器官或局部组织的血管扩张，内含血量增多。Arterial hyperemia(hyperemia，充血)u an augmented blood flow inducing arteriolar and capillary dilation Venous hyperemia(congestion，淤血)u accumulation of blood in small veins and capillaries result from drainage difficulty of veinsHYPEREMIA&CONGESTIONHyperemia:active process;r
8、ed,raised temperature,increased volume;enhanced function;Congestion:passive process;general of local;reddish blue color(cyanosis),low temperature,increased volume,edema;decreased function TypesPhysiological:shy,exercise,taking meal Pathological:inflammatory,post-decompressed Significance Benefits pl
9、enty supply of O2,functional enhancement,nutrition substance Hazards headache,hemorrhage,stroke HYPEREMIAMorphology小动脉和毛细血管扩张，充满红细胞 色泽鲜红，体积可轻度增大，温度高HYPEREMIACauses:Systemic:general or pulmonary cardiac dysfunction(right or left)Local:local venous compression or obstruction external compression-tumor
10、,bandage occlusion of lumen-thrombosis,embolism thickening of venous wall paralysis of neurogenic modulation-burn,frostbiteCONGESTIONCONGESTIONChronic congestion Raised venous pressure Anoxia Metabolite accumulation Enlarged interendothelial gap Base membrane degeneration Parenchymal Interstitial fi
11、brosis Atrophy Reticular fiber collapsed Increase permeability Degeneration Collagen increased Necrosis Fibroblast proliferation Microscopic scarring Edema Hemorrhage Congestive sclerosisMorphology Grossly hemorrhagic and wet Microscopically rich of red blood cells in small vessels CONGESTIONCONGEST
12、IONLungAcute Pulmonary CongestionGross:Plump swollen lung with shining pleura,edematous fluid flowing out while cutting the lung LM:Alveolar capillaries highly dilated and engorged with blood rosary-like appearance Alveolar cavity filled with eosinophilic edema fluid Manifestation Pink colored foamy
13、 sputumLung CONGESTIONCONGESTIONLung Chronic Pulmonary CongestionGross:Hard,with brown spots scattered Brown Induration 褐色硬化褐色硬化LM:Septa thickened and fibrosis heart failure cells 心衰细胞心衰细胞 hemosiderin-laden macrophages Manifestation rusty sputum,dyspnea,etc.CONGESTIONLiver 右心衰竭右心衰竭 下腔静脉、肝静脉回流受阻下腔静脉、
14、肝静脉回流受阻CONGESTIONLiver Acute Hepatic CongestionLM:Dilation of central vein and sinusoids with blood Atrophy,degeneration and necrosis of central hepatocytesCONGESTIONLiver Chronic Hepatic CongestionNutmeg Liver“槟榔肝槟榔肝”Gross:red-brown zones accentuated against the yellow surrounding zonesLM:centrilob
15、ular necrosis and congestion,and perilobular fatty change;fibrosisLong-standing,severe hepatic congestion:congestive hepatic fibrosis(cardiac cirrhosis)superficial small granular“猪皮猪皮”Nutmeg Liver 槟榔肝 病因病因 肝硬化肝硬化 慢性心力衰竭慢性心力衰竭CONGESTIONSpleen 脾淤血-病变 Gross：体积增大、包膜增厚(玻璃样变)切面暗红色、白髓减少、小梁增多 LM：脾窦扩张淤血、白髓受压
16、萎缩、窦壁纤维增生tobacco nodules or Gandy-Gamma nodules含铁小结/烟草小结 脾窦内巨噬细胞含铁血黄素。含铁血黄素脾窦内巨噬细胞含铁血黄素。含铁血黄素与铁盐、钙盐组成。肉眼针尖大小、中央与铁盐、钙盐组成。肉眼针尖大小、中央呈黄色，周围为褐色。呈黄色，周围为褐色。HEMORRHAGE（出血）CausesCauses Rupture of blood vesselsRupture of blood vessels Trauma TraumaPeptic ulcer,aneurism,atherosclerosisPeptic ulcer,aneurism,ath
17、erosclerosis DiapedesisDiapedesisEnlarged interendothelial gap(basement membrane injury).Enlarged interendothelial gap(basement membrane injury).The integrity of the vessels remains intact The integrity of the vessels remains intactInjury to vascular wall:severe infection,anoxia,toxinsChange in numb
18、er and quality of platelets uremia,leukemia,idiopathic uremia,leukemia,idiopathic Disturbance of coagulation mechanism congenital disease,DIC,deficiency of Vit.Kcongenital disease,DIC,deficiency of Vit.KHEMORRHAGE petechiae purpuras ecchymoses hematoma hemothorax hemopericardium hemoperitoneum hemoa
19、rthrosisThe clinical significance depends on the volume,the rate of loss and the site.Hemorrhagic shock Stroke Normal hemostasis Maintain blood in a fluid,clot-free state Localized hemostatic plugThrombosis（血栓形成）Blood clot(thrombus，血栓)formation in cardiovascular system of a living body在在活体活体心血管系统内血液
20、发生凝集和凝固而形成心血管系统内血液发生凝集和凝固而形成固体固体的过程的过程HEMOSTASIS&THROMbOSISHEMOSTASISThree componentsvascular wallplateletscoagulation cascadeEvents in hemostasisvasoconstrictionprimary hemostasissecondary hemostasisantithrombotic counter-regulationHEMOSTASIS&THROMbOSIS Endothelium Antithrombotic antiplatelet antic
21、oagulant fibrinolytic ProthromboticHEMOSTASIS&THROMbOSIS Platelet adhesion secretion aggregation Coagulation casecadeTHROMbOSIS Pathogenesis endothelial injury turbulence of blood flow hypercoagulabilityVirchow Triangle 屏障作用消失血小板靠壁和凝集 内皮细胞vWF血小板表面粘附分子 胶原纤维暴露XII内源性凝血系统 TNF和IL-1组织因子外源性凝血系统 纤溶酶原激活物抑制因子
22、 血液涡流形成（一）心血管内皮细胞的损伤血栓形成的主要影响因素对心脏和动脉内血栓的形成尤为重要心肌梗死、心瓣膜炎严重动脉粥样硬化时有溃疡形成的斑块创伤/炎症性血管损伤损伤因素创伤、缺氧、化学物质、感染、免疫反应 高胆固醇血症、高血压、高胱氨酸尿、放射线（一）心血管内皮细胞的损伤（二）血流缓慢和涡流形成 轴流有形成分 正常血液流动 边流无形成分血流缓慢 轴流破坏血小板靠边 局部凝血物质 白细胞附壁 涡流不规则血管腔 扩张或狭窄血流缓慢 心力衰竭、手术后及久卧床者 涡流形成 动脉粥样硬化溃疡性斑块 动脉瘤 风湿性心瓣膜病 二尖瓣狭窄（二）血流缓慢和涡流形成u静脉血栓形成的主要原因The major
23、 factor in the development of venous thrombi Incidence of thrombosis V:A=4:1 Veins of upper limb:lower limb=1:3（二）血流缓慢和涡流形成凝血系统 纤维蛋白溶解系统-遗传性高凝状态 第因子基因突变、抗凝血酶以及C蛋白、S蛋白先天性缺乏-继发性高凝状态严重创伤、手术或产后大面积烧伤 晚期肿瘤 肾病综合症 （三）血液凝固性升高（三）血液凝固性升高 数目血小板 粘性 合成凝血因子 灭活大面积烧伤严重创伤手术后或产后晚期肿瘤等2个阶段 血小板的沉积与凝集 血液的凝固内皮损伤-血小板小丘、小梁-白
24、细胞粘附-纤维蛋白网架-红细胞-阻塞管腔-红色血栓血栓头（白色血栓）血栓体（混合血栓）血栓尾（红色血栓）THROMbOSIS 血栓头 白色血栓 血栓体 混合血栓 血栓尾 红色血栓 纤维蛋白红细胞与血管壁紧密粘着血小板+少量纤维蛋白构成血小板小梁中性白细胞 纤维蛋白红细胞THROMbOSISTHROMbOSISLines of Zahn pale platelet and fibrin layers dark erythrocyte-rich layersLines of ZahnTHROMbOSISLM:platelets trabeculae +neutrophil fibrin+red c
25、ellsTHROMbOSISTypes Mural thrombus 附壁血栓 Occlusive thrombus闭塞性血栓 Globular thrombus 球型血栓 Vegetation 赘生物Bacterial thrombusTumor thrombusPale thrombusMixed thrombusRed thrombusHyaline thrombusu Pale thrombusplatelets&fibrinthe head of a venous/propagating thrombus locate in the cardiac valves,chambers o
26、r the aorta(eg.Vegetation)u Mixed thrombuspale trabaculaes alternating with erythrocytes rich layersthe body of a venous/propagating thrombus THROMbOSISu Red thrombuserythrocytes&fibrintail of a venous/propagating thrombusu Hyaline thrombus(microthrombus)fibrinrelates to disseminated intravascular c
27、oagulation(DIC)THROMbOSISTHROMbOSISMural thrombusGlobular thrombusOcclusive thrombusTHROMbOSISVegetation tumor thrombusbacterial thrombusTHROMbOSISTHROMbOSISDifference between thrombus and postmortem clot Thrombus Postmortem clots干干 dry wet and gelatinous “chicken fat”supernatant糙糙 rough surface smo
28、oth surface硬硬 hard soft脆脆 fragile gelatinous层层 Lines of Zahn homogenous 紧紧 firmly attached no attachment裂裂 slit due to contraction,fragmentation,generate embolus no slitTHROMbOSISFate Obstruction Dissolution Embolization Organization&Recanalization Calcification THROMbOSIS Arterial thrombi originate
29、 from injury sites Venous thrombi(phlebothrombi)originate from the sites of stasisboth extend to the heart THROMbOSISClinical correlations Venous thrombosis(phlebothrombosis)varicosities,embolism(sometimes fatal),DVT,trauma,surgery,post partum cancer associated thrombosis Cardiac and arterial thromb
30、osis mural thrombus(MI,AS)myocardiac infarction,rheumatic heart disease Embolize peripherally,brain,kidney,spleen,etcTHROMbOSISDIC(Disseminated Intravascular Coagulation)Usually happens in many severe disorders severe bacterial or viral infection,allergic disease,anoxia,trauma,shock,malignancy,etc.C
31、oagulation System is Activated Microthrombi are formed in Cap.of many organs Platelets+Fibrin (lung,brain,kidney,liver,GI tract,adrenal gland,etc.)Consumption of coagulation substance and activation of fibrinolytic system hemorrhage diathesis,multiorgan dysfunction consumption coagulopathy/defibrina
32、tion syndrome 消耗性凝血病/去纤维蛋白综合征EMbOlISM（栓塞）Occlusion of cardiovascular system by some insoluble mass.血液循环中出现的不溶于血液的异常物质(embolus)，随血流运行阻塞血管腔的现象称为栓塞The mass-Embolus（栓子）（栓子）:solid,liquid,gaseous mass Thromboembolism 99%Fat,air,amniotic fluid,tumor fragments,bits of bone marrow,etc.EMbOlISMRoute of emboli
33、 Arterial emboli systemic embolism Venous emboli pulmonary embolism Portal vein emboli hepatic embolism Paradoxical emboli Emboli from veins of the general circulation pass through an atrial or ventricular septal defect,entering arteries of the general circulation.Retrograde emboliEMbOlISMIncidence:
34、20-25/100,000 hospitalized patientsSource:95%from DVT above the kneePulmonary ThromboembolismEMbOlISMResults:depends on the size,number and the clinical setting Few Emboli with Small Size:asymptomatic infarction(pain and dyspnea)Numerous Small Emboli:decrease the volume of pulmonary circulation shar
35、ply,pulmonary hypertension and right ventricular failure Medium Sized Emboli:hemorrhage,usually no infarction,Why?Large Emboli:sudden death,saddle embolusPulmonary ThromboembolismEMbOlISM Source:80%from intracardiac mural thrombi;MI,aortic aneurysms,ulcerated AS plaques,vegetations Target sites:lowe
36、r extremities,brain,intestines,kidney,spleen Consequences:infarctionSystemic ThromboembolismEMbOlISMThromboembolism 99%Non-thrombotic embolism Fat embolism Gas embolism Amniotic fluid embolism Can you answer these questions:Where do they come from?Where do they lodge?What are the features of their i
37、mpairment?FAT EMbOlISM 脂肪栓塞Released from the bone marrow and soft tissue due to severe injury long bone fracture soft tissue trauma or burns squeeze of the fatty changed liverMainly occurs in the lung and the brainMostly asymptomatic,only 10%of severe skeletal injuries have some clinical manifestati
38、onFAT EMbOlISM Results depend on the diameter and the quantity of the fat droplets 20m,pulmonary embolism 20 m,cerebral embolism other organ embolism Special staining Osmium staining(Sudan III)Fatty Embolus in the Vascular Lumen Pathogenesisobstruction&toxic effect of free fatty acid the role of pla
39、telets adhesion and coagulation Symptomstachypnea,dyspnea,tachycardia;irritability,restlessness,delirium or coma;anemia and thrombocytopenia diffuse petechial rash(in 20-50%cases)FAT EMbOlISMGAS EMbOlISM气体栓塞Source:air or N2 bubbles Exogenic:transfusion,operation or trauma in the neck or chest,artifi
40、cial pneumothorax,pneumoperitoneum Endogenic:decompression sickness or caisson disease kesn Results:Small amount of gas may be absorbedOccupies the heart ventricle,interrupted the blood flow cause death Gas embolism in multiple organs(esp.brain&pulmonary)Symptoms:Pains,sudden deathTreatments:Recompr
41、essionGAS EMbOlISMAMNIOTIC FluID EMbOlISM 羊水栓塞羊水栓塞Low Incidence(1/40,000)with high mortality rate(70%80%)Source Sinusoids which placenta attached Torn cervical vesselsComponents of Amniotic Fluid:squamous epithelial cells,lanugo hair,fat,fetal feces,mucin and TXA2Squamous cells and Keratinization su
42、bstancesSymptoms:sudden severe dyspnea,cyanosis and ShockCause of death:multiple embolism;pulmonary embolism;reflex vasoconstriction;allergic shock;DICAlcian Blue PAS stainingAMNIOTIC FluID EMbOlISMINFARCTION（梗死形成）The formation of a localized area of ischemic necrosis within a tissue or organ due to
43、 impaired arterial supply or the venous drainage.由于部分动脉或静脉阻塞引起局部组织或器官供血不足或停止而发生的坏死,称为梗死(infarct)。The necrosis area is called infarct.其过程称梗死形成(infarction).An extremely important cause of clinical illness:myocardiac infarctioncerebral infarctionCauses Occlusion of arterial supply or venous drainageThr
44、ombosis,embolism,athermanous plaques,external compression Functional spasm of arterioleTypes White infarcts(anemic infarcts)Red infarcts(hemorrhagic infarcts)Septic infarcts INFARCTION脏器血供特点、组织的结构疏密程度、血管阻塞程度、是否有淤血、有无感染INFARCTIONWhite infarctionArterial occlusionSolid,compact organsFew collateral cir
45、culation(spleen,kidney,heart,brain,etc.)Morphology GrossDull pale,dry,wedge-shaped necrotic lesion A hemorrhagic zone surrounding陈旧梗死灶陈旧梗死灶机化、瘢痕、凹陷机化、瘢痕、凹陷INFARCTIONLMIschemic coagulative necrosis Hemorrhagic zone:inflammatory and granulation tissue.Most undergo organization and scarring in the end.
46、Kidney InfarctionINFARCTIONSpleen InfarctionINFARCTIONCardiac InfarctionINFARCTIONBrain Infarction(liquefied necrosis)INFARCTIONRed infarction Arterial occlusion Venous occlusion Loose tissue Dual circulations:lung,small intestine previously congested re-established blood flow to a site of previous
47、arterial occlusion and necrosisINFARCTIONHemorrhagic infarction of the lungGross Roughly wedged shapedDark red,solid area Base beneath the pleura Fibrin exudation LM Coagulative necrosisLarge amounts of RBC filled in alveolar spaceObscure structureINFARCTIONHemorrhagic infarction of the intestineINF
48、ARCTIONSeptic Infarction Bacteria containing emboli May form abscess and pusINFARCTIONFate of Infarct Enzymatic lysis,liquefaction and absorption Organization with scar formation Encapsulation and CalcificationINFARCTIONFactors that influence development of an infarct Nature of the vascular supply R
49、ate of development of occlusion Vulnerability to hypoxia Oxygen content of bloodTerms cyanosis edema sclerosis heart failure cell brown induration nutmeg liver mixed thrombus hyaline thrombus organization recanalization phlebolith&arteriolith crossed embolism or paradoxical embolism retrograde embol
50、ism thromboembolism caisson disease decompression sickness amniotic fluid embolism septic infarct After giving birth to a child,doctors usually ask the mother to have proper activities instead of just lying in bed.Why is it necessary to ask the mother to get up and walk around as soon as possible af
