病理學：2 Hemodynamic Disorders

1、Hemodynamic DisordersAn 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 blood volume HomeostasisNor

2、mal homeostasis vessel wall integrity intravascular pressure osmolarity normal hemostasisEdemaHyperemia & congestionThrombosis & EmbolismInfarctionHemorrhageShockThree Major Causes of morbidity and mortality myocardial infarction pulmonary embolism cerebral vascular accidentCirculation Disturbance G

3、eneral (systemic) Some severe situation affecting all over the body: cardiac dysfunction, shock LocalAbnormal blood volume and the velocity of blood flow: hyperemia and ischemiaAbnormality of vascular integrity and permeability: edema and hemorrhage Occlusion of the vessel lumen: thrombosis, embolis

4、m and infarction 12Terms cyanosisedemasclerosisheart failure cellbrown indurationnutmeg livermixed thrombushyaline thrombusorganizationrecanalizationparadoxical embolismretrograde embolismthromboembolismdecompression sicknesscaisson disease amniotic fluid embolismwhite infarctred infarctseptic infar

5、ctEDEMA (水腫)Increased fluid in the interstitial tissue spacesGeneral & localPathogenesisVascular hydrostatic pressurePlasma colloid osmotic pressureLymphatic drainageEDEMAIncreased hydrostatic pressure ( cardiac edema, etc.)Reduced plasma osmotic pressure (nephrotic, hepatic, malnutrient edema, etc.

6、 )Lymphatic obstruction (filariasis infection elephantiasis，breast surgery, etc )Sodium and water retention (ARF, etc)Minimal Change DiseaseelephantiasisPitting edemaEDEMAMost common typesSubcutaneous edemaPulmonary edemaEdema of the brainMorphologyLight Microscope （LM）:Clearing and separation of th

7、e extracellular matrix elementsCell swellingHydrothorax hydropericardium hydroperitoneum (ascites) anasarcaEDEMAClinical correlation from annoying to fatal indicate subtle disease benefit or harmfulHYPEREMIA & CONGESTIONA local increased volume of blood in a particular tissueArterial hyperemia (hype

8、remia，充血) an augmented blood flow inducing arteriolar and capillary dilation Venous hyperemia (congestion，淤血) accumulation of Blood in Small Veins and capillaries result from drainage difficulty of veinsHYPEREMIA & CONGESTIONHyperemia:active process;red, raised temperature, increased volume ;enhance

9、d function;Congestion: passive process;General or local;reddish blue color (cyanosis), low temperature, increased volume, edema;decreased functionTypesPhysiological: shy, exercise, taking meal Pathological: inflammatory, post-decompressed Significance Benefits plenty supply of O2, functional enhance

10、ment, nutrition substance Hazards headache , hemorrhage, stroke HYPEREMIACauses: Systemic: general or pulmonary cardiac dysfunction (right or left)Local: local venous compression or obstruction external Compression - tumor, bandage occlusion of lumen - thrombosis, embolism thickening of venous wall

11、paralysis of neurogenic modulation - burn, frostbiteCONGESTIONCONGESTION Discussion The consequences of chronic congestion Please take chronic hepatic congestion for exampleWhat is the possible reason for hepatic congestion?What are the consequences of hepatic congestion?What are the morphological f

12、eatures of chronic hepatic congestion? CONGESTIONChronic congestion Raised venous pressure Anoxia Metabolite accumulation Enlarged interendothelial gap Base membrane degeneration Parenchymal Interstitial fibrosis Atrophy Reticular fiber collapsed Increase permeability Degeneration Fibroblast prolife

13、ration Necrosis Collagen increased Microscopic scarring Edema Hemorrhage Congestive sclerosis Discussion The consequences of chronic congestion Please take chronic hepatic congestion for exampleMorphologyGrossly hemorrhagic and wetMicroscopically rich of red blood cells in small vessels CONGESTIONCO

14、NGESTIONLungacute 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 appearanceAlveolar cavity filled with eosinophilic edema fluid Manifestation pink color

15、ed foamy sputumCONGESTIONLung chronic pulmonary congestionGross: Hard, with brown spots scattered Brown IndurationLM: Septa thickened and fibrosisheart failure cells hemosiderin-laden macrophages Manifestation rusty sputum, dyspnea, etc.CONGESTIONLiver acute hepatic congestionLM: Dilation of central

16、 vein and sinusoids with blood Atrophy, degeneration and necrosis of central hepatocytesCONGESTIONLiver chronic hepatic congestionNutmeg LiverGross: red-brown zones accentuated against the yellow surrounding zonesLM: centrilobular necrosis and congestion, and perilobular fatty changeLong-standing, s

17、evere hepatic congestion: hepatic fibrosis (cardiac cirrhosis)Hemorrhage （出血）CausesRupture of blood vessels TraumaPeptic ulcer, aneurism, atherosclerosis DiapedesisEnlarged interendothelial gap (basement membrane injury). The intergrity of the vessels remains intactInjury to vascular wall: severe in

18、fection, anoxia, toxinsChange in number and quality of platelets uremia, leukemia, idiopathic Disturbance of coagulation mechanism congenital disease, DIC , deficiency of Vit. KhemorrhagepetechiaepurpurasecchymoseshematomahemothoraxhemopericardiumhemoperitoneumhemoarthrosisThe clinical significance

19、depends on the volume, the rate of loss and the site. Hemorrhagic shock Stroke Normal hemostasisMaintain blood in a fluid, clot-free stateLocalized hemostatic plugThrombosis （血栓形成）Blood clot (thrombus，血栓) formation in cardiovascular system of a living bodyHemostasis & thrombosisHemostasisThree compo

20、nentsvascular wallplateletscoagulation cascadeEvents in hemostasisvasoconstrictionprimary hemostasissecondary hemostasisantithrombotic counter-regulationHemostasis & thrombosisEndotheliumAntithromboticantiplateletanticoagulantfibrinolyticProthromboticAntithromboticantiplateletanticoagulantfibrinolyt

21、icProthromboticHemostasis & thrombosisPlateletadhesionsecretionaggregationCoagulation casecadethrombosis Pathogenesisendothelial injuryAbnormal blood flowhypercoagulabilityVirchow TrianglePlease list the causes of turbulent blood flow.Pay attention to the nature of the heart and vessels:e.g. Large a

22、rtery: thick wall, 3 layers, higher pressure, atherosclerosis plaques, bifurcationVein: thin wall, larger capacity, easy to be out of shape, venous valvesHeart: Atrioventricular valves and Semilunar valves, Valvular heart disease (stenosis/ insufficiency); cardial infarction (injure the endothelium)

23、Pay attention to the environmental factor: Cold, compression, gravity, etc.Slow blood flow: The conc. of procoagulants The platelets and neutrophils are more close to the wall.Quick blood flow and turbulence: The endothelia is more likely to be injured Discussion Which of the followings is definitel

24、y not related to hypercoagulable state?Late stage of pregnancy.Disseminated cancerSurgerySevere injurySmokingOral Contraceptive pillsDisseminated intravascular coagulationMyocardial infarctionMutation in factor V geneNone Discussion thrombosisMorphologyArterial thrombioriginate from injury sitesVeno

25、us thrombi originate from the sites of stasisboth extend to the heart pale platelet and fibrin layersLines of Zahn dark erythrocyte-rich layersthrombosisLines of ZahnthrombosisLM: platelets trabeculae + neutrophil fibrin + red cellsthrombosisTypes Mural thrombusOcclusive thrombusGlobular thrombusVeg

26、etationBacterial thrombusTumor thrombusPale thrombusMixed thrombusRed thrombusHyaline thrombus Pale thrombusplatelets & fibrinthe head of a venous/propagating thrombus locate in the cardiac valves, chambers or the aorta (eg. Vegetation, mural thrombus, etc) Mixed thrombuspale trabaculaes alternating

27、 with erythrocytes rich layersthe body of a venous/propagating thrombus thrombosis Red thrombuserythrocytestail of a venous/propagating thrombus Hyaline thrombus (microthrombus)fibrinrelates to disseminated intravascular coagulation (DIC)thrombosisthrombosisMural thrombusVegetation Hyaline Thrombuso

28、cclusive thrombusglobular thrombusthrombosistumor thrombusbacterial thrombusthrombosisthrombosisDifference between thrombus and postmortem clot Thrombus Postmortem clots干 dry wet and gelatinous“chicken fat” supernatant糙 rough surface smooth surface硬 hard soft脆 fragile gelatinous層 Lines of Zahn homog

29、enous 緊 firmly attached no attachment裂 slit due to contraction, fragmentation, generate embolus no slitthrombosisFate Propagation and obstructionDissolutionEmbolizationOrganization and recanalizationCalcification thrombosisClinical correlationsVenous thrombosis (phlebothrombosis)varicosities, emboli

30、sm (sometimes fatal), DVT, trauma, surgery, post partumcancer associated thrombosis Cardiac and arterial thrombosismural thrombus (MI, AS)myocardiac infarction, rheumatic heart diseaseEmbolize peripherally, brain, kidney, spleen, etcthrombosisDIC (Disseminated intravascular coagulation) Usually happ

31、ens in many severe disorders severe bacterial or viral infection, allergic disease, anoxia, trauma, shock, malignancy ,etc. Coagulation System is Activated Microthrombi are Formed in Capillaries of Many Organs Platelets + Fibrin ( lung ,brain ,kidney, liver, GI tract, adrenal gland, etc.) Consumptio

32、n of coagulation substance and activation of fibrinolytic system hemorrhage diathesis, mutiorgan dysfunction consumption coagulopathy / defibrination syndrome 消耗性凝血病/ 去纖維蛋白綜合征Embolism （栓塞）Occlusion of cardiovascular system by some insoluble mass. The mass is termed as “Embolus （栓子）”.solid, liquid, g

33、aseous massThromboembolism 99%Fat, air, amniotic fluid, tumor fragments, bits of bone marrow, etc EmbolismRoute of emboliArterial emboli systemic embolismVenous emboli pulmonary embolismPortal vein emboli hepatic embolismParadoxical emboli Emboli from veins of the general circulation pass through an

34、 atrial or ventricular septal defect, entering arteries of the general circulation.Retrograde emboli Discussion Arterial emboli & Venous emboli Where do the emboli come from?Where do they lodge?What are the symptoms?What can be done to treat the disease?EmbolismIncidence: 20-25/100,000 hospitalized

35、patientsSource: 95% from DVT above the kneePulmonary ThromboembolismEmbolismResults: depends on the size, number and the clinical setting A Few Emboli with Small Size : asymptomatic infarction (pain and dyspnea)Numerous Small Emboli : decrease the volume of pulmonary circulation sharply, pulmonary h

36、ypertension and right ventricular failureMedium Sized Emboli: hemorrhage, usually no infarction, Why?Large Emboli: sudden death, saddle embolusPulmonary ThromboembolismEmbolismSource: 80% from intracardiac mural thrombi; MI, aortic aneurysms, ulcerated AS plaques, vegetations Target sites: lower ext

37、remities, brain, intestines, kidney, spleenConsequences: 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 im

38、pairment?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 manifestat

39、ionFat EmbolismResults depend on the diameter and the quantity of the fat droplets 20m, pulmonary embolism 20 m, cerebral embolism other organ embolism Special staining (Sudan III ) Osmium stainingFatty Embolus in the Vascular LumenPathogenesisobstruction & toxic effect of free fatty acid the role o

40、f platelets adhesion and coagulationSymptomstachypnea, dyspnea, tachycardia; irritability, restlessness, delirium or coma; anemia and thrombocytopenia diffuse petechial rash ( in 20-50% cases)Fat EmbolismGAS Embolism氣體栓塞Source: air or N2 bubbles Exogenic: transfusion, operation or trauma in the neck

41、 or chest, artificial 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, sudd

42、en deathTreatments: RecompressionGAS EmbolismAmniotic Fluid Embolism 羊水栓塞Low Incidence (1/40,000) with high mortality rate (70%80%)SourceSinusoids which placenta attached Torn cervical vesselsComponents of Amniotic Fluid:squamous epithelial cells, lanugo hair, fat, fetal feces, mucin and TXA2Squamou

43、s cells and Keratinization substancesSymptoms: 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 localizad area of ischemic ne

44、crosis within a tissue or organ due to impaired arterial supply or the venous drainageThe necrosis area is called “infarct” (梗死灶).An extremely important cause of clinical illness:myocardiac infarctioncerebral infarctionCausesOcclusion of arterial supply or venous drainageThrombosis, embolism, atherm

45、anous plaques, external compressionFunctional spasm of arterioleTypesWhite infarcts (anemic infarcts)Red infarcts (hemorrhagic infarcts)Septic infarcts INFARCTIONINFARCTIONWhite infarctionArterial occlusionSolid, compact organsFew collateral circulation (spleen, kidney, heart, brain, etc.)Morphology GrossDull pale, dry, wedge-shaped necrotic lesion A hemorrhagic zone surroundingINFARCTIONLMIschemic coagulative necrosis Hemorrhagic zone : inflammatory and granulation tissue. Most undergo organization and scarring in the end.INFARCTIONSpleen InfarctionINFARCT