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1、18-4-2012PathologyThrombosis,Embolism,InfarctionLaboratory 6*William E.Winter,MD*Corresponds to lecture 8.Instructions-1.Each team is to work through these slides(and problems).Do not rush.You have 50 minutes to complete this exercise.2.ANSWERING(or trying to ANSWER)THE QUESTIONS IS VERY IMPORTANT F
2、OR THE LEARNING PROCESS.3.Medicine is a team sport.Become comfortable working in a team now.4.Teach one another.Refer to the lecture notes as needed.SOP(standard operating procedures)i)Sign-in to confirm your attendance at lab.ii)Complete the challenge question posted at 30 minutes after the hour(th
3、is is not graded but must be completed as part of professionalism).Learning objectives(1)At the conclusion of this exercise,students should be able to answer the following questions-How do the terms thrombus and blood clot differ and how are the same?How can thrombi be classified?How do we know that
4、 a blood coagulum is a thrombus and not a clot?What is a“mural”thombus?What is an embolus and what variety of emboli exist?What happens to thrombi that are not cleared completely by fibrinolysis?What is infarction?Learning objectives(2)At the conclusion of this exercise,students should be able to an
5、swer the following questions-What is acute versus chronic passive pulmonary congestion?What is pulmonary edema?How do platelets contribute to the formation of a thrombus?Milikowski,Fig 3-6Arterial(white)thrombusNote:the color of the coagulum(white versus red)is what is observed on the gross exam whe
6、n the coagulum is not stained with dyes.Tissue sections are routinely stained to allow visual examination under the microscope.White thrombus-an opaque dull white thrombus on gross visual examination composed predominantly of blood platelets.Such thrombi are characteristic of thrombi in arteries.Syn
7、:pale thrombus.Red thrombus-a thrombus formed rapidly by the coagulation of stagnating blood,composed mainly of red blood cells rather than platelets.Such thrombi are characteristic of thrombi in veins when more RBCs become trapped in the thrombus.This is a gross picture of a thrombus in a vein.Does
8、 this appear to be a red thrombus or a white thrombus?Red thrombus.(Courtesy of S.Normann,MD,PhD)Express your answer to your team mates.How do we know that a blood coagulum is a thrombus and not a clot?The lines of Zahn indicate that the coagulum is a thrombus that occurred at a site of blood flow.T
9、he lines of Zahn are rib-like markings seen by the naked eye on the surface of antemortem(before death)blood coagulum that formed in a blood vessel.The layers consist of a branching framework of platelets and fibrin separating the coagulated blood cells.Express your answer to your team mates.What is
10、 an embolus?A plug,composed of a detached thrombus,mass of bacteria,or foreign body,etc.occluding a vessel.Express your answer to your team mates.What type of embolus is indicated by the arrow?Thromboembolism to a major pulmonary artery.Because the embolus straddles the bifurcation of one artery int
11、o 2 arteries,this can be called a saddle embolism.(Courtesy of S.Normann,MD,PhD)Express your answer to your team mates.52 y/o male presented w/exertional fainting and low BP.Right heart failure was present as were DVTs bilaterally in the legs.Upon hospitalization progressive hypoxia developed despit
12、e heparinization.What does the arrow identify?A saddle embolus(the contrast in the blood vessel is white,the embolus is darker gray)Note:An urgently performed CT revealed a large saddle embolus.Express your answer to your team mates.The patient was then treated with a drug that accelerates thromboly
13、sis the drug was tissue plasminogen activator(tPA).What does the image on the right now show?The pulmonary embolus has resolved with restoration of blood flow.Note:thrombi appear as filling defects(as on the left).NEJM 2002;347:1161Express your answer to your team mates.What type of embolus is indic
14、ated by the arrow?This small pulmonary vessel contains tumor cells.When small clumps of tumor emboli lodge in the vessels and grow,they may become the site of a metastsis.(Courtesy of S.Normann,MD,PhD)This is a bone marrow embolus(click)from a patient who had CPR.The section shows viable marrow frag
15、ments in a medium-sized artery.Such emboli are common postmortem findings following CPR(e.g.,rib fractures from compression result in scattered bone marrow emboli).What type of embolus is indicated by the arrow?This is a fat embolus in the pulmonary circulation.Like bone marrow emboli,fat emboli can
16、 occur following the fracture of a large bone(e.g.,a femur).Normally the marrow includes adipose cells.(Courtesy of S.Normann,MD,PhD)20What do you see?What type of emboli could cause this?NEJM 2006;354:1294The patient was a 72 y/o male who presented with unstable angina.The bluish discoloration of t
17、he toes and feet occurred 12 hours following urgent cardiac catheterization with stent placement in his right coronary artery.Fracture of atheromatous(aortic)plaques by angioplasty during the stent placement produced cholesterol emboli.Cholesterol emboli also affected the patients kidneys as his cre
18、atinine doubled.The patient recovered uneventfully(e.g.,there was no infarction).PathogenesisContact w/atherosclerotic aortaVDistruption of plaqueVCholesterol emboli to feetAortaDistal embolization of damaged plaque to feetCatheter via femoral arteryThis is the characteristic histologic picture of a
19、 cholesterol embolus.Cholesterol crystals from a rupture atherosclerotic plaqueWhat do you observe in this thrombus?Recanalization.The arrows point out endothelial cells forming the new channels that will ultimately interconnect to fully reopen this formerly occluded blood vessel.(Courtesy of S.Norm
20、ann,MD,PhD)What is infarction?Infarction is a macroscopic area of coagulative necrosis that results,most commonly,from a sudden(acute)reduction or cessation in the blood supply to a tissue or organ.The causes of infarction include thrombosis,embolism and mechanical factors(e.g.,vessel compression).T
21、he answers are in the notes.Can you find the answers before you go forward?What process do you see in these 2 images?Figure 4-19 Examples of infarcts.A,Hemorrhagic,roughly wedge-shaped pulmonary infarct.B,Sharply demarcated white infarct in the spleen.In a hemorrhagic infarction,bleeding occurs into
22、 the tissue with infarction.This can occur in the lung because the lung has a dual blood supply.In a white infarction,arterial occlusion caused ischemia and infarction.Without blood,the organ is pale.Following a significant myocardial infarction,cardiac output declines raising left ventricular end d
23、iastolic pressure.This raises pressures in the left atrium and in the pulmonary circulation.What is shown in the image of the lung?Passive congestion of the lung.The accumulation of blood in the lung can also be termed“passive hyperemia.”In the clinical setting of AMI,this is acute congestion.NOTE:A
24、t this point in the disease process while the alveoli are not filled with pulmonary edema fluid(e.g.,a transudate),the airways are certainly narrowed by the increased volume of blood in the lung that is not being“pumped out”because of heart failure.This contributes to shortness of breath(SOB).(Court
25、esy of S.Normann,MD,PhD)What is shown in this image of the lung in a person with longstanding cardiac failure?Chronic passive congestion of the lung.The alveolar capillaries are engorged with blood.Rupture of engorged capillaries has caused minute intra-alveolar hemorrhages(e.g.,bleeding into the al
26、veolus)and subsequent phagocytosis of hemoglobin breakdown products by macrophages.These cells are termed“hemosiderin-laden macrophages”that indicate that this process is chronic.(Courtesy of S.Normann,MD,PhD).What process is illustrated concerning platelets?(IEL=internal elastic lamina)Platelet adh
27、esion to damaged endothelium.VWF links the platelet to the underlying,exposed collagen.VWF attaches to GPIb on the platelet surface while also binding to exposed collagen.Blood vesselExpress your answer to your team mates.What process is illustrated concerning the interaction of one platelet to anot
28、her platelet?Platelet aggregation.Fibrinogen links platelets one to the other during aggregation via attachment to GPIIb/IIIa.When platelets first adhere to collagen exposed by endothelial damage,they become activated and GPIIb/IIIa is then able to bind fibrinogen to accomplish aggregation.Express y
29、our answer to your team mates.What process is illustrated concerning platelets?Left panel:scanning EM;right panel:transmission EMPlatelet aggregation.The many pseudopodia of the activated platelets are observed that intertwine to essentially form a syncytia.This reminds one of a type of biological“Velcro.”Express your answer to your team mates.What is the ultimate product of secondary and early tertiary hemostasis that serves to stabilize aggregated platelets?Cross-linked fibrin.THE END