03血液循环

nullChapter 3：Haemodynamic DisordersChapter 3：Haemodynamic DisordersDepartment of Pathology School of Basic Medical Sciences Southern Medical University Ding YanqingnullSection 1 Hyperemia & CongestionnullDefinition: Increased blood in an area compared to normal normalischemia hyperemiacongestionHyperemiaHyperemiaHyperemia is an active process resulting from augmented tissue inflow due to arteriolar dilation . It’s always a physiological state or is good for body. e.g. skeletal muscle during exercise, in stomach replete with food, and inflammation. Pathological changes Pathological changes Gross: The affected tissue are redder, warm, swelling. Hyperemia in PneumoniaHyperemia in PneumoniaHyperemiaInfection (Pneumonia)Pathological changes – microscope nullCongestion is a passive process resulting from impaired outflow from a tissue. Systemic congestion: in heart failure. Local congestion: isolated venous obstruction. CongestionPathological changes Gross: The affected tissue are blue-red color (cyanosis), edema, hemorrhage and degeneration or death of parenchyma. Congestion and edema are commonly occur together.Pathological changes nullLocal increased volume of blood in a particular tissuenullLong standing (chronic) congestion Chronic hypoxia leads to degeneration, death, fibrosis. Capillary rupture leads to accumulation of red cell debris in the macrophages.Congestion of capillary bed  edemaChronic HypoxiaCapillary RuptureMajor organs affectedMajor organs affectedSubcutaneous tissues Organs Liver Spleen Lung Cavities Hydrothorax Hydropericardium AscitesPulmonary congestionPulmonary congestionCauses: left heart failure • Etiology of heart failure: includes myocardial damage associated with valvular, coronary arterial, or intrinsic myocardial injury • Other causes: include blood loss and peripheral vasodilatation (shock) pathological changespathological changes Acute pulmonary congestion Alveolar capillaries filled with blood Maybe associated septal edema / intra-alveolar hemorrhagenullAcute pulmonary congestion• Heavy wet lungs • Deep red • Ooze bloody fluid on sectioning deeper redAcute pulmonary congestionAcute pulmonary congestionFoamy fluid effusion Ooze bloody fluid on sectioning Acute pulmonary congestionAcute pulmonary congestionAlveolar capillaries filled with blood, intra-alveolar edema fluidAcute pulmonary congestionAcute pulmonary congestion•Dilated blood vessels containing abundant RBC’s •Protein-rich edema fluid may also be present (pulmonary edema) •intra-alverolar hemorrhagenull chronic pulmonary congestion Septa thickens and fibrosed Alveolar spaces contain haemosiderin laden macrophages ) —— Heart Failure Cells Gross: enlarge, heavy, firm dark red (fixed by formalin) or rusty discoloration Chronic congestion of lungChronic congestion of lung• The septa became thickened and fibrotic • Scattered RBC’s may be found in the alveoli • Hemosiderin-laden macrophages (heart failure cells) in the alveoli •congested capillaries in alveolar septumHemosiderin-laden macrophagesCongestion and fibrous thickening of alveolar septumLiver congestionLiver congestionCauses: right heart failure Any disease that results in right heart failure can cause chronic passive congestion of the liver.Chronic Passive CongestionChronic Passive CongestionRight heart failure results in delayed emptying of the great veins and retention of blood primarily in the central veins of the liver. This results in dilatation of central veins and pooling of blood in the sinusoids towards the center of the liver lobule. Pathological changesPathological changesAcute liver congestion Central vein, sinusoids: distended with blood Central hepatocyte degenerationnullChronic liver congestion Gross: central regions red brown and depressed; surrounding uncongested liver :nutmeg liver Micro: centrilobular necrosis with periportal fatty change Dead cells replaced by fibrosis cardiac cirrhosisHepatic congestion (Nutmeg liver)Hepatic congestion (Nutmeg liver)Causes: right heart failure• slightly enlarged • capsule is tense and smooth, • color are dark red and yellow • somewhat soft. nullNutmeg liver: on cut surface, it resembles a bisected nutmegHow is the nutmeg-like apprearance formed?nullNutmeg-like appearance on cut section is produced by a combination of dilated, congested central veins and the surrounding brownish-yellow, often fatty liver cells.Chronic liver congestionChronic liver congestion• Dilated of the central vein full of blood • Congestion of the sinusoids in the central part of the hepatic lobular • Atrophy of hepetocytes of the central zone of lobule • Fatty degeneration in hepatocytes in midzone of lobule • Sometimes, there are necrosis and hemorrhage in the central labularnull necrosis of the central zone of the liver lobularnecrosissummarysummaryDefinition: Increased blood in an area compared to normal. Hyperemia is an active process resulting from augmented tissue inflow due to arteriolar dilation . Congestion is a passive process resulting from impaired outflow from a tissue. Major organs affected of congestion are lung and liver. Pathological changes: The affected tissue are blue-red color (cyanosis), edema, hemorrhage and degeneration or death of parenchyma.Section 3 Section 3 Haemodynamic DisordersTHROMBOSISThrombosisThrombosisDefinition: Thrombosis is the pathologic formation of a solid mass （blood clot） from the constituents of blood within the non-interrupted heart or vascular system in a living organism. Thrombus —The mass itself is termed thrombus. Hemostasis & ThrombosisHemostasis & ThrombosisHemostasis is the normal, rapid formation of a localized “plug” at the site of vascular injury. Normal —blood flows without clotting Injury —blood clots This works due to a constant interaction between the vascular wall, platelets and the coagulation cascadeNormal endotheliumNormal endothelium Endothelial cells modulate several aspects of normal hemostasis. The balance between endothelial anti- and prothrombotic activities determines whether thrombus formation, propagation, or dissolution occurs. Antithrombotic Properties Antiplatelet Anticoagulant Fibrinolytic effects Prothrombotic Properties Platelet effects Procoagulant AntifibrinolyticPLATELETSPLATELETSPlatelets play a critical role in normal hemostasis. After vascular injury, platelets encounter ECM constituents and additional proteins (vWF being critical). Upon contact with these proteins, platelets undergo three reactions: (1) adhesion and shape change, (2) secretion (release reaction), (3) aggregation Sequence of platelet eventsnullSubendotheliumPlatelet adhesion and aggregation Cited 《Robbins Basic Pathology》1. Endothelial Injury1. Endothelial InjuryThis is a dominant influence, since endothelial loss by itself can lead to thrombosis. It is particularly important for thrombus formation occurring in the heart or in the arterial circulation. Platelet Aggregation Platelet Aggregation Endothelial injury exposes the underlying basement membrane ECM; platelets adhere to the ECM and become activated by binding to vWF through GpIb platelet receptors. Upon activation, platelets secrete granule products that include calcium and ADP. Activated platelets also synthesize TXA2. Activated platelets expose phospholipid complexes that provide an important surface for coagulation-protein activation. Released ADP stimulates formation of a primary hemostatic plug by activating platelet GpIIb-IIIa receptors that in turn facilitate fibrinogen binding and cross-linking. The formation of the definitive secondary hemostatic plug requires the activation of thrombin to cleave fibrinogen and form polymerized fibrin via the coagulation cascade. COAGULATION CASCADECOAGULATION CASCADEProenzymes - Enzymes - Thrombin formation Fibrinogen – Fibrin Fibrinolytic cascade – Plasmin Fibrin – FDP Coagulation FactorsCoagulation Factors Coagulation occurs via the sequential enzymatic conversion of a cascade of circulating and locally synthesized proteins. Tissue factor elaborated at sites of injury is the most important initiator of the coagulation cascade; at the final stage of coagulation, thrombin converts fibrinogen into insoluble fibrin, which helps to form the definitive hemostatic plug. Coagulation is normally constrained to sites of vascular injury by: 1. Limiting enzymatic activation to phospholipid complexes provided by activated platelets; 2. Natural anticoagulants elaborated at sites of endothelial injury or during activation of the coagulation cascade 3. Induction of fibrinolytic pathways involving plasmin through the activities of various PAs Factors in thrombosisFactors in thrombosisThree major influences predispose to thrombosis Endothelial damage Alterations in normal blood flow HypercoagulabilityVirchow triad in thrombosisinjure to endotheliuminjure to endothelium Injury to endothelium lead to: Exposes subendothelial ECM Leads to adhesion of platelets Release of tissue factor Local depletion of PGI2 and plasminogen activators Common place of injure to endotheliumCommon place of injure to endotheliumSites of myocardial infarction Ulcer plaques of atherosclerosis Cardiac surgery Infections of myocardium Inflammatory or prosthetic valves Dysfunctional endothelium Dysfunctional endothelium Note: endothelium need not be denuded or physically disrupted to contribute to the development of thrombosis; any perturbation in the dynamic balance of the prothrombotic and antithrombotic activities of endothelium can influence local clotting events Significant endothelial dysfunction : Hypertension (Haemodynamic stress) Turbulent flow over scarred valves Bacterial endotoxins Even relatively subtle influences (e.g. homocystinuria, hypercholesterolemia, radiation, or products absorbed from cigarette smoke) 2. ALTERATION IN NORMAL BLOOD FLOW2. ALTERATION IN NORMAL BLOOD FLOWNormal axial flow of blood - LAMINAR FLOW Turbulence → arterial and cardiac thrombi Stasis → venous thrombi schematic diagram of laminar flow axial flowvessel wall ALTERATION IN NORMAL BLOOD FLOWALTERATION IN NORMAL BLOOD FLOWdisrupted laminar flow brings platelets into contact with endothelium prevents dilution by fresh flow of blood and hepatic clearance of activated coagulation factors retards inflow of inhibitors of clotting factors Promotes endothelial cell activation Turbulence and stasis lead to thrombosisTurbulence and stasis lead to thrombosisclinical settings: -ulcerated atherosclerotic plaques -aneurysms -myocardial infarction -healed rheumatic mitral stenosis -atrial fibrillation and arrhythmias -sickle cell anaemia 3. Hypercoagulability 3. Hypercoagulability generally contributes less frequently to thrombotic states but is nevertheless an important component in the equation Hypercoagulable statesHypercoagulable statesPrimary (Genetic) Common   Mutation in factor V gene (factor V Leiden)   Mutation in prothrombin gene   Mutation in methyltetrahydrofolate gene Rare   Antithrombin III deficiency   Protein C deficiency   Protein S deficiency Very rare   Fibrinolysis defectsSecondary (Acquired) High risk for thrombosis   Prolonged bedrest or immobilization   Myocardial infarction   Atrial fibrillation   Tissue damage   Cancer   Prosthetic cardiac valves   DIC Heparin-induced thrombocytopenia   Antiphospholipid antibody syndrome Lower risk for thrombosis   Cardiomyopathy   Nephrotic syndrome   Hyperestrogenic states (pregnancy)   Oral contraceptive use   Sickle cell anemia   Smoking Types and Morphology of thrombus: Can occur anywhere in the CVS Cardiac chambers Valve cusps Arteries Veins Capillaries *The size and shape of a thrombus depend on the site of origin and the cause. * An area of attachment to underlying vessel or heart wall Types and Morphology of thrombus:ARTERIAL THROMBIARTERIAL THROMBIAt sites of turbulence / damaged endothelium Usually occlusive. Grow in retrograde fashion from point of attachment - Site / order of frequency: Coronary - Cerebral - Femoral Superimposed on damaged endothelium Firmly adherent to injured arterial wall Gray white friable, tangled mass of platelets and fibrin, RBCs and degenerating WBCsnullThrombus in coronary arterynullThrombus in coronary arteryMixed ThrombusMixed ThrombusMass (a friable meshwork ) of platelets and fibrin, RBCs and degenerating WBCslines of Zahnlines of ZahnThrombi(mixed) apparences laminations called lines of Zahn that in grossly (and microscopically); these represent pale platelet and fibrin layers alternating with darker erythrocyte-rich layers. Such lines are significant only in that they represent thrombosis in the setting of flowing blood; their presence can therefore potentially distinguish antemortem thrombosis from the bland nonlaminated clots that occur in the postmortem state. LayeringLayeringnullpale platelet and fibrin layersdarker erythrocyte-rich layersmural thrombimural thrombiOccurring in heart chambers or in the aortic lumen. they usually adhere to the wall of the underlying structure. 1.Abnormal myocardial contraction (e.g. arrhythmias, dilated cardiomyopathy, or myocardial infarction) 2.Endomyocardial injury (e.g. myocarditis, catheter trauma) 3.ulcerated atherosclerotic plaques and aneurysmal dilation. nullMural ThrombusCardiac Mural ThrombusCardiac Mural ThrombusnullLaminated thrombus in a dilated abdominal aortic aneurysm abdominal aortaVENOUS THROMBI (Phlebothrombosis)VENOUS THROMBI (Phlebothrombosis)At sites of stasis Almost invariably occlusive Extend in the direction of blood flow Often creates a long cast of vein lumen More RBCs, hence called red / stasis thrombi Most common site: veins of lower extremities(90%) Less common sites: upper extremities, periprostatic plexus, ovarian and periuterine veinsRed /stasis thrombusRed /stasis thrombusConstitution: large numbers erythrocytes, platelets, fibrin. Location: venous system. at the end part of venous thrombus. Gross: dark red, moist, elastic (fresh) VEGETATIONSVEGETATIONS Thrombotic masses on valves are called vegetations Infective endocarditis Non-bacterial thrombotic endocarditis Libman-Sacks endocarditis (SLE) nullVegetations ( Pale thrombus) Constitution: fibrin, platelets, few entrapped erythrocytes. Location: arteria, cardiac valves and the initiative part of venous thrombus. Morphological changes: gray-white, friable, firmly adherent to the wall,nullVegetations on the mitral valve in rheumatic endocarditis. Note the small pink vegetations along the line of closure. These thrombi are made of platelets. left atriumleft ventriclemitral valvevegetationsvegetations (Pale thrombus)vegetations (Pale thrombus)A) The histology consists of homogeneous sheets of fibrin without any inflammatory response. B) Organization of the thrombus by an in growth of fibroblasts may be seen, Fibrin thrombus( Microthrombus)Fibrin thrombus( Microthrombus) Constitution: fibrin Location: micro-circulation in DIC. Especially in capillaries of kidney, lung, brain and liver FATE OF THROMBIFATE OF THROMBIPropagation Embolization Dissolution Organisation and RecanalisationThrombus Propagated into the Inferior Vena CavaThrombus Propagated into the Inferior Vena CavanullOrganisationRecanalisationOrganization and recanalization of thrombusOrganization and recanalization of thrombus Mixture of red blood cells, platelets and fibrin Over a few days capillaries, smooth muscle cells and fibroblasts grow into the embolus from the vessel wall Surface of the embolus will become endothelialized Recanalization may occur EFFECTS OF THROMBUSEFFECTS OF THROMBUSArterial: - Atherosclerosis is a major initiator - infarction of dependent parts - myocardial infarction, cerebral infarction Venous: - associated with stasis - infarction rare due to collateral bypass channels - local pain and distal edema - embolisation to lungs, causing death ARTERIAL v/s VENOUS THROMBUSARTERIAL v/s VENOUS THROMBUSAt sites of turbulence / damaged endothelium Usually occlusive Grow in retrograde fashion from point of attachment Site / order of frequency: Coronary - Cerebral - Femoral Gray white friable, tangled mass of platelets and fibrin, RBCs and degenerating WBCs At sites of stasis Almost invariably occlusive Extend in the direction of blood flow Most common : veins of lower extremities Less common : upper extremities, periprostatic plexus, ovarian and periuterine veins More RBCs, hence called red / stasis thrombiSUMMARY: Thrombosis SUMMARY: Thrombosis 1.Thrombus development depends on the relative contribution of the components of Virchow's triad: Endothelial injury; Abnormal blood flow; Hypercoagulability (primary or secondary) 2.Thrombi may propagate, resolve, organization, or embolize. 3.Thrombosis causes tissue injury by local vascular occlusion or by distal embolization. Haemodynamic DisordersHaemodynamic DisordersSection 4 embolismDefinitionDefinitionDetached, intravascular, solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin Types of emboliTypes of emboliThromboembolism(99%) Bubbles of air / nitrogen gas (decompression sickness) Droplets of fat Bone marrow Atheromatous (cholesterol) Amniotic fluid Tumor fragments Foreign bodies(such as bullets)Gas embolismFat embolismThromboembolismThromboembolismnullAn embolism is usually thrombotic unless otherwise specified hence the term thromboembolismAn embolism is usually thrombotic unless otherwise specified hence the term thromboembolismnullIschemic necrosis (infarction) of downstream tissue. Emboli may lodge anywhere in the vascular tree; the clinical outcomes are best understood from the standpoint of whether emboli lodge in the pulmonary or systemic circulations. The consequences of thromboembolismOrigin of emboliOrigin of emboliOrigin in systemic vein and right heart → pulmonary embolism → infarction, death, or no any clinical symptom. Origin in left heart and systemic arteries → distal systemic arteries embolism → infarction.Pulmonary embolismPulmonary embolismThe emboli originate in systemic veins and right heart Over 95% of pulmonary thrombi come from the deep leg vein above the level of the knee The most serious form of thromboembolism Clinical effect:Clinical effect:Majority – clinically silent (60-80%), undergo organization If > 60% of pulmonary circulation is obstructed → SUDDEN DEATH, right heart failure (RHF) Main pulmonary trunk Saddle emboli Smaller branches Small multiple emboli PULMONARY THROMBOEMBOLISMPULMONARY THROMBOEMBOLISM If Main pulmonary trunk(massive emboli) → sudden death If medium sized vessels : usually congestion (haemorrhage), no infarction If small end: infarction Multiple emboli : pulmonary hypertension with right ventricular failure Pulmonary thromboembolismPulmonary thromboembolismnullnullnullCauses of Pulmonary thromboembolism cardiac diseases cancer prolonged immobilization Hypercoagulable statesnullClinical significance depends on Extent of emboli Number of emboli Circulatory state nullFATE OF EMBOLI may resolve by fibrinolysis unresolved pulmonary hypertension pulmonary vascular sclerosis chronic cor pulmonale 30 % chance of developing second emboli null Prophylaxis: Elevation Elastic bandage Early ambulation Embolectomy UMBRELLA filter in inferior vena cava Thrombolysis followed by anti coagulation with monitoring SYSTEMIC EMBOLISMSYSTEMIC EMBOLISMEmbolism in arterial circulation. SOURCE : 80 % ～ 85 % from intracardia