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normal vessels maintain blood fluid, clot-free vessel injury induce rapid localized hemostatic plug
Hemostasis
Thrombosis
inappropriate activation of normal hemostatic processes
Endothelium
Normal: antithrombotic 1. Anticoagulant - heparin-like molecules thrombomodulin 2. Antiplatelet barrier between plt and ECM; PGI2, NO, ADPase 3. Fibrinolytic t-PA
Injured, activated: prothrombotic 1. Procoagulant tissue factor 2. Platelets - vWF 3. Antifibrinolytic - PAI
Virchow's
Thrombosis
Alteration of: 1. Vessel wall - endothelial injury - dominant 2. Blood flow- stasis, turbulence 3. Blood hypercoagulability may combine
1.
Vessel wall endothelial injury dominant exposure of subendothelial collagen + adherence of platelets exposure of tissue factor, local depletion of prostacyclin and plasminogen activator Atherosclerosis ulceration Necrosis myocardial infarction Trauma Inflammation vasculitis Hypertension, turbulent flow, bact. endotoxins Homocystein, cholesterol, radiation, smoking
3. Hypercoagulability
Any alteration of coagulation pathway predisposing to thrombosis Primary (genetic) Mutations in factor V = Leiden mutation 2-15% of popul. APC resistance antithrombin III, protein C, S deficiencies fibrinolysis def., hyperhomocysteinemia prothrombin levels - 1%, allelic variations Thrombo(embolism) recurrent, young, no or insignificant other causes Secondary (acquired) - high risk or low risk
3. Hypercoagulability
Secondary (acquired) High risk of thrombosis -immobilization, myoc. infarction, tissue damage (trauma, burns, surgery), cancer, prosthetic cardiac valves, DIC, heparin-induced thrombocytopenia, antiphospholipid antibody syndrome (with/out autoimmune dis. - SLE) Lower risk of thrombosis -atrial fibrillation, cardiomyopathy, nephrotic syndrome, hyperestrogenic states, oral contraceptives (3x), pregnancy (8x), sickle cell anemia, smoking
Thrombotic diathesis - often complicated, multifactorial
Thrombi - overview of morphology, localisation relationship to the vessel wall, lumen mural OR occlusive; line of attachment localization anywhere - heart (chambers, valves), arteries, veins, capillaries sizes, shapes, components (colours) red, white, mixed (coral), hyaline mechanism arteries, heart: endothelial injury, turbulence veins: stasis
Thrombi
Localization - detailed Arterial occlusive; mixed coronary, cerebral, femoral atherosclerosis, vasculitis, trauma Venous occlusive, long cast; red; 90% legs autopsy dif. dg. postmortem clot Heart valves vegetations infective or sterile (rheum., NBTE, SLE) Heart chambers, aneurysms of heart or aorta Mural; infarction; embolisation: brain, kidney, spleen
Embolism
a detached intravascular mass - solid, liquid, gaseous carried by the blood to a site distant from its origin Thrombus 99% Fat Gas Fluid amniotic; Atherosclerotic debris, tumor fragments, foreign bodies
Pulmonary thromboembolism
SOURCE: DEEP LEG VEIN THROMBI ABOVE THE KNEE Clinical manifestation 1. Clin. silent (75%), organization, fibrous bridging web 2. Acute cor pulmonale sudden death (60% circ.) 3. Pulmonary hemorrhage/infarction 4. Pulmonary hypertension (multiple emb.) Saddle embolus Paradoxical embolism
Systemic thromboembolism
Emboli travelling in the syst. arterial circulation SOURCE: intracardiac mural thrombi (80%) aort. aneurysms, atherosclerotic plaques, valvular vegetations; paradoxical emboli RECIPIENTS: various legs (75%), brain (10%), intestines, kidneys, spleen, upper extr. CONSEQUENCES: collateral blood supply, tissue vulnerability to ischaemia, size of the occluded vessel MAINLY INFARCTION
Fat embolism
fractures of long bones, soft tissue trauma, burns 90% of people with severe skeletal injuries only 10% symptomatic
sudden onset: tachypnea, dyspnea, tachycardia, neurol. symptoms, petechiae; (thrombo, ery ) mechanical and biochemical injury may be lethal
HISTOLOGICAL DIAGNOSIS
Air embolism
Gas bubbles Obstetric procedures Dural venous sinuses Neck, chest wall trauma
Decompression sickness - nitrogen bubbles focal ischemia: muscles, joints bends; brain, heart; lungs - RDS (chokes) treatment: compression chamber Chronic decompression sickness caisson disease persistence of gas emboli multiple foci of ischemic necrosis(heads of femur, tibia, humerus)
SHOCK
Systemic hypoperfusion caused by reduction of cardiac output effective circulating blood volume hypotension, hypoperfusion, hypoxia Cellular injury: first reversible if persistence of shock - irreversible
SHOCK
1. Cardiogenic pump failure (intrinsic myoc. cause IM, ventr. arrhytmias, extrinsic compression tamponade, outflow obstr.- emb.) 2. Hypovolemic - loss of blood or plasma (hemorrhage, burns, trauma) 3. Septic systemic microbial infection (G- endotoxic, G+, fungal) 4. Neurogenic spinal cord injury - VSD 5. Anaphylactic gener. IgE-med. response, VSD, vascular permeability vascular bed capacitance
Stages of shock
1. Nonprogressive neurohumoral compensatory mechanisms, vital organ perfusion 2. Progressive tissue hypoperfusion, anaerobic glycolysis, lactate acidosis, VSD, cardiac output, anoxic injury of endothelium, DIC risk; vital organs begin to fail 3. Irreversible lysosomal enzyme leakage
Morphology of shock
Hypoxic injury, multiple organ systems
Brain - ischemic encephalopathy Heart - coagulation necrosis, hemorrhage Kidneys - acute tubular necrosis Lungs - shock lung (normally resistant to hypoxia) Adrenals - cortical lipid depletion GIT - hemorrhages and necroses Liver - fatty change, central hemorrhagic necrosis
DIC
Thrombotic and hemorrhagic diathesis
Consequences Microthrombi infarctions
hemorrhages
DIC
1. obstetrics 50%; abruptio placentae, retained dead fetus, septic abortion, amniotic fluid embolism, toxemia 2. neoplasms 30%; adenocarcinomas, AML 3. infections gram-negative sepsis 4. trauma, burns, extensive surgery 5. other snakebite, heat stroke, giant hemangioma, aortic aneurysm etc.
DIC
Morphology kidneys lungs brain adrenals placenta microthrombi hemorrhages
CLIN.: microangiopathic hemol. anemia, RDS, neurologic sympt., oliguria, ac. ren. and circul. failure, SHOCK
Thrombotic microangiopathies thrombotic thrombocytopenic purpura (TTP) hemolytic-uremic syndrome (HUS) Versus Disseminated intravascular coagulation Common: hyaline thrombi !!Differences: DIC: primary importance:
Thrombotic microangiopathies
related clinical syndromes thrombotic thrombocytopenic purpura (TTP) hemolytic-uremic syndrome (HUS) ENDOTHELIAL INJURY WIDESPREAD HYALINE MICROTHROMBI OVERLAP - common features (TTP, HUS): thrombocytopenia microangiopathic hemolytic anemia fever
Thrombotic microangiopathies
TTP HUS