Thrombosis in Body
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Transcript of Thrombosis in Body
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NORMAL HEMOSTASIS
After injury and vessel rupture Brief period of vasoconstriction(reflex neurogenic
mechanism at the arteriole level).
Attraction of plateletsto site of ruptureattracted by the
exposed subendothelial extracellular matrix. Activation of the coagulation system(by tissue factor and
secreted platelet factors); The activated coagulation systemproduces polymerized fibrin.
Adherent platelets + aggregated fibrin + entrapped bloodcells form a hemostatic plug.
Counterregulatory mechanisms are activated to limitpropagation of the hemostatic plug to the injury site.
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HemostasisA protective processthat provides for the rapid generation of alocalized hemostatic plug at the site of a vascular injury - while
maintaining clot-free blood in normal vessels.Thrombosis
An inappropriate activation of the hemostaticprocessleading tothe formation of a clot (thrombus)inside a blood vessels
during life, obstructing the flow of blood through the circulatorysystem.apathologic process
. Thromboembolismis a general term describing both
thrombosis and its main complication which is
embolisation.they are of variable size and shape ,depending
on causes.
http://en.wikipedia.org/wiki/Embolismhttp://en.wikipedia.org/wiki/Embolism -
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Thrombosis
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VESSEL WALL
COLLAGENTISSUE FACTOR
CLOTPLATELETS
INTRINSIC
PATHWAY EXTRINSIC
PATHWAY
COMMON PATHWAY
Fibrinogen FibrinThrombin
HEMOSTATIC SYSTEM
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Causes
Classically, thrombosis is caused by abnormalities inone or more of the following (Virchow's triad):
Changes in the composition of the blood favouringplatelet aggregation and fibrin formation
(hypercoagulablility). Quality of the vessel wall(endothelial damage or
altered endothelial function)eg.thrombi on endocardium , MI ,orulcerated atheromatous plaques in artery walls.bacterial toxin.
Nature of the blood flow (slowing and perturbation)
stasis as in polycythemia or aneurysms results in loss of laminar blood flow andallow platelets to adher to the endothelium also allow the local accumulation ofactivated coagulation factor.turbulence causes reduction in endothelial PGI2 and t-PA formation
http://en.wikipedia.org/wiki/Rudolf_Virchowhttp://en.wikipedia.org/wiki/Rudolf_Virchow -
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THROMBOSIS
Virchows TRIANGLEENDOTHELIAL
INJURY
ABNORMAL FLOW
(NON-LAMINAR)
HYPER-
COAGULATION
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ENDOTHELIAL INJURYany perturbation in the dynamic balance
of the pro- and antithrombotic effects ofendothelium, not only physical damage
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ENDOTHELIUM ANTI-Platelet PROPERTIES
Protection from the subendothelial ECM
Degrades ADP (inhib. Aggregation)
ANTI-Coagulant PROPERTIES Membrane HEPARIN-like molecules
Makes THROMBOMODULIN Protein-C TISSUE FACTOR PATHWAY INHIBITOR
FIBRINOLYTIC PROPERTIES (TPA)
PROTHROMBOTIC PROPERTIESMakes vWF, which binds
PlatsCollMakes TISSUE FACTOR (with plats
Makes Plasmino en inhibitors
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ABNORMAL FLOW
NON-LAMINARFLOW TURBULENCE EDDIES
STASIS
DISRUPTED ENDOTHELIUM
ALL of these factors may bring plateletsinto contact with endothelium and/orECF
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1HYPERCOAGULABILITY(INHERITED)
COMMONEST: Factor V and Prothrombindefects
Common: Mutation in prothrombin gene,Mutation in methyltetrahydrofolate gene
Rare: Antithrombin III deficiency, Protein C
deficiency, Protein S deficiency Very rare: Fibrinolysis defects
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2 HYPERCOAGULABILITY
(ACQUIRED)
Prolonged bed rest or immobilization
Myocardial infarction
Atrial fibrillation
Tissue damage (surgery, fracture, burns)
Cancer (TROUSSEAU syndrome, i.e., migratory thrombophlebitis)
Prosthetic cardiac valves
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia
Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)
Lower risk for thrombosis: Cardiomyopathy
Nephrotic syndrome
Hyperestrogenic states (pregnancy)
Oral contraceptive use
Sickle cell anemia Smokin Obesit
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ARTERIAL/CARDIAC THROMBI ACUTE MYOCARDIAL INFARCTION = OLD
ATHEROSCLEROSIS + FRESH THROMBOSIS ARTERIAL THROMBI also may send fragments
DOWNSTREAM, but these fragments may
contain flecks of PLAQUE also LODGING is PROPORTIONAL to the % of
cardiac output the organ receives, i.e., brain,
kidneys, spleen, legs, or the diameter of the
downstream vessel
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Atherosclerosis is characterized by intimal lesions calledatheromas, or atheromatousor fibrofatty plaques, that protrude
into and obstruct vascular lumina, weaken the underlying media,
and may undergo serious complications.
http://www.robbinspathology.com/content/lightbox.cfm?action=add&ImgID=F011007&ImgBody=graphics/S01871-011-f007.jpg&ID=iBoxhttp://www.robbinspathology.com/content/lightbox.cfm?action=add&ImgID=F011007&ImgBody=graphics/S01871-011-f007.jpg&ID=iBox -
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ATHEROSCLEROTIC PLAQUE
NORMAL ARTERY ATHEROSCLEROTIC
PLAQUE
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60% Narrowing of Coronary Artery
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90% Blockage of Coronary Artery
calcified arearemaining lumen
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Thrombus Causing MI
needle-like white spots are cholesterol crystals
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Atherosclerotic Plaque Histology
cholesterol crystal (cleft) foam cells
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Myocardial Infarction Histology
necrosed muscle cells red blood cells
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Myocardial Infarction Histology
normal muscle cells remaining macrophages and the
beginnings of scar tissue
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Type of thrombi (appearance)
White thrombi (pale) Arterial: blood flow
rapid,firm aggregate of plt, fibrin, fewWBC/RBC
Red thrombi :venous:; blood flow slower,soft
dark red: RBC trapped in fibrin mesh
Mixed: pale and red(laminated appearance)
ADHERENCE TO VESSEL WALLHEART (MURAL)
ARTERY (OCCLUSIVE/INFARCT)VEIN
OBSTRUCTIVE vs. NON-OBSTRUCTIVE
RED, YELLOW, GREY/WHITE
ACUTE, ORGANIZING, OLD
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Sequels of Block
Collateral circulation:
Ischemia,
Infarction,Gangrene
Haemorrhage
f
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Fate of thrombus
Spread (propagation)Accumulation of moreplatelets and fibrin, becoming larger
Detachment: to form embolus(embolization) Removal (dissolution)
1. shrinkage of thrombus by contraction
2.lysis by plasmin and proteolytic enz
3.organization-digestion by macrophageand ingrowth of fibrovascular ts.
4.endothelialization,incorporation into vessel
wall by growth of endothelum over its
surface Organization and recanalizationthrombi may induce inflamation and fibrosis(organization)and
may eventually recanalized or they may be incorporatedinto a thickened vascular wall.
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SCHEMATIC ON THE FATE OF A THROMBUS