B8 - Thrombosis, Embolism and Tissue Infarction Flashcards
abnormal clotting can lead to ischaemia infarction
- Most vascular disease is the result of narrowing or blockage of the lumen of a hollow tube
○ Blockage may lead to leakage somewhere else- This results in tissues being deprives of oxygen and nutrients (especially glucose)
- It also results in the build up of toxic metabolites that can cause damage and cell death
- Pro coagulant: platelets, clotting factors, VWF, fibrinogen etc.
- Anti coagulant: protein S, protein C, anti thrombin 2, fibrinolytic cascade
Blood clot formation
○ Initiating event/endothelial injury ○ Platelet plug ○ Coagulation § Activation of clotting factors § Formation of fibrin ○ Fibrinolysis § Plasminogen from liver is in circulation § Activated to form plasmin (enzymes) § Plasmin cleaves fibrin
- Oxygen deprivation
○ Ischaemia (reduced blood flow)
§ May have normal O2 content
□ Don’t confuse it with hypoxia (low oxygen in blood)
§ Usually due to obstruction of the blood vessel
□ Thrombosis, embolus, microvascular disease etc.
○ An infarct is an area of ischaemic necrosis caused by occlusion of the vascular supply to the affected tissue
§ Infarction is the process that leads to an infarct
§ Usually due to an arterial occlusion
□ Causes include thrombus, embolus, vasospasm, expansion of atherosclerotic plaque, torsion or compression of vessels, trauma/physical disruption of vessels, vasculitis
§ Less commonly due to increase pressure in surrounding tissues e.g. sever oedema, venous congestion
thrombosis
- Inappropriate formation of a blood clot within a vessel
- Impact of thrombus depends on site, size, type of vessel
- Thrombus in coronary artery, one cause of myocardial infarction
- Thrombus in cerebral venous sinuses of brain (failure of venous drainage, congestion, increased pressure, cerebral infarction, stroke)
- Thrombus in dilated anal venous plexus (haemorrhoid), pain, usu. No serious sequalae
- Virchow’s triad
virchow’s triad - endothelial injury
§ Required to begin the process
§ Direct physical injury
§ Chemical/metabolic abnormality (hypercholesterolaemia, homocysteinaemia, tobacco, drugs, etc.) - more common reason
□ Cholesterol irritates vessel walls
□ Tobacco increases likelihood of endothelial injury
§ Atherosclerosis
□ Fatty plaques building up on the walls of blood vessels
§ Infection
□ Eg. Meningitis
□ Cause of the rash that doesn’t go way
§ Chronic inflammation
§ Leads to
□ Activation of endothelial cells - changes in gene and proteins expression towards pro-coagulant state
® Downregulation in thrombomodulin and subsequent overactivity of thrombin
® Inflammation of endothelium downregulates protein C and other anticoagulant proteins
® Antifibrinolytic effects - plasminogen inhibitors, decreased production of t-PA
□ Activation of platelets
§ Major contributor to thrombosis in high flow/high pressure environment (e.g. heart and aorta)
virchow’s triad - abnormal blood flow
§ Normal blood flow is laminar
§ Cells tend to flow in the centre of the lumen
§ Plasma tends to flow at the periphery and is slower moving
§ turbulent flow
□ Disrupts laminar flow, brings platelets into contact with the vessel wall
□ Creates counter-currents, pockets of increased shear stress on walls (endothelial injury), pockets of relative stasis
§ Stasis
□ Blood flow slows down
□ Allows activation of clotting cascade, platelet aggregation and activation, fibrin aggregation
□ Keeps platelets and clotting factors in contact with vessel wall
□ Prevents washout/dilution of activated clotting factors by fresh flowing blood and prevents the inflow of clotting factor inhibitors
□ Myocardial infarction
® Heart muscle repairs by forming a scar
® Blood gets caught in the area where there is no muscle leading to stasis and clot formation
® Not made of muscle so it cant contract/relax
leads to ventricular aneurism
® Blood flowing through a ventricle - in the scarred area will flow more slowly because it isnt surrounded by muscle so it forms a clot
§ turbulent flow
□ Disrupts laminar flow, brings platelets into contact with the vessel wall
□ Creates counter-currents, pockets of increased shear stress on walls (endothelial injury), pockets of relative stasis
§ Stasis
□ Blood flow slows down
□ Allows activation of clotting cascade, platelet aggregation and activation, fibrin aggregation
□ Keeps platelets and clotting factors in contact with vessel wall
□ Prevents washout/dilution of activated clotting factors by fresh flowing blood and prevents the inflow of clotting factor inhibitors
□ Myocardial infarction
® Heart muscle repairs by forming a scar
® Blood gets caught in the area where there is no muscle leading to stasis and clot formation
® Not made of muscle so it cant contract/relax
leads to ventricular aneurism
® Blood flowing through a ventricle - in the scarred area will flow more slowly because it isnt surrounded by muscle so it forms a clot
□ Myocardial infarction
® Heart muscle repairs by forming a scar
® Blood gets caught in the area where there is no muscle leading to stasis and clot formation
® Not made of muscle so it cant contract/relax
leads to ventricular aneurism
® Blood flowing through a ventricle - in the scarred area will flow more slowly because it isnt surrounded by muscle so it forms a clot
virchow’s triad - hypercoagulibility
§ Hypercoagulability (also called thrombophilia) - altered coagulation
§ Any disorder of the blood that predisposes to thrombosis
primary hypercoagulability
□ Factor V
® 2-15% of causasians carry a single nucleotide variation in factor V called factpr V leiden
® Loss of antithrombotic counterregulatory pathways
® Heterozygotes have a 5x increased risk of venous thrombosis, and homozygotes have a 50x increase
□ Prothrombin
® 1-2% of the population carry a single nucleotide variation (G20210A) in the prothrombin gene
® Don’t form prothrombin properly
® Leads to elevated prothrombin levels and a 3x increased risk of venous thrombosis
Factor V leiden mutation causing hypepercoagulability
® 2-15% of causasians carry a single nucleotide variation in factor V called factpr V leiden
® Loss of antithrombotic counterregulatory pathways
® Heterozygotes have a 5x increased risk of venous thrombosis, and homozygotes have a 50x increase
prothrombin mutation causing hypercoagulability
® 1-2% of the population carry a single nucleotide variation (G20210A) in the prothrombin gene
® Don’t form prothrombin properly
® Leads to elevated prothrombin levels and a 3x increased risk of venous thrombosis
§ Secondary - acquired (more common) causes of hypercoagulabilitu
□ Immobilisation - venous part of the circulation doesn’t move as effectively
□ Major trauma - triggers hypercoagulable state
® Increase of likelihood of creating a thrombus because activated coagulating proteins are circulating
□ Malignancy
□ DIC: breakdown of cell membrane of some bacteria in septicaemia leads to consumptions of clotting factors (consumptive coagulopathy) which results is paradoxical clotting and bleeding simultaneously
□ Drugs eg. Oral contraceptive pill
□ Many others
Characteristics of thrombi
○ Thrombi are attached to the vessel surface and tend to propagate toward the heart, and may detach
§ Tend to pick up more cells - grow
§ Take longer to dissolve than to form
○ Thrombi may have laminations called lines of zahn
§ Platelet and fibrin layers alternating with darker red cell-rich layers
§ Only seen In flowing blood - can distinguish antemortem thrombosis from non-laminated clots that form in postpartum state
§ Higher flow = more prominent laminations (i.e. arterial > venous)
§ Must have formed when the person was still alive - formed in flowing blood
§ Tend to happen more with high flow
○ Large thrombi attached to wall of heart or aorta termed mural (meaning wall) thrombi
○ Arterial or cardiac thrombi typically arise at sites of endothelial injury or turbulence
§ Tend to be platelet rich (injury triggers platelet activation) often occlusive and more likely to have lines of zahn
○ Venous thrombi characteristically occur at sites of stasis
§ Can form a long cast within the lumen
§ Tend to contain more enmeshed red cells, fewer platelets, less often have lines of zahn
§ Deep veins of the lower extremities most commonly affected (90% of venous thromboses)
§ Can occur in the upper extremities, periprostatic plexus, or ovarian and periuterine veins, and under special circumstances they may be found in the dural sinuses, portal vein, or hepatic vein
