Pathophysiology: Hemodynamics: Thrombosis, Embolism, and Infarction

Hemostasis and Thrombosis

Hemostasis: Normal physiologic process, Two main functions

Thrombosis: innapropraite activation of normal hemostatic processes in unijured vasculature. THrombotic occlusion of a blood cessel after minor injury

Sequence of Events in Normal Hemostasis

Vascular injury

Vasoconstriction

Primary hemostasis

Secondary hemostasis

Tertiary hemostasis

Guards against inappropriate clot formation

Normal vascular endothelium has smooth layer of endothelial cells- nitric oxide, prostacyclin, thrombomodulin

Normal blood flow is streamlined

Clotting mechanism has checks and balances to control clot formation

Influences in thrombus formation

Endothelial injury/abnormality in vessel lining and wall

Stasis or turbulence of blood flow

Blood hypercoagulability

Endothelial injury as a cause of thrombosis

Dominant influence of thrombus formation in heart and arterial circulation is due to disease in the lining and wall of the artery

Venous circulation: Thrombosis via diminished flow of blood (stasis)

Veins are thin-walled

Predisposes vascular lumen to thrombus formation by three mechanisms

• Exposure of platelets to subendothelial collagen

• Release of tissue factor

• Anti-thrombotics depleted at site of injury

Stasis and turbulence as causes of thrombosis

Turbulence:

Direct cause of endothelial injury

Formation of counter-currents

Formation of local pockets of stasis

Aneurysm can cause abnormal blood flow patterns: outpouching or dilation of the wall of a blood vessel caused by weakening of the vessel wall

Effects of turbulence or stasis: Disruption of laminar flow, Prevents dilution of activated coagulation factors, Slow influx of clotting factor inhibitors, Continued endothelial cell activation

Venous stasis: Long periods of immobility, Heart failure, Atrial fibrillation

Clinical settings leading to turbulence or stasis: Atherosclerotic plaque, Aneurysm, Myocardial infarction, Mitral valve stenosis (narrowing)

Hypercoagulability as a cause of thrombosis

Hypercoagulability:Abnormally heightened coagulation response to vascular injury

Primary or secondary

Factor V Leiden, most common. Mutation of the factor 5 gene

Proteins C & S : Thrombin activates thrombomodulin, This complex activates the Protein C zymogen, Activated Protein C (APC) binds with Protein S, Protein C-S complex inactivates Va & VIIIa

Proteins C & S require NORMAL Factor V: Inactivates Va at the arginine residue at position 506, FVL – arginine is substituted with glutamine.

Stays active for longer so more clot formation

Secondary (acquired): Heparin-induced thrombocytopenia, Administration of heparin can induce antibody formation against heparin/platelet factor 4 complex

Thrombus morphology

Consist of varying amounts of: Platelets, fibrin, RBCs, WBCs

Precise morphology is dependent upon the conditions under which it formed

Fate of thrombus

Dissolution, Organization and recanalization, Propagation, Embolization

Embolism

Detached intravascular mass that is carried by blood to a site distant from point of origin with lodgment in a new location

Embolus= the physical mass

Examples: Dislodged thrombus (thromboemboli), Fat, Air

99% is due to dislodged clot

Thromboembolism

Pulmonary thromboembolism

Origin- deep leg vein

Major portion of pulmonary arterial supply occluded

Effects: Clinically asymptomatic, Sudden death, Infarction

Systemic Thromboembolism

Arterial circulation

Origin : Intracardiac mural thrombosis (80%), Aortic aneurysm, Atherosclerotic plaques, Fragmentation of valvular vegetation

Destinations: Lower extremity (75%), Brain (10%), stroke, MI

Causes of Pulmonary Embolism

Age, Heart failure, Atrial fibrillation, Long-term immobility, Obesity, Pregnancy, Recent surgery

Infarction

Area of ischemic necrosis caused by occlusion of either arterial supply or venous drainage in tissue

Thrombotic/embolitic events

Inflammatory reaction at interface with viable tissue

Neutrophils and macrophages clean up the area

Outcome: scar tissue

Factors influencing development of an infarction: Nature of the vascular supply, Rate of development of occlusion, Vulnerability of a tissue to hypoxia, O2 content of blood

Stages in Acute Myocardial Infarction

Ischemia

Injury

Infarction

Atherosclerosis

‘Hardening of the arteries’

Aorta, its large branches, medium sized arteries supplying areas of the extremities, brain, heart, major internal viscera

Atheroma – atherosclerotic plaque

Elevated mass of fatty material

Fibrous connective tissue

Secondary deposits of Ca2+ salts and blood products

Begins in the inner layer of vessel wall and projects into the lumen

Macrophages release growth factor

Etiology: Genetics, Elevated serum cholesterol levels (LDL), Diabetes, Hypertension, Cigarette smoking

Consequences: Compete occlusion of artery, Thrombosis, Aneurysm