Thrombosis/Embolism/Infarction/Shock Flashcards
Thrombus definition
Intravascular clot, often impeding or preventing blood flow
Thrombosis definition
Formation or presence of a thrombus
May result in infarction
Uncontrolled or pathologic stoppage of bleeding
What components make up Virchow’s triad?
Endothelial Injury
Alterations in blood flow
Hypercoagulability
Endothelial injury
Loss of endothelial cell barrier
Increased prothrombic activity caused by hemodynamic stress; hypertension, homocystinuria, hypercholesterolemia, radiation, cytokines, endotoxin
What types of alterations in blood flow can cause Thrombosis
Stasis
Turbulence
How does turbulence effect Thrombosis
Increases the chance for endothelial cell injury and activation
Can lead to a hypercoagulative state
How does stasis effect Thrombosis
Stasis disrupts laminar flow (platelets move to the periphery of the vessel) - this allows for a concentration of clotting factors and it activates endothelial cells
What are some inherited conditions that can increase Hypercoagulability?
Factor V Leiden mutation - favor Va cannot be degraded
ATIII deficiency
Prothrombin mutation
What are some acquired conditions that can increase Hypercoagulability?
Prolonged bed rest Extensive tissue injury Pregnancy Cancer Anti-phospholipid antibody syndrome
Where do Arterial Thrombi tend to occur?
Sites of turbulence or endothelial injury and loss
Emboli lodge in smaller arteries, often causing infarction
What does an Arterial Thrombi look like?
Pale white appearance
They have distinct Lines of Zahn
May be occlusive or mural
Venous Thrombi
Have a dark maroon color (“red”) and indistinct Lines of Zahn
Often form in the deep veins of the legs
What are the different Fates of Thrombi
Propagation
Embolization
Dissolution
Organization
Propagation of Thrombi
Enlarge by additional fibrin/platelet deposition
Embolization of Thrombi
Entire thrombus dislodges or a piece breaks loose
Dissolution of Thrombi
Lysis by fibrolytic activity
Organization of Thrombi
Ingrowth of fibroblasts and smooth muscle cells, leads to deposition of collagen (replacing the fibrin) and recanalization, which may reestablish some flow through the thrombus
Disseminated Intravascular Coagulation
Widespread activation of the coagulation cascade and fibrinolytic system leading to depletion of coagulation factors and platelets and accumulation of fibrin split products
This can be associated with widespread formation of microthrombi and risk of hemorrhage
What conditions are associated with Disseminated Intravascular Coagulation
Infection (especially gram-) Obstetric complications (placental abruption, retained dead fetus) Neoplasm Shock Massive Injury Others
Embolism definition
A solid, liquid, or gas carried from one point to another point in the vascular system
What is the origin of a pulmonary embolism?
Usually they arise from deep veins in the legs
Less frequently, they can originate from pelvic veins, right heart chambers, and others
What is the treatment for Disseminated Intravascular Coagulation?
Highly variable
Depends upon management of the underlying disorder
What is the most common embolus?
Dislodged thrombus material (Thromboembolism)
What are the clinical consequences of pulmonary thromboemboli?
- No clinical manifestation - small emboli cause no ischemia due to the double blood supply, bronchial and pulmonary arteries in the lungs
- Pulmonary hemorrhage and hematemesis due to ischemia injury without infarction
- Pulmonary infarction
- Sudden death - due to large emboli obstructing a large pulmonary artery or straddling the bifurcation of the pulmonary arterial trunk
- Pulmonary hypertension - gradual obstruction of many small pulmonary arteries by repeated embolization over time can result in pulmonary hypertension
Paradoxical embolus definition
Embolus that arises in a systemic vein and crosses a communication from the venous side to the arterial side of circulation
Where is the communication that leads to a Paradoxical Embolus?
Usually in the heart through a patent foramen ovale, atrial septal defect, or other anomalous communication
Systemic embolization
Origin usually the left atrium or left ventricle, or ulcerated atherosclerotic plaque
Can travel to any systemic artery
What are some other types of emboli?
Fat
Air - chest wall injury, bends, etc
Amniotic fluid - rare complication of pregnancy associated with DIC
Atherosclerotic - debris form the central core of an atherosclerotic plaque
Infarction definition
Ischemic necrosis involving all cell types in a segment of an organ or an entire organ - irreversible injury associated with hypoxia
Major contributor to mortality associated with cardiovascular disease
What causes an infarction?
Usually due to arterial obstruction; and less often due to vessel twisting, venous obstruction, or slow flow from other cause such as shock
What are the two major types of infarction
Red (hemorrhagic) infarcts
White (pale) infarcts
When does red infarction occur?
It’s seen in areas where the venous side of blood flow is blocked off and the vein is impacted, but the artery is still pushing blood there
White (pale) infarcts
Occur with arterial occlusions in solid organs
Where tissue density limits blood seepage from adjacent vascular beds
What is the gross morphology of infarcts?
Tend to be wedge-shaped with the point of the wedge at the site of the arterial obstruction
What is notable about the histology of infarctions?
The histologic changes of coagulation necrosis do not develop for several hours after the infarct has occurred
The infarct becomes more distinct over time
What follows an infarction?
An acute inflammatory response that begins within several hours and peaks at 2 to 3 days
How does healing of an infarction occur
Healing occurs by granulation tissue ingrowth, starting at the edge of the infarct, followed by scar formation
What do infarcts in the brain result in?
Liquefactive necrosis and heal with the formation of a cystic space
What factors influence infarct development?
Nature of vascular supply
Rate of development of occlusion - slow occlusion allows time for collateral vessels
Vulnerability to hypoxia - more vulnerable = more danger
Oxygen carrying capacity of the blood
Shock definition
Systemic hypoperfusion of tissue
What are the pathophysiologic categories
Cardiogenic - loss of pumping capacity of the heart
Hypovolemic - blood loss
Septic - bacterial infection
Anaphylactic - hypersensitive reaction mediated by IgE
Neurogenic - loss of vascular tone (anesthesia, spinal cord injury)
What is the pathogenesis of septic shock?
Pathogen-associated molecular patterns (PAMPs; including LPS)
PAMPS bind to toll-like receptors (TLRs) on monocytes and neutrophils, mediating the release of IL-1 and TNF
Secondary release of other cytokines in response
Vasodilation, hypotension, endothelial cell activation and injury, reduced myocardial contractility occur in response to the release of the secondary cytokines
What are the stages of Shock?
Nonprogressive
Progressive
Irreversible
Nonprogressive stage of shock
Compensatory mechanisms maintain perfusion - maintains tissue perfusion by tachycardia, renal conservation of water, redistribution of blood to vital organs and away from skin by peripheral vasoconstriction
Progressive stage of shock
Inadequate perfusion - we have metabolic imbalances such as acidosis and increased lactic acid. The acidosis reduces vasomotor responses to sympathetic stimulation leading to pooling of blood and reduced perfusion
Hypoxic injury to endothelium can lead to DIC
Irreversible shock
Tissue injury that can not be reversed by reprofusion
Clinical manefestations of shock
Tachycardia Tachypnea Hypotension Cool, clammy skin (may be warm, flushed with septic shock) Decreased urinary output Confusion Low blood pH (acidosis)
