Lecture 5 - Thrombosis/ Embolism/ Infarction/ Shock Flashcards
what is thrombosis in terms of an endothelial injury?
- loss of endothelial barrier
- increased prothrombotic activity caused by hemodynamic stress; hypertension, homocystinuria, hypercholestolemia, radiation, cytokines, endotoxin
turbulence induces endothelial ____ and ______
dysfunction and activation
stasis disrupts what?
disrupts laminar flow (platelets move to periphery of the vessel)
stasis allows concentration of what?
clotting factors
stasis activates what?
endothelial cells, major factor in venous thrombi and some intra-cardiac thrombi
alterations in blood flow can lead to aneurysms ot
atherosclerotic plaques
what are inherited conditions of hypercoagulability? (3 of them)
- factor V Leiden mutation associated with a factor V that cannot be degraded by protein C
- Prothrombin mutation
- Deficiencies of anticoagulant proteins such as AT III
what are acquired conditions of hypercoagulability (5 of them)
- prolonged bed rest
- extensive tissue damage for example burns and surgery
- cancer
- antiphospholipid antibody syndrome also called lupus anticoagulant
- pregnancy
where do arterial thrombi tend to occur?
at sites of turbulence or endothelial injury and loss
what appearance do arterial thrombi have?
pale (“white”) appearance (kind of like me in the winter) with distinct lines of Zahn and may be occlusive or mural
where do emboli usually lodge?
in smaller arteries, often causing infarction
what are sterile (non-infectious) thrombi on hear valves called?
nonbacterial thrombotic endocarditis (NBTE)
what appearance do venous thrombi typically have
dark maroon color (“red”) (cabernet, blood, merlot, pino noir - could be any of these, have to be ready for all possibilties) and indistinct lines of Zahn
where do venous thrombi often form?
deep veins of the legs
fate of thrombi:
definition of propagation
enlarge by additional fibrin/ platelet deposition
fate of thrombi: definition of embolization
entire thrombus dislodges or a piece breaks loose
fate of thrombi: definition of dissolution
lysis by fibrinolytic activity
fate of thrombi definition of organization
ingrowth of fibroblasts and smooth muscle cells, leads to deposition of collagen (replacing the fibrin) and recanalization, which may re-establish some flow through the thrombus
what is disseminated intravascular coagulation (DIC)
- 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 microthromni and risk of hemorrhage
what are conditions that are associated with DIC?
- infection (especially with gram negative bacteria),
- obstetric complications (placental abruption, retained dead fetus)
- neoplasm
- shock
- massive injury
definition of embolism
a solid, liquid or gas (bubble) carried from one point to another point in the vascular system
thromboemboli that lodge in pulmonary arteries usually arise from…
deep veins in the legs
*less frequently from pelvic veins, right heart chambers, other sites
what are consequences of pulmonary embolism
- 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 ischemic 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 (called a “saddle” embolus)
- gradual obstruction of many small pulmonary arteries by repeated embolization over time can result in pulmonary hypertension
definition of paradoxical embolus
embolus that arises in a systemic vein and crosses a communication from the venous side to the arterial side of the circulation
- the communication is usually in the heart through a patent foramen ovale, atrial septal defect or other anomalous communication
definition of shock
systemic hypoperfusion of tissues
definition of cardiogenic
loss of pumping capacity of the heart
hypovolemlic
blood loss
septic
bacterial infection
anaphylactic
hypersensitivity reaction mediated by IgE
neurogenic
loss of vascular tone (anesthesia, spinal cord injury)
pathogenesis of septic shock
- pathogen associated molecular patterns (PAMPs, including LPS)
- secondary release of other cytokines
- vasodilation, hypotension, endothelial cell activation and injury, reduced myocardial contractilty
PAMPs bind to toll-like receptors (TLRs) on _______ and ______
monocytes and neutrophils mediating the release of IL-1 and TNF
what are the stages of shock (3 of them)
nonprogressive
progressive
irreversible
nonprogressive stage of shock
compensatory mechanisms (catecholamines, renin, ADH, sympathetic nervous system stimulation) maintain 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 with metabolic imbalances such as acidosis and increased lactic acid
- the acidosis reduces vasomotor response to sympathetic stimulation leading to pooling of blood and reduced perfusion
- hypoxic injury to endothelium results in DIC
irreversible stage of shock
tissue injury that cannot be reversed by reperfusion
what are pathologic changes in shock?
- Ischemic necrosis of neurons in the brain (most susceptible areas include hippocampus and cerebellum)
- Contraction band necrosis in the heart
- Necrosis of tubular epithelial cells in the kidney (acute tubular necrosis)
- Diffuse alveolar damage in the lungs due to endothelial injury (clinically called adult respirator distress syndrome or ARDS)
- Mucosal hemorrhage and necrosis in the intestinal tract
- Centrizonal necrosis in the liver
what are the clinical manifestations of shock
- tachycardia
- tachypnea
- hypotension
- cool clammy skin (may be warm and flushed in SPETUM SHOCK)
- decreased urinary output
- confusion
- low blood pH (acidosis) with elevated lactic acid
