Lectures 18-21 Flashcards
tumor angiogenesis process
- growth factor/induction signal secreted by tumor cell 2. degradation of ECM 3. tip cell detaches from its neighbors, senses growth factor gradient, changes polarity and moves outward (tip cell never proliferates) 4. stalk cell behind the tip cell actively proliferates 5. two stalk cells fuse and lumen forms
VEGF role in tumor metastasis
induces junction breakage between endothelial cells; tumor upregulates VEGF to make tumor vessels leaky
RIP-Tag model of angiogenic switch in pancreatic islet cell tumor progression
signals to the bone marrow cause it to release cells that secrete MMP-9; MMP-9 releases VEGF from ECM, making it available to its receptors on tumor cells (this is why only subset of tumor cells become angiogenic)
genetically linked cancers
ovarian and breast; colon and endometrial (Lynch)
pathophysiologic categories of edema (4)
increased hydrostatic pressure, reduced plasma osmotic pressure, lymphatic obstruction, sodium (and water) retention
congestive heart failure: which pathophysiologic category of edema, mechanism
increased hydrostatic pressure; increased hydrostatic pressure in alveolar capillaries due to left ventricular failure –> pulmonary edema; hypoperfusion of kidneys causes secondary hyperaldosteronism
3 major causes of increased hydrostatic pressure in capillaries
venous obstruction, impaired venous return, arteriolar dilation
major cause of reduced plasma osmotic pressure
excessive loss of albumin
causes of albumin loss (2)
nephrotic syndrome (protein-losing), liver disease (reduced synthesis)
causes of water and salt retention (2)
excessive salt intake with renal insufficiency, acute reduction of renal function (glomerulonephritis)
pulmonary edema: seen most commonly in ???
left ventricular failure
hyperemia: what is it, active/passive, cause, where it happens
increase in blood volume within a tissue; active process; due to increased blood flow and arteriolar dilation; occurs at sites of inflammation or exercising skeletal muscles
congestion: what is it, active/passive, cause, in what organs does this normally occur
increase in blood volume within a tissue; passive process; due to increased/impaired outflow of venous blood; liver and lungs
morphology of chronic passive congestion of liver
central regions of liver lobules near central vein are congested; periportal regions remain oxygenated
morphology of congested lungs in heart failure
heart failure cells: macrophages containing broken down RBCs that have leaked from the capillaries in long-standing heart failure
primary hemostasis: 5 steps
- platelet adhesion mediated by von Willebrand factor 2. platelet shape change 3. granule release 4. recruitment of additional platelets 5. aggregation (hemostatic plug)
secondary hemostasis: 4 steps
- damaged endothelial cells release tissue factor 2. phospholipid complex expression 3. thrombin activation (converts fibrinogen –> fibrin) 4. fibrin polymerization (seals platelet plug)
clotting cascade involves ??? and ??? pathways leading to ???, important to ??? hemostasis
intrinsic, extrinsic, activation of thrombin and therefore the conversion of fibrinogen to fibrin, secondary
inherited bleeding disorder
Glanzmann’s thrombasthenia
petechial hemorrhages: size, what factors are they associated with (4)
1-2 mm; low platelet counts, platelet dysfunction; loss of vascular wall support; local pressure
1-2 mm hemorrhages in skin, mucous membrane, or mucosal/serosal surfaces
petechial hemorrhages
purpura: size, what factors are they associated with (7)
>3 mm; same as petechiae (low platelet counts, platelet dysfunction; loss of vascular wall support; local pressure), trauma, vasculitis, vascular fragility
ecchymoses: size, what they are
> 1-2 cm; subctaneous hematomas associated with trauma (bruises)
factors that inhibit thrombosis (4)
tissue factor pathway inhibitor, thrombomodulin-mediated (protein C and protein S), prostaglandins, antithrombin III
describe thrombomodulin-mediated inhibition of thrombosis
protein C and protein S are anticoagulant molecules that shut down clotting factors 5 and 8
how do prostaglandins inhibit thrombosis?
inhibit platelet aggregation
list inherited (1) and acquired (3) hypercoagulable states
inherited: factor 5 leiden acquired: malignancy, estrogens, antiphospholipid antibody syndrome
factor 5 leiden: mechanism
inherited hypercoagulable state, single point mutation in cleavage site for Protein C which usually shuts factor 5 down
antiphospholipid antibodies: ??? clotting in vitro, ??? clotting in vivo
inhibit; promote
what are the components of Virchow’s Triad in thrombosis?
endothelial injury, abnormal blood flow, hypercoagulability
venous thrombi: mechanism; is there associated inflammation?
stasis due to immobilization or prolonged bed rest –> reduced action of leg muscles and reduced venous return; no
DVT may break off and travel to ???
lungs
common causes of fat emboli
fractures of long bones, soft tissue trauma/burns
common causes of air emboli
obstetric procedures, chest wall injuries, diving
thromboemboli from right heart may travel into ???
lung
thromboemboli from left heart may travel into ???
systemic arterial circulation
trace the path of pulmonary embolism from a DVT in leg
deep veins of leg –> right atrium –> right ventricle –> pulmonary arteries
difference between red and white infarcts, what organs each are seen in
red: hemorrhagic, happens in loos tissues where blood can collect, classic example is lung infarct secondary to embolus; white: anemic, occur in solid organs with end-arterial circulation like spleen and kidney
causes of infarction (2)
occlusion of arterial supply or venous drainage
difference between a hematoma and a hemorrhagic infarct
in a hemorrhagic infarct, blood is intermixed with necrotic tissue; in a hematoma, blood is collected and forms a solid mass
what kind of shock leads to cool, clammy, cyanotic skin?
cardiogenic
what kind of shock leads to skin initially being warm and flushed?
septic
septic shock is most often caused by ???
gram positive bacteria
