Lectures 18-21

Question 1

tumor angiogenesis process

Answer 1

1. 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

Question 2

VEGF role in tumor metastasis

Answer 2

induces junction breakage between endothelial cells; tumor upregulates VEGF to make tumor vessels leaky

Question 3

RIP-Tag model of angiogenic switch in pancreatic islet cell tumor progression

Answer 3

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)

Question 4

genetically linked cancers

Answer 4

ovarian and breast; colon and endometrial (Lynch)

Question 5

pathophysiologic categories of edema (4)

Answer 5

increased hydrostatic pressure, reduced plasma osmotic pressure, lymphatic obstruction, sodium (and water) retention

Question 6

congestive heart failure: which pathophysiologic category of edema, mechanism

Answer 6

increased hydrostatic pressure; increased hydrostatic pressure in alveolar capillaries due to left ventricular failure –> pulmonary edema; hypoperfusion of kidneys causes secondary hyperaldosteronism

Question 7

3 major causes of increased hydrostatic pressure in capillaries

Answer 7

venous obstruction, impaired venous return, arteriolar dilation

Question 8

major cause of reduced plasma osmotic pressure

Answer 8

excessive loss of albumin

Question 9

causes of albumin loss (2)

Answer 9

nephrotic syndrome (protein-losing), liver disease (reduced synthesis)

Question 10

causes of water and salt retention (2)

Answer 10

excessive salt intake with renal insufficiency, acute reduction of renal function (glomerulonephritis)

Question 11

pulmonary edema: seen most commonly in ???

Answer 11

left ventricular failure

Question 12

hyperemia: what is it, active/passive, cause, where it happens

Answer 12

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

Question 13

congestion: what is it, active/passive, cause, in what organs does this normally occur

Answer 13

increase in blood volume within a tissue; passive process; due to increased/impaired outflow of venous blood; liver and lungs

Question 14

morphology of chronic passive congestion of liver

Answer 14

central regions of liver lobules near central vein are congested; periportal regions remain oxygenated

Question 15

morphology of congested lungs in heart failure

Answer 15

heart failure cells: macrophages containing broken down RBCs that have leaked from the capillaries in long-standing heart failure

Question 16

primary hemostasis: 5 steps

Answer 16

1. platelet adhesion mediated by von Willebrand factor 2. platelet shape change 3. granule release 4. recruitment of additional platelets 5. aggregation (hemostatic plug)

Question 17

secondary hemostasis: 4 steps

Answer 17

1. damaged endothelial cells release tissue factor 2. phospholipid complex expression 3. thrombin activation (converts fibrinogen –> fibrin) 4. fibrin polymerization (seals platelet plug)

Question 18

clotting cascade involves ??? and ??? pathways leading to ???, important to ??? hemostasis

Answer 18

intrinsic, extrinsic, activation of thrombin and therefore the conversion of fibrinogen to fibrin, secondary

Question 19

inherited bleeding disorder

Answer 19

Glanzmann’s thrombasthenia

Question 20

petechial hemorrhages: size, what factors are they associated with (4)

Answer 20

1-2 mm; low platelet counts, platelet dysfunction; loss of vascular wall support; local pressure

Question 21

1-2 mm hemorrhages in skin, mucous membrane, or mucosal/serosal surfaces

Answer 21

petechial hemorrhages

Question 22

purpura: size, what factors are they associated with (7)

Answer 22

>3 mm; same as petechiae (low platelet counts, platelet dysfunction; loss of vascular wall support; local pressure), trauma, vasculitis, vascular fragility

Question 23

ecchymoses: size, what they are

Answer 23

> 1-2 cm; subctaneous hematomas associated with trauma (bruises)

Question 24

factors that inhibit thrombosis (4)

Answer 24

tissue factor pathway inhibitor, thrombomodulin-mediated (protein C and protein S), prostaglandins, antithrombin III

Question 25

describe thrombomodulin-mediated inhibition of thrombosis

Answer 25

protein C and protein S are anticoagulant molecules that shut down clotting factors 5 and 8

Question 26

how do prostaglandins inhibit thrombosis?

Answer 26

inhibit platelet aggregation

Question 27

list inherited (1) and acquired (3) hypercoagulable states

Answer 27

inherited: factor 5 leiden acquired: malignancy, estrogens, antiphospholipid antibody syndrome

Question 28

factor 5 leiden: mechanism

Answer 28

inherited hypercoagulable state, single point mutation in cleavage site for Protein C which usually shuts factor 5 down

Question 29

antiphospholipid antibodies: ??? clotting in vitro, ??? clotting in vivo

Answer 29

inhibit; promote

Question 30

what are the components of Virchow’s Triad in thrombosis?

Answer 30

endothelial injury, abnormal blood flow, hypercoagulability

Question 31

venous thrombi: mechanism; is there associated inflammation?

Answer 31

stasis due to immobilization or prolonged bed rest –> reduced action of leg muscles and reduced venous return; no

Question 32

DVT may break off and travel to ???

Answer 32

lungs

Question 33

common causes of fat emboli

Answer 33

fractures of long bones, soft tissue trauma/burns

Question 34

common causes of air emboli

Answer 34

obstetric procedures, chest wall injuries, diving

Question 35

thromboemboli from right heart may travel into ???

Answer 35

lung

Question 36

thromboemboli from left heart may travel into ???

Answer 36

systemic arterial circulation

Question 37

trace the path of pulmonary embolism from a DVT in leg

Answer 37

deep veins of leg –> right atrium –> right ventricle –> pulmonary arteries

Question 38

difference between red and white infarcts, what organs each are seen in

Answer 38

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

Question 39

causes of infarction (2)

Answer 39

occlusion of arterial supply or venous drainage

Question 40

difference between a hematoma and a hemorrhagic infarct

Answer 40

in a hemorrhagic infarct, blood is intermixed with necrotic tissue; in a hematoma, blood is collected and forms a solid mass

Question 41

what kind of shock leads to cool, clammy, cyanotic skin?

Answer 41

cardiogenic

Question 42

what kind of shock leads to skin initially being warm and flushed?

Answer 42

septic

Question 43

septic shock is most often caused by ???

Answer 43

gram positive bacteria