SFP: hemodynamic disorders II

Question 1

define hemostasis

Answer 1

the arrest of bleeding in which anti and pro clotting factors are balanced

Question 2

describe general outcomes of too many anti clotting factors

Answer 2

hemorrhage > hypotension > shock

Question 3

describe the general outcomes of too many pro clotting factors

Answer 3

thrombus > embolism > infarction

Question 4

what are the main components of hemostasis

Answer 4

vascular wall, platelets, and coagulation cascade

Question 5

describe the general pattern of hemostatic response to vascular injury

Answer 5

1. injury leads to local response at the endothelium
2. primary hemostasis: platelets connect to form a primary plug
3. secondary hemostasis: the coagulation cascade stabilizes the platelets to form a secondary plug
4. counter regulation: makes sure the clot is only at the site of injury and is appropriate size

Question 6

describe the local response when an injury occurs

Answer 6

there is a brief arteriolar vasoconstriction due to neurogenic reflex and release of endothelin from the endothelium. the basement membrane is exposed to the formed elements.

Question 7

describe the formation of the primary hemostatic plug

Answer 7

1. platelets adhere to the exposed basement membrane, stabilized by vWF secreted by the endothelium.
2. platelets activate and secrete granules like ADP and TXA2
3. more platelets are recruited by the granule release
4. platelet aggregation forms a soft primary plug

Question 8

describe the formation of a secondary hemostatic plug

Answer 8

1. endothelium secretes tissue factor
2. tissue factor initiates the extrinsic portion of the coagulation cascade
3. thrombin activates and cleaves fibrinogen to fibrin
4. fibrin and platelets form a permanent plug

Question 9

describe anti-thrombotic counter-regulation

Answer 9

1. endothelium secretes tPA to lyse fibrin and convert plasminogen to plasmin
2. endothelium expresses thrombomodulin to block further coagulation
3. hemostatic process is limited to site of injury

Question 10

which is considered the brain of clotting: endothelial cells or platelets

Answer 10

endothelial cells

Question 11

describe the function of thrombin in endothelial cells

Answer 11

thrombin binding stimulates secretion of PGI2 and NO to inhibit platelet binding

Question 12

describe the function of TFPI in endothelium

Answer 12

inhibits clotting factors VII and X

Question 13

describe the function of ADPase on endothelium

Answer 13

ADP promotes platelet aggregation, so an ADPase prevents it!

Question 14

describe the function of heparin-like molecules on endothelium

Answer 14

binds antithrombin III and prevents clotting via inactivating thrombin, factor X, and factor IX

Question 15

describe the function of thrombomodulin in endothelium

Answer 15

binds thrombin and inactivates protein C. protein C cleaves V and VIII, so these get inactivated as well.

Question 16

what is the function of tPA in endothelium

Answer 16

clears fibrin

Question 17

what is the function of the von willebrand factor in endothelium?

Answer 17

assists platelet binding to collagen

Question 18

what is the function of tissue factor? what can stimulate it?

Answer 18

it activates the extrinsic clotting pathway; cytokines like IL-1

Question 19

what is the function of PAI

Answer 19

secreted by endothelial cells to inhibit plasminogen activators and prevent fibrinolysis

Question 20

what molecule is required for the coagulation cascade

Answer 20

calcium

Question 21

how does ADP further contribute to the formation of a secondary plug

Answer 21

it enhances GpIIb-IIIa receptor binding to fibrinogen to cause further growth

Question 22

what in the clotting process can stimulate neutrophil and monocyte attachment

Answer 22

thrombin and fibrin split products

Question 23

what is the coagulation cascade

Answer 23

a series of conversions that turn proenzymes to active enzymes resulting in the formation of thrombin

Question 24

describe the intrinsic coagulation cascade

Answer 24

1. hageman factor is activated by damaged endothelium
2. XI is cleaved to be active
3. IX is cleaved to be active
4. X is cleaved to be active in the presence of a phospholipid membrane, cofactor, and calcium

Question 25

describe the extrinsic coagulation cascade

Answer 25

1. VII is cleaved to be active with TF as a cofactor and calcium
2. X is cleaved to be active

Question 26

describe the common coagulation cascade

Answer 26

1. thrombin is cleaved to be active in the presence of phospholipid, calcium, and cofactor V
2. thrombin cleaved fibrinogen to fibrin
3. fibrin cross-links

Question 27

what does partial thromboplastin time measure

Answer 27

determines if the intrinsic pathway is working

Question 28

what does prothrombin time measure

Answer 28

determines if the extrinsic pathway is working

Question 29

what are the two inhibitors of the coagulation cascade

Answer 29

• antithrombin III that binds heparin-like molecules on endothelial cells
• thrombomodulin that binds thrombin and activates protein C to inactivate clotting factors

Question 30

which step of the coagulation cascade does plasminogen activator inhibitor act on

Answer 30

the conversion of fibrinogen to fibrin

Question 31

differentiate between fibrin split products and fibrin degradation products

Answer 31

fibrin split: products of cleaving fibrinogen to fibrin during clot formation

fibrin degradation: products of the fibrinolytic. pathway

both lead to acute inflammation

Question 32

what is thrombosis? what causes it?

Answer 32

formation of a blood clot in uninjured vessels

• caused by endothelial injury, abnormal blood flow, and hyper-coagulability

Question 33

what are two examples of abnormal blood flow that can injure endothelium

Answer 33

turbulence and stasis; both disrupt laminar flow

Question 34

what are some causes of secondary hypercoagulability

Answer 34

bed rest, contraceptives, tumor products, age, heparin, reduced PGI2

Question 35

what is the biggest genetic cause of hyerpcoagulability

Answer 35

factor V mutation

Question 36

describe cardiac thrombus: cause and characteristics

Answer 36

• caused by turbulence and endothelial damage
• mural thrombi attached the the wall and lines of Zahn, which are fibrins and platelets bordered by RBCs that tell you the patient was alive when this happened

Question 37

describe arterial thrombus: cause and characteristics

Answer 37

• cause: turbulence and endothelial damage
• biggest dangers are occlusion and infarct; the clot elongates in the opposite direction of flow

Question 38

describe venous thrombus: cause and characteristics

Answer 38

cause: stasis

characteristics: often in lower extremities. danger is in DVT and embolism. can also block blood flow to the lung and elongate towards the heart

Question 39

describe organization in terms of a thrombus

Answer 39

there can be an ingrowth of fibroblasts, smooth muscle cells, and endothelial cells that results in making a new canal to restore vessel flow; the thrombus gets incorporated into the wall

Question 40

describe DIC

Answer 40

a condition secondary to other disease states that results in sudden formation of many microscopic thrombi in microcirculation. this and hypoxia activates fibrinolytic mechanisms, causing bleeding at the microvascular level. as all clotting proteins were consumes in forming the thrombi, the bleeding cannot be controlled and the disorder evolves. this is tricky and is often fatal.