SFP: hemodynamic disorders II Flashcards
define hemostasis
the arrest of bleeding in which anti and pro clotting factors are balanced
describe general outcomes of too many anti clotting factors
hemorrhage > hypotension > shock
describe the general outcomes of too many pro clotting factors
thrombus > embolism > infarction
what are the main components of hemostasis
vascular wall, platelets, and coagulation cascade
describe the general pattern of hemostatic response to vascular injury
- injury leads to local response at the endothelium
- primary hemostasis: platelets connect to form a primary plug
- secondary hemostasis: the coagulation cascade stabilizes the platelets to form a secondary plug
- counter regulation: makes sure the clot is only at the site of injury and is appropriate size
describe the local response when an injury occurs
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.
describe the formation of the primary hemostatic plug
- platelets adhere to the exposed basement membrane, stabilized by vWF secreted by the endothelium.
- platelets activate and secrete granules like ADP and TXA2
- more platelets are recruited by the granule release
- platelet aggregation forms a soft primary plug
describe the formation of a secondary hemostatic plug
- endothelium secretes tissue factor
- tissue factor initiates the extrinsic portion of the coagulation cascade
- thrombin activates and cleaves fibrinogen to fibrin
- fibrin and platelets form a permanent plug
describe anti-thrombotic counter-regulation
- endothelium secretes tPA to lyse fibrin and convert plasminogen to plasmin
- endothelium expresses thrombomodulin to block further coagulation
- hemostatic process is limited to site of injury
which is considered the brain of clotting: endothelial cells or platelets
endothelial cells
describe the function of thrombin in endothelial cells
thrombin binding stimulates secretion of PGI2 and NO to inhibit platelet binding
describe the function of TFPI in endothelium
inhibits clotting factors VII and X
describe the function of ADPase on endothelium
ADP promotes platelet aggregation, so an ADPase prevents it!
describe the function of heparin-like molecules on endothelium
binds antithrombin III and prevents clotting via inactivating thrombin, factor X, and factor IX
describe the function of thrombomodulin in endothelium
binds thrombin and inactivates protein C. protein C cleaves V and VIII, so these get inactivated as well.
what is the function of tPA in endothelium
clears fibrin
what is the function of the von willebrand factor in endothelium?
assists platelet binding to collagen
what is the function of tissue factor? what can stimulate it?
it activates the extrinsic clotting pathway; cytokines like IL-1
what is the function of PAI
secreted by endothelial cells to inhibit plasminogen activators and prevent fibrinolysis
what molecule is required for the coagulation cascade
calcium
how does ADP further contribute to the formation of a secondary plug
it enhances GpIIb-IIIa receptor binding to fibrinogen to cause further growth
what in the clotting process can stimulate neutrophil and monocyte attachment
thrombin and fibrin split products
what is the coagulation cascade
a series of conversions that turn proenzymes to active enzymes resulting in the formation of thrombin
describe the intrinsic coagulation cascade
- hageman factor is activated by damaged endothelium
- XI is cleaved to be active
- IX is cleaved to be active
- X is cleaved to be active in the presence of a phospholipid membrane, cofactor, and calcium
describe the extrinsic coagulation cascade
- VII is cleaved to be active with TF as a cofactor and calcium
- X is cleaved to be active
describe the common coagulation cascade
- thrombin is cleaved to be active in the presence of phospholipid, calcium, and cofactor V
- thrombin cleaved fibrinogen to fibrin
- fibrin cross-links
what does partial thromboplastin time measure
determines if the intrinsic pathway is working
what does prothrombin time measure
determines if the extrinsic pathway is working
what are the two inhibitors of the coagulation cascade
- antithrombin III that binds heparin-like molecules on endothelial cells
- thrombomodulin that binds thrombin and activates protein C to inactivate clotting factors
which step of the coagulation cascade does plasminogen activator inhibitor act on
the conversion of fibrinogen to fibrin
differentiate between fibrin split products and fibrin degradation products
fibrin split: products of cleaving fibrinogen to fibrin during clot formation
fibrin degradation: products of the fibrinolytic. pathway
both lead to acute inflammation
what is thrombosis? what causes it?
formation of a blood clot in uninjured vessels
- caused by endothelial injury, abnormal blood flow, and hyper-coagulability
what are two examples of abnormal blood flow that can injure endothelium
turbulence and stasis; both disrupt laminar flow
what are some causes of secondary hypercoagulability
bed rest, contraceptives, tumor products, age, heparin, reduced PGI2
what is the biggest genetic cause of hyerpcoagulability
factor V mutation
describe cardiac thrombus: cause and characteristics
- 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
describe arterial thrombus: cause and characteristics
- cause: turbulence and endothelial damage
- biggest dangers are occlusion and infarct; the clot elongates in the opposite direction of flow
describe venous thrombus: cause and characteristics
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
describe organization in terms of a thrombus
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
describe DIC
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.
