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Path 2 > hemodynamics part 2 > Flashcards

hemodynamics part 2 Flashcards

1
Q

define hemostasis

A
  • is the result of a well regulated and balanced process of maintaining blood in a fluid state while allowing for controlled and focused clotting to prevent blood loss
  • Prothombotic vs antithrombotic
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2
Q

what are the components that contribute to hemostasis

A
  • endothelium/vascular wall
  • platelets (bricks)
  • coagulation cascade (fibrin - cement)
  • *occur concurrently**
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3
Q

describe the sequence of clot formation

A

1) initial injury causes brief vasoconstriction (less flow)
2) endothelial damage exposes subendothelium causing PLATELETs to become activated and adhere
3) tissue factor is released and activates the coagulation cascade forming fibrin
4) platelet activation furthers coagulation
5) fibrin and platelets form a clot thereby plugging the defect to prevent blood loss

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4
Q

describe the antithrombotic mechanisms of endothelium

A
  • endothelium acts as a barrier to the subendothelium
  • Prostacyclin (PGI2) and Nitric oxide (NO) INHIBIT platelet aggregation
  • -> Thrombin and several cytokines stimulate PGI2 and NO synthesis (keeps blood fluid)
  • Adensoine diphosphatase degrades ADP thereby inhibiting platelet aggregation
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5
Q

what are the anticoagulant activites of endothelium

A
  • Heparin-like molecules are cofators to antithrombin
  • thrombomodulin converts thrombin to an anticoagulant
  • Fibrinolytic = endothelial cells make tissue plasminogen activator (tPA)
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6
Q

describe the prothrombotic mechanisms of endothelium

A
  • endothelial cell synthesize VON WILLEBRAND FACTOR, which serves to firmly bind platelets to the subendothelium
  • Endotoxin and some cytokines induce endothelial cell to make TISSUE FACTORS
  • endothelial cells secrete PLASMINOGEN ACTIVATOR INHIBITOR (inhibits TPA)
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7
Q

describe the role of endothelium in hemostasis

A
  • general, under normal conditions endothelial cells inhibit platelet adherence and blood clotting
  • injury or activation of endothelial cells results in procoagulant state
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8
Q

describe non-activated platelets

A
  • small, irregularly-shaped anuclear cell fragments derived from fragmentation of precursor MEGAKARYOCYTES
  • platelets contain alpha granules and dense granules
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9
Q

what are the three steps of platelets

A

1) adhesion
2) secretion and activation
3) aggregation

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10
Q

describe platelet adhesion

A
  • initial adherence is to the subendothelial ECM. (BUT NOT RESPONSIBLE FOR FIRM adherence
  • VON WILLEBRAND FACTOR (vWF) links the subendothelium to GLYCOPROTEIN Ib RECEPTORS on platelets which mediates the FIRM ADHERENCE of platelets to the vessel wall
  • adhesion activates the platelets causing the release of their granules
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11
Q

describe platelet activation/ granules contents

A
  • platelet activation results in granule contents being released
  • What are the granule contents
  • -> calcium
  • -> ADP
  • -> Platelet factor 4
  • -> Serotonin
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12
Q

function of Calcium

A
  • critical for coagulation cascade
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13
Q

function of ADP

A
  • mediates platelet aggregation which drives increasing platelet aggregation at the site
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14
Q

function of platelet factor 4

A
  • Heparin binds to platelet factor 4 results in its INACTIVATION
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15
Q

Function of serotonin

A

induces vasoconstriction

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16
Q

describe platelet aggregation

A
  • ADP and THROMBOXANE released by platelets stimulate further platelet aggregation
  • fibrinogen links platelets via GpIIb-IIIa (inhibits THROMBOSIS)
  • THOMBIN also binds to platelet surface
  • platelet activation causes expression of phospholipid complexes on the surface of platelets which act as surfaces to bind coagulation factors and calcium, thereby promoting coagulation
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17
Q

GpIb binds what?

A

GpIb on the surface of platelets binds to VONWILLEBRAND FACTOR

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18
Q

GpIIb-IIIa binds what?

A

GpIIb-IIIa on the surface of platelets binds to fibrinogen forming connections to other platelets

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19
Q

describe the role of ADP, TxA2 (thomboxane)?

A

recruitment of more platelets

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20
Q

Define coagulation factors

A
  • sequential enzyme cascade whose activation results in the formation of a fibrin clot
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21
Q

What is the function of thrombin

A
  • converts fibrinogen to fibrin monomer, but also effects local vasculature, inflammation and fibrinolysis
22
Q

what substances are required for assembly of the coagulation factors

A
  • coagulation factor assembly requires cofactors and calcium in order for it to take place on the phospholipid surface
23
Q

what is the role of fibrin

A
  • fibrin monomer crosslinks to fibrin forming “glue” for platelet plug
24
Q

describe the Extrinsic pathway of tissue coagulation

A

1) TISSUE FACTOR is released when tissue is injured and ACTIVATES Factor VII
2) Factor VII + calcium activates Factor X
3) Factor Xa + calcium activates Factor V
4) Factor Va + Xa and calcium form a COMPLEX that converts Prothrombin (factor II) into Thombin (requires phospholipid surface)
5) Thombin converts FIBRINOGEN (factor I) to FIBRIN in the presence of Ca2+

25
Q

How does the cross linking of fibrin occur

A
  • Factor XIII + Ca2+ crosslinks fibrin to make it more sturdy
26
Q

Describe the Intrinsic pathway of tissue coagulation

A

1) HAGEMAN FACTOR (Factor XII) is activated by Prekallikrein via lots of mechanisms
2) Activated Hagemans factor (Factor XIIa) activates Factor XI
3) activated Factor XIa activates Factor IX
4) Factor IXa, VIIIa and Ca2+ form a complex on the PHOSPHOLIPID SURFACE that ACTIVATES Factor X
5) then common pathway

27
Q

describe Prothrombin time (PT) and what inhibits it

A
  • Prothombin time is a measure of the Extrinsic pathway
  • Prolonged by warfarin (inhibited)
  • -> factors II, VII, IX, X, Protein C and Protein S
28
Q

describe partial thromboplastin time (PTT)

A
  • Partial thromboplastin time measures Intrinsic pathway (generally a longer)
  • Prolonged by HEPARIN (inhibited), hemophilia and antiphospholipid antibody
  • ALL FACTORS except VII and XIII involved
29
Q

describe thrombosis

A
  • clot that blocks the patency of the vessel
30
Q

Describe the role of Antithrombin III

A
  • Anticoagulant
  • Directly INACTIVATES serine proteases
  • -> Thrombin and Xa (inactivates these serine proteases)
  • -> can also inhibit IXa, XIa and XIIa
  • Potentiated by heparin
31
Q

describe the role of Protein C

A
  • Anticoagulant
  • inhibits (cleaves) the cofactors Va and VIIIa
  • signifantly decreases the rate of clot formation
  • requires activation
32
Q

describe the role of plasmin

A
  • breaks down fibrin
33
Q

Describe the role of protein S

A
  • ENHANCES activity of Protein C
34
Q

describe teh role of thrombomodulin

A
  • activated by thrombin
  • bins to thrombin to ALTER ITS CONFORMATION
  • Complex activates protein C
35
Q

describe the role of Tissue pathway factor inhibitor

A
  • inhibits VIIa-tissue factor complex

- inhibits extrinsic arm

36
Q

describe the restrictions of PLASMIN activity

A
  • activity is optimized at sites of fibrin deposition
  • free plasmin is inactivated by circulating alpha2-antiplasmin
  • tPA is inactivated by PAI (plasminogen activator inhibitor)
  • endothelial cells modulate coagulation/anticoagulation balance by releasing PAI (thombin and various cytokines increase PAI)
37
Q

What is a plasminogen activator

A
  • Plasminogen is activated to plasmin, which breaks down fibrin (prevents vascular bed from clogging with clots)
38
Q

Define Urokinase

A
  • present in plasma and various tissues

- activates plasminogen

39
Q

define tPA (tissue plasminogen activator)

A
  • primarily synthesized by ENDOTHELIAL CELLS and achieves the most activation which attached to fibrin
  • Activates plasminogen
40
Q

define streptokinase

A
  • a bacterial product used clinically to ACTIVATE PLASMINOGEN
41
Q

describe the role of Plasminogen activator inhibitor complex (PAI1)

A
  • inhibits plasmin from dissolving fibrin clots

- produced by endothelial cells

42
Q

define thrombus

A
  • blood clot that forms abnormally WITHIN a blood vessel
43
Q

define embolus

A
  • dislodged blood clot which travels through the bloodstream
44
Q

describe anticoagulant drugs

A
  • HEPARIN and WARFARIN

- used for acute coronary syndromes, Deep vein thrombosis (DVT), pulmonary embolism, and surgery

45
Q

describe the drug Heparin

A
  • Prevents formation and extension of blood clots (does not disintegrate preexisting clots)
  • Heparin BINDS and actibates antithrombin III and inhibits Thrombin, Factor IXa and Factor Xa
  • given intravenously or subcutaneous injection
  • AFFECTS MORE OF THE INTRINSIC PATHWAY
46
Q

describe the drug Warfarin (coumadin)-

A
  • Oral medication
  • decreases blood coagulation by INTERFERING WITH VITAMIN K METABOLISM
  • -> Fitamin K-dependent clotting factors = VII, IX, X, II
  • Stops blood from clotting within the blood vessel
  • stops existing clots from getting BIGGER (as in DVT)
  • stops parts of clots breaking off and forming emboli (as in PE)
  • affects more of the EXTRINSIC PATHWAY
47
Q

what are the Vitamin K dependent clotting factors

A
  • VII
  • IX
  • X
  • II
    • LIVER PRODUCES THEM**
48
Q

What are the affects of Dabigatran

A
  • Direct thrombin inhibitor
49
Q

what are the effects of Rivaroxaban and apixaban

A
  • direct factor Xa inhibitors

- both have “X” in them

50
Q

what are the effects of TFPI

A
  • Tissue factor pathway inhibitor

- inhibits VIIa-TF complex

Path 2 (11 decks)

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