L23- Blood clotting cascade Flashcards

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1
Q

haemostasis

A

Stopping the flow of blood- is the human body’s response to blood vessel injury and bleeding.

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2
Q
A
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3
Q

Hemostasis includes three steps that occur in a rapid sequence:

A

(1) Vasoconstriction, a brief and intense contraction of blood vessels;
(2) Formation of a platelet plug; and
(3) Blood clotting or coagulation, which reinforces the platelet plug with fibrin mesh that acts as a glue to hold the clot

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4
Q

the clotting cascade has three parts

A

intrinsic

extrinsic

common pathway

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5
Q

intrinsic pathway is stimulated when

A

endothelial lining is damaged- promote binding of factor XII

  • more important for amplification of cascade
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6
Q

extrinsic pathway is stimulated when

A

due to trauma- release of tissue factor III

-faster to produce fator X

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7
Q

both the intrinsic and extrinsic pathways lead to the

A

common pathway

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8
Q

outline the intrinsic cascade

A

Slower- more stages

  1. Damaged endothelial lining of blood cells promotes binding of factor XII (Hageman factor)
  2. Factor XII binds to sub endothelial surface
  3. Kallikrein cleaves (activates) XII à XIIa
  4. XIIa cleaves XIà XIa
  5. XIa cleaves IX à IXa
  6. IXa binds VIII and cleaves X à Xa
  7. Xa enters the common pathway
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9
Q

outline the extrinsic cascade

A
  1. Trauma activates factor VII à VIIA
  2. Tissue Factor binds VIIa and activates Xà Xa
  3. Xa enters the common pathway
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10
Q

outline common pathway

A
  1. Factor X cleaves prothrombin to thrombin
  2. Thrombin cleave fibrinogen to fibrin
  3. Cross-linking of fibin causes mesh clot
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11
Q

the clotting cascade allows

A

formation of a clot from activation of a very small amount of intita factor –> quick and precise

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12
Q

prothrombin

A

Prothrombin is a plasma protein produced by the liver. Clotting is caused by a series of clotting factors which activate each other, including the conversion of prothrombin to thrombin.

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13
Q

the protease (thrombin) part of prothrombin is contained in the

A

C-terminal domain of the protein (SERINE PROTEASE)

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14
Q

two kringle domains in prothrombin help keep

A

prothrombin in the inactive form

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15
Q

gla domains target it to

A

the appropriate site for it action

  • addition of COOh groups to glutamate resides (In GLA) form carboxy glutamate
  • allows itneraction with sites of damage and brings together clotting factor
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16
Q
A
17
Q

what cleaves prothrombin to form thrombin

A

Xa- stimulated by Va

18
Q

thrombin function

A

to cleave fibrinogen to fibrin

19
Q

fibrin

A

an insoluble protein formed from fibrinogen during the clotting of blood. It forms a fibrous mesh that impedes the flow of blood.

20
Q

structure of fibrinogen

A
  • 340kDa protein
  • 2 sets of tripeptides, a, b, g, joined at N-termini by disulphide bonds
  • N-terminal regions of alpha and B chains are highly negatively charged and prevent aggregation of fibrinogen
21
Q

formation of fibrin clot

A

1) Thrombin cleaves fibrinopeptides A and B from the central globular domains of fibrinogen
2) Globular domains at the C-terminal ends of the B and Y chains interact with exposed sequences at the N termini of the cleaved b and a chains to form a fibrin mesh/ clot
3) The newly formed clot is stabilised by the formation of amide bonds between the side chains of lysine and glutamine residues in different monomers.
4) This cross-linking reaction is catalysed by transglutaminase, which is activated by protransglutaminase by thrombin

22
Q

classic haemophilia is a defect in

A

factor VIII

23
Q

factor VIII

A

VIII (antihaemophilic factor) is not a protease, but markedly stimulates the activity of factor IXa, a serine protease

24
Q

activity of VIII is markely increased by

A

limited proteolysis by thrombin and factor Xa

25
Q

clotting cascade is an example of

A

positive feedback

26
Q

treatment for classic haemophilia

A

recombinant factor VIII

27
Q

stopping the clotting process

A

1) dilution of prothrombin by blood flow and removal by liver
2) digestion by proteases
3) specific inhibiters

28
Q

digestion of clotting proteases

A

factors va and VIIIa are degraded by protein C

29
Q

protein C is activated by

A

thrombin binding to the endothelial receptor thrombomodulin

30
Q

defects in protein C can cause

A

thrombotic disease

31
Q

specific inhibitors that stop the clotting cascade

A

antithrombin II (AT3)

  • enhanced by heparin binding
32
Q

fibrinolysis

A

breakdown of clots

33
Q

which enzymes cause fibrinolysis

A

T-PA

and

streptokinase

–> activate plasminiogen to become plasmin

–> plasmin dissolves the fibrin clot to become fibrin fragments