Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardio > Cardio L17 Blood Clotting > Flashcards

Cardio L17 Blood Clotting Flashcards

1
Q

Blood Clotting

The need →

A

to avoid blood loss when blood vessels damaged (excessive blood loss produces shock and death).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Problems associated with blood clotting →

A

Inadequate e.g. haemophilia and some venom gives excessive bruising and haemorrhaging.

Inappropriate e.g. deep vein thrombosis, coronary thrombosis, stroke and other venoms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

A blood clot consists of a

A

plug of platelets enmeshed in a network of insoluble fibrin molecules:
2 components:
1. Platelets → are cell fragments made from megakaryocyte (no nucleus).
2. Fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Process:

1. Tissue damage activates

A

a. Conversion of Prothrombin to thrombin via a complex proteolytic cascade
i. Proteolytic cleavage of fibrinogen to fibrin which polymerises to form clot.
b. Activation and aggregation of platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Platelets aggregation:

A

Von Willebrand factor

Serotonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Von Willebrand factor

A

links collagen exposed on damaged blood vessels to platelets.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

• The activated platelets release factors such as

A

as ADP and thromboxane to activate more platelets causing aggregation that forms a plug of platelets.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Serotonin

A

is also released causing local vasoconstriction as are other factors that enhance thrombin cleavage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Aggregation of activated platelets: (3)

A
  1. Platelet activation causes changes in the shape of platelets and conformation changes in glycoprotein IIb/IIIa receptors
  2. ADP and thromboxane binding lads to a conformation change in IIB/IIIa receptors = active receptors.
  3. The activated receptors can be cross-linked by fibrinogen to form bridges between adjacent platelets and facilitate platelet aggregation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Fibrinogen (precursor molecules) structure

A

3 component chains with globular units and alpha helices with cleavage sites:

  1. Gamma
  2. Beta → cleaved by thrombin
  3. Alpha → cleaved by thrombin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Process: of fibrinogen

A
  1. Thrombin cleaves of peptides from alpha and beta subunits.
  2. Produces a truncated fibrin which can polymerise as the ends can bind into groves → this polymerisation is the formation of a clot (soft – rapid formation).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Hard clot →

A

Clot is stabilised by cross-linking glutamines with lysines using a transglutaminase (Factor XIIIa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do we activate the Thrombin:

A

thrombin is a proteolytic reaction catalysed by a serine protease factor Xa together with a stimulatory protein factor Va.

Cleavage → 2 places (see below) by proteases factor Xa and Va

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cleavage two sites:

A

Kringle domain

Gla domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Kringle domain →

A

a triple loop structure stabilised by 3 dulsphide bonds → involved in protein interactions between blood clotting factors and mediators.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q
  1. Gla domain →
A

contains 10 gamma-carboxyglutamte.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Gla domain cleavage requires

A

a. This cleavage requires calcium to bind the gamma-carboxyglutamate residues of the Gla region.
b. The calcium binds the prothrombin to the phospholpds of the platelet cell membranes at the damage site.
c. Gamma-carboxyglutamate is formed form glutamate by a vitamin K dependent carboxylation reaction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Enzyme inhibited fibrin Gla domain cleavage

A

d. This enzyme is inhibited by dicoumarol (found in spoiled sweet clover that cause haemorrhagic disease in cattle) and warfarin (rat poison) used to prevent blood clots in patients prone to DVT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Gamma-carboxyglutamate information:

A

Found

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Gamma-carboxyglutamate information: During platelet activation prothrombin is cleaved to thrombin how:

A

Cleavage requires calcium to bind to the gamma-carboxyglutamate residues in this region.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Gamma-carboxyglutamate information: Calcium recruitment

A

Calcium binds to prothrombin to allow binding to phospholipids on the platelet membrane (damamge site)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Gamma-carboxyglutamate information: Gamma-carboxyglutamate formed from

A

From glutamate by a vitamin K dependent carboxylation reaction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Gamma-carboxyglutamate information: Inhibited by

A

By dicoumarol which inhibits vit K reductase

24
Q

Thrombin =

A

Blood clotting therefore control is upstream

25
Q

Thrombin produced by

A

TF Xa and Va

26
Q

Tissue factors

A

Serum proteases that cleave

27
Q

Reason for cascade of proteases

A

To amplify the process

28
Q

Extrinsic pathway: factors involved

A

(3,7,10)

29
Q

Extrinsic pathway process

A
  1. Trauma causes the release of TF III.
  2. TF VIIa is a proteases that causes TF 10 to 10a
  3. TF is another serum protease
30
Q

TF III location

A

Exposed on damaged tissue

31
Q

TF III type

A

Trans-membrane protein

32
Q

TF III function

A

Binds and activates factor VII to VIIa

33
Q

Intrinsic pathway: factors involved

A

(12,11,9,8,10)

34
Q

Intrinsic pathway process

A

Release Kinogens and Kalikreins

  1. Once activated stimulated factor XII to XIIa (12) activated
  2. XIIa proteolytic cleaves Xi → Xia
  3. Xia converts IX to IXa
  4. IXa in conjunction with VIIa cleaves
  5. X to Xa
35
Q

Factor IXa interaction with VIIIa →

A

clinically haemophilia A (X linked).
• Actor 8 stimulates the conversion of factor 10 to 10a by factor 9a
• Factor 10 a activates factor 8 (need a small amount to accelerate the factor 9 function)

36
Q

Haemophilia A →

A

factor 8a missing.

37
Q

Von Willebrand factor → interacts with

A

Factor VIII as well as binding platelets to collagen on the damaged blood vessel wall.

38
Q

Controlling the blood clotting cascade:

A

Clot formation is a balancing act → too much and clost form where they should Not; too little and you bleed to death. Hence an anti-clotting cascade starts almost as soon as vclotting begins.

39
Q

The extrinsic pathway blocked by

A
  • Tissue Factor Pathway Inhibitor (TFPI)
  • Antithrombin III (AT3)
  • Protein C and S
40
Q

TFPI structure and function

A

Has three tandem protease inhibitory domains which inhibit Factor Xa and the factor VIIa-Tissue Factor Complex.

41
Q

TFPI circulates in the blood predominantly bound to

A 
To lipproteins (LDL, HDL, lipoprotein a).
In addition, platelets carry about 10% of the TFPI.
42
Q

Antithrombin III: Structure

A

Is a protein synthesized by hepatocytes and endothelial cells.

43
Q

Antithrombin III: Functions

A

By inhibiting the serine proteases activity of the clotting factors – especially thrombin and Factor Xa

44
Q

Antithrombin III: Heparin

A

A highly sulphated oligosaccharide, enhance the inhibitory effect of AT£ by 10000 times! Hence its anticoagulant properties. It is secreted by stimulated mast cells.

45
Q

Proteins C and S: Description

A

Are Vitamin K-dependent serine proteases synthesized in the liver and circulating in the blood as an inactive form (zymogen)

46
Q

Activation and function of Protein C

A

Protein C is activated by thrombin complexed to thrombomodulin and its protease activity inhibits the activity of factors Va and VIIIa

47
Q

Function Protein s

A

Protein S is a cofactor in this process and significantly potentiates the action of Protein C.

48
Q

Thrombomodulin

A

Is a receptor expressed on the surface of endothelila cells which converts hrombin into a conformation that activates Protein C and hence enhancing its anticoagulant activity.

49
Q

Dissolving blood clots: Involves

A

Tissue plasminogen Activator

50
Q

TPA Action

A

Converts plasminogen to Plasmin

51
Q

Plasmin

A

Capable of breaking down fibrin clots producing fibrin split products which are soluble.

52
Q

TPA

A

Serine protease normally found on the surface of endothelial cells of veins, capillaries, the pulmonary artery, heart and uterus
Secreted after vascular injury

53
Q

Urokinase

A

Also aids dissolving the clot by breaking down plasminogen to plasmin

54
Q

TPA clinically

A

Clot busting – older treatment.

55
Q

Plasminogen Activator-inhibitors

A

There to control the breakdown

Cardio (108 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions