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Applied Biochem > Blood Coagulation And Wound Repair- Exam III > Flashcards

Blood Coagulation And Wound Repair- Exam III Flashcards

1
Q

When does the blood coagulation process occur?

A

When there is injury to a blood vessel

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2
Q

What are the 4 steps to the coagulation process?

A
  1. Blood vessels constrict
  2. Activated platelets stick to injury site
  3. Platelets aggregate together & form plug
  4. Platelets and damage tissue release clotting factors
  5. Mesh of fibrin is formed (clot)
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3
Q

Vasoconstriction and platelet response is part of what stage of hemostasis?

A

Primary hemostasis

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4
Q

In primary hemostasis, platelet aggregation at the site of injury is mediated by:

A

Platelet receptors
Platelet derived agonists
Platelet derived adhesion proteins
Plasma derived adhesion proteins

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5
Q

What stage of hemostasis does the clotting cascade occur?

A

Secondary hemostasis

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6
Q

The clotting cascade consists of a cascade of coagulation of:

A

Serine proteases

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7
Q

The coagulation of serine proteases culminates the cleave of:

A

Soluble fibrinogen by thrombin

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8
Q

What does thrombin cleave?

A

Soluble fibrinogen

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9
Q

Once the thrombin cleaves the soluble fibrinogen, the fibrinogen is converted into:

A

Insoluble fibrin

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10
Q

The insoluble fibrin formed from the cleavage of fibrinogen (by thrombin) forms ____ at the site of injury?

A

Cross-linked fibrin mesh

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11
Q

What occurs simultaneous to platelet aggregation?

A

Fibrin generation

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12
Q

Clotting cascade:
1. Damage to the blood vessel results in release of _____.
2. The clotting factors catalyze the conversion of ______ to _____.
3. Thrombin cleaves ______ to ______.
4. The fibrin strands adhere to the plug to form a _____.

A
  1. Clotting factors
  2. Prothrombin -> thrombin
  3. Soluble fibrinogen—> insoluble fibrin
  4. Clot
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13
Q

Platelet activation and its response:

A

Primary hemostasis

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14
Q

When you have an exposed epithelium or ECM, this will cause the platelets to stick to ___.

A

Collagen

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15
Q

The initial binding of the platelets to the exposed collagen makes them undergo a release reaction to release:

A

Von willebrand factor

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16
Q

When von willebrand factor is released from exposed collagen, what will bind to it?

A

GP1b

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17
Q

The binding of von willebrand factor to GP1b is very:

A

Weak

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18
Q

As a result of the weak binding of von willebrand factor and GP1b the platelets that do stick will undergo a release reaction to secrete:

A

Serotonin, thromboxane A2, ADP

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19
Q

Serotonin and thormboxane A2 stimulate:

A

Vasoconstriction

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20
Q

When serotonin and thormboxane stimulate vasoconstriction this results in:

A

Reduced blood flow to the wound

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21
Q

ADP and thromboxane A2 cause other platelets to: (3)

A

Become sticky, attach, and undergo platelet release reaction

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22
Q

The platelet release reaction continues until:

A

Platelet plug is formed

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23
Q

Anuclear sacks of vessels and molecules with dense granules that contain ADP, ATP, serotonin, calcium, epinephrine, histamine, other coagulation factors, growth factors and adhesion molecules

A

Platelets

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24
Q

Serotonin is synthesized from what amino acid?

A

Tryptophan

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25
Q

What cells produce serotonin? (In the gut)

A

Enterochromaffin cells

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26
Q

Thromboxane A2 is initially synthesized from:

A

Arachadonic acid

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27
Q

How does arachidonic acid form thormboxane A2?

A

Arachidonic acid—-> cyclooxygenase enzyme—-> Endoperoxidase—-> Thromboxane synthetase—-> thromboxane A2

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28
Q

Thromboxane A2 action is antagonized by:

A

Prostacyclins

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29
Q

What two molecules are formed from arachidonic acid?

A

Thromboxane A2 & prostacyclins

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30
Q

Platelets are a store house of:

A

Thromboxane A2

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31
Q

What cells produce the prostacyclins?

A

Endothelial cells

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32
Q

Prostacyclins and thromboxane A2 will oppose eachother in terms of:

A

Relaxation and contraction

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33
Q

Gp1b and GP1a, GP2b-3a are all

A

Glycoproteins

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34
Q

The initial activating event when platelets bind to Von Willebrand factor is mediated by:

A

GP1b

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35
Q

Firm adhesion of platelets to the subendothelia is mediated by:

A

GP2b-3a

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36
Q

What activates platelets?

A

GpVI

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37
Q

When platelet is resting describe the state of GP2b-3a complex

A

Not active

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38
Q

When platelet is activated, describe the state of GP2b-3a complex?

A

Activated - can now strongly bind

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39
Q

When the platelet is activated, why can GP2b-3a complex bind so strongly?

A

Because GP2b-3a undergoes a conformational change exposing new binding site for VFW or fibrinogen

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40
Q

The activated GP2b-3a that binds strongly to VWF promotes strong adhesion to the vessel wall, what part of aggregation is this?

A

Primary

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41
Q

Platelet aggregation is dependent upon _____ which allows a quicker activation and sustained response.

A

ADP

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42
Q

The clotting cascade involves how many pathways?

A

3

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43
Q

What pathway in the clotting cascade is activated by external trauma causing blood to escape the vascular system?

A

Extrinsic

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44
Q

What clotting cascade pathway functions quickly?

A

Extrinsic

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45
Q

What clotting factors does the extrinsic pathway involve?

A

Clotting facto VII

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46
Q

What clotting cascade pathway is activated by trauma inside the vascular system? (Activated by platelets, exposed endothelium, chemicals, or collagen)

A

Intrinsic pathway

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47
Q

What clotting cascade pathway has a slow response?

A

Intrinsic pathway

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48
Q

What clotting factors are involved in the intrinsic pathway?

A

XII, XI, IX, VIII

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49
Q

The intrinsic and extrinsic pathways both converge and finish the clot production in the:

A

Common pathway

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50
Q

What clotting factors are involved in the common pathway?

A

I, II, V, X

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51
Q

The activated partial thromboplastin time measures:

A

The intrinsic pathway

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52
Q

The prothrombin time:

A

Measure the extrinsic pathway

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53
Q

In the coagulation cascade most of our factors exist in _____ forms and have to be converted into a ____ form.

A

Inactive, active

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54
Q

Common name for Factor I:

A

Fibrinogen

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55
Q

What cleaves fibrinogen into fibrin

A

Thrombin

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56
Q

Common name for Factor II

A

Prothrombin

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57
Q

Prothrombin is active on surface of activated platelets by:

A

Prothrombinase complex

58
Q

What is an important modification that takes place in many factors of the coagulation process?

A

Formation of carboxyglutamate residues

59
Q

Thrombin, factor 7, factor 9 and factor 10 all contain a:

A

Uniquely modified glutamate residue

60
Q

The uniquely modified glutamate residues on thrombin, factor 7, 9 and 10, will:

A

Anchor them on cell surface in a stable form

61
Q

The uniquely modified glutamate residues (carboxyglutamate) on thrombin, factor 7,9 and 10, will undergo reactions that are dependent upon:

A

Vitamin K

62
Q

Vitamin K is important in the:

A

Clotting cascade

63
Q

What are the fat soluble vitamins?

A

ADEK

64
Q

What is the name of the inactive form of the factor that undergoes a vitamin K-dependent carboxylation reaction?

A

Prozymogen

65
Q

What is the prozymogen in the vitamin-k carboxyglutamate reaction?

A

Glutamate residue

66
Q

In the vitamin-K carboxyglutamate reaction:

The glutamate residue (the prozymogen) in the presence of vitamin K and molecular oxygen leads to teh addition of a ___ on the side chain of the glutamate.

A

Gamma-carboxyglutamate residue

67
Q

WHen a glutamate residue undergoes a vitamin K-dependent carboxylase it forms a: ______ and _____

A

Vitamin K epoxide, and carboxylated prozymogen

68
Q

In the carboxy glutamate reaction:

The vitamin K epoxide gets converted back into:

A

Vitamin K hydroquinone

69
Q

In a carboxy glutamate reaction, the vitamin K epoxide gets converted back into the vitamin K hydroquinone via what two enzymes:

A

Vitamin K epoxide reductase and then vitamin K reductase

70
Q

In a carboxyglutamate reaction, why must some of the vitamin K epoxide return back to the hydroquinone form?

A

To keep adequate levels of the vitamin K hydroquinone form available for carboxyglutamate carboxylations

71
Q

What are the extrinsic, intrinsic, and common factors dependent on vitamin K?

A

Extrinsic: 7
Intrinsic: 9
Common: 10 and 2

72
Q

If vitamin K levels are not adequate, factors II, VII, IX, and X cannot properly form:

A

A fibrin clot

73
Q

What is the initial strength of the platelets inside the platelet plug?

A

Weak

74
Q

What has to happen in order to solidify the platelet plug to prevent further bleeding?

A

Fibrin mesh

75
Q

Due to the cleavage of fibrinogen by thrombin, the fibrinogen initially forms

A

Fibrin monomers

76
Q

The fibrin monomers created by thrombin acting on fibrinogen ultimately aggregate and cross-link by an enzyme called

A

Transglutaminase or factor 13

77
Q

name the domains on the fibrin molecules:

A

Two D domains and one E domain (in middle)

78
Q

What subunits make up the D-domain of the fibrin molecule

A

Gamma and beta subdomains

79
Q

The cross-linking of the fibrin domains by transglutaminase forms ______ between the domains

A

Peptide bonds

80
Q

The cross-linking of the domains of fibrin forms a:

A

Mesh of fibrin

81
Q

Peptide bonds between the domains of fibrin are created by:

A

Transglutaminase

82
Q

We start with two fibrin molecules and the transglutaminase takes a side chain ______ on one monomer and then a side chain _____ on the other monomer and cross-links them to form a peptide bond.

A

Lysine residue & glutamine residue

83
Q

What molecule is the fibrin mesh broken down by?

A

Plasmin

84
Q

What is plasmin derived from?

A

Plasminogen

85
Q

Further processing of plasmin gives rise to:

A

Krinkle proteins

86
Q

Krinkle proteins are part of the:

A

Angiostatin molecule system

87
Q

Plasmins main role in the blood coagulation system is to break down fibrin monomers into:

A

Fragments

88
Q

The conversion of plasmin from plasminogen involves what factors?

A

TPA, urokinase, factor 11a, factor 12a and Kallikrein

89
Q

Inhibitors of plasminogen conversion to plasmin include:

A

Alpha 2 anti plasmin , and alpha2 macroglobulin

90
Q

Wound healing is a ______ process in which skin or other tissues repairs itself after injury

A

Complex

91
Q

The classical model of wound healing can be divided into 4 sequential overlapping phases that include:

A
  1. Hemostasis phase
  2. Inflammatory phase
  3. Proliferative phase
  4. Remodeling phase
92
Q

Within minutes post-injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding

A

Hemostasis

93
Q

Bacteria and debris are phagocytoses and removed from the wound site. Factors are released that cause migration and division of cells involved in the proliferative phase.

A

Inflammatory phase

94
Q

Angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction occur in what phase of wound healing?

A

Proliferative phase

95
Q

Collagen is remodeled and is realigned along tension force lines and cells no longer need are removed by apoptosis- what phase of wound healing?

A

Remodeling phase

96
Q

Platelets are involved in what stage of wound healing?

A

Hemostasis

97
Q

Neutrophils, monocytes, macrophages, and growth factors are involved in what stage of wound healing?

A

Inflammation

98
Q

Keratinocytes, fibroblasts, and endothelial cells are involved in what stage of wound healing?

A

Proliferation and remodeling

99
Q

____ serves as both a regulator of platelet function and a mediator of hemostasis

A

Fibronectin

100
Q

Fibronectin exists in what two forms?

A

Plasma form & cellular form

101
Q

The plasma form of fibronectin is secreted by ______, and modulates _____.

A

Hepatocytes; platelet function

102
Q

The cellular form of fibrinogen is secreted by cells as part of the _______ and functions as a _______ protein.

A

ECM and scaffolding protein

103
Q

What are two types of anticoagulants in blood tube?

A

Acid citrate dextrose solution & EDTA

104
Q

How do the blood tube anticoagulants work?

A

Bind calcium to prevent clotting

105
Q

A test used to help detect and diagnose a bleeding disorder or excessive clotting disorder

A

Prothrombin Time (PT)

106
Q

INR stand for:

A

International normalized ratio

107
Q

Calculated from PT result and used to monitor how well blood thinning medication (especially Coumadin/ Warfarin) is working to prevent blood clots

A

INR

108
Q

Developed to standardize the results of prothrombin time universally

A

INR

109
Q

A measure of the integrity of the extrinsic and final common pathways of the coagulation cascade (consists of tissue factor, and factors VII, II (prothrombin), V, X, and fibrinogen

A

PT

110
Q

The prothrombin time is measured in _____ and compared to a _____.

A

Seconds and normal range

111
Q

Normal INR range

A

Below 1.1

112
Q

INR of 2-3

A

Effective therapeutic range or mechanical heart valve

113
Q

When the INR is higher than recommended range:

A

Means blood clots slowly

114
Q

When INR is lower than the recommended range

A

Blood clots quicker than desired

115
Q

Diseased states that can interfere with wound health I guess include:

A

DM, venous/arterial disease, old age, & infection

116
Q

List the medications that are used to prevent/reduct blood coagulation (blood thinners) (5)

A
  1. Warfarin
  2. Pradaxa
  3. Xarelto
  4. Eliquis
  5. Plavix
117
Q

Blood thinners are most commonly used in patients with a hx of:

A

DVT

118
Q

Warfarin competitively inhibits:

A

Vitamin K epoxide reductase complex 1 (VKORC1)

119
Q

Warfarin functions by not allowing the epoxide to return back to:

A

Hydroquinone form

120
Q

Warfarin can deplete functional:

A

Vitamin K reserves

121
Q

Warfarin can be neutralized by:

A

High dose of vitamin K

122
Q

Xarelto and Eliquis target what factor:

A

Factor Xa

123
Q

Eliquis and Xarelto are competitive inhibitors of what factor?

A

Factor Xa

124
Q

Factor Xa is necessary for conversion of:

A

Prothrombin —> thrombin

125
Q

What drug directly inhibits thrombin?

A

Pradaxa

126
Q

What is an X-linked recessive disorder that results in decreased factor VIII

A

Hemophilia A

127
Q

Hemophilia A can be treated with:

A

Recombinant factor VIII

128
Q

X-linked recessive disorder resulting in decreased factor IX known as Christmas disease

A

Hemophilia B

129
Q

Hemophilia B can be treated with:

A

Recombinant factor IX

130
Q

Who is prominent family that had hemophilia B?

A

Queen victorias family

131
Q

Enzyme that cleaves protein substrates into different parts?

A

Protease

132
Q

Trypsin prefers to cleave at what residues?

A

Argenine & lysine

133
Q

What type of protease is trypsin?

A

Serine

134
Q

Activation of a zymogen commonly occurs by:

A

Proteolytic cleavage

135
Q

Protein kinases usually add phosphate to what amino acids on the side chains of proteins?

A

Serine, threonine, & tyrosine

136
Q

Chemical compound that sequesters calcium ions and draws it always from coagulation proteins

A

EDTA

137
Q

_____ represent calcium binding sites on coagulation proteins and bone proteins

A

GLA residues

138
Q

Liquid phase of clotted blood after spinning out clot

A

Serum

139
Q

Liquid phase of unclotted blood still containing clotting proteins (cells have been centrifuged away)

A

Plasma

140
Q

Inhibitor of cyclooxygenase which catalyzes formation of prostaglandin E2 and other prostaglandins and other leukotrienes:

A

Aspirin (NSAID)

141
Q

Where is a site of metabolism of fat soluble vitamin K

A

Gut bacteria

Applied Biochem (18 decks)

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