Blood Surface Interactions (Part 2)- Exam 3 Flashcards

0
Q

What do erythrocytes do?

A

Uptake, transport, removal oxygen and carbon dioxide

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1
Q

What are 3 major types of blood cells?

A

RBCs, WBCs, platelets

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2
Q

What are two main types of leukocytes?

A

Granulocytes

Agranulocytes

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3
Q

What are 3 types of granulocytes?

A

Neutrophils
Eosinophils
Basophils

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4
Q

What percent are neutrophils? What do they do?

A

60-70%; destroy bacterial and phagocytosis

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5
Q

What percent are eosinophils? What do they do?

A

2-4%; destroy complex products antigen-antibody reactions

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6
Q

WHat percent are basophils? What do they do?

A

0.5-1%; release histamine and heparin; vasodilation

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7
Q

What are two types of agranulocytes?

A

Monocytes

Lymphocytes

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8
Q

What percent are monocytes? What do they do?

A

3-8%; transform into tissue macrophages

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9
Q

What percent are lymphocytes? What do they do?

A

20-25%; attach destroy/ deactivate bacteria, viruses, other foreign cells, acquired immune response

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10
Q

What are platelets (thrombocytes) involved in?

A

Coagulation

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11
Q

What are the 5 major cell types involved in blood surface interactions?

A
Platelets
Neutrophils
Monocytes
Lymphocytes
Endothelial Cells
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12
Q

Platelets- Initial/Early Activation

A

Surface contact with ECC
Heparin (increases sensitivity)
Circulating thrombin (agonist, probably initial activator)
Platelet-activating (PAF)

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13
Q

Platelets - Late Activation

A
Activated Complement (C5b - C9)
Plasmin
Hypothermia
Interleukin-6
Cathepsin G
Serotonin
Epinephrine
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14
Q

Platelets respond to activation with immediate _____.

A

shape change

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15
Q

What shape changes do platelets in response to activation?

A

Express pseudo pods
Express surface receptors (GP2b/3a and GP1b)
Secrete receptors from granules (P-selectin)

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16
Q

5 actions of platelets responding to activation

A

1) Immediate shape change
2) GP2b/3a receptors bind to surface adsorbed fibrinogen (use fibrinogen as bridge to bind to other platelets)
3) P-selectin receptors bind to monocytes & neutrophils to form aggregates
4) Some platelets break off forming emboli
5) Some platelets release a variety of chemicals and proteins

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17
Q

Examples of the variety of chemicals and proteins that platelets release in response to activation

A

thromboxane-A2
platelet factor 4
beta-thromboglobulin
serotonin

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18
Q

_____ = very strong activation

A

neutrophils

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19
Q

Principal agonists of neutrophil

A

Kallikrein and C5a

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20
Q

Other neutrophil agonists are:

A
Factor 7a
Heparin
MAC
Interleukin 1 Beta
Interleukin 8
TNF
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21
Q

Events in neutrophil activation

A
  • Release contents of granules
  • Express MAC-1 (CD11b/CD18) & CD11c/CD18 receptors
  • Express L-selectin receptor
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22
Q

Lysosomal enzymes, elastase, myeloperoxidase, hydrogen peroxide, hydroxyl radicals, hypochlorous acid, hypobromous acid, acid hydrolyses, and collagenases are contents released from _____ during neutrophils activation.

A

Granules

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23
Q

What does L-selectin receptor bing with?

A

P-selectin expressed by endothelial cells and platelets

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24
Q

What plays a major role in ischemia-reperfusion injury and responsible for much of inflammatory response associated with bypass?

A

Neutrophils

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25
Q

Monocyte activation is _____ during CPB.

A

slow

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26
Q

Monocyte activation is slow activation during CPB by (3):

A

C5a
Thrombin
Bradykinin

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27
Q

Monocytes are activated in ____ and ____.

A

wound and circuit

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28
Q

Monocytes form conjugates with platelets via ____ and express ____.

A

GMP-140

Tissue Factor

29
Q

Delayed increase in tissue factor is seen ____ post CPB

A

20 hours

30
Q

Monocyte activation produces and releases _____.

A

Cytokines

31
Q

What cytokines are produced and released during and post CPB?

A

IL-6

IL-8

32
Q

What cytokines are produced only after CPB?

A

IL-1
IL-2
IL-4

33
Q

The number of lymphocyte cells are ____ first week after bypass?

A

reduced

34
Q

Reduced lymphocyte response causes an _____ susceptibility of postoperative infections like septic shock and endocarditis.

A

increased

35
Q

Endothelial cell activation agents are: (4)

A

Thrombin
C5a
Various Cytokines
TNF

36
Q

____ cells produce prosstacyclin, heparan sulfate, thrombodulin, protease nexin-1, protein S, tissue factor and vasoactive substance like NO, endothelia, PAF, histamine, norepinephrine, and bradykinin.

A

Endothelial

37
Q

What receptors do endothelial cells produce (5)?

A
Tissue Factor
P-selectin
E-selectin
ICAM-1
VCAM-1
38
Q

4 actions of activated endothelial cells:

A

1) Synthesize tissue factor to generate thrombin
2) Initiate fibrinolysis
3) Contribute to the overall acute inflammatory response
4) Allow fluid and leukocytes to enter the interstitial space

39
Q

What 3 hematologist factors activated by CPB are soluble factors?

A

Coagulation cascade
Complement cascade
Fibrinolytic system

40
Q

What 5 hematologist factors activated by CPB are cellular factors?

A
Platelets
Neutrophils 
Monocytes
Lymphocytes
Endothelial cells
43
Q

What active mediators are generated by the coagulation cascade?

A

Kallikrein
HMWK
Thrombin

44
Q

What active mediators are generated by platelets?

A

TXA2

Serotonin

45
Q

What active mediators are generated by neutrophils?

A

Oxygen radicals

Elastase

46
Q

What active mediators are generated by monocytes?

A

Oxygen radicals

Cytokines

47
Q

What active mediators are generated by lymphocytes?

A

Cytokines

48
Q

What active mediators are generated by endothelial cells?

A

T-PA

Cytokines

49
Q

What are the 6 non-platelet related causes of possible contributions to bleeding after CPB?

A

Hyper fibrinolysis
Heparin excess (inadequate neutralization, rebound)
Hypothermia
Protamine excess
Consumption of soluble coagulation factor(s)
Decreased vWF

50
Q

What are the 8 platelet related causes of possible contributions to bleeding after CPB?

A
  • Thrombocytopenia
  • Aspirin-induced platelet dysfunction
  • Impaired aggregation response to agonists (epi, collagen, ADP, thrombin)
  • Selective loss of youngest (most functional) platelets
  • Impaired platelet-mediated clot retraction
  • Plasmin-induced platelet activation/dysfunction
  • Platelet activation/dysfunction by C5b-9
51
Q

What % of normal Factor 12 (Hageman factor) concentration is needed for coagulation?

A

None

52
Q

What % of normal Factor 11 (Plasma thromboplastin antecedent) concentration is needed for coagulation?

A

20

53
Q

What % of normal Factor 9 (Christmas factor) concentration is needed for coagulation?

A

40

54
Q

What % of normal Factor 8 (Antihemophilic factor) concentration is needed for coagulation?

A

30

55
Q

What % of normal Factor 7 (Proconvertin, serum prothrombin conversion accelerator) concentration is needed for coagulation?

A

25

56
Q

What % of normal Factor 10 (Stuart factor) concentration is needed for coagulation?

A

40

57
Q

What % of normal Factor 5 (Proaccelerin, labile factor) concentration is needed for coagulation?

A

40

58
Q

What % of normal Factor 2 (Prothrombin) concentration is needed for coagulation?

A

40

59
Q

How much of normal Factor 1 (Fibrinogen) concentration is needed for coagulation?

A

100 mg/dL

60
Q

What are 3 ways to control blood-surface interface?

A
  • Develop biomaterial that mimics the endothelial cell layer.
  • Prevent or block activation of the blood during bypass.
  • Prevent activated blood from reaching your circuit.
61
Q

What active mediators are generated by the fibrinolytic system?

A

Plasmin

62
Q

What active mediators are generated by the complement cascade?

A

C3a
C5-
C5b-9

63
Q

What is a way to prevent activated blood from reaching your circuit?

A

Sequestered cardiotomy suction

64
Q

What are 5 claims of using surface-bound circuit?

A
  • Suppress thrombin formation
  • Reduce blood loss and transfusion requirements
  • Attenuate inflammatory response
  • Depress platelet activation
  • Decrease in clinical indicators of morbidity
65
Q

What current systems have heparin coating?

A

Medtronic Carmeda
Medtronic Trillium
Maquet Bioline

66
Q

How can we prevent or block activation of the blood during bypass?

A

Blood modification

67
Q

4 processes of blood modification

A
  • Preop administration of corticosteroids
  • Antifibrinolytic agents
  • Platelet anesthesia
  • Complement inhibition
68
Q

What is the purpose of administering corticosteroids preoperatively?

A

Attenuates complement activation

69
Q

What does Aprotinin do?

A

Inhibits plasmin directly

70
Q

What happens with high doses of Aprotinin?

A

Partially inhibits kallikrein–platelet sparing

71
Q

What do W-aminocarboxylic acids do?

A

Inhibit cleavage of plasminogen to plasmin

72
Q

3 types of platelet anesthesia

A
  • Reversible inhibition of platelets during procedure
  • Eptifibatide (Integrilin) with or without NO
  • NO provides partial protection
73
Q

2 types of complement inhibition

A
  • Pexelizumab

- TP 10