Topic 13 Part 1

Question 1

Heparin has been given:

No direct inhibition of coagulation: accelerates action of

Answer 1

antithrombin

Question 2

Heparin has been given:

Direct activation of other blood components (5)

Answer 2

platelets
factor XII
complement system
neutrophils
monocytes

Question 3

Heparin has been given:

Some patients display allergic response to heparin such as

Answer 3

heparin-induced thrombocytopenia

Question 4

Heparin Induced Thrombocytopenia (HIT)
____% of patients receiving heparin
Causes ______

Answer 4

2-5%

bleeding

Question 5

Heparin Induced Thrombocytopenia and Thrombosis (HITT)
_____% of patients receiving heparin
Causes ______

Answer 5

0.1-0.2%

thrombosis

Question 6

HIT and HITT Mechanism:

1. Heparin binds to _____ and induces formation of ___ antibodies
2. Heparin/PF4-IgG complex activates ______
   - ______ circulating number of platelets
   - HIT defined as ____% decrease
   - HITT involves ____ AND any evidence of _____

Answer 6

1. Heparin binds to PF4 (platelet factor 4) and induces formation of IgG antibodies
2. Heparin/PF4-IgG complex activates platelets
   - Decreases circulating number of platelets
   - HIT defined as 40-50% decrease
   - HITT involves decrease AND any evidence of thrombosis

Question 7

We are on bypass: Quick exposure of whole blood mass to biomaterials of ECC: (4)

Answer 7

plasma protein adsorption onto surface of ECC
contact activation of blood
emboli formation
increased interstitial fluid

Question 8

We are on bypass: emboli formation (5)

Answer 8

surgery
blood activation
homologous blood (if not filtered)
crystalloid solutions
roller pumps

Question 9

plasma protein adsorption onto surface of ECC:
•very _____
•amount adsorbed depends on ____ & ______
•correlation between physical / chemical properties of biomaterial and activation of blood are made ______ – _____ possible to predict the response

Answer 9

• very quick
• amount adsorbed depends on [protein] & intrinsic surface activity of biomaterial
• correlation between physical / chemical properties of biomaterial and activation of blood are made retrospectively – not possible to predict the response

Question 10

plasma protein adsorption onto surface of ECC:
•wettability
•\_\_\_\_\_ / \_\_\_\_\_ ratio
•surface \_\_\_ and \_\_\_\_\_
•roughness / \_\_\_\_\_
•subsurface \_\_\_\_\_
•distribution of functional \_\_\_\_\_\_

Answer 10

• wettability
• hydrophilic / hydrophobic ratio
• surface chemistry and electrical properties
• roughness / porosity
• subsurface features
• distribution of functional receptor sites

Question 11

contact activation of blood: stimulates and alters what (3)

Answer 11

coagulation cascade stimulation
complement system stimulation
alteration of cell signaling substances

Question 12

contact activation of blood: exposes receptor sites for (5)

Answer 12

• blood cells
• plasma proteins
  
  • factor XII
  • complement protein 3
• platelets

Question 13

emboli from surgery= (2)

Answer 13

1. Wound Debris (fibrin, fat, calcium, cellular debris)
2. Surgical Manipulation
   •plaque debris (arterial cannulation / cross clamping
   •air emboli (cannulation, incomplete deairing)

Question 14

emboli from blood activation= (5)

Answer 14

Blood Activation and Trauma
•fibrin emboli
•macroaggregates of proteins and lipoproteins
•fat globules
•platelet & leukocyte aggregates

Question 15

emboli from homologous blood (if not filtered)= (4)

Answer 15

• platelet & leukocyte aggregates
• fibrin
• lipid precipitates
• red cell debris

Question 16

emboli from crystalloid solutions= (2)

Answer 16

• inorganic debris

* dust

Question 17

emboli from roller pumps=

Answer 17

•spallation

Question 18

increased interstitial fluid= (2)

Answer 18

• increased capillary permeability

* accumulation proportional to duration of bypass

Question 19

End Result: Many different reactions between

Answer 19

blood constituents AND exposed tissue of wound AND undefined monolayer of proteins (ECC)

Question 20

End Result: Huge number of reactions changes what (2)

Answer 20

changes composition of the blood

changed blood reaches every organ / tissue / cell

Question 21

End Result: Change in blood composition triggers normal endothelial cells to do what (2)

Answer 21

1. additional blood proteins converted to active enzymes
2. all blood cells stimulated to expose various receptors, release granule contents and to synthesize new enzymes & chemicals

Question 22

End Result: Whole body _____ and temporary _____

Answer 22

Whole body inflammation and temporary organ dysfunction

Question 23

Key Players: Five Protein Systems

“Creates an Imperfect Excessive Feuding Concoction”

Answer 23

Contact Activation System
Intrinsic Coagulation
Extrinsic Coagulation
Fibrinolysis
Complement Activation

Question 24

Plasma Contact Activation: Four proteins

Answer 24

factor XII
prekallikrein
high-molecular-weight kininogen (HMWK)
factor XI

Question 25

Plasma Contact Activation: Activated by contact with

Answer 25

ECC

Question 26

Plasma Contact Activation: factor XII adsorbed onto foreign surface of ECC -____ & _____ must be present

Answer 26

prekallikrein & HMWK

Question 27

Plasma Contact Activation: factor XII changes shape producing -active protease ____ & _____

Answer 27

factor XIIa and XIIf

Question 28

Active Protease Factor XIIa: 3 roles

Answer 28

1. Cleaves prekallikrein to kallikrein 2. Cleaves HMWK to bradykinin 3. Activates factor XI to XIa

Question 29

When Protease Factor XIIa Cleaves prekallikrein to kallikrein, what the strong and weak agonists?

Answer 29

kallikrein strong neutrophil agonist | factor XIIa weak neutrophil agonist

Question 30

When Protease Factor XIIa Cleaves HMWK to bradykinin, what does bradykinin do?

Answer 30

bradykinin potent vasodilator

Question 31

When Protease Factor XIIa Activates factor XI to XIa, what does XIa then activate and what must be present

Answer 31

factor XIa activates intrinsic coagulation cascade – thrombin production kallikrein & HMWK must be present

Question 32

Intrinsic Coagulation Cascade is initiated by what (2)

Answer 32

Initiated by plasma contact activation | Initiated directly by blood contact with the ECC

Question 33

Extrinsic Coagulation Cascade is initiated by what

Answer 33

Initiated by the expression of tissue factor on nonvascular cells

Question 34

Extrinsic Coagulation Cascade has what 2 forms of tissue factor

Answer 34

cell bound tissue factor | soluble plasma tissue factor

Question 35

Extrinsic Coagulation Cascade: the tissue factor Binds to and activates

Answer 35

VII which then activates factor X and so on

Question 36

Thrombin Actions - Production of _____ - ____ fibrin - Activating _____ - Stimulating the production of ______ activator by endothelial cells

Answer 36

- Production of fibrin from fibrinogen - Cross-linking fibrin - Activating platelets - Stimulating the production of tissue plasminogen activator (t-PA) by endothelial cells

Question 37

Complement System: _(#)_ proteins – most inactive ______ Classical pathway: Initiated by ______ complexes

Answer 37

30+ proteins – most inactive enzyme precursors | Classical pathway: Initiated by antigen-antibody complexes

Question 38

Complement System: Alternative pathway - Initiated by ___ (a product of the classical pathway) - Initiated by ____ activation on a _____ basis - Feedback loop for ______

Answer 38

- Initiated by C3b (a product of the classical pathway) - Initiated by spontaneous activation on a continuous basis - Feedback loop for amplification

Question 39

Complement System: Terminal Pathway - Classical and Alternative merge at the level of ____ - End products work to prevent / limit damage from _____

Answer 39

- Classical and Alternative merge at the level of C3 convertase production - End products work to prevent / limit damage from invading organism or toxin

Question 40

End Product-Membrane Attack Complex: | Works to prevent / limit damage from invading organism or toxin by (7)

Answer 40

``` opsonization lysis agglutination neutralization of viruses chemotaxis activation of mast cells and basophils inflammation ```

Question 41

End Product-Membrane Attack Complex: opsonization= (2)

Answer 41

* neutrophils & macrophages activated | * they engulf bacteria to which antigen-antibody complex is attached

Question 42

End Product-Membrane Attack Complex: lysis= (2)

Answer 42

* final product called lytic complex or terminal complement complex * creates a pore in the cell membrane of bacteria or other invading organisms that allows the influx of ions and water into the cell

Question 43

End Product-Membrane Attack Complex: agglutination= (2)

Answer 43

* complement products change surface of invading organisms | * organisms adhere to each other

Question 44

End Product-Membrane Attack Complex: neutralization of viruses=

Answer 44

•products can attack structures of some viruses and render them non-virulent

Question 45

End Product-Membrane Attack Complex: chemotaxis= (2)

Answer 45

* C5a causes chemotaxis of neutrophils & macrophages | * large number phagocytes migrate to area

Question 46

End Product-Membrane Attack Complex: activation of mast cells and basophils= (3)

Answer 46

* activated by C3a, C4a, & C5a * cells release histamine and other substances into local fluids * results increased local blood flow & increased leakage of fluid and protein into the tissue

Question 47

End Product-Membrane Attack Complex: inflammation = (3)

Answer 47

* increased capillary permeability * altered vasomotor tone * impaired cardiac function

Question 48

Both pathways activated by cardiopulmonary bypass- what causes (6)

Answer 48

``` cellular damage endothelial and leukocyte activation histamine release increased vascular permeability generalized inflammatory response platelet activation ```

Question 49

Classical pathway activation: (4)

Answer 49

Surface contact activation of factor XII Heparin-protamine complexes Ischemia reperfusion Blood-air interface

Question 50

Alternative pathway activation: (3)

Answer 50

Contact with foreign surface Activated pericardium and suction blood Ischemia reperfusion

Question 51

Complement System & CPB: Activated by both pathways but _____ pathway principal pathway during CPB

Answer 51

alternate

Question 52

Complement System & CPB: anaphylatoxins with vasoactive properties

Answer 52

C3a, C4a, C5a

Question 53

Complement System & CPB: major neutrophil agonist

Answer 53

C5a

Question 54

Complement System & CPB: opsonization is from

Answer 54

C3b, C4b

Question 55

Complement System & CPB: Terminal complement complex does what

Answer 55

- accelerates thrombin formation via action on prothrombinase complex - activates platelets