test 10

Question 1

Heparin

Answer 1

 No direct inhibition of coagulation
         accelerates action of ATIII
 Direct activation of other blood components
         platelets
         factor XII**
         complement system
         neutrophils
         monocytes

Question 2

Allergic rxn to heparin : HIT and HITT mechanism

Answer 2

 Heparin binds to PF4 (platelet factor 4) and induces formation of IgG antibodies
 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 3

plasma protein adhere to surface of ECC

Answer 3

• 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 4

contact activation of blood stimulate

Answer 4

 coagulation cascade stimulation
 complement system stimulation
 alteration of cell signaling substances
- Expose receptor sites for:
        • blood cells
        • plasma proteins
                • factor XII
                • C3
        • platelets

Question 5

emboli formation debris from surgery

Answer 5

• fibrin
• fat
• calcium
• cellular debris
• other foreign material
• air emboli
• plaque debris (arterial cannulation / cross clamping
• air emboli (cannulation, incomplete deairing)

Question 6

emboli formation from blood activation and trauma

Answer 6

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

Question 7

emboli formation from homologous blood (if not filtered)

Answer 7

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

Question 8

emboli formation from crystalloid solutions

Answer 8

• inorganic debris

* dust

Question 9

emboli formation from roller pumps

Answer 9

• spallation from tubing

Question 10

Embolic Material – Cardiopulmonary Bypass

Answer 10

 Fibrin
 Fat
         free / denatured lipoproteins / chylomicrons
 Denatured protein
 Platelet aggregates
 Leukocyte aggregates
 Red cell debris
 Gas
         nitrogen / oxygen
 Foreign material
         calcium / tissue debris / suture material
 Spallated material

Question 11

increased interstitial fluid

Answer 11

• increased capillary permeability

* accumulation proportional to duration of bypass

Question 12

end result of response to exposure of whole blood mass to biomaterials of
ECC

Answer 12

 Multiple separate reactions between blood constituents and exposed tissue of wound and undefined monolayer of proteins (ECC)
 abruptly changes composition of the blood
 changed blood reaches every organ / tissue / cell
 additional blood proteins converted to active enzymes
 all blood cells stimulated to expose various receptors
 all blood cells stimulated to release granule contents
 all blood cells stimulated to synthesize new enzymes & chemicals

Question 13

Overall end result is

Answer 13

Whole body inflammation and temporary organ dysfunction (Cardiac, renal, pulmonary, GI, hepatic, CNS)

Question 14

Mild inflammatory response

Answer 14

 Fever, leukocytosis

Question 15

significant inflammatory response

Answer 15

 Tachycardia, ↑CO, ↓SVR, ↑O2 consumption, ↑capillary permeability

Question 16

Very bad Inflammatory response can lead to

Answer 16

 Organ dysfunction
 Multiple organ dysfunction
 Death

Question 17

Inflammatory Response changes from patient to patient based on

Answer 17

 Pre-existing conditions
 Age
 Duration of surgery
 Genetic makeup of patient

Question 18

Five Protein Systems (KEY)

Answer 18

 Contact Activation System
 Intrinsic Coagulation
 Extrinsic Coagulation
 Fibrinolysis
 Complement Activation

Question 19

Plasma Contact Activation Four proteins

Answer 19

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

Question 20

Activated by contact with ECC

Answer 20

 factor XII adsorbed onto foreign surface of ECC
 prekallikrein & HMWK must be present
 factor XII changes shape producing
 active protease factor XIIa

Question 21

Active Protease Factor XIIa

Answer 21

 Cleaves prekallikrein to kallikrein
 kallikrein strong neutrophil agonist
 factor XIIa weak neutrophil agonist
 Kallikrein cleaves HMWK to bradykinin
 bradykinin potent vasodilator
 Activates factor XI to XIa
 kallikrein & HMWK must be present
 factor XIa activates intrinsic coagulation cascade – thrombin production

Question 22

Intrinsic Coagulation Cascade

Answer 22

 Initiated by plasma contact activation
 Initiated directly by blood contact with the ECC
 Starts with activation of Factor XII
 Contact activation
 Damaged endothelium
 Exposure to foreign surface

Question 23

Extrinsic Coagulation Cascade

Answer 23

 Initiated by the expression of tissue factor on nonvascular cells
1. cell bound tissue factor
 Expressed by epicardium, adventitia, muscle, fat, bone (NOT pericardium)
2. soluble plasma tissue factor
 Normally circulates. Increased in diseases (ACS, sepsis, trauma, OHS with CPB)
 Binds to and activates factor VII => activates factor IX and X

Question 24

Thrombin Actions

Answer 24

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