test 10 part 2

Question 1

Complement System

Answer 1

• part of the innate immunity
   Defense mechanism brought into play nonspecifically in response to invading organisms
   “Complements” the actions of antibodies
   Primary mechanism activated by antibodies to kill foreign cells
• enzyme precursors (trigger one you trigger them all)
   End products work to prevent / limit damage from invading organism or toxin

Question 2

Classical pathway initiated by

Answer 2

 Antigen-antibody complexes

Question 3

Alternative pathway initiated by

Answer 3

 C3b (a product of the classical pathway)
 Spontaneous activation on a continuous basis
 Feedback loop for amplification

Question 4

Terminal Pathway initiated by

Answer 4

 Classical and Alternative merge at the level of C3 convertase production

Question 5

Complement activation results in

Answer 5

• Recruitment of inflammatory cells
• Opsinization of pathogens
• Killing of pathogens

Question 6

the whole goal of the complement cascade is to

Answer 6

• Work to prevent / limit damage from invading organism or toxin

Question 7

complement cascade prevent / limit damage from invading organism or toxin by:

Answer 7

• Opsonization and phagocytosis (activates neutrophils)
• Lysis: (MAC)
• Agglutination: which prevents invader from going anywher
• Neutralization of viruses
• Chemotaxis (C5a causes neutrophil and macrophage chemotaxis)
• Activaiton of maxt cells and basophils (C3a, C4a, and C5a)
• Inflammation (permeability and cardiac function)

Question 8

Both pathways activated by cardiopulmonary bypass

Answer 8

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

Question 9

CPB Complement Classical Pathway Activation

Answer 9

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

Question 10

CPB Complement Alternative Pathway Activation

Answer 10

• Contact with foreign surface
• Activated pericardium and suction blood
• Ischemia reperfusion

Question 11

principal pathway during CPB

Answer 11

• alternate pathway

- activated by both pathways

Question 12

C3a, C4a, C5a

Answer 12

• anaphylatoxins with vasoactive properties

Question 13

C5a

Answer 13

• major neutrophil agonist

Question 14

C3b, C4b

Answer 14

• opsonization

Question 15

Terminal complement complex

Answer 15

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

Question 16

5 types of blood cells

Answer 16

• Platelets
• Neutrophils
• Monocytes
• Lymphocytes
• Endothelial Cells

Question 17

Platelets – Initial / Early Activation

Answer 17

• Surface contact with ECC
• Heparin : increases sensitivity
• Circulating thrombin
  - powerful agonist and probably initial activator
• Platelet-activating factor (PAF)

Question 18

Platelets – Late Activation

Answer 18

• Activated Complement (C5b – C9)
• Plasmin
• Hypothermia
• Interleukin-6
• Cathepsin G (protein in neutrophils to aid in killing engulfed pathogen)
• Serotonin
• Epinephrine

Question 19

Platelets – Response to Activation

Answer 19

• Immediate shape change

- express surface receptors (GPIIb/IIIa)

Question 20

Neutrophil – Very Strong Activation

Answer 20

• Principal agonists - kallikrein and C5a
• release contents of granules
• Express MAC
• Express selectin receptor
• Major role in ischemia-reperfusion injury & responsible for much of inflammatory response associate with bypass

Question 21

Monocyte Activation

Answer 21

• Slow activation during CPB by : C5a, thrombin, and bradykinin
• Activated in wound and circuit
• Produce and release cytokines (IL’s)

Question 22

Lymphocyte Response

Answer 22

• Number of cells - reduced first week after bypass (increases chance of infection)

Question 23

Endothelial Cell Activation agents

Answer 23

• thrombin, C5a, various cytokines, TNF

Question 24

Activated endothelial cells express various receptors

Answer 24

• tissue factor and selectin

Question 25

What do Activated Endothelial Cells do

Answer 25

• Synthesize tissue factor to generate thrombin
• Initiate fibrinolysis
• Contribute to the overall acute inflammatory response
• Allow fluid and leukocytes to enter the interstitial space

Question 26

Control of Blood-Surface Interface

Answer 26

• Develop biomaterial that mimics the endothelial cell layer
• Prevent or block activation of the blood during bypass
• limit activation of blood

Question 27

Surface-Bound Heparin

Answer 27

• ionic (weak)
• covalent (strong) : we want this so it doesn’t go into the blood stream
• claims to provide much better outcomes

Question 28

Terumo X CoatingTM

Answer 28

• Non-heparin coating
• Reduced protein denaturing and platelet adhesion
• Good for heparin sensitivities
• Can be applied to all types of materials

Question 29

Medtronic CarmedaTM

Answer 29

• Gold Standard
• Everything can be coated with it
• Problem : it uses heparin
• Less blood products use
• Less perioperative blood loss
• Shorter ventilator time
• Shorter hospital stay
• Reduced impact on contact, coagulation, fibrinolytis, complement and cytokines
• Reduced impact on platelets, rbc, leukocytes

Question 30

Medtronic Trillium Biosurface

Answer 30

• Negative charge surface
• Heparin coated
• Hydrophilic = body wants to interact => mimics the endothelium

Question 31

Medtronic Balance® Biosurface

Answer 31

• Negative charge surface
• Non-Heparin coated
• Hydrophilic = body wants to interact => mimics the endothelium

Question 32

Maquet Bioline

Answer 32

• Mimics endothelium
• Albumin and Heparin coated
• doesn’t want to interact with platelets and also takes up

Question 33

Maquet Softline

Answer 33

• Mimics endothelium
• Albumin coated but no heparin
• doesn’t want to interact with platelets and also takes up

Question 34

Sorin P.h.i.s.i.o

Answer 34

• Based on phosphorylcholine molecule
• Stable and durable
• Improves platelet preservation
• Reduces activation of coagulation factors
• Reduces inflammatory reactions
• Limits post operative blood loss

Question 35

other than altering our circuit, what else can we do to help our clotting factors and platelets

Answer 35

• give corticosteroids
• colloid priming (keeps water in the casculature)
• antifibrinolytic agents
• platelet anesthesia
• complement inhibitors

Question 36

other than altering our circuit, what pump modifications can we do to help our clotting factors and platelets

Answer 36

• Centrifugal pump
• Pulsatile flow
• Mini circuits
• Off pump
• Ultrafiltration
• Leukodepletion
• Shed blood management