test 10 part 2 Flashcards
Complement System
- 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
Classical pathway initiated by
Antigen-antibody complexes
Alternative pathway initiated by
C3b (a product of the classical pathway)
Spontaneous activation on a continuous basis
Feedback loop for amplification
Terminal Pathway initiated by
Classical and Alternative merge at the level of C3 convertase production
Complement activation results in
- Recruitment of inflammatory cells
- Opsinization of pathogens
- Killing of pathogens
the whole goal of the complement cascade is to
- Work to prevent / limit damage from invading organism or toxin
complement cascade prevent / limit damage from invading organism or toxin by:
- 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)
Both pathways activated by cardiopulmonary bypass
- cellular damage
- endothelial and leukocyte activation
- histamine release
- increased vascular permeability
- generalized inflammatory response
- platelet activation
CPB Complement Classical Pathway Activation
- Surface contact activation of factor XII
- Heparin-protamine complexes
- Ischemia reperfusion
- Blood-air interface
CPB Complement Alternative Pathway Activation
- Contact with foreign surface
- Activated pericardium and suction blood
- Ischemia reperfusion
principal pathway during CPB
- alternate pathway
- activated by both pathways
C3a, C4a, C5a
- anaphylatoxins with vasoactive properties
C5a
- major neutrophil agonist
C3b, C4b
- opsonization
Terminal complement complex
- accelerates thrombin formation via action on prothrombinase complex
- activates platelets
5 types of blood cells
- Platelets
- Neutrophils
- Monocytes
- Lymphocytes
- Endothelial Cells
Platelets – Initial / Early Activation
- Surface contact with ECC
- Heparin : increases sensitivity
- Circulating thrombin
- powerful agonist and probably initial activator - Platelet-activating factor (PAF)
Platelets – Late Activation
- Activated Complement (C5b – C9)
- Plasmin
- Hypothermia
- Interleukin-6
- Cathepsin G (protein in neutrophils to aid in killing engulfed pathogen)
- Serotonin
- Epinephrine
Platelets – Response to Activation
- Immediate shape change
- express surface receptors (GPIIb/IIIa)
Neutrophil – Very Strong Activation
- 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
Monocyte Activation
- Slow activation during CPB by : C5a, thrombin, and bradykinin
- Activated in wound and circuit
- Produce and release cytokines (IL’s)
Lymphocyte Response
- Number of cells - reduced first week after bypass (increases chance of infection)
Endothelial Cell Activation agents
- thrombin, C5a, various cytokines, TNF
Activated endothelial cells express various receptors
- tissue factor and selectin
What do Activated Endothelial Cells do
- Synthesize tissue factor to generate thrombin
- Initiate fibrinolysis
- Contribute to the overall acute inflammatory response
- Allow fluid and leukocytes to enter the interstitial space
Control of Blood-Surface Interface
- Develop biomaterial that mimics the endothelial cell layer
- Prevent or block activation of the blood during bypass
- limit activation of blood
Surface-Bound Heparin
- ionic (weak)
- covalent (strong) : we want this so it doesn’t go into the blood stream
- claims to provide much better outcomes
Terumo X CoatingTM
- Non-heparin coating
- Reduced protein denaturing and platelet adhesion
- Good for heparin sensitivities
- Can be applied to all types of materials
Medtronic CarmedaTM
- 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
Medtronic Trillium Biosurface
- Negative charge surface
- Heparin coated
- Hydrophilic = body wants to interact => mimics the endothelium
Medtronic Balance® Biosurface
- Negative charge surface
- Non-Heparin coated
- Hydrophilic = body wants to interact => mimics the endothelium
Maquet Bioline
- Mimics endothelium
- Albumin and Heparin coated
- doesn’t want to interact with platelets and also takes up
Maquet Softline
- Mimics endothelium
- Albumin coated but no heparin
- doesn’t want to interact with platelets and also takes up
Sorin P.h.i.s.i.o
- Based on phosphorylcholine molecule
- Stable and durable
- Improves platelet preservation
- Reduces activation of coagulation factors
- Reduces inflammatory reactions
- Limits post operative blood loss
other than altering our circuit, what else can we do to help our clotting factors and platelets
- give corticosteroids
- colloid priming (keeps water in the casculature)
- antifibrinolytic agents
- platelet anesthesia
- complement inhibitors
other than altering our circuit, what pump modifications can we do to help our clotting factors and platelets
- Centrifugal pump
- Pulsatile flow
- Mini circuits
- Off pump
- Ultrafiltration
- Leukodepletion
- Shed blood management
