Blood Surface Interactions (Part 1) - Exam 3 Flashcards
How does heparin work?at
No direct inhibition of coag; accelerates action of antithrombin
Direct activation of other blood components
What blood components does heparin activate?
Platelets Factor XII Complement system Neutrophils Monocytes
What allergic response can occur from heparin?
HIT
HIT
Heparin Induced Thrombocytopenia
Causes bleeding
What percent of patients receiving heparin develop HIT?
2-5% of patients receiving heparin
HITT
Heparin Induced Thrombocytopenia and Thrombosis
causes thrombosis
What percent of patients develop HITT?
0.1-0.2% of patients receiving heparin
What is the mechanism for HIT and HITT?
Heparin binds to PF4 and induces IgG formation
Heparin/PF4-IgG complex activates plts
PF4
Platelet factor 4
What does the formation of heparin/PF4-IgG result in?
Decreases circulating number of platelets
HIT is defined as what percent decrease in platelets?
40-50% decrease
What does HITT involve?
Decrease in number of platelets and any evidence of thrombosis
What does quick exposure of whole blood mass to biomaterials of ECC result in?
Plasma protein adsorption on to surface of ECC
Contact activation of blood
Emboli formation
Increased Interstitial fluid
How fast does plasma protein adsorption onto the surface of ECC occur?
Very quick
What does the amount of plasma proteins absorbed onto ECC depend on?
- Protein and intrinsic surface activity of biomaterial
- Wettability
- Hydrophilic/ hydrophobic ratio
- Surface chemistry
- surface electrical properties
- roughness/ porosity
- subsurface features
- distribution of function receptor sites
What does activation of blood correlate with?
Physical/Chemical properties of biomaterial
Is plasma protein adsopriton onto surface of ECC predictable?
No; correlation is made retrospectively
What does contact activation of blood to ECC stimulate?
Coagulation cascade
Complement system
Alteration of cell signaling substances
Contact activation of blood to ECC exposes receptor sites for what?
Blood cells
Plasma proteins (FXII, Complement protein 3)
Platelets
Surgery Emboli Formation Sources: Wound Debris
Fibrin Fat Calcium Cellular debris Other foreign material Air emboli
Surgery Emboli Formation Sources: Surgical Manipulation
Plaque debris (arterial cannulation, XC) Air emboli (cannulation, incomplete deairing)
Blood Activation/Trauma Emboli Formation Sources
Fibrin emboli
Macroaggregates of proteins and lipoproteins
Fat flobules
Platelet and Leukocyte aggregates
Homologous Blood (unfiltered) Emboli Formation
Platelet & Leukocyte aggregates
Fibrin
Lipid precipitates
red cell debris
Crystalloid Solutions: emboli formation
Inorganic debris
dust
Roller Pumps: Emboli Formation
Spallation
Embolic Material
Fibrin Fat (Free/denatured lipoproteins/chlyomicrons) Denatured protein Platelet aggreagtes Leukocyte aggregates Red cell debris Gas (Nitrogen, oxygen) Foreign material (Ca, Tissue debris, sutures) Spallated material
What type of fats can be embolic material?
Free fat
denatured lipoproteins
Chylomicrons
Chylomicrons
a droplet of fat present in the blood or lymph after absorption form the small intestine
What is the accumulation of interstitial fluid proprotional to?
Duration of bypass
What can cause increased interstitial fluid?
Increased capillary permeability
CPB can result in
Whole Body Inflammation
Temporary Organ Dysfunction
What are the Five Protein Systems
Contact Activation System Intrinsic Coagulation System Extrinsic Coagulation System Fibrinolysis Complement Activation
What are the four proteins involved with plasma contact activation?
Factor XII
Prekallikrein
HMWK
Factor XI
What does FXII do when activated by contact with ECC?
Adsorbed onto foreign surface of ECC
Changes shape produces active protease FXIIa and XIIf
What must be present for FXII to be adsorbed onto foreign surface of ECC?
Prekallikrein and HMWK
What does active protease FXIIa do?
- Cleaves prekallikrein to kellikrein
- Cleaves HMWK to bradykinin
- Activates FXi to FXIa
What is a strong neutrophil agonist?
Kallikrein
What is a weak neutrophil agonist?
FXIIa
What must be present for FXIIa to activate FXI to FXIa?
Kallikrein and HMWK must be present
What does FXIa do?
Activates intrinsic coagulation cascade; results in thrombin production
How is the intrinsic coagulation cascade initiated?
Plasma contact activation; initiated directly by blood contact with the ECC
How is the exntrinsic coagulation cascade initiated?
By the expression of tissue factor on nonvascular cells
What are the 2 forms of tissue factor?
- Cell bound tissue factor
2. Soluble plasma tissue factor
What does tissue factor do?
Binds to and activates FVII; which activates FX
What are the actions of thrombin?
Production of fibrin from fibrinogen
Cross-linking fibrin
Activating platelets
Stimulating the production of tissue plasminogen activator (t-PA) by endothelial cells
How many proteins are involved in the complement system?
30+ proteins; most inactive enzyme precursors
What pathways are involved in the complement system?
Classical Pathway
Alternative pathway
Terminal Pathway
How is the classical pathway of the complement system activated?
Antigen-antibody complexes
How is the alternative pathway of the complement system activated?
C3b (a produce of classical pathway)
Inititated by spontaneous activation on a continuous basis
What is alternative pathway
A feedback loop for amplification
What is the terminal pathway in the complement system?
Classical and alternative merge at the level of C3 convertase production
What do the end products of the complement system do?
Work to prevent/ limit damage from invading organism or toxins
How does the end produce membrane attack complex work to prevent damange from invading organism?
Opsonization Lysis Agglutination Neutralization of viruses Chemotaxis Activation of mast cells and basophils Inflammation
Describe opsonization.
Neutrophils and macrophages activated
They engulf bacterial to which antigen-antibody complex is attached
Describe Lysis.
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
Describe agglutination
Complement produces change surface of invading organisms; organisms adhere to each other
Neutralization of viruses
Products can attack structures of some viruses and render them non-virulent
What causes chemotaxis of neutrophils and macrophages?
C5a
What happens during chemotaxis?
Large number of phagocytes migrate to the area
What are mast cells nad basophils activated by?
C3a, C4a, C5a
What do mast cells release?
Histamine and other substances into local fluids
What does activation of mast cells and basophils result in?
Increased local blood flow and increased leakage of fluid and protein into the tissue
What does inflammation result in?
INcreased capillary permeability
Altered vasomotor tone
Impaired cardiac function
What does the activation of classical and alternative pathway result in?
Cellular damange Endothelial and leukocyte activation Histamine release Increased vascular permeability Generalized inflammatory response Platelet activation
What 4 things initiate the classical pathway?
Surface contact activation of FXII
Heparin-protamine Complexes
Ischemia reperfusion
Blood-air interface
What 3 things activate the alternative pathway?
Contact with foreign surface
Activated pericardium and suction blood
Ischemia reperfusion
What activates complement system?
Classical and alternative pathways
What are 3 anaphylatoxins with vasoactive properties?
C3a, C4a, C5a
What is a major neutrophil agonist?
C5a
What results in opsonization?
C3b, C4b
What does the terminal complement complex do?
Accelerates thrombin formation via action on prothrombinase complex
Activates platelets
