Blood Surface Interactioms Part 1 Flashcards
HIT
Heparin induced thrombocytopenia
2-5% patients recieving heparin
Causes bleeding
Blood components directly activated by heparin
Platelets Factor VII Complement Neutrophils Monocytes
HITT
Heparin induced thrombocytopenia and thrombosis
0.1-2% patients receiving heparin
HIT and HITT mechanism
Heparin binds platelet factor 4 and induces formation of IgG
Heparin/PF4-IgG complex activates platelets
-decreases number of circulating platelets
-HIT defined as 40-50% decrease in platelets
-HITT involves decrease AND any sign of thrombosis
Plasma proteins absorb onto surface of ECC. Factors affecting absorption:
Very quick
Amount absorbed depends on concentration and intrinsic surface activity of biomaterial
Cannot predict response of loos to biomaterial
Wettability
Hydrophilic/hydrophobic ratio
Roughness
Subsurface features
Distribution of functional receptor sites
Contact activation of blood
Stimulates coagulation cascade
Stimulates complement system
Alteration of cell signaling substances
Expose receptor sites for: blood cells, plasma proteins (factor XII, CP3), platelets
Emboli formation
- Surgery
- Wound debris: fibrin, fat, calcium, cellular debris, foreign material, air emboli
- Surgical manipulation: plaque debris ( arterial cannulation, cross clamp), air emboli (cannulation, incomplete deairing)
- Blood activation and trauma: fibrin emboli, macroaggregates of proteins and glycoproteins, fat globules, platelet and leukocyte aggregates
- Nonfiltered homologous blood: platelet and leukocyte aggregates, fibrin, lipid precipitates, red cells debris
- Crystal loud solution: inorganic debris, dust
- Roller pumps: spallation
Embolic material on CPB
Fibrin Fat Denatured protein Platelet aggregates Leukocyte aggregates Red cell debris Gas(nitrogen, oxygen) Foreign material (calcium, tissue debris, suture material) Spallated material
Increased interstitial fluid
Increased capillary permeability
Accumulation proportional to duration of bypass
End results of blood exposure to ECC
High number of different reactions: changes composition of blood–changed blood reaches every organ, tissue, cell
Change in blood composition triggers normal endothelial cells- additional blood proteins converted to active enzymes, stimulated to expose various receptors, stimulated to release granule contents, stimulated to synthesize new enzymes and chemicals
2 major results
Whole body inflammation
Temporary organ dysfunction
5 key protein systems
Contact activation system Intrinsic coagulation Extrinsic coagulation Fibrinolysis Complement actovation
Four proteins of platelet contact activation
Factor XII
Prekallikrein
High molecular weight kininogen (HMWK)
Factor XI
Proteins activated by contact with ECC
Factor XII: absorbed onto foreign surface of ECC (prekallikrein and HMWK must be present)
Factor XI: changes shape producing active protease factor XIIa and XIIf
Functions of active protease factor XIIa
- Cleaves prekallikrein to kallikrein (kallikrein strong neutrophil agonist, factor XIIa is weak neutrophil agonist)
- Cleaves HMWK to bradykinin (potent vasodilator)
- Activates factor XI to XIa (kallikrein and HMWK must be present, activates intrinsic coagulation cascade-thrombin production)
Initiation of intrinsic coagulation cascade
Initiated by plasma contact activation
Initiated directly by blood contact with ECC
Initiation of extrinsic coagulation cascade
Initiated by expression of tissue factor on nonvascular cells
2 forms: cell bound tissue fiber, soluble plasma Tissue factor
Binds to and activates factor VII which activates factor X
Thrombin actions
Production of fibrin from fibrinogen
Cross-linking fibrin
Activating platelets
Stimulating production of tissue plasminogen activator (tPA) by endothelial cells
Factors in fibrinolysis
Extrinsic: tPA and urokinase
Intrinsic: factor XIIa, kallikrein, HMWK
Exogenous: streptokinase
Initiation of classical pathway in complement system
Antigen-antibody complexes
Initiation of alternative pathway in complement system
C3b (product of classical pathway)
Spontaneous activation on continuous basis
Feedback Loop for amplification
Terminal pathway of complement system
Classical and terminal merge at level of c3 convertase production
End products work to prevent/limit damage from invading organism or toxin
MAC: opsonization
Neutrophils and macrophages activates
Engulf bacteria to which antigen-antibody complex is attached
MAC: Lysis
Final product called lyric complex or terminal complement complex
Creates pore in cell membrane of bacteria or invading organism that allows influx of water and ions into the cell
