Topic 13 Part 1 Flashcards
Heparin has been given:
No direct inhibition of coagulation: accelerates action of
antithrombin
Heparin has been given:
Direct activation of other blood components (5)
platelets factor XII complement system neutrophils monocytes
Heparin has been given:
Some patients display allergic response to heparin such as
heparin-induced thrombocytopenia
Heparin Induced Thrombocytopenia (HIT)
____% of patients receiving heparin
Causes ______
2-5%
bleeding
Heparin Induced Thrombocytopenia and Thrombosis (HITT)
_____% of patients receiving heparin
Causes ______
0.1-0.2%
thrombosis
HIT and HITT Mechanism:
- Heparin binds to _____ and induces formation of ___ antibodies
- Heparin/PF4-IgG complex activates ______
- ______ circulating number of platelets
- HIT defined as ____% decrease
- HITT involves ____ AND any evidence of _____
- 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
We are on bypass: Quick exposure of whole blood mass to biomaterials of ECC: (4)
plasma protein adsorption onto surface of ECC
contact activation of blood
emboli formation
increased interstitial fluid
We are on bypass: emboli formation (5)
surgery blood activation homologous blood (if not filtered) crystalloid solutions roller pumps
plasma protein adsorption onto surface of ECC:
•very _____
•amount adsorbed depends on ____ & ______
•correlation between physical / chemical properties of biomaterial and activation of blood are made ______ – _____ possible to predict the response
- 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
plasma protein adsorption onto surface of ECC: •wettability •\_\_\_\_\_ / \_\_\_\_\_ ratio •surface \_\_\_ and \_\_\_\_\_ •roughness / \_\_\_\_\_ •subsurface \_\_\_\_\_ •distribution of functional \_\_\_\_\_\_
- wettability
- hydrophilic / hydrophobic ratio
- surface chemistry and electrical properties
- roughness / porosity
- subsurface features
- distribution of functional receptor sites
contact activation of blood: stimulates and alters what (3)
coagulation cascade stimulation
complement system stimulation
alteration of cell signaling substances
contact activation of blood: exposes receptor sites for (5)
- blood cells
- plasma proteins
- factor XII
- complement protein 3
- platelets
emboli from surgery= (2)
- Wound Debris (fibrin, fat, calcium, cellular debris)
- Surgical Manipulation
•plaque debris (arterial cannulation / cross clamping
•air emboli (cannulation, incomplete deairing)
emboli from blood activation= (5)
Blood Activation and Trauma •fibrin emboli •macroaggregates of proteins and lipoproteins •fat globules •platelet & leukocyte aggregates
emboli from homologous blood (if not filtered)= (4)
- platelet & leukocyte aggregates
- fibrin
- lipid precipitates
- red cell debris
emboli from crystalloid solutions= (2)
- inorganic debris
* dust
emboli from roller pumps=
•spallation
increased interstitial fluid= (2)
- increased capillary permeability
* accumulation proportional to duration of bypass
End Result: Many different reactions between
blood constituents AND exposed tissue of wound AND undefined monolayer of proteins (ECC)
End Result: Huge number of reactions changes what (2)
changes composition of the blood
changed blood reaches every organ / tissue / cell
End Result: Change in blood composition triggers normal endothelial cells to do what (2)
- additional blood proteins converted to active enzymes
- all blood cells stimulated to expose various receptors, release granule contents and to synthesize new enzymes & chemicals
End Result: Whole body _____ and temporary _____
Whole body inflammation and temporary organ dysfunction
Key Players: Five Protein Systems
“Creates an Imperfect Excessive Feuding Concoction”
Contact Activation System Intrinsic Coagulation Extrinsic Coagulation Fibrinolysis Complement Activation
Plasma Contact Activation: Four proteins
factor XII
prekallikrein
high-molecular-weight kininogen (HMWK)
factor XI
Plasma Contact Activation: Activated by contact with
ECC
Plasma Contact Activation:
factor XII adsorbed onto foreign surface of ECC
-____ & _____ must be present
prekallikrein & HMWK
Plasma Contact Activation:
factor XII changes shape producing
-active protease ____ & _____
factor XIIa and XIIf
Active Protease Factor XIIa: 3 roles
- Cleaves prekallikrein to kallikrein
- Cleaves HMWK to bradykinin
- Activates factor XI to XIa
When Protease Factor XIIa Cleaves prekallikrein to kallikrein, what the strong and weak agonists?
kallikrein strong neutrophil agonist
factor XIIa weak neutrophil agonist
When Protease Factor XIIa Cleaves HMWK to bradykinin, what does bradykinin do?
bradykinin potent vasodilator
When Protease Factor XIIa Activates factor XI to XIa, what does XIa then activate and what must be present
factor XIa activates intrinsic coagulation cascade – thrombin production
kallikrein & HMWK must be present
Intrinsic Coagulation Cascade is initiated by what (2)
Initiated by plasma contact activation
Initiated directly by blood contact with the ECC
Extrinsic Coagulation Cascade is initiated by what
Initiated by the expression of tissue factor on nonvascular cells
Extrinsic Coagulation Cascade has what 2 forms of tissue factor
cell bound tissue factor
soluble plasma tissue factor
Extrinsic Coagulation Cascade: the tissue factor Binds to and activates
VII which then activates factor X and so on
Thrombin Actions
- Production of _____
- ____ fibrin
- Activating _____
- Stimulating the production of ______ activator by endothelial cells
- Production of fibrin from fibrinogen
- Cross-linking fibrin
- Activating platelets
- Stimulating the production of tissue plasminogen activator (t-PA) by endothelial cells
Complement System:
(#) proteins – most inactive ______
Classical pathway: Initiated by ______ complexes
30+ proteins – most inactive enzyme precursors
Classical pathway: Initiated by antigen-antibody complexes
Complement System: Alternative pathway
- Initiated by ___ (a product of the classical pathway)
- Initiated by ____ activation on a _____ basis
- Feedback loop for ______
- Initiated by C3b (a product of the classical pathway)
- Initiated by spontaneous activation on a continuous basis
- Feedback loop for amplification
Complement System: Terminal Pathway
- Classical and Alternative merge at the level of ____
- End products work to prevent / limit damage from _____
- Classical and Alternative merge at the level of C3 convertase production
- End products work to prevent / limit damage from invading organism or toxin
End Product-Membrane Attack Complex:
Works to prevent / limit damage from invading organism or toxin by (7)
opsonization lysis agglutination neutralization of viruses chemotaxis activation of mast cells and basophils inflammation
End Product-Membrane Attack Complex: opsonization= (2)
- neutrophils & macrophages activated
* they engulf bacteria to which antigen-antibody complex is attached
End Product-Membrane Attack Complex: lysis= (2)
- 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
End Product-Membrane Attack Complex: agglutination= (2)
- complement products change surface of invading organisms
* organisms adhere to each other
End Product-Membrane Attack Complex: neutralization of viruses=
•products can attack structures of some viruses and render them non-virulent
End Product-Membrane Attack Complex: chemotaxis= (2)
- C5a causes chemotaxis of neutrophils & macrophages
* large number phagocytes migrate to area
End Product-Membrane Attack Complex: activation of mast cells and basophils= (3)
- activated by C3a, C4a, & C5a
- cells release histamine and other substances into local fluids
- results increased local blood flow & increased leakage of fluid and protein into the tissue
End Product-Membrane Attack Complex: inflammation = (3)
- increased capillary permeability
- altered vasomotor tone
- impaired cardiac function
Both pathways activated by cardiopulmonary bypass- what causes (6)
cellular damage endothelial and leukocyte activation histamine release increased vascular permeability generalized inflammatory response platelet activation
Classical pathway activation: (4)
Surface contact activation of factor XII
Heparin-protamine complexes
Ischemia reperfusion
Blood-air interface
Alternative pathway activation: (3)
Contact with foreign surface
Activated pericardium and suction blood
Ischemia reperfusion
Complement System & CPB: Activated by both pathways but _____ pathway principal pathway during CPB
alternate
Complement System & CPB: anaphylatoxins with vasoactive properties
C3a, C4a, C5a
Complement System & CPB: major neutrophil agonist
C5a
Complement System & CPB: opsonization is from
C3b, C4b
Complement System & CPB: Terminal complement complex does what
- accelerates thrombin formation via action on prothrombinase complex
- activates platelets
