Topic 13 Part 2 Flashcards
Red Blood Cells (erythrocytes) role is
uptake / transport / removal oxygen & carbon dioxide
White Blood Cells (leukocytes): types of Granulocytes
neutrophils
eosinophils
basophils
neutrophils: % and role
(60 to 70%)
destroy bacteria via phagocytosis
eosinophils: % and role
(2 to 4 %)
destroy complex products antigen-antibody reactions
basophils: % and role
(.5 to 1%) (release histamine & heparin – vasodilation)
White Blood Cells (leukocytes): types of Agranulocytes
monocytes
lymphocytes
monocytes: % and role
(3 to 8%)
transform into tissue macrophage
lymphocytes: % and role
(20 to 25%)
attach destroy/deactivate bacteria, viruses, other foreign cells – acquired immune response
Platelets (thrombocytes) role
coagulation
Key Players: Five Cells
Platelets Neutrophils Monocytes Lymphocytes Endothelial Cells
Platelets – Initial / Early Activation:
- Surface contact with ___
- Heparin: increases _____
- Circulating thrombin: powerful ____/ probably initial __
- ____-activating factor
- Surface contact with ECC
- Heparin: increases sensitivity
- Circulating thrombin: powerful agonist/ probably initial activator
- Platelet-activating factor (PAF)
Platelets – Late Activation: (7)
Activated Complement (C5b – C9) Plasmin Hypothermia Interleukin-6 Cathepsin G Serotonin Epinephrine
Platelets – Response to Activation: Immediate shape change -express \_\_\_\_ pods -express surface receptors (2) -secrete receptors from granules: \_\_\_\_
- express pseudo pods
- express surface receptors: GPIIb/IIIa and GPIb
- secrete receptors from granules: P-selectin
Platelets – Response to Activation:
____ receptors bind to surface adsorbed fibrinogen – use fibrinogen as bridge to bind to other _____
GPIIb/IIIa receptors bind to surface adsorbed fibrinogen – use fibrinogen as bridge to bind to other platelets
Platelets – Response to Activation:
_____ receptors bind to _____ & _____ to form aggregates
P-selectin receptors bind to monocytes & neutrophils to form aggregates
Platelets – Response to Activation:
Some platelets break off forming
emboli
Platelets – Response to Activation:
Some platelets release a variety of chemicals and proteins (4)
thromboxane-A2
platelet factor 4
Beta-thromboglobulin
serotonin
Neutrophil – Very Strong Activation:
Principal agonists
kallikrein and C5a
Neutrophil – Very Strong Activation: Other agonists (6)
factor XIIa heparin MAC interleukin 1 Beta interleukin 8 TNF
Neutrophil – Very Strong Activation: Release contents of granules (9)
lysosomal enzymes elastase myeloperoxidase hydrogen peroxide hydroxyl radicals hypochlorous acid hypobromous acid acid hydrolases collagenases
Neutrophil – Very Strong Activation: Express MAC-1 (CD11b/CD18) & CD11c/CD18 receptors which bind to (2)
- binds to fibrinogen, complement fragment, endothelial cells, collagen
- binds with factor X and fibrinogen to facilitate thrombin formation
Neutrophil – Very Strong Activation: Express L-selectin receptor which binds to
binds with P-selectin expressed by endothelial cells and platelets
Neutrophil – Very Strong Activation: Major role in
ischemia-reperfusion injury & responsible for much of inflammatory response associate with bypass
Monocyte Activation: Slow activation during CPB by (3)
C5a
thrombin
bradykinin
Monocyte Activation:
- Activated in ___ and ____
- Form conjugates with platelets via ____ and _____
- Delayed increase of tissue factor seen __ hours post CPB
- Activated in wound and circuit
- Form conjugates with platelets via GMP-140 and express tissue factor
- Delayed increase of tissue factor seen 20 hours post CPB
Monocyte Activation:
Produce and release cytokines:
- IL-6 and IL-8 during and post CPB
- IL-1, IL-2, IL-4 post CPB
Lymphocyte Response
- Number of cells - reduced ____ after bypass
- Cell responsiveness to ____ / other agonist is reduced
- Number of cells - reduced first week after bypass
- Cell responsiveness to mitogens / other agonist – reduced
Lymphocyte Response
Increases susceptibility of postoperative infections (2)
Septic shock
Endocarditis
Endothelial Cell Activation: Activation agents
thrombin, C5a, various cytokines, TNF
Endothelial Cell Activation: Cells produce (7)
prostacyclin heparan sulfate thrombomodulin protease nexin-1 protein S tissue factor pathway inhibitor t-PA
Endothelial Cell Activation: Cells produce vasoactive substances like (6)
nitric oxide endothelin PAF histamine norepinephrine bradykinin
Endothelial Cell Activation: Express various receptors (5)
tissue factor P-selectin E-selectin ICAM-1 VCAM-1
Activated Endothelial Cells:
- Synthesize _____ to generate _____
- Initiate _____
- Contribute to the overall acute ______ response
- Allow ___ and ____ to enter the interstitial space
- Synthesize tissue factor to generate thrombin
- Initiate fibrinolysis
- Contribute to the overall acute inflammatory response
- Allow fluid and leukocytes to enter the interstitial
Hematologic Factors Activated by CPB: Activation Pathway- soluble factors
coagulation cascade
complement cascade
fibrinolytic system
Hematologic Factors Activated by CPB:Activation Pathway- cellular factors
platelets neutrophils monocytes lymphocytes endothelial cells
Hematologic Factors Activated by CPB: Active Mediators Generated- soluble factors
Kallikrein, HMWK, thrombin
C3a, C5a, C5b-9
Plasmin
Hematologic Factors Activated by CPB:Active Mediators Generated- cellular factors
TXA2, serotonin Oxygen radicals, elastase Oxygen radicals, cytokines Cytokines T-PA, cytokines
Possible Contributions to Bleeding After CPB
Platelet Related Causes (8)
- Thrombocytopenia
- Aspirin-induced platelet dysfunction
- Impaired aggregation response to agonists (epinephrine, collagen, ADP, thrombin
- Selective loss of youngest (most functional) platelets
- Platelet fragmentation / loss of membrane receptors
- Impaired platelet-mediated clot retraction
- Plasmin-induced platelet activation / dysfunction
- Platelet activation / dysfunction induced by C5b-9
% of Normal Conc Needed for Coagulation:
Intrinsic System Only
XII Hageman factor
none
% of Normal Conc Needed for Coagulation:
Intrinsic System Only
XI Plasma thromboplastin antecedent
20
% of Normal Conc Needed for Coagulation:
Intrinsic System Only
IX Christmas factor
40
% of Normal Conc Needed for Coagulation:
Intrinsic System Only
VIII Antihemophilic factor A
30
% of Normal Conc Needed for Coagulation:
Extrinsic System Only
VII Proconvertin
25
% of Normal Conc Needed for Coagulation:
Common Pathway
X Stuart factor
40
% of Normal Conc Needed for Coagulation:
Common Pathway
V Proaccelerin, labile factor
40
% of Normal Conc Needed for Coagulation:
Common Pathway
II Prothrombin
40
% of Normal Conc Needed for Coagulation:
Common Pathway
I Fibrinogen
100 mg/dL
Control of Blood-Surface Interface:
Develop biomaterial that mimics the endothelial cell layer (2)
surface-bound heparin
surface-modifying additives
Control of Blood-Surface Interface:
Prevent or block activation of the blood during bypass=
blood modification
Control of Blood-Surface Interface:
Prevent activated blood from reaching your circuit=
Sequestered cardiotomy suction
Surface-Bound Heparin is ____ and _____
ionic and covalent
Surface-Bound Heparin claims (5)
suppress thrombin formation
reduce blood loss & transfusion requirements
attenuate inflammatory response
depress platelet activation
decrease in clinical indicators of morbidity
Results of Surface-Bound Heparin:
Neither showed much decrease in thrombin formation
Mixed results for: (3)
No study showed clinical benefits from using a circuit with surface-bound heparin
- post-op bleeding and transfusion requirements
- attenuation of complement
- decreased activation of neutrophils and monocytes
Surface-Modifying Additives for Terumo
X Coating (poly(2-methoxyethylacrylate) (PMEA)-NO heparin)
Surface-Modifying Additives for Medtronic (3)
- Carmeda (HEPARIN coating – covalent bonded)
- Trillium (HEPARIN coating – covalent bonded)
- Balance Biosurface (hydrophilic polymer coating-NO heparin)
Surface-Modifying Additives for Maquet (2)
- Bioline (combined albumin and HEPARIN coating )
2. Softline (hydrophilic & hydrophobic polymer coating-NO heparin)
Surface-Modifying Additives for Sorin
P.h.i.s.i.o (synthetic phosphorylcholine-NO heparin)
Blood Modification:
Preop administration of ______ attenuates complement activation
corticosteroids
Blood Modification: Antifibrinolytic agents: Aprotinin=
inhibits plasmin directly
high dose partially inhibits kallikrein – platelet sparing
Blood Modification: Antifibrinolytic agents: W-aminocarboxylic acids=
inhibit cleavage of plasminogen to plasmin
Blood Modification: Antifibrinolytic agents: (4)
Aprotinin
W-aminocarboxylic acids
Tranexamic acid
ε-aminocaproic acid
Blood Modification:
Platelet anesthesia= (3)
Reversible inhibition of platelets during procedure
Eptifibatide (Integrilin) with or without nitric oxide
Nitric oxide provides partial protection
Blood Modification: Complement inhibition= (2)
Pexelizumab
TP 10