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“ Coagulation and Inflammation Physiological Process for Numerical Studies”

Instituto Superior Técnico. UTAustin | Portugal Workshop on Modeling and Simulation of Physiological Systems December 6-8, 2012, Lisbon, Portugal. “ Coagulation and Inflammation Physiological Process for Numerical Studies”.

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“ Coagulation and Inflammation Physiological Process for Numerical Studies”

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  1. Instituto Superior Técnico UTAustin | Portugal Workshop on Modeling and Simulation of Physiological Systems December 6-8, 2012, Lisbon, Portugal “ Coagulation and Inflammation Physiological Process for Numerical Studies” Carlota Saldanha and Ana Silva - Herdade

  2. Instituto Superior Técnico UTAustin | Portugal Workshop on Modeling and Simulation of Physiological Systems December 6-8, 2012, Lisbon, Portugal “ Coagulation and Inflammation Physiological Process for Numerical Studies” Inflammation Hemostasis ( Platelets, Coagulation, Fibrinolysis, Anticoagulation) Interrelation between Hemostasis and Inflammation and Vice Versa Carlota Saldanha and Ana Silva - Herdade

  3. Vessels of Circulatory System arteriole venule

  4. Blood Components

  5. Swelling of Endothelial Cell Obstruct RBC flow Granular Blood Flow Rouleaux Pre Stasis WBC Cell free Plasma Rigid RBC In: Exempla Haemorheologica Booklet 3. The Microcirculation in the terminal vascular bed

  6. Microcirculation RBC and WBC Flow Intravital microscopy image of blood flow in mice venule

  7. Acute inflammation Resulting from Infection by leukocytes onC-type sensors nerves fibres

  8. Inflammatory Response to a Tissue Injury http://drugline.org/medic/term/inflammatory-response/

  9. Neutrophil and Endothelium in Inflammation TISSUE INJURED

  10. Type I Activation of Endothelial Cell Stimulation- Rapid response independent of new genes expression Typically mediated by ligands P-Selectin PAF Resolves due receptor desensitization Nature Reviews Immunology 7, 803-815(October 2007)

  11. Type II Activation of Endothelial Cell in Acute Inflammation More sustained inflammatory response Slow response dependent of new genes expression TNFα; IL-1 are derived from activated leukocytes Open gaps Leakage of fibrinogen Hard swelling Leukocytes recruitment more effective E –Selectin IL-8 VENULES (-) AP1 shut of E-Selectin >>VCAM1; ICAM-1 (+ by Cytokines) Mononuclear –cell rich infiltrates CAPILLARIES TNFα; IL-1. IFNγ EC death Favours thrombosis; apoptotic cells lose their anticoagulant sheding hepa ran sulphate ; exocytosis microparti cles Shuting off NOS3 and Trombomodulin by TNFα; TNFα; IL-1 induce Tf microparticles shed from cell surface Thrombus: fibrin +plateles wall of infe cted tissue limit spread of microbes juxtacrine Resolves by removal stimulus; by terminus NFk-β Nature Reviews Immunology 7, 803-815(October 2007)

  12. Microcirculation Normal / Inflamed Creates a provisional matrix to support leukocytes entry to tissues

  13. Acute Phase Proteins Kidney International, Vol. 58, Suppl. 76 (2000), pp. S-96–S-103

  14. Plug Clot

  15. Extrinsic and Intrinsic Coagulation Cascade Interwined Pathways colagen * Activation by Thrombin * * * * FXIIIa Fibrin Plolymer TFPI

  16. Endothelial Cell in Resting Non inflamed state Nature Reviews Immunology 2007; 7, 803-815

  17. Physiological Anticoagulants Biochemia Medica 2012;22(1):49-62.

  18. Coagulation Fibrinolysis

  19. Recovery of Vessel Wall

  20. Inflammation/ Hemostasis Restore the Integrity of damaged tissues Bleeding Hemostatic Clot Can trap invading microbe;> vascular permeability Antimicrobial lysis Gram+

  21. Inflammation Affects Hemostasis Proinflammatory Cytokines TNFα, IL-1, IL-6 Brist J Haemat 2005; 131:417- 431 Circulation 2004;109:2698-2704 J Leukoc Biol 2008; 83:536-545 Biochemia Medica 2012;22(1):49-62

  22. Inflammation Affects Fibrinolytic System +Platelets release PAI-1 • 1st >> tPA • 2nd >>PAI-1(ECs TN-Fα, IL-1β) • << fibrin removal • 3rd endothelium dysfunction sustain <<tissue plasminogen activator (tPA)

  23. Inflammation Activates Coagulation Biochemia Medica 2012;22(1):49-62

  24. Inflammation Affects Hemostasis Platelet acting as proinflammatory cell Biochemia Medica 2012;22(1):49-62

  25. Platelet acting as proinflammatory cell Hematology 2011; 2011:51-61

  26. Contribute of Coagulation in Inflammation GF TNFα; IL-β CD40L IL-1β; PAF-4 MHC; ROS PSGPL P-Selectin IL-8; MCP-1 IL-1β TNFα Mac-1 PSGPL Fibrina Tf – FVIIa-FXa ICAM; VCAM ECs IL-6;IL-8; MCP-1 ECs (PARs) Activated platelet monocyte neutrophil

  27. Contribute of Coagulation in Inflammation and Vice Versa IL-6 TNFα; IL-1β ROS leukocytes adhesion PAR-2 + ECs adhesion TNFα, IL-1βon monocytes IL-8; MCP-1on ECs PAR-1, 3, 4 Monocytes Fibg/Fibrin activate leukocyte recruitment (TLR ) Thol like receptor ; and expression Blood 1996;87:5051-5060 Circ Res 2005;96:1217 Critical Concepts 2007 PAR-2 establish cross talk between inflammation-coagulation

  28. Instituto Superior Técnico UTAustin | Portugal Workshop on Modeling and Simulation of Physiological Systems December 6-8, 2012, Lisbon, Portugal “ Coagulation and Inflammation Physiological Process for Numerical Studies” Thank you

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