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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”. - PowerPoint PPT Presentation
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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
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
Instituto Superior Técnico
InflammationHemostasis ( Platelets, Coagulation, Fibrinolysis, Anticoagulation) Interrelation between Hemostasis and Inflammation and Vice Versa
arteriole
venule
Vessels of Circulatory System
Blood Components
RouleauxPreStasis
Granular Blood Flow
Cell freePlasma
RigidRBC
Swelling ofEndothelial CellObstruct RBC flow
In: Exempla Haemorheologica Booklet 3. The Microcirculation in the terminal vascular bed
WBC
RBC and WBC Flow
Microcirculation
Intravital microscopy image of blood flow in mice venule
Acute inflammation Resulting from Infection
by leukocytes on C-typesensors nerves fibres
Inflammatory Response to a Tissue Injury
http://drugline.org/medic/term/inflammatory-response/
Neutrophil and Endothelium in Inflammation
TISSUE INJURED
Type I Activation of Endothelial Cell
Nature Reviews Immunology 7, 803-815 (October 2007)
Stimulation- Rapid response independent of new genes expression Typically mediated by ligands
P-SelectinPAFResolves due receptor desensitization
Type II Activation of Endothelial Cell in Acute Inflammation
Nature Reviews Immunology 7, 803-815 (October 2007)
More sustained inflammatory responseSlow response dependent of new genes expression
TNFα; IL-1 are derivedfrom activated leukocytes
Open gapsLeakage of fibrinogenHard swelling
Leukocytes recruitmentmore effective
E –Selectin IL-8
VENULES(-) AP1 shut of E-Selectin>>VCAM1; ICAM-1 (+ byCytokines) Mononuclear –cell rich infiltrates
CAPILLARIES TNFα; IL-1. IFNγ EC deathFavours thrombosis; apoptotic cellslose their anticoagulant sheding heparan sulphate ; exocytosis microparticlesShuting off NOS3 and Trombomodulinby TNFα; TNFα; IL-1 induce Tf microparticles shed from cell surfaceThrombus: fibrin +plateles wall of infected tissue limit spread of microbes
Resolves by removal stimulus; by terminus NFk-β
juxtacrine
Creates a provisional matrix to support leukocytesentry to tissues
Microcirculation Normal / Inflamed
Kidney International, Vol. 58, Suppl. 76 (2000), pp. S-96–S-103
Acute Phase Proteins
Plug
Clot
*
**
* Activation by Thrombin
Extrinsic and Intrinsic Coagulation CascadeInterwined Pathways
Fibrin Plolymer
FXIIIa
colagen
*
TFPI
Endothelial Cell in Resting Non inflamed state
Nature Reviews Immunology 2007; 7, 803-815
Physiological Anticoagulants
Biochemia Medica 2012;22(1):49-62.
Fibrinolysis
Coagulation
Recovery of Vessel Wall
Inflammation / Hemostasis
Hemostatic ClotCan trap invading microbe;> vascular permeabilityAntimicrobial lysis Gram+
Bleeding
Restore theIntegrity of damaged tissues
Proinflammatory Cytokines TNFα, IL-1, IL-6
Inflammation Affects Hemostasis
Brist J Haemat 2005; 131:417- 431 Circulation 2004;109:2698-2704J Leukoc Biol 2008; 83:536-545 Biochemia Medica 2012;22(1):49-62
Inflammation Affects Fibrinolytic System
•1st >> tPA•2nd >>PAI-1(ECs TN-Fα, IL-1β)<< fibrin removal•3rd endothelium dysfunction sustain <<tissue plasminogen activator (tPA)
+Platelets releasePAI-1
Inflammation Activates Coagulation
Biochemia Medica 2012;22(1):49-62
Biochemia Medica 2012;22(1):49-62
Inflammation Affects HemostasisPlatelet acting as proinflammatory cell
Platelet acting as proinflammatory cell
Hematology 2011; 2011:51-61
Fibrina
neutrophil
TNFα
CD40LIL-1β; PAF-4
GF
Tf – FVIIa-FXa
monocyte
MHC; ROS
Activated platelet
Mac-1
(PARs)
TNFα; IL-β
IL-6;IL-8; MCP-1
Contribute of Coagulation in Inflammation
IL-1β
ICAM; VCAM
P-Selectin
PSGPL
PSGPL
ECsECs
IL-8; MCP-1
Monocytes
IL-6TNFα; IL-1β
Blood 1996;87:5051-5060Circ Res 2005;96:1217Critical Concepts 2007
adhesion
adhesion
ROSleukocytes
TNFα, IL-1β on monocytes
IL-8; MCP-1 on ECs PAR-1, 3, 4
PAR-2
Contribute of Coagulation in Inflammationand Vice Versa
ECs
+
Fibg/Fibrin activate leukocyte recruitment(TLR ) Thol like receptor ; and expression
PAR-2 establish cross talk between inflammation-coagulation
UTAustin | Portugal Workshop on Modeling and Simulation of Physiological Systems
December 6-8, 2012, Lisbon, Portugal
“ Coagulation and Inflammation
Physiological Process for Numerical Studies”
Instituto Superior Técnico
Thank you