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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”.

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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”

Carlota Saldanha and Ana Silva - Herdade


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”

Inflammation

Hemostasis ( Platelets, Coagulation, Fibrinolysis, Anticoagulation)

Interrelation between Hemostasis and Inflammation and Vice Versa

Carlota Saldanha and Ana Silva - Herdade


Coagulation and inflammation physiological process for numerical studies

Vessels of Circulatory System

arteriole

venule


Coagulation and inflammation physiological process for numerical studies

Blood Components


Coagulation and inflammation physiological process for numerical studies

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


Coagulation and inflammation physiological process for numerical studies

Microcirculation

RBC and WBC Flow

Intravital microscopy image of blood flow in mice venule


Coagulation and inflammation physiological process for numerical studies

Acute inflammation Resulting from Infection

by leukocytes onC-type

sensors nerves fibres


Coagulation and inflammation physiological process for numerical studies

Inflammatory Response to a Tissue Injury

http://drugline.org/medic/term/inflammatory-response/


Coagulation and inflammation physiological process for numerical studies

Neutrophil and Endothelium in Inflammation

TISSUE INJURED


Coagulation and inflammation physiological process for numerical studies

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)


Coagulation and inflammation physiological process for numerical studies

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)


Coagulation and inflammation physiological process for numerical studies

Microcirculation Normal / Inflamed

Creates a provisional

matrix to support leukocytes

entry to tissues


Coagulation and inflammation physiological process for numerical studies

Acute Phase Proteins

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


Coagulation and inflammation physiological process for numerical studies

Plug

Clot


Coagulation and inflammation physiological process for numerical studies

Extrinsic and Intrinsic Coagulation Cascade

Interwined Pathways

colagen

* Activation by Thrombin

*

*

*

*

FXIIIa

Fibrin

Plolymer

TFPI


Coagulation and inflammation physiological process for numerical studies

Endothelial Cell in Resting Non inflamed state

Nature Reviews Immunology 2007; 7, 803-815


Coagulation and inflammation physiological process for numerical studies

Physiological Anticoagulants

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


Coagulation and inflammation physiological process for numerical studies

Coagulation

Fibrinolysis


Coagulation and inflammation physiological process for numerical studies

Recovery of Vessel Wall


Coagulation and inflammation physiological process for numerical studies

Inflammation/ Hemostasis

Restore the

Integrity of

damaged

tissues

Bleeding

Hemostatic Clot

Can trap invading microbe;> vascular permeability

Antimicrobial lysis Gram+


Coagulation and inflammation physiological process for numerical studies

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


Coagulation and inflammation physiological process for numerical studies

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)


Coagulation and inflammation physiological process for numerical studies

Inflammation Activates Coagulation

Biochemia Medica 2012;22(1):49-62


Coagulation and inflammation physiological process for numerical studies

Inflammation Affects Hemostasis

Platelet acting as proinflammatory cell

Biochemia Medica 2012;22(1):49-62


Coagulation and inflammation physiological process for numerical studies

Platelet acting as proinflammatory cell

Hematology 2011; 2011:51-61


Coagulation and inflammation physiological process for numerical studies

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


Coagulation and inflammation physiological process for numerical studies

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


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”

Thank you


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