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1. Inflammation Part 4 click to watch the earlier videos of inflammation Inflammation 1: https://www.youtube.com/edit?o=U&vide... Inflammation 2: https://www.youtube.com/edit?o=U&vide... Inflammation 3: https://www.youtube.com/edit?o=U&vide... 3. MEDIATORS OF INFLAMMATION 4. Overview • General Properties • Types of mediators • Histamine and Serotonin 5. Mediators of inflammation These are the substances that INITIATE REGULATE& Inflammatory reactions 6. General properties These mediators can be produced Locally, by the CELLS Derived from inactive precursors present in plasma CELL- DERIVED PLASMA -DERIVED Preformed/ Ready made! Synthesised de novo/ made if needed! 1 7. They can be produced only in response to agents that stimulate inflammation They can stimulate the release of another mediator They have short lifespan! They can act on wide variety of cells 2 3 4 5 8. Preformed Synthesised de novo • Histamine • Serotonin • Arachidonic acid metabolites • Platelet activating factor • NO • Reactive oxygen species • Cytokines • Chemokines Compliment activation Factor XII activation • C3a • C3b • C5a • Coagulation system • Kinin system Cell - Derived Plasma - Derived CHEMICAL MEDIATORS OF INFLAMMATION 9. HISTAMINE & SERATONIN Vasoactive amines Are the first mediators to be released during inflammation Once formed it can be either stored or rapidly inactivated Derived from the decarboxylation of the amino acid histidine 10. Sources Mast cells Basophils Platelets Stimulus Substances inducing inflammation like heat,cold, irradiation,trauma etc C3a & C5a: Anaphylatoxins IL-1 & IL8. Histamine releasing factors from cells like neutrophils, monocytes and Platelets. 11. ACTIONS Increase in Vascular permeability Vasodilatation It is responsible for the Wheal & Flare reaction in the skin. Responsible for itching and pain Also mediates bronchial Asthma and anaphylactic shock By Increasing Blood Flow and Endothelial Barrier Disruption 12. ACTIONS Increase in Vascular permeability By Increasing Blood Flow and Endothelial Barrier Disruption Vasodilatation It is responsible for the Wheal & Flare reaction in the skin. Responsible for itching and pain Also mediates bronchial Asthma and anaphylactic shock Resulting from nitric oxide release Contraction of extravascular smooth muscles eg:bronchus By the excitation of a subset of unmyelinated C-fibers which are pruriceptive. 13. SEROTONIN 5- Hydroxytryptamine Stored in platelets and mast cells Also in chromaffin cells of GIT, spleen and nervous tissue Actions are similar to Histamine but less potent. 14. Summary • General Properties • Types of mediators • Histamine and Serotonin