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INFLAMMATION:

CHEMICAL
MEDIATORS
R. HUGO MARTÍNEZ LOZANO, M.D.

August 31, 2006.


LEARNING OBJECTIVES: K & U
 GENERAL FEATURES
 ORIGIN
 TYPES
 ROLES
 CORRELATION
 OUTCOMES OF THE ACUTE
INFLAMM.
CHEMICAL MEDIATORS
TYPES, ROLES & CORRELATION OF:
- VASOACTIVE AMINES
- KININES
- COMPLEMENT SYSTEM
- CLOTTIN SYSTEM
- A. A. METABOLITES
CHEMICAL MEDIATORS
- PAF
- CYTOKINES AND CHEMOKINES
- NO
- LEUCOCYTE´S GRANULES
- FREE R. AND NEUROPEPTIDES
CORELATE WITH MEDICAL
SIGNIFICANCE!!!
CHEMICAL MEDIATORS
I.- GENERAL FEATURES:
- ORIGIN
- ACTIVATION
- PRIMARY OR SECONDARY
- MOST: - QUICKLY DECAI, OR
- ARE INACTIVATED
- POTENTIALLY HARMFULL
CHEMICAL MEDIATORS
II) ORIGIN:
CELLS:
- PREFORMED (HISTAMINE, SEROTONIN)
- SYNTHESIZED DE NOVO (PG, CYTOKINES,
ETC.)
- CELLULAR SOURCES:
- PLATELETS
- NEUTROPHILES
- MONOCYTIC/MACROPHAGIC SYSTEM
- OTHER
CHEMICAL MEDIATORS
V) VASOACTIVE AMINES:
- HISTAMINE:
-STORED IN: MAST CELLS, BASOPHILES,
PLAT.
- DEGRANULATION:
- PHYSICAL INJURY
- IMMUNE
- C3a AND C5a
- LEUCOCYTES´ PRODUCTS
- NEUROPEPTIDES
- CYTOKINES
MUCOUS
PLUG
CHEMICAL MEDIATORS
- SEROTONIN:
- STORED IN: PLATELETS & E-CROM. CELLS

- DEGRANULATION: - PLAT. AGGREGATION

- ACTIONS: SIMILAR TO HISTAMINE


CHEMICAL MEDIATORS
VI) PLASMA PROTEASES:
A)- C. SYSTEM:
- C3a, C5a: ANAPHYLOTOXINS:

- VASODILATION
- INCREASE VASCULAR PERMEAB.
- ACTIVATES: LO-PATHWAY
- C5a--- CHEMOTAXIS
- C3b, C3BI--- OPSONINS
- C5-C9--- MAC
CHEMICAL MEDIATORS
VI) PLASMA PROTEASES:
COMPLEMENT SYSTEM:
- ACTIVATION:
- CLASSICAL PATH.
- ALTERNATIVE PATH.
- PLASMIN
- LYSOSOMAL PRODUCTS
CHEMICAL MEDIATORS
V) PLASMA PROTEASES:
B) KININ SYSTEM:
- KININOGENS
- IMPORTANT ELEMENTS:
- BRADIKININ: SIMILAR TO HISTAMINE
- KALLICREIN: - ACTIVATES HAGEMAN´S
- CHEMOTAXIS
- C5---C5a.
CHEMICAL MEDIATORS
C) CLOTTING SYSTEM:
- LINKS COAGULATION/INFLAMMATION:
A)THROMBIN (IIa) - VASC. PERMEABILITY
- CHEMOTAXIS
- OTHER
B) FACTOR Xa------ VASC. PERMEABILITY
ALSO: CLOSE INTERACTION: KININ/PLASMINO
GEN-PLASMIN/COMPLEMENT AND CLOTTING
SYSTEMS
CHEMICAL MEDIATORS:
MEDICAL SIGNIFICANCE
15 YEAR-OLD BOY WITH ABDOMINAL
PAIN, 24 HOURS OF EVOLUTION.
FEVER AND VOMITING DURING THE
LAST 18 HOURS. AT THE P.E.:
SEVERE PAIN AT THE LOWER RIGHT
CUADRANT. NO BOWEL MOVEMENTS
AND ABDOMINAL MUSCLES
RESISTENCE AT PALPATION.
UNDERWENT SURGICAL
EXPLORATION...
(-) REGULATORS:
-LIPOXINS
-RESOLVINS (?)
GANGRENE
“WET”
GANGRENE
CLOSTRIDIUM P.
CHEMICAL MEDIATORS
VII) PAF:
- NATURE
- SOURCES
- ACTIONS
CHEMICAL MEDIATORS
VIII) CYTOKINES AND CHEMOKINES:
DEFINITIONS:
- CYTOKINES...
- CHEMOKINES...
IMPORTANT ELEMENTS:
- IL-1, TNF (ALFA AND BETA)
- CHEMOKINES: -CXC (ALFA) –IL-8
-C-C (BETA) –MCP-1
-C (GAMMA) –LT
LEPROSY
CHEMICAL MEDIATORS
IX) NO:
CHEMICAL MEDIATORS
X) LYSOSOMAL CONSTITUENTS:
BRONCHOPNEUMONIA
CHEMICAL MEDIATORS
XI) OXIGEN DERIVED FREE RADICALS
- O2-
- H2O2
- OH.
CHEMICAL MEDIATORS
XII) NEUROPEPTIDES:
- SUBSTANCE P
- NEUROKININ A
NEUROPEPTIDES:
- VASC. PERMEAB.
- PAIN
OUTCOMES
 RESOLUTION
 COMPLICATIONS
 HEALING/FIBROSIS
CHEMICAL MEDIATORS:

QUESTIONS?