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INFLAMMATION: INFLAMMATION: CHEMICAL CHEMICAL
MEDIATORSMEDIATORS
R. HUGO MARTÍNEZ LOZANO, M.D.R. HUGO MARTÍNEZ LOZANO, M.D.
August 31, 2006.August 31, 2006.
LEARNING OBJECTIVES: K & ULEARNING OBJECTIVES: K & U
GENERAL FEATURESGENERAL FEATURES ORIGINORIGIN TYPESTYPES ROLESROLES CORRELATIONCORRELATION OUTCOMES OF THE ACUTE INFLAMM.OUTCOMES OF THE ACUTE INFLAMM.
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
TYPES, ROLES & CORRELATION OF:TYPES, ROLES & CORRELATION OF:
- VASOACTIVE AMINES- VASOACTIVE AMINES
- KININES- KININES
- COMPLEMENT SYSTEM- COMPLEMENT SYSTEM
- CLOTTIN SYSTEM- CLOTTIN SYSTEM
- A. A. METABOLITES- A. A. METABOLITES
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
- PAF- PAF
- CYTOKINES AND CHEMOKINES- CYTOKINES AND CHEMOKINES
- NO- NO
- LEUCOCYTE´S GRANULES- LEUCOCYTE´S GRANULES
- FREE R. AND NEUROPEPTIDES- FREE R. AND NEUROPEPTIDES
CORELATE WITH MEDICALCORELATE WITH MEDICAL
SIGNIFICANCE!!!SIGNIFICANCE!!!
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
I.- GENERAL FEATURES:I.- GENERAL FEATURES:
- ORIGIN- ORIGIN
- ACTIVATION- ACTIVATION
- PRIMARY OR SECONDARY- PRIMARY OR SECONDARY
- MOST: - QUICKLY DECAI, OR- MOST: - QUICKLY DECAI, OR
- ARE INACTIVATED- ARE INACTIVATED
- - POTENTIALLY HARMFULLPOTENTIALLY HARMFULL
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
II) ORIGIN:II) ORIGIN:
CELLS:CELLS: - - PREFORMED (HISTAMINE, SEROTONIN)PREFORMED (HISTAMINE, SEROTONIN)
- SYNTHESIZED DE NOVO (PG, CYTOKINES, ETC.)- SYNTHESIZED DE NOVO (PG, CYTOKINES, ETC.)
- CELLULAR SOURCES:- CELLULAR SOURCES:
- PLATELETS- PLATELETS
- NEUTROPHILES- NEUTROPHILES
- MONOCYTIC/MACROPHAGIC SYSTEM- MONOCYTIC/MACROPHAGIC SYSTEM
- OTHER- OTHER
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
V) VASOACTIVE AMINES:V) VASOACTIVE AMINES: - HISTAMINE:- HISTAMINE: -STORED IN: MAST CELLS, BASOPHILES, -STORED IN: MAST CELLS, BASOPHILES,
PLAT.PLAT. - DEGRANULATION:- DEGRANULATION: - PHYSICAL INJURY- PHYSICAL INJURY - IMMUNE- IMMUNE - C3a AND C5a- C3a AND C5a - LEUCOCYTES´ PRODUCTS- LEUCOCYTES´ PRODUCTS - NEUROPEPTIDES- NEUROPEPTIDES - CYTOKINES- CYTOKINES
DEATH AFTER ASMATHIC CRISIS
MUCOUS PLUG
BRONCHIOLAR PLUG
MUCOUS PLUG & EOSINOPHILS
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
- - SEROTONIN:SEROTONIN: - STORED IN: PLATELETS & E-CROM. CELLS- STORED IN: PLATELETS & E-CROM. CELLS
- DEGRANULATION: - PLAT. AGGREGATION- DEGRANULATION: - PLAT. AGGREGATION
- ACTIONS: SIMILAR TO HISTAMINE- ACTIONS: SIMILAR TO HISTAMINE
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
VI) PLASMA PROTEASES:VI) PLASMA PROTEASES: A)- C. SYSTEM:A)- C. SYSTEM:
- - C3a, C5a: ANAPHYLOTOXINSC3a, C5a: ANAPHYLOTOXINS: :
- - VASODILATIONVASODILATION - INCREASE VASCULAR PERMEAB.- INCREASE VASCULAR PERMEAB. - ACTIVATES: LO-PATHWAY- ACTIVATES: LO-PATHWAY
- C5a--- CHEMOTAXIS- C5a--- CHEMOTAXIS - C3b, C3BI--- OPSONINS- C3b, C3BI--- OPSONINS - - C5-C9--- MACC5-C9--- MAC
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
VI) PLASMA PROTEASES:VI) PLASMA PROTEASES:
COMPLEMENT SYSTEM:COMPLEMENT SYSTEM:
- ACTIVATION:- ACTIVATION:
- CLASSICAL PATH.- CLASSICAL PATH.
- ALTERNATIVE PATH.- ALTERNATIVE PATH.
- PLASMIN- PLASMIN
- LYSOSOMAL PRODUCTS- LYSOSOMAL PRODUCTS
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
V) PLASMA PROTEASES:V) PLASMA PROTEASES:
B) KININ SYSTEM:B) KININ SYSTEM:
- KININOGENS - KININOGENS
- IMPORTANT ELEMENTS:- IMPORTANT ELEMENTS: - BRADIKININ: SIMILAR TO HISTAMINE- BRADIKININ: SIMILAR TO HISTAMINE
- KALLICREIN: - ACTIVATES HAGEMAN´S- KALLICREIN: - ACTIVATES HAGEMAN´S
- CHEMOTAXIS- CHEMOTAXIS
- C5---C5a.- C5---C5a.
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
C) C) CLOTTING SYSTEM:CLOTTING SYSTEM: - LINKS COAGULATION/INFLAMMATION:- LINKS COAGULATION/INFLAMMATION: A)THROMBIN (IIa) - VASC. PERMEABILITYA)THROMBIN (IIa) - VASC. PERMEABILITY - CHEMOTAXIS - CHEMOTAXIS - OTHER - OTHER B) FACTOR Xa------ VASC. PERMEABILITYB) FACTOR Xa------ VASC. PERMEABILITYALSO: CLOSE INTERACTION: KININ/PLASMINOALSO: CLOSE INTERACTION: KININ/PLASMINOGEN-PLASMIN/COMPLEMENT AND CLOTTING GEN-PLASMIN/COMPLEMENT AND CLOTTING
SYSTEMSSYSTEMS
CHEMICAL MEDIATORS: CHEMICAL MEDIATORS: MEDICAL SIGNIFICANCEMEDICAL SIGNIFICANCE
15 YEAR-OLD BOY WITH ABDOMINAL 15 YEAR-OLD BOY WITH ABDOMINAL PAIN, 24 HOURS OF EVOLUTION. PAIN, 24 HOURS OF EVOLUTION.
FEVER AND VOMITING DURING THE FEVER AND VOMITING DURING THE LAST 18 HOURS. AT THE P.E.: LAST 18 HOURS. AT THE P.E.:
SEVERE PAIN AT THE LOWER RIGHT SEVERE PAIN AT THE LOWER RIGHT CUADRANT. NO BOWEL MOVEMENTS CUADRANT. NO BOWEL MOVEMENTS
AND ABDOMINAL MUSCLES AND ABDOMINAL MUSCLES RESISTENCE AT PALPATION. RESISTENCE AT PALPATION.
UNDERWENT SURGICAL UNDERWENT SURGICAL EXPLORATION... EXPLORATION...
(-) REGULATORS:-LIPOXINS-RESOLVINS (?)
BURNS
GANGRENE
“WET”GANGRENE
CLOSTRIDIUM P.
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
VII) PAF:VII) PAF:
- NATURE- NATURE
- SOURCES- SOURCES
- ACTIONS- ACTIONS
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
VIII) CYTOKINES AND CHEMOKINES:VIII) CYTOKINES AND CHEMOKINES: DEFINITIONS:DEFINITIONS: - CYTOKINES...- CYTOKINES... - CHEMOKINES...- CHEMOKINES... IMPORTANT ELEMENTS:IMPORTANT ELEMENTS: - IL-1, TNF (ALFA AND BETA)- IL-1, TNF (ALFA AND BETA) - CHEMOKINES: -CXC (ALFA) –IL-8- CHEMOKINES: -CXC (ALFA) –IL-8 -C-C (BETA) –MCP-1-C-C (BETA) –MCP-1 -C (GAMMA) –LT-C (GAMMA) –LT
TB
LEPROSY
LEPROSY WITH LUCIO’S REACTION
CACHEXIA
CACHEXIA
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
IX) NO:IX) NO:
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
X) LYSOSOMAL CONSTITUENTS:X) LYSOSOMAL CONSTITUENTS:
BRONCHOPNEUMONIA (MULTIFOCAL PNEUMONIA)
GRAM (+) PHAGOCYTOSIS (B. & B. STAIN)
BRONCHOPNEUMONIA
BRONCHOPNEUMONIA
PNEUMONIC EXUDATE
IDEM: CLOSE-UP
BRONCHOPNEUMONIA
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
XI) OXIGEN DERIVED FREE RADICALSXI) OXIGEN DERIVED FREE RADICALS
- O2-- O2-
- H2O2- H2O2
- OH.- OH.
INTESTINAL INFARCT
CHEMICAL MEDIATORSCHEMICAL MEDIATORS
XII) NEUROPEPTIDES:XII) NEUROPEPTIDES:
- SUBSTANCE P- SUBSTANCE P
- NEUROKININ A- NEUROKININ A
NEUROPEPTIDES:- VASC. PERMEAB.- PAIN
OUTCOMESOUTCOMES
RESOLUTIONRESOLUTION COMPLICATIONSCOMPLICATIONS HEALING/FIBROSISHEALING/FIBROSIS
M.R.: LOBAR PNEUMONIA
CHEMICAL MEDIATORS:CHEMICAL MEDIATORS:
QUESTIONS?QUESTIONS?