Chemical Mediators

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?