1 Hadassah University Hospital Dr. Slosser Dr. Slosser Plastic Surgery Seminars Plastic Surgery...
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Transcript of 1 Hadassah University Hospital Dr. Slosser Dr. Slosser Plastic Surgery Seminars Plastic Surgery...
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Hadassah University Hospital
Dr. SlosserDr. Slosser
Plastic Surgery SeminarsPlastic Surgery Seminars
June 15, 2001June 15, 2001
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IntroductionIntroduction
In history burn injury
described as an “ internal inflammation”.
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Causes of death:Causes of death:
90% due to INFECTION 60% pneumonia 40% sepsis (Gram N) < 10% wound sepsis
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3 3 LINES of Resistance:LINES of Resistance:
Mechanical barrier The nonspecific immune
response The specific immune response
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SUPRESSION OF THE IMMUNE RESPONCE
Open contaminated wound Increase metabolic
requirements Decrease nutritional intake
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Mechanical BarrierMechanical Barrier
Normal skin G.I. Mucosa Respiratory mucosa
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SKINSKIN Burn damages the skin ( physical
barrier allowing microbial invasion). All lines - entry points to offending
organisms. EscharEschar - ideal ground for
microorganisms (avascular tissue is not accessible to most systemic antibiotics).
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ESCHAR Toxic ProductsESCHAR Toxic ProductsLipid Protein Complex (LPC)Lipid Protein Complex (LPC) LPC - is produced by cross linkage of a
complex of 6 skin cell membrane- lipid-
associated proteins. Damages cell ultrastructure and its
metabolic function. Inhibits T-cell proliferation. Inhibits IgG production. LPC effects continue until eschar excision
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Hansbrough 1984 - Hansbrough 1984 - show that show that immediate eschar excision immediate eschar excision avoided immunosupression.avoided immunosupression.
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G.I. Mucosal BarrierG.I. Mucosal Barrier Translocation of microbes and
endotoxins occurs rapidly+extensively after burn injury. - 1 hour after burn
- proportional to the severity. Translocation increases with
parenteral nutrition and reduced with enteral feeding.
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Respiratory Mucosal BarrierRespiratory Mucosal Barrier
In inhalation injury, damaged epithelium allows bacterial invasion.
Intubation allows for colonization of airway with opportunistic organisms.
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Nonspecific Immune ResponceNonspecific Immune Responce
A- Vascular component B- Cellular component C- Humoral component
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A- VASCULAR COMPONENTA- VASCULAR COMPONENT
Minor thermal injury
- Local vasodilatation.
- Increase capillary permeability.
- Chemotaxis of PMN & monocytes. Severe thermal injury
- Venous stasis.
- Microvascular thrombosis.
- Endothelial cell slough.
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B- CELLULAR ROLEB- CELLULAR ROLE
Phagocytes ( blood born and tissue) Neutrophils (PMN) Macrophages - monocytes
- fixed phagocytic cells of
RES
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C- HUMORAL ROLEC- HUMORAL ROLE
Arachidonic acid metabolites Endotoxines Thromboxane Complement system Fibronectin
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Chemical mediatorsChemical mediators
Serotonin -from platelets, mast cells Histamine- mast cells, basophils Platelet activating factor (PAF) -
basophils, neutrophils, macropages Hyaluronidase Peroxides, free radicals
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Chemical mediatorsChemical mediators
Neutrophil chemotactic factor (NCF) -mast cells
IL-8 -monocytes, lymphocytes C3a - complement C3 C5a - complement C5 Bradykinine - kinin system (kininogen) Fibrinopeptides - clotting system
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Chemical mediatorsChemical mediators
Prostaglandin E2 (PGE-2) - cyclo-oxygenase pathway
Leukotriene B4 (LTB-4) -lipoxygenase pathway
Leukotriene D4 (LTD-4) -lipoxygenase pathway
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Effect of Endogenous Mediators Effect of Endogenous Mediators on Inflammation Postburnon Inflammation Postburn
Increased microvascular permeability Vasoactive amines (histamine) Kinin system (bradykinine) Acidic lipides ( Pg, Pc, Leukotrienes C-4, D-4, E-4.
Complement system byproducts C3a
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Effect of Endogenous Mediators Effect of Endogenous Mediators on Inflammation Postburnon Inflammation Postburn Leukocytic infiltration ( chemotaxis)
Complement system byproducts -C5a
Acidic lipids ( Leukotriens B4)
Lysosomal components (cationic proteins) Tissue damage
Lysosomal components (neutral proteases)
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SPECIFIC Immune ResponceSPECIFIC Immune Responce
COMPOSED OF TWO COMPONENTS Cell mediated immunity component
(T-lymphocytes and its subgroups) Humoral immunity component (B-
lymphocytes and its product antibodies)
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CELL MEDIATED ImmunityCELL MEDIATED Immunity
T-lymphocytes subdivided according to function into:
Cytotoxic T-cells (killer)
Helper T-cells
Supressor T-cells
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CELL MEDIATED ImmunityCELL MEDIATED Immunity
Cytokines - Cytokines - intracellular signalling proteins which amplify the nonspecific defence response and recruit other noncommitted lymphoid cells as well as monocytes, neutrophils and eosinophils.
Macrophages Macrophages play a key role
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CELL MEDIATED ImmunityCELL MEDIATED Immunity
Some key lymphokines are:Some key lymphokines are:
Interleukin 1
Interleukin 2
TNF
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HUMORAL Mediated ImmunityHUMORAL Mediated Immunity
B-cells under influence of the T-cells committed to become antibody producing cell when stimulated by the presence of particular antigens
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FUNCTIONS of ANTIBODIESFUNCTIONS of ANTIBODIES
Opsonization of bacteria Neutralization of viruses and
bacterial toxins Bactericidal antibodies lyse bacteria
on contact in presence of compliment
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Effect of BURN on the Specific Effect of BURN on the Specific Immune ResponceImmune Responce CELL MEDIATED IMMUNITY
-Prolonged survival of skin allografts
-Altered skin test reactivity - energy
-T-lymphocytes (A)-decrease in total count
(B)-depressed primary and secondary responses to T-dependent antigens
-Blast transformation- diminished response to mitogens/ MLS
-Cytotoxity - reduced activity
-T-cell subpopulations - increase in nonspecific supressor T-cells
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Postburn Alteration in Humoral Postburn Alteration in Humoral Immunity Immunity
B-lymphocytes - increase in number with a T- or B-cell shift
Immunoglobulins - reduction in IgG with lesser reductions in IgA and IgM
Antibody responce - increase in anamnestic secondary responce; decrease in primary humoral antibody responce
Proteins - increase in levels of acute phase reactants (C-active protein, haptoglobine); decrease in alpha2- macro globulin and prealbumin
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IMMUNIZATION THERAPYIMMUNIZATION THERAPY
ACTIVE IMMUNIZATIONACTIVE IMMUNIZATION
-Psedomonas aeruginosa -dominant pathogen in burn patients
PASSIVE IMMUNIZATION PASSIVE IMMUNIZATION
-Administration of immunoglobulins
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IMMUNOMODULATIONIMMUNOMODULATION
A - General support - Fluid resuscitation
-Early nutrition
-Early excision B - Remove supressors ( Plasma
exchange, early wound excision, topical
Cerium nitrate, Polymyxin B ) C - Stimulate target cells
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Immunomodulating AgentsImmunomodulating Agents Killed vaccine of Corynebacter parvum IL-1, IL-2 FFP Vitamin A and Vitamin E Thymosin Levamisole TP-5 ( Thymopentin) Fibronectine Cyclophosphamide