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Transcript
Hadassah University Hospital Dr. Slosser Plastic Surgery Seminars June 15, 2001 1 Introduction In history burn injury described as an “ internal inflammation”. 2 Causes of death: 90% due to INFECTION 60% pneumonia 40% sepsis (Gram N) < 10% wound sepsis 3 3 LINES of Resistance: Mechanical barrier The nonspecific immune response The specific immune response 4 SUPRESSION OF THE IMMUNE RESPONCE Open contaminated wound Increase metabolic requirements Decrease nutritional intake 5 Mechanical Barrier Normal skin G.I. Mucosa Respiratory mucosa 6 SKIN Burn damages the skin ( physical barrier allowing microbial invasion). All lines - entry points to offending organisms. Eschar - ideal ground for microorganisms (avascular tissue is not accessible to most systemic antibiotics). 7 ESCHAR Toxic Products Lipid Protein Complex (LPC) LPC - is produced by cross linkage of a complex of 6 skin cell membrane- lipidassociated proteins. Damages cell ultrastructure and its metabolic function. Inhibits T-cell proliferation. Inhibits IgG production. LPC effects continue until eschar excision 8 Hansbrough 1984 - show that immediate eschar excision avoided immunosupression. 9 G.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. 10 Respiratory Mucosal Barrier In inhalation injury, damaged epithelium allows bacterial invasion. Intubation allows for colonization of airway with opportunistic organisms. 11 Nonspecific Immune Responce A- Vascular component B- Cellular component C- Humoral component 12 A- VASCULAR COMPONENT Minor thermal injury - Local vasodilatation. - Increase capillary permeability. - Chemotaxis of PMN & monocytes. Severe thermal injury - Venous stasis. - Microvascular thrombosis. - Endothelial cell slough. 13 B- CELLULAR ROLE Phagocytes ( blood born and tissue) Neutrophils (PMN) Macrophages - monocytes - fixed phagocytic cells of RES 14 C- HUMORAL ROLE Arachidonic acid metabolites Endotoxines Thromboxane Complement system Fibronectin 15 Chemical mediators Serotonin -from platelets, mast cells Histamine- mast cells, basophils Platelet activating factor (PAF) basophils, neutrophils, macropages Hyaluronidase Peroxides, free radicals 16 Chemical mediators Neutrophil chemotactic factor (NCF) mast cells IL-8 -monocytes, lymphocytes C3a - complement C3 C5a - complement C5 Bradykinine - kinin system (kininogen) Fibrinopeptides - clotting system 17 Chemical mediators Prostaglandin E2 (PGE-2) - cyclooxygenase pathway Leukotriene B4 (LTB-4) -lipoxygenase pathway Leukotriene D4 (LTD-4) -lipoxygenase pathway 18 Effect of Endogenous Mediators on 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 19 Effect of Endogenous Mediators on Inflammation Postburn Leukocytic infiltration ( chemotaxis) Complement system byproducts -C5a Acidic lipids ( Leukotriens B4) Lysosomal components (cationic proteins) Tissue damage Lysosomal components (neutral proteases) 20 SPECIFIC Immune Responce COMPOSED OF TWO COMPONENTS Cell mediated immunity component (T-lymphocytes and its subgroups) Humoral immunity component (Blymphocytes and its product antibodies) 21 CELL MEDIATED Immunity T-lymphocytes subdivided according to function into: Cytotoxic T-cells (killer) Helper T-cells Supressor T-cells 22 CELL MEDIATED Immunity Cytokines - intracellular signalling proteins which amplify the nonspecific defence response and recruit other noncommitted lymphoid cells as well as monocytes, neutrophils and eosinophils. Macrophages play a key role 23 CELL MEDIATED Immunity Some key lymphokines are: Interleukin 1 Interleukin 2 TNF 24 HUMORAL Mediated Immunity B-cells under influence of the Tcells committed to become antibody producing cell when stimulated by the presence of particular antigens 25 FUNCTIONS of ANTIBODIES Opsonization of bacteria Neutralization of viruses and bacterial toxins Bactericidal antibodies lyse bacteria on contact in presence of compliment 26 Effect of BURN on the Specific Immune 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 nonspecific27 supressor T-cells Postburn Alteration in Humoral Immunity B-lymphocytes - increase in number with a Tor 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 28 IMMUNIZATION THERAPY ACTIVE IMMUNIZATION -Psedomonas aeruginosa -dominant pathogen in burn patients PASSIVE IMMUNIZATION -Administration of immunoglobulins 29 IMMUNOMODULATION 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 30 Immunomodulating Agents Killed vaccine of Corynebacter parvum IL-1, IL-2 FFP Vitamin A and Vitamin E Thymosin Levamisole TP-5 ( Thymopentin) Fibronectine Cyclophosphamide 31