1 Hadassah University Hospital Dr. Slosser Dr. Slosser Plastic Surgery Seminars Plastic Surgery Seminars June 15, 2001 June 15, 2001.

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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