Transcript Hadassah University Hospital

Hadassah University Hospital
Dr. Slosser
Plastic Surgery Seminars
June 15, 2001
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Introduction
In history burn injury
described as an “ internal
inflammation”.
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Causes of death:
 90%
due to INFECTION
 60% pneumonia
 40% sepsis (Gram N)
 < 10% wound sepsis
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3 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 Barrier
 Normal
skin
 G.I. Mucosa
 Respiratory mucosa
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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).
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ESCHAR Toxic Products
Lipid Protein Complex (LPC)

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


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
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Hansbrough 1984 - show that
immediate eschar excision
avoided immunosupression.
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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.
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Respiratory 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 Responce
 A- Vascular component
 B-
Cellular component
 C- Humoral component
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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.
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B- CELLULAR ROLE

Phagocytes ( blood born and tissue)
 Neutrophils (PMN)
 Macrophages
- monocytes
- fixed phagocytic cells of
RES
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C- HUMORAL ROLE
 Arachidonic
acid metabolites
 Endotoxines
 Thromboxane
 Complement
system
 Fibronectin
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Chemical mediators

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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 mediators

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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 mediators



Prostaglandin E2 (PGE-2) - cyclooxygenase pathway
Leukotriene B4 (LTB-4) -lipoxygenase
pathway
Leukotriene D4 (LTD-4) -lipoxygenase
pathway
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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
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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)
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SPECIFIC Immune Responce
COMPOSED OF TWO COMPONENTS

Cell mediated immunity component
(T-lymphocytes and its subgroups)
 Humoral immunity component (Blymphocytes and its product
antibodies)
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CELL 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 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
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CELL MEDIATED Immunity

Some key lymphokines are:
Interleukin 1
Interleukin 2
TNF
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HUMORAL Mediated Immunity
 B-cells
under influence of the Tcells committed to become
antibody producing cell when
stimulated by the presence of
particular antigens
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FUNCTIONS 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
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
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IMMUNIZATION THERAPY

ACTIVE IMMUNIZATION
-Psedomonas aeruginosa -dominant
pathogen in burn patients
 PASSIVE IMMUNIZATION
-Administration of immunoglobulins
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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
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Immunomodulating Agents
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Killed vaccine of Corynebacter parvum
IL-1, IL-2
FFP
Vitamin A and Vitamin E
Thymosin
Levamisole
TP-5 ( Thymopentin)
Fibronectine
Cyclophosphamide
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