Transcript Wounds: Care and Treatment

Wounds: Care and Treatment
William R. Dougherty, MD FACS
Associate Professor of Surgery
Goals
• Identify elements of wound healing
• Define differences between acute and
chronic wounds
• Treatment options of acute wounds
• Treatment options of chronic wounds
Healing and Regeneration
• Starfish and salamanders heal by
regeneration (whole limbs)
• Mammals heal by a combination of
scarring and regeneration.
Surgeons Invocation
Give us the ability to operate on the things
that cannot be healed
To heal the things that can be healed,
And the wisdom to know the difference.
Acute Wounds
• Acute wounds normally heal in a very orderly
and efficient manner.
• Healing is characterized on a four distinct but
overlapping faces.
• Hemostasis, Inflammation, Proliferation, and
Remodeling
• Specific biologic markers characterize and
orchestrate the phases healing of the acute
wounds.
Cytokines
• Originally identified cell growth factors,
now recognized to have diverse effects.
• Endocrine, autocrine, paracrine and
intracrine.
• Cell migration, matrix production, enzyme
expression and cell differentiation
Cytokines
Cytokine
Cell of Origin
Function
PDGF
Platelets
Macrophages
Endothelial cells
Cell chemotaxis
Mitogenic for fibroblasts
Stimulates angiogenesis
Stimulates wound contraction
TGF-alpha
Macrophages
T lymphocytes
Keratinocytes
Mitogenic for keratinocytes and
fibroblasts
Stimulates keratinocyte
migration
TGF-beta
Platelets
T lymphocytes
Macrophages
Endothelial cells
Keratinocytes
Cell chemotaxis stimulates
angiogenesis and fibroplasia
EGF
Platelets
Macrophages
Mitogenic for keratinocytes and
fibroblasts
Stimulates keratinocyte
migration
Fibroblast growth factor
Macrophages
Mast cells
T lymphocytes
Endothelial cells
Chemotactic and mitogenic for
fibroblasts and keratinocytes
Stimulates angiogenesis
Cytokines
Fibroblast growth factor
Fibroblasts
Stimulates keratinocyte migration,
differentiation, and proliferation
TNF
Macrophages
Mast cells
T lymphocytes
Activates macrophages
Mitogenic for fibroblasts
Stimulates angiogenesis
Interleukin (IL)–1, IL-2, IL-6, and IL8
Macrophages
Mast cells
Keratinocytes
Lymphocytes
IL-1 - Induces fever and
adrenocorticotropic hormone
release, enhances TNF-alpha and
interferon (INF)–gamma, activates
granulocytes and endothelial cells,
and stimulates hematopoiesis
IL-2 - Activates macrophages, T
cells, natural killer cells, and
lymphokine-activated killer cells;
stimulates differentiation of
activated B cells; stimulates
proliferation of activated B and T
cells; and induces fever
IL-6 - Induces fever and enhances
release Keratinocyte of acutephase reactants by the liver
IL-8 - Enhances neutrophil
adherence, chemotaxis, and
granule release
INFs (IFN-alpha, -beta, and -delta)
Lymphocytes
Fibroblasts
Activate macrophages
Inhibit fibroblast proliferation
Thromboxane A2
Destroyed wound cells
Potent vasoconstrictor
Hemostatic Phase
• Platelets come into
contact with collagen and
extracellular matrix.
• Contact triggers the
release of clotting factors
as well as essential
growth factors and
cytokines.
• PDGF platelet derived
growth factor
• TGFβ transforming
growth factor beta
Inflammatory Phase
• Neutrophils enter the
wound site first to remove
foreign materials,
bacteria and image
tissue.
• Macrophages continue
the process of
phagocytosis and release
more PDGF and TGFβ
• Rubor, Tumor, Calor and
Dolor
Proliferative Phase
• In response to PDGF and
TGFβ fibroblasts migrate in to
deposit collagen and
extracellular matrix.
• College is the most abundant
protein in the animal kingdom,
accounting for 30% of the total
protein in the human body.
• Epithelial migration and new
vessel formation are prominent
features.
Proliferative Phase
• Hydroxyproline is key in
maintaining tertiary
college and structure.
• Vitamin C deficiency and
hypoxia both reduce
hydroxyproline
• Lysyl oxidase (inhibited
by steroids) is
responsible for crosslinking collagen from
Collagen
• Type I - Located in all connective tissue except hyaline
cartilage and basement membranes
• Type II - Located in hyaline cartilage
• Type III - Located in distensible connective tissue (blood
vessels)
• Type IV - Located in basement membranes
• Type V - Located in all tissues
• Type VI - Located in all tissues
• Type VII - Located in the dermal-epidermal junction
• Type VIII - Located in the Descemet membrane
• Type IX - Located in hyaline cartilage
• Type X - Located in hypertrophic cartilage and hyaline
cartilage
Remodeling Phase
• The new collagen matrix is
metabolized, cross-link and
organized.
• Native collagen approaches
the strength of steel on a
weight per weight basis
• Defects in remodeling main
result in low tensile strength or
hypertrophic scaring
• The healed wound reaches
80% of the surrounding normal
tissue strength in six to eight
weeks
Wound healing phases:
Overview
Normal Wound Healing
Scar maturation
Collagen fibril cross-linking
REMODELING
Endothelial cells
Epithelial cells
Collagen
Fibroblasts
PROLIFERATION
Lymphocytes
Macrophages
Neutrophils
INFLAMMATION
Proteoglycans
Fibrin
Platelets
HEMOSTSIS
Time from injury
Factors that influence wound
healing
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Nutrition
Bacterial contamination
Necrotic tissue / debris
Immune / Bone marrow competence
Edema
Underlying medical conditions
Drug therapy
Radiation therapy
What’s new: Stem Cells
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Bone marrow derived stem cells
Circulating and fixed
Responders to the cell signaling
Regenerative components
Acute Wounds: Etiology
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Trauma
Burns
Vascular
Immune
Surgical
Pressure
Infection
Chronic Wounds
• Unique biologic markers characterize pathologic
healing responses that resulting fibrosis and
chronic nonhealing wounds.
• The efficient and orderly processes lost and the
wounds are locked in to the state of chronic
inflammation and fibrosis.
• This is associated with abundant neutrophil
infiltration, reactive oxygen species and district
in enzymes.
Fibrosis
• In most conditions of fibrosis are
characterized by an increased density of
mast cells. Mast cells contain specialized
enzymes capable of processing
procollagen and it has been suggested
that abnormal peptides are produced that
can actually stimulate collagen synthesis
thus producing fibrosis.
Keloid versus Hypertrophic Scar
• There is one very significant biological
marker that distinguishes keloids from
hypertrophic scars and that is the absence
of myofibroblasts in keloids and an
abundance of these contractile cells in
hypertrophic scars.
Common Factors
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Loss of epithelial integrity
Devascularized tissue
Contamination
Stimulation of cytokine cascade
Stimulation of stem cell migration
Coagulation, Inflammation, Proliferation
and Remodeling
Effects of Pressure
• Landis (1930)
– Average pressure in arteriolar limb 32 mmHg
• Husain (1953)
– Microscopic changes in muscle after 100 mmHg for
one hour
• Dinsdale (1974)
– >70 mmHg over 2 hours; irreversible damage
– >240mmHg with intermittent relief; no damage
Location of Pressure Sores
The Progression of Disease
• Hyperemia
– Seen within 30 minutes
– Disappears after 1 hour
• Ischemia
– Seen after 2 hours
– Erythema disappears after 36 hours
• Necrosis
– Seen after 6 hours
• Ulceration
– Within 2 weeks
Edberg, Cerny, Stauffer. Phys Ther 53:246, 1973.
Stages
The Simple Solution
Treatment for Acute Wounds
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Debride
Decontaminate
Moist wound healing
Early Closure
Treatment for Chronic Wounds
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Debride
Anti-inflammation therapy
Antibiotic therapy
Synthetic substitutes – mod. Cytokines
MMPs
• Recruit stem cells