ABSITE Review: Wound Healing ABSITE Review: Wound Healing

www.downstatesurgery.
org
ABSITE Review: Wound Healing
Aparna Kolli
Kolli, M
M.D
D
SUNY Downstate Medical Center
November 14, 2008
www.downstatesurgery.org
ACGME Core
C
Competencies
t i
1. Patient Care
2. Medical Knowledge
3 Practice-based
3. Practice based Learning and Improvement
4. Interpersonal and Communication Skills
5. Professionalism
6. Systems-based Practice
Wound Healing
• Significant portion of health care budget
– Cost of diabetic foot ulcers/amputations in
2001 was $10.9 billion
– Care of diabetic foot ulcers is
approximately 10% of the annual health
care budget spent on diabetics
– Yearly cost for venous stasis ulcers
averages $10,000
Janis JE and Attinger CE, Plastic and Reconstructive Surgery, June Supplement 2006; 117(7S): 4S-5S
Wound Healing
• Divided into three phases
– Inflammation
– Proliferation
– Remodeling
Broughton II, G et al, Plastic and Reconstructive Surgery, June Supplement 2006; 117(7S): 1eS-32eS
Inflammatory Phase
• Occurs
O from
f ti
time off iinjury
j tto d
days 4
4-6
6
• Characterized by hemostasis and
inflammation
• Vasoconstriction occurs
• Fibrin clot is formed
– Collagen, platelets, thrombin, fibronectin
– Serves as a scaffolding
Inflammatory Phase
• Chemotaxis and activation
– Generation of cellular signals
– Cellular responders
• Neutrophils
• Macrophages
• Leukocytes
Proliferative Phase
• Days 4 – 14
• Characterized by
– Epithelialization
– Angiogenesis
– Formation of granulation
tissue
– Collagen deposition
Proliferative Phase
• Epithelialization
– Re-establishes a protective barrier
– Stimulated by inflammatory cytokines
• IL-1, TNF-α, EGF
• Angiogenesis
– Stimulated
Sti l t d b by TNF
TNF-α
– Capillary formation to supply nutrients
• Provisional Matrix
– Synthesized by fibroblasts
– Includes collagen type III
Goldman R, Adv Skin Wound Care 2004; 17: 24-35

Maturation and Remodeling

• Days 8 – one year
• Characterized by
collagen
ll d
deposition
iti
– Net collagen synthesis
for 4-5wks after injury
• Organization of matrix
Goldman R, Adv Skin Wound Care 2004; 17: 24-35

Maturation and Remodeling

• Wound strength
– Increases over time but never reaches
100%
– Increase in tensile strength
g
• Week 1 – 3% of final strength
• Week 3 – 30% of final strength
• >3 months – 80% of final strength
Broughton II, G et al, Plastic and Reconstructive Surgery, June Supplement 2006; 117(7S): 12S-34S
Cells of Wound Healing

• Platelets
• p
Neutrophils
• Macrophages
• y
Monocytes
• Fibroblasts
• Keratinocytes
• Endothelial cells
• Lymphocytes
• Platelets
– Aggregate to form clot
– Release growth factors and cytokines
– Activate coagulation pathway
– Chemoattractant for neutrophils and fibroblasts
• Neutrophils
– Role
R l iin phagocytosis
h t i and
d wound
dddebridement
b id t
• Macrophages
– Complete phagocytosis and wound debridement
– Major secretor of cytokines and growth factors
– Involved in angiogenesis, fibroplasia, matrix synthesis
• Monocytes
y

• Fibroblasts
– Release cytokines and growth factors
– Chemoattractant
– Synthesizes proteogylcans and and fibronectin to create matrix
– Transforms to myofibroblasts to contract and close wound
• Keratinocytes
– Directed by fibroblast release of KGF-1 and -2
– Proliferate, migrate and differentiate into epidermis
– Stimulate neovascularization by secreting VEGF
• Endothelial cells
– Involved in angiogenesis
• Lymphocytes
Role of Interleukins in Wound Healing
Role of Growth Factors in Wound Healing
• PDGF
• VEGF
• EGF
• α
TGF-α
TGF
• FGF
• KGF
• TGF-β
g
• PDGF
– Secreted by macrophages, monocytes, fibroblasts
– Involved in chemotaxis and proliferation
• VEGF
– Receptors on endothelial cells, stimulation results
in angiogenesis
• EGF
– Released by platelets
– Receptors
R t on endothelial
d th li l cells
ll and
d fib
fibroblasts
bl t
– Involved in chemotaxis, angiogenesis and
g
collagenase activity
y
• TGF-α
– Produced by activated macrophages, platelets, keratinocytes
– Involved in cell growth and chemotaxis
• FGF
– Involved in cell proliferation, angiogenesis, collagen
synthesis, wound contraction, epithelialization
• KGF
– Only found in damaged tissue
– Involved in keratinocyte proliferation and motility
• TGF-β
– Stimulates monocytes to secrete other growth
factors
– Chemotactic for macrophages and fibroblasts
– Stimulates fibroblast and epithelial cell proliferation
– Potent stimulant for collagen synthesis
– Involved in organization of extracellular matrix,
scar remodeling and wound contracture
Factors Affecting Wound Healing

• Systemic factors
• Local factors
– Age
– Ischemia – Obesity
– Cardiovascular disease
– Infection – Respiratory disease
– Adequate blood oxygenation
– Foreign bodies
– Metabolic disease
– Edema – Endocrine
doc e disease
d sease
– Renal failure
– Hepatic failure
Nutrition and Wound Healing

• Factors affecting • Injury increases
healing – Metabolic rates
– Changes in energy, – Catecholamine
CHO, protein, fat, levels
vitamin and mineral – Loss of total body
metabolism water
• Ex. Loss of protein
– Cellular p
protein
decreases wound
o nd
tensile strength turnover
*Result is overall catabolism
Arnold M and Barbul A, Plastic and Reconstructive Surgery, June Supplement 2006; 117(7S): 42S-58S

• Wounds require energy • Micronutrients
for collagen synthesis – Essential to cellular
function
– Ex. Magnesium
• Protein deprivation • cofactor to enzymatic
activity in protein and
– Impairs healing collagen
ll synthesis
th i
• Impaired collagen – Ex. Zinc
synthesis/degradation
• cofactor to RNA/DNA
• Increased rates of polymerase
infection • Involved in DNA, protein
synthesis
• Involved in cell
proliferation
lif ti
• Vitamins
– Vitamin C
• Deficiency leads to:
– Decreased collagen deposition
deposition, angiogenesis
– Hemorrhage
– Increased infection
– Vitamin A
• Enhances inflammatory response
– Vitamin E
• Stabilizes cell membrane
• Antioxidant
• Anti-inflammatory agent
Debridement: Definitions
• Acute wound * Bacteria
– Recent wound – Produce wound
– To progress through inhibiting enzymes
stages of healing
– Consume resources
• Chronic wound
– Wound arrested in a
healing stage
• Debridement
– Removal of necrotic
tissue, foreign material
and bacteria
Attinger CE et al, Plastic and Reconstructive Surgery, June Supplement 2006; 117(7S): 72S-109S
Principles of Debridement
• Goal: Excise wound to reach normal,
y, well-vascularized tissue
healthy,
– Healthy, viable tissue can then proceed
through
g the sequential
q stages
g of wound
healing
• Sharp
p dissection only
y - to avoid
damaging underlying healthy tissue
Attinger CE et al, Plastic and Reconstructive Surgery, June Supplement 2006; 117(7S): 72S-109S
Summary of Wound Healing
Questions?
Questions
1. The three phases of wound healing
include:
a. injury, hemostasis, epithelialization
b. Inflammation, hemostasis, epithelialization
c. Inflammation, chemotaxis, proliferation
d. Inflammation, proliferation, maturation
e. Inflammation, epithelialization, maturation
Answer: d
Questions
2. The first cells to arrive at the injury site and
their function are:
a. N
Neutrophils
t hil - clear
l away b bacteria
t i andd cellular
ll l
debris
b. Macrophages
p g - secrete enzymes/cytokines
y y and
aid transition to proliferative phase
c. Fibroblasts - synthesize and deposit collagen
d Neutrophils - deposit the fibrin clot
d.
e. Leukocytes - activate macrophages
Answer: a
Questions
3. At three months the tensile wound
strength is what percent of its final
strength?
a. 100%
b. 10%
c. 50%
d
d. 60%
e. 80%
Answer: e
Questions
4. TGF-β is involved in
a. Hemostasis
b Involved in organization of extracellular
b.
matrix, scar remodeling and wound
contracture, stimulant for collagen synthesis
c. Angiogenesis
d. Scar remodeling only
e Not involved in the wound healing
e.
process
Answer: b
Questions
5. Principles of debridement dictate that
a. blunt dissection is used
b. blunt and sharp dissection are used
c. wounds are excised to healthy, viable
tissue so they can progress through the
stages of wound healing
d wounds
d. d are excised
i d to avoid
id ffoull smells
ll
e. wound debridement is actually
unnecessary
Answer: c
References
1. Janis JE and Attinger CE, Plastic and Reconstructive Surgery, June
Supplement 2006; 117(7S): 4S-5S
2. Broughton II, G et al, Plastic and Reconstructive Surgery, June Supplement
2006; 117(7S): 1eS-32eS
1eS 32eS
3. Broughton II, G et al, Plastic and Reconstructive Surgery, June Supplement
2006; 117(7S): 12S-34S
4. Arnold M and Barbul A, Plastic and Reconstructive Surgery,
g y June
Supplement 2006; 117(7S): 42S-58S
5. Attinger CE et al, Plastic and Reconstructive Surgery, June Supplement
2006; 117(7S): 72S-109S
6
6. G ld
Goldman R
R, Ad
Adv Ski
Skin W
Wound
dCCare 2004
2004; 17
17: 24
24-35
35

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ABSITE Review: Wound Healing

4. Interpersonal and Communication Skills

• Divided into three phases

Goldman R, Adv Skin Wound Care 2004; 17: 24-35

Maturation and Remodeling

Goldman R, Adv Skin Wound Care 2004; 17: 24-35

Maturation and Remodeling

Cells of Wound Healing

Cells of Wound Healing

Role of Interleukins in Wound Healing

Role of Growth Factors in Wound Healing

Factors Affecting Wound Healing

Nutrition and Wound Healing

Nutrition and Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

Summary of Wound Healing

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