Wound Healing, Wound Types, Wound Dressings, & Drainage Devices
Chapter 7 Wound Healing of the... · During wound healing, endothelial cells released cytokines,...
Transcript of Chapter 7 Wound Healing of the... · During wound healing, endothelial cells released cytokines,...
Chapter 7
Wound Healing
長庚皮膚科 R2 劉人鳳2015.12.11
CHAPTER SUMMARY
Wound healing occurs in orderly, overlapping phases: the inflammatory,
the proliferative, and the remodeling phases.
The depth of the wound determines the degree of contraction and the
location and source of keratinocytes that serve as a reservoir for re-
epithelialization.
Acute wounds created by a scalpel heal faster than wounds created by
destructive or ablative methods.
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CHAPTER SUMMARY
Platelets are the first cell to appear in the healing process, and
macrophages are the most important cell in the healing process;
they both mediate their actions through cytokines or growth factors.
Wound healing is highly regulated by signals from the serum and
surrounding extracellular matrix.
Physicians can accelerate wound healing by
avoiding placing toxic substances on the wound
keeping the wound free of necrotic and potentially infected tissue
appropriate use of occlusive dressings to create a moist wound
environment
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TYPES OF WOUNDS
Acute versus chronic wounds
Healing time
Anatomic location, shape, wound cause, patient age, and physical
condition
Ex: an elliptical wound on the face of a healthy child will likely heal faster
than a circular burn wound on an elderly person with multiple comorbidities
Patient age is a critical factor
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Primary versus secondary intention healing
Acute wound heals without intervention, primarily by contraction of
myofibroblasts
Second intention healing
A surgeon directs closure of the wound
Primary intention healing
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Methods of creating acute wounds
Scalpel (steel), laser (heat), liquid nitrogen (cold), or chemicals (acid)
Accidental trauma, thermal, or chemical burns
Wounds created by sharp steel (surgical incisions)
Heal faster
Healing of traumatic wounds may be slowed
• foreign substances prolongation of the inflammatory phase
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PHASES OF WOUND HEALING
Inflammatory phase
Inflammatory phase
Local vasodilatation, blood and fluid leakage into the extravascular space,
and blocking of lymphatic drainage
rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio
laesa (loss of function)
Usually lasts 24–48 h, may persist for up to 2 weeks (chronic inflammation)
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Inflammatory phase
Tissue injury blood vessel disruption and bleeding activates
keratinocytes release interleukin1 (IL1)
Platelets
Homeostasis
Release of important mediators: platelet derived growth factor (PDGF),
epidermal growth factor (EGF), and TGFβ1.
Leukocytes, mast cells, basophils, and eosinophils
Monocytes Macrophages: phagocytosis, initiation of formation of
granulation tissue
長庚皮膚科 R2 劉人鳳
https://www.studyblue.com/notes/note/n/31-
hemostasisthrombosis/deck/2392686
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Inflammatory phase -- Vascular
response
Initially, vasoconstriction hemostasis
Histamine is released into the area from mast cells, basophils, and platelets
vasodilatation and increased permeability
Hemostasis:
development of a fibrin clot
coagulation
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長庚皮膚科 R2 劉人鳳
http://www.pharmacology2000.com/Coagulation/coagulation1.htm
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Inflammatory phase -- Cellular
response
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Leukocytes – Neutrophils
Within 1 hr of the onset of inflammation
endothelium of the venules covered with neutrophils = Margination
Inflammation persists, neutrophils (days)
macrophages (tissue-derived monocytes)
Chemotactic factors from
Mast cells -- TNF, histamine, proteases, leukotrienes, and cytokines (interleukins)
Coagulation cascade (fibrinogen, FDP) -- kallikrein, fibrinopeptides
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Leukocytes – Monocytes,
Macrophages
Phagocytosis Chronic inflammation
angiogenesis and granulation tissue
formation ~ Proliferative phase
Fibroblasts; Collagen deposition
Produce growth factors: PDGF, fibroblast
growth factor (FGF), vascular endothelial
growth factor (VEGF), TGF-β, and TGF-α
Cell migration, proliferation, and matrix
production
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Mast cells
Trigger inflammation, vasodilatation and increased vascular permeability
• histamine and TNF
Regulate hemostasis
• platelet-activating factor (PAF), heparin, tryptase, chymase, and t-
plasminogen activator (tPA)
Recruit leukocytes
• TNF, histamine, proteases, leukotrienes, and cytokines (interleukins)
Angiogenesis, extracellular matrix deposition, and remodeling
• histamine, heparin, cytokines, and growth factors
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Inflammatory phase -- Chemical
mediators of inflammation
Histamine
Mast cells (mainly), blood platelets and basophils
H1 receptor dilatation of arterioles and increase permeability
Heparin: anticoagulation during early phase
Serotonin
Platelets and mast cells
Potent vasoconstrictors
Fibroblast proliferation and the cross-linking of collagen molecules
Kinins
Brdykinin, released from plasma protein
Vasodilatation
Rapidly destroyed with limited activity長庚皮膚科 R2 劉人鳳
Prostaglandins
Prostaglandin E2 (PGE2): increase vascular permeability, attract leukocytes
Sensitize pain receptors (proinflammatory) or as inhibitors
Synthesis of mucopolysaccharides
Inhibited by steroids or NSAIDs in chronic inflammation
Complement system
Ag – Ab – complement cascade of sequential
reaction facilitate phagocytosis
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Growth factors
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Inflammatory phase –
Chronic inflammation
> 2 weeks, often months or years
Granulocytes disappear, mononuclear cells (lymphocytes, monocytes,
macrophages) persist
Necrotic tissue
Contaminated with pathogens
• Bacterial lipopolysaccharide inhibit Keratinocyte migration
Contain foreign material cannot be phagocytized
• Fibroblasts produce collagen granuloma
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PHASES OF WOUND HEALING
Proliferative phase
Re-epithelialization
Migration & Proliferation of epidermal keratinocytes
Neoepithelium to stratified epidermis
Restoration of an intact basement membrane zone
Repopulation of specialized cells
• Merkel’s cells which direct sensory function
• Melanocytes that foster pigmentation
• Langerhans cells that regulate immune functions
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Keratinocyte migration
Within 24 h
Also occurs from the remaining skin appendages, including the hair follicle
“leap frog” theory -- epidermal cells migrate two or three cell lengths from
their initial position and slide over epidermal cells previously implanted in
the wound
Migrating keratinocytes produce matrix metalloproteinases (MMPs):
disrupts and allows for continued migration
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Restoration of the basement
membrane zone
Within 7–9 days
The BMZ of the skin consists of many extracellular matrix proteins, with
collagens and laminins being the major components
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Reconstitution of the dermis
Granulation tissue begins to form within 3–4 days of injury
Provisional extracellular matrix or fibronectin rich fibrin clot --
• Providing scaffolding and contact guidance for cells to migrate
• Angiogenesis
• Fibroplasia
Formation of granulation tissue
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Mechanism of wound contraction
In direct proportion to depth
Full-thickness wounds -- peaks at 2 weeks, up to a 40% decrease in wound
size
Partial-thickness wounds -- parts of the adnexa remain and allow
epithelialization, contract less than full-thickness wounds
Myofibroblasts
By day 7, fibroblasts begin to change into myofibroblasts
Contraction resulting in “skin tension lines”
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Wound angiogenesis
During wound healing, endothelial cells released cytokines, low oxygen
tension, lactic acid, and biogenic amines stimulate angiogenesis
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Angiogenic growth factors
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PHASES OF WOUND HEALING
Remodeling phase
Deposition of matrix materials
Occurs through the whole process of wound repair
Total amount of collagen increases
• maximum 2 and 3 weeks
Tensile strength (functional assessment of collagen) increases to 40%, and
continue to increase for up to 1 year
• Never greater than 80% of its pre injury strength
Type III collagen is the major collagen in granulation tissue
• > 1 yr, the dermis returns to the preinjury phenotype (type I collagen)
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Extracellular matrix
In part comprised of glycosaminoglycans and
proteoglycans
Dermal compliance, flexibility, and integrity
Strength, support, and density to tissue
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Extracellular matrix
Hyaluronic acid is nonsulfated glycosaminoglycan
• peak within the first 4–5 days
• Stimulus for fibroblast proliferation and migration, absorb large amounts of
water space for the migration of fibroblasts
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Extracellular matrix
Sulfated glycosaminoglycans are proteoglycans
• Stable and resilient matrix that inhibits cell migration and proliferation
• Chondroitin-4-sulfate and dermatan sulfate eventually replace
hyaluronic acid as the major glycosaminoglycan on days 5–7
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Extracellular matrix
Non-weight-bearing skin
• Progressive decrease of glycosaminoglycan content from fetal
development to maturity
Weight-bearing skin, such as the plantar aspect of the foot
• Minimal change in glycosaminoglycan
Chondroitin sulfate, are proportionally altered in pathologic skin states,
such as Dupuytren’s contracture or hypertrophic scarring
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Collagen
80% of dry weight of the dermis
providing structure, strength, and stiffness to dermal tissue
In normal adults
• type I collagen -- 80% type III collagen -- 10%
Type III type I collagen during wound healing process
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Biosynthesis of collagen
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Elastic fibers
Elastin
• Provides elasticity and extensibility to the dermis
• Assists in recovery from deformation
Comprising only 2% of the total protein in the dermis
With aging, the amount of elastin increases
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Proteinases and tissue remodeling
The most important protein are MMPs
Partly controlled by a family of tissue inhibitors of
metalloproteinases (TIMP1, TIMP2, TIMP3, TIMP4)
The balance between MMPs and TIMPs is critical to
the wound repair process and remodeling
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FACTORS AFFECTING WOUND
HEALING
Systemic factors
Malnutrition, protein deprivation, and deficiencies of vitamin A and vitamin
C
Vitamin C -- cofactor for the collagen crosslinking
Vitamin A -- potentiates epithelial repair and collagen synthesis by enhancing
inflammatory reactions
Zinc deficiency reduces the rate of epithelialization
Corticosteroids, penicillamine, nicotine, NSAIDs, and antineoplastic agents
penicillin decreases collagen cross-linking
Chronic debilitating illness, endocrine disorders, systemic vascular
disorders, and connective tissue disease
Advancing age 長庚皮膚科 R2 劉人鳳
Systemic steroids in the first 3 days postwounding
blocks initial inflammation
prolongation of healing time
loss of skin turgor
suppress the mitotic activity of fibroblasts
Ameliorated with administration of local and systemic vitamin A, and a
single injection of TGFβ
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Local factors
Poor surgical techniques (excessive tension or excess devitalized tissue)
Vascular disorders (arteriosclerosis or venous insufficiency), tissue ischemia
Infectious processes
Certain topically applied medications, extravasation of antineoplastic
drugs
Hemostatic agents such as aluminum chloride or ferric subsulfate
Foreign body reactions
Adverse wound microenvironment (dry vs occlusive dressings)
Pressure, neuropathy, and chronic radiation injury
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OPTIMIZING OUTCOMES
Surgical techniques
Aseptic surgical techniques
Use of buried deep sutures – lessen risk for hematoma and subsequent
infection
Proper hemostasis and elimination of necrotic tissue
Apposition of wound edges, not closed too tightly – prevent ischemia and
necrosis
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Topical skin adhesives
Novel, noninvasive alternative
Degrade with skin cells
Hemostatic, occlusive dressing, antimicrobial barrier
Similar rates of infection and scarring
Higher rates of wound dehiscence
2 classes: butyl and octylcyanoacrylates
• Dermabond® (Johnson and Johnson, New Brunswick, NJ) advanced has
the greatest strength and is the most flexible
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Occlusive dressings
Healed up to 40% faster than those left exposed to air
Film dressings: face and other cosmetically important areas
Hydrocolloid dressings: exudative wounds
Foam dressings: wound associated pain
To be left in place until the exudate leaks from the dressing (early removal
can strip away newly formed epithelium)
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Emerging dressings/topicals
Honey
decreases oxidative stress
Increase proinflammatory cytokines TNF-α, IL-1β, IL-6
reduce healing time in superficial and partial thickness burn wounds
But NOT for chronic leg ulcers
Protein kinase C
keratinocyte and fibroblast migration and differentiation, matrix deposition
Topical bacteriophage-based preparation
Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli
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Emerging dressings/topicals
Human amniotic membrane allograft
many growth factors
facilitate angiogenesis, dampen inflammation, prevent infection, and promote healing
Thymosin beta-4
released by macrophages and platelets
interacts with actin and promotes angiogenesis, cell mobilization, migration, and tissue regeneration, decreasing myofibroblasts
Connexin 43
downregulates cell migration at wound edges
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Investigational tissue and cell therapy
Activated allogeneic white blood cells, monocytes, macrophages,
neutrophils, and lymphocytes from healthy donors (topical or injected)
Living, growth-arrested keratinocytes and fibroblasts (spray)
release of growth factors
Bone marrow derived mesenchymal stem cells
heal chronic wounds
Human processed lipoaspirate -- contains stem cells and is easily harvested
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Future growth factors
Topical fibroblast growth factor 1
Chemotaxis, proliferation of fibroblasts and keratinocytes, increase the
expression of TGF-β
5-amino acid deleted recombinant human hepatocyte growth factor
chronic wounds
promoting re-epithelialization, angiogenesis, and granulation tissue
formation
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Partial-thickness versus
full-thickness wounds
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Partial-thickness versus
full-thickness wounds
Early fetal skin wounds
regeneration can take place after dermal injury
higher concentrations of type III collagen and glycosaminoglycans
decreased inflammatory response and amounts of TGF-β1 長庚皮膚科 R2 劉人鳳
Summary
Wound healing is a complex process
Understanding of its underlying mechanisms is vital for practitioners
Older patients
slower healing
less tensile strength, secondary to reduced amounts of collagen
less scarring
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Thank You For Your Attention