wound healing lec

Wound HealingWound Healing

Wallace Medina, MD, FPCS,FPSGS,FPALES

Terminology

• Wound repair- ability to restore normal function and structure

• Regeneration – perfect restoration, no scar formation

* All tissues proceed through the same series of events

Terminology

• Acute wounds - orderly and timely reparative process

•Chronic wounds – no restoration of functional integrity, stops at inflammatory phase

Types of Wound Closure

Primary or first intention

Secondary or spontaneous

Tertiary or delayed primary

Phases of Wound Healing

A. Inflammatory or reactive phase

- immediate response to injury

- goals: hemostasis, debridement , sealing of the wound



Events

1.Increase vascular permeability

2.Chemotaxis

3.Secretion of cytokines

4.Growth factor

Phases of Wound HealingA. Inflammatory or reactive phase

Inflammatory cells

PMN

- Migration of PMN stops when wound contamination has been controlled

- Don’t survive more than 24 hours

- Increase contamination stimulates PMN resulting to delayed wound healing and destruction of tissues.

- Not essential for wound healing



Inflammatory cells

Macrophages

- Orchestrate release of cytokines/ Process of wound healing/ release of growth factors

- 24 – 48 hours

- Source of TNF /interleukin 1, 6, 8

Macrophage Activities During Wound Healing

Activity Mediators

Phagocytosis Reactive oxygen species Nitric oxide

Débridement Collagenase, elastase

Cell recruitment and activation

Growth factors: PDGF, TGF-, EGF, IGF Cytokines: TNF-, IL-1, IL-6 Fibronectin

Matrix synthesis Growth factors: TGF-, EGF, PDGF Cytokines: TNF-, IL-1, IFN-Enzymes: arginase, collagenase ProstaglandinsNitric oxide

Angiogenesis Growth factors: FGF, VEGFCytokines: TNF- Nitric oxide

Table 8-2 Growth Factors Participating in Wound Healing

Stimulates fibroblasts, keratinocytes, chondrocytes, myoblasts

Mitogenesis: mesoderm and neuroectoderm

Stimulation of angiogenesis (by stimulation of endothelial cell proliferation and migration)

Fibroblasts, endothelial cells, smooth muscle cells, chondrocytes

Fibroblast growth factor (FGF)

Stimulation of collagen synthesis

Stimulation of angiogenesis

Mitogenesis: fibroblasts, smooth muscle cells

Chemotaxis: fibroblasts, smooth muscle, monocytes, neutrophils

Platelets, macrophages, monocytes, smooth muscle cells, endothelial cells

Platelet-derived growth factor (PDGF)

Cellular and Biological EffectsWound Cell OriginGrowth Factor


Keratinocyte growth factor (KGF)

Keratinocytes, fibroblasts Significant homology with FGF; stimulates keratinocytes

Epidermal growth factor (EGF)

Platelets, macrophages, monocytes (also identified in salivary glands, duodenal glands, kidney, and lacrimal glands)

Stimulates proliferation and migration of all epithelial cell types

Transforming growth factor- B (TGF- B )

Keratinocytes, platelets, macrophages

Homology with EGF; binds to EGF receptor

Mitogenic and chemotactic for epidermal and endothelial cells

Transforming growth factor- alpha (TGF- alpha ) (3 isoforms: 1, 2, 3)

Platelets, T lymphocytes, macrophages, monocytes, neutrophils

Stimulates angiogenesis TGF- 1stimulates wound

matrix production (fibronectin, collagen glycosaminoglycans); regulation of inflammation

TGF- 3 inhibits scar

formation


Insulin-like growth factors (IGF-1, IGF-2)

Platelets (IGF-1 in high concentrations in liver; IGF-2 in high concentrations in fetal growth)

Likely the effector of growth hormone action

Promotes protein/extracellular matrix synthesis

Increase membrane glucose transport

Vascular endothelial growth factor (VEGF)

Macrophages, fibroblasts, keratinocytes

Similar to PDGF

Mitogen for endothelial cells (not fibroblasts)

Stimulates angiogenesis

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

Macrophage/monocytes, endothelial cells, fibroblasts

Stimulates macrophage differentiation/proliferation



Inflammatory cells

Lymphocytes

- Peak on 7th day

- Affects fibroblast

- Stimulate cytokines

- Not essential for acute wound healing


B. Proliferative phase

Goal: granulation tissue formation

Events:

1.Angiogenesis

2.Fibroplasia

3.Epithelization



Decrease collagen synthesis at 4 weeks after injury

Epithelization begins hours after injury, sealed by clot then covered by epithelial eells, establishment of basement membrane



Extracellular matrix

- Scaffold for cellular migration

- Composed of fibrin, fibrinogen, fibronectin, vitronectin

Fibronectin and type 3 collagen = early matrix

Type 1 collagen – wound strength later



Collagen – 25% total protein

Type 1 found in skin and bone - most common

Adults – 80% type 1, 20% type 3

Neonates – type 3 predominates



Hydroxylation results in stable triple stranded helix

Vitamin C, TGF B, IgF 1, IgF 2- increase collagen synthesis

Interferon Y , steroids – decreases collagen synthesis


C. Maturation phase

Goal: scar contraction with collagen cross-linking, shrinking and loss of edema

Events:

1.Scarring

2.Contraction

3.Remodeling of scar


C. Maturation phase

Remodelling – wound strength increases 1-6 weeks, plateau 1 year after injury, tensile strength is only 30%

Scar more brittle and less elastic


C. Maturation phase

Wound contraction – centripetal movement of full thickness of skin

Decreases amount of disorganized scar

Wound contracture, physical restriction, limitation of function- result of wound contraction

Appearance of stimulated fibroblast known as myofibroblast

Factors affecting wound healing

Proliferative Scar

Collagen deposition versus Collagen degradation

Keloid and hypertrophic scar-excessive collagen deposition

Keloid – beyond borders , darkly pigmented individuals, genetic predisposition, clavicle, trunk, upper extremity, face

Wound Dressing

Two concepts

A.Occlusion

- increase rate of epithelization – acidic pH, low oxygen tension- good environment for fibroblast and granulation tissue

B. Absorption

Types of Wound Dressing

Non Adherent

Absorptive

Occlusive

Creams/ointment/solution

Covering a wound with a dressing mimics the barrier role of epithelium

Table 8-7 Desired Characteristics of Wound Dressings

Convenience

Cost-effectiveness

Nontraumatic removal

Safety

Permeability to gas

Nonallergenic and nonirritating

Odor control

Pain control

Conformability

Promote wound healing (maintain moist environment)

wound healing lec

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