WOUND HEALING:

Definition of a wound is broad:

ANY disruption of normal anatomy

ETIOLOGY
- trauma
- radiation
- infection
- iatrogenic etc.

Wound Healing Is the Physiologic Response to Tissue Trauma:

It is related to tissue reconstitution (e.g. skin, GI-tract) which is the process by which the body
replenishes cells that are being lost by normal physiologic events. In both processes similar events
occur in varying degrees. The same basic molecular mechanisms governing growth and
differentiation are active to a different extent. Without these being properly in place, even old
wounds may be become subject to “re-opening” (e.g. scurvy-Vitamin C deficiency in sailors).

Types of Wound Healing:

The 3 categories of wound closure are primary, secondary, and tertiary.

Primary healing involves closure of a wound within hours of its creation, Union takes place by formation of
epitheliazation and connective tissue formation.

Secondary healing involves no formal wound closure; the wound closes spontaneously by wound contraction,
connective tissue formation and reepithelialization.

Tertiary wound closure, also known as delayed primary closure or secondary suturing, involves initial debridement of
the wound for an extended period and then formal closure with suturing or by another mechanism.
Phases of Wound Healing/Elements of Wound Healing:-

The entire wound healing process is a complex series of events that begins at the moment of
injury and can continue for months to years. This overview will help in identifying the various
stages of wound healing.

I. Inflammatory Phase

A) Immediate to 2- 4 days

B) Homeostasis

• Vasoconstriction
• Platelet aggregation
• Thromboplastic makes clot

C) Inflammation

• Vasodilatation
• Phagocytosis
- Platelets release platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-b) from their
alpha granules to attract neutrophils and macrophages. Neutrophils scavenge for bacteria and foreign debris.
Macrophages are the most important mediators of wound healing. Macrophages continue to emit growth
factors to attract fibroblasts and usher in the next phase of wound healing

II. Proliferative Phase

A) 3 days to 3 weeks

B) Granulation

• Fibroblasts lay bed of collagen

• Fills defect and produces new capillaries

C) Contraction

• Wound edges pull together to reduce defect

D) Epithelialization

• Crosses moist surface

• Cell travel about 3 cm from point of origin in all directions

Overlaps with the inflammatory phase. The most important cell is the fibroblast. Fibroblasts peak approximately day
7 from injury and are responsible for initiating angiogenesis, epithelialization, and collagen formation.
Epithelialization is from the basement membrane if the basement membrane remains intact (eg, first-degree burn).

If the basement membrane is not intact, the epithelialization is from the wound edges. Fibroblasts produce mainly
type III collagen during this phase. Granulation tissue, formed in this phase, is particularly important in wounds
healing by secondary intention. When collagen synthesis and breakdown become equal, the next phase of wound
healing has begun.
III. Remodeling Phase

A) 3 weeks to 2 years

B) New collagen forms which increases tensile strength to wounds

C) Scar tissue is only 80 percent as strong as original tissue

The initial type III collagen is replaced by type I collagen until a type I:type II ratio of 4:1 is reached, which is equal
to normal skin.

Also, fibroblasts differentiate into myofibroblasts, causing tissue contraction during this phase of wound healing.
Collagen reorganizes along lines of tension and crosslinks, giving added strength.

Strength eventually approaches 80- of the strength of uninjured tissue. Vascularity decreases, producing a less
hyperemic and more cosmetically appealing wound as this phase progresses.

Collagen types and locations are as follows:

• 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

Wound Healing Terms

Primary closure: A wound closed surgically with sutures or by other means soon after creation is considered a primary
closure.

Secondary closure: This type of closure is appropriate for infected or contaminated wounds in areas of poor blood
supply. The wound fills with granulation tissue, contracts, and reepithelializes. This leads to a worse scar from a
prolonged inflammatory phase.

Tertiary closure (delayed primary closure): This type of closure allows for a superior cosmetic appearance to the
closure of a contaminated wound. The wound is allowed to stay open and undergo repeat dressing changes for a few
days. This decreases the burden of the wound and allows for a decreased infection rate after surgical closure a few
days later.

Acute wound: A wound is acute if it occurred in the last 4-6 weeks.

Chronic wound: A wound is chronic if it has been present for longer than 4-6 weeks.
PHASES OF HEALING:

1. Lag Phase: During the first few days, when the wound has no strength, little seems to be happening.

2. Preparation Phase: There is intense enzymatic and leucocytic activity with breakdown and removal of
devitalized tissue.

3. Poliferation / Fibroplasia: during the next few weeks the scene is dominated by proliferation of cells and capillaries.
Neutrophils and macrophages are prominent and fibroblast lay down collagens in increasing amounts.
PATIENT FACTORS AFFECTING WOUND HEALING
SYSTEMIC FACTORS:
Drugs:
steroids
- inhibit macrophage function, decrease inflammatory response
- inhibit prolyl/lysyl hydroxylase - unstable collagen bonds
inhibitory effects reversed by Vit A, anabolic steroids
- inactivates complement
- leads to T and B cell dysfunction
- decreases leucocyte bactericidal activity
anti-neoplastic agents
- decreased WBC’s, decreased fibroblast proliferation, decreased wound contraction, decreased protein
synthesis
- if given greater than 14 days post-op - no apparent long-term effects on wound healing (noted early
decreased wound strength)
- colchicine - decreased collagen precursors, decreased collagen secretion (cellular constipation),
increases activity of collagenases
- penicillamine - Ca chelator (Ca required for collagen x-linking)
- NSAIDs
- decrease collagen synthesis by 45- even at normal levels

Vitamins: (supra-normal levels of Vitamins are not beneficial)

- vitamin A
- co-factor collagen synthesis and x-linking - increases wound strength
- capable of reversing inhibitory effects of steroids and Vit E
- does not increase wound healing in absence of steroids
may reactivate disease for which steroids are given
- vitamin C
- co-factor for proline hydroxylation
- absence (scurvy) - causes capillary fragility and wound healing problem
vitamin E
- decreases collagen synthesis, inhibits wound healing inhibited and decreases tensile strength

Trace Metals
Zinc
- enzyme constituent
- cofactor for collagen synthesis
Copper
- extracellular cofactor
- required for collagen crosslinking
Magnesium
- cofactor in glycolization

Nutritional Status
- catabolic state (net -ve nitrogen balance) inhibits wound healing
- protein depletion - prolongs inflammatory phase, impairs fibroplasia
- methionine required for forming disulfide bonds in collagen synthesis
- carbohydrates - energy source for WBC’s
- fats - no significant effects, but fats are essential elements of all cell membranes

Associated Illnesses/Immunity
- cancer, infection, peripheral vascular disease, COPD/ hypoxia, obesity smoking - all negatively affect wound
healing
- diabetes - affects wound healing in numerous ways - associated peripheral vascular disease, neuropathy,
immuno-dysfunction (decreases chemotaxis, phagocytosis, intracellular killing),
decreases collagen synthesis
Patient Age
- associated with delayed onset of healing, protraction of phases and an inability to reach same level of healing
- associated with decreased tensile strength and wound closure rate

LOCAL FACTORS:
pO2
- in a person with normal nutritional status, oxygen level in healing wound is the rate limiting step (requires
adequate inspired oxygen, Hb for transport, adequate tissue perfusion via large and small vessels)
- local ability to supply oxygen to healing wound process is inhibited by peripheral vascular disease,
previous radiation, chronic inflammation, diabetes mellitus, infection;
- a paucity of vascularization limits the development of an adequate inflammatory reaction
- required for collagen synthesis
proline hyroxylation
collagen secretion
- required for leucocyte killing capacity (phagosomal peroxidation)
- also needed for growth factor secretion and fibroblast proliferation
- hyperbaric O2
- increases fibroblast proliferation (requires adequate perfusion)
- Localized Infection
- pus lowers local pO2, has collagenolytic effect, prolongs inflammatory phase, inhibits re-epithelialization
- Foreign Body
- clot, necrotic debris, dirt, suture, glass etc. prolong inflammatory phase, lead to increased susceptibility
for infection and increased duration of re-epithelialization
- Mechanical Stress
- affects quantity, aggregation and orientation of collagen fibers
- Wound Hydration
- moist wound healing environment increases rate of re-epithelialization
- Temperature
- environment temperature greater than 30oC increases tensile strength
- Previous Radiation Therapy
- acute radiation changes cause vascular stasis and associated decreased wound healing
- chronic radiation changes include irreversible damage to skin with progressive obliterative endarteritis
and an inability for fibroblasts to replicate or contract resulting in progressive skin changes and inability to
heal minor wounds, the wound is chronically hypoxic
- Pressure
- undue pressure may lead to ischaemia of the wound, therefore, all wounds, particularly chronic wounds,
should be off-loaded.