DEPARTMENT OF SURGERY

UNIVERSITY OF PRETORIA

PLASTIC SURGERY

WOUND HEALING & WOUNDS 2003

PF COETZEE
A WIDGEROW
A MADAREE
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WOUND HEALING & WOUNDS 2003

P F COETZEE
A WIDGEROW
A MADAREE
I. INTRODUCTION

Wound and wound healing abnormalities number amongst the main causes of
patient morbidity and mortality. South Africa with an abnormally high incidence
of violence and road accidents, an ageing population and an epidemic of HIV/
AIDS and malnutrition is no exception. The allocation of resources towards more
dramatic diseases like cancer chemotherapy and organ transplantation is
worldwide disproportional.

One of the great challenges to health carers has always been the ability
to achieve wound closure by either operative or nonoperative methods.
Different methods included dressings, surgery, treatment of systemic disease
and control of infection and also the use of modalities like hyperbaric oxygen.

During the past 20 years more advances were made in wound care than
the previous 2000 years. This all came as a result of the rapid expansion
in knowledge of the intricate mechanisms of the healing process at
molecular level. Present wound-care methods have dramatically improved the
ability to heal wounds with fewer complications.

One of the most promising recent advents is the therapeutic use of growth
factors and local antibodies to generate new tissue. An even more
exciting technology creating new tissue, is that of tissue engineering.
Since 1987 this multi-disciplinary field combining biological science and
engineering technology, has developed rapidly to produce commercially
available live skin substitutes and cartilage. Research has created
live cultured cells fixed to an extracellular matric and eventually supported
by a three-dimensional vascular structure. We are on the brink of producing
through stem cell manipulation, live organs to replace alloplastic implantations
and donor transplantations.

The vision of the Wound Healing Association of South Africa (WHASA) is to

promote clinical wound care at all levels, to educate and expand wound care
knowledge amongst all roll players and to stimulate research in this field.
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II. GENERAL

a) THE PHYSIOLOGY OF WOUND HEALING: PART 1 – INFLAMMATION

The physiology of wound healing forms the basis on which wound care is based.
A wound is a pathological state in which tissue becomes separated or destroyed.
Wound healing is the complex sequence of events directed towards closure of
the defect, usually by replacement with scar-forming connective tissue. This
process of repair by scar tissue replacement contrasts with the process of
regeneration where damaged tissue is replaced with identical cells. The many
revolutionary changes that have been made in this field in the past decade are a
direct result of a greater understanding of the events occurring within minutes of
wounding. Many experts believe that efforts aimed at improving the speed of
wound healing, the nature of the healing process and even the eventual scar
outcome, need to be concentrated on events that begin almost instantly with the
process of injury.
Wound healing is aimed at reversing the loss of structural integrity caused by
injury to the tissue. This process of wound healing can be divided into a number
of dynamic, overlapping phases:
1. The initial response is vascular. To prevent localized haemorrhage, the
coagulation cascade is initiated. The damaged ends of the blood vessels
immediately constrict. Platelets in the blood escaping from the injured
vessels release Thromboxane A2 to slow the loss of blood. During
vasoconstriction, vessels turn inward and narrow. This vasoconstriction
lasts only a few minutes, long enough for blood clots to seal the leaking
blood vessel. The coagulation cascade starts with the release of platelet
factors (thromboplastins) and other substances from the damaged cells.
The extrinsic and intrinsic pathways of the coagulation cascade are initiated,
thromboplastins activate conversion of prothrombin to thrombin, and thrombin
converts soluble fibrinogen into insoluble fibrin. Eventually, an aggregate of fibrin,
red blood cells and platelets grows large enough to plug the capillary and stop
the flow of blood.
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As the clot dries it forms a scab, which protects the wound site from dehydration
and pathogen invasion. Concurrently vasodilatation ensues – ten to thirty
minutes after injury, mast cells in connective tissue release serotonin and
histamine causing vessels to dilate and increase their permeability. This
increased blood flow causes heat release and a temperature rise in the skin
around the wound. The increased permeability results from separation of
endothelial cells in the vessel walls induced by serotonin and histamine. Thus
plasma migrates into the interstitium, nourishing the wounded tissue and
leukocytes leak into the extracellular spaces surrounding the wound.

2. Tissue damage and the activation of clotting factors during the vascular phase
stimulate the release of inflammatory mediators - bioactive substances -
constituting the early aspect of wound healing known as the inflammatory phase.
This reaction, which begins within seconds of wounding, is the same whether the
cause is a surgical cut, or a wound invaded by pathogenic bacteria. The
qualitative nature and duration of this phase is critical in determining the eventual
outcome of wound healing, from the successful closure of the defect to the
quality of the resultant scar. The response occurs rapidly and can be detected by
the presence of localized heat, swelling, erythema, and discomfort, which usually
restricts function.
When it comes to the inflammatory process, permeability of the intravascular
space results in leakage of plasma, soluble components, and cellular
constituents arriving in the following sequence: first platelets, then neutrophils,
followed by monocytes and lymphocytes which differentiate into macrophages
as they enter the connective tissue.
The migration of epithelial cells then begins, resurfacing the injured tissue (Fig
1). The macrophage is the key player in the degradation of injured tissue debris
and in the reparative phase of wound healing, initiating the transition from initial
inflammation to the early repair phase of wound healing.
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The inflammatory phase of wound healing is a complex, dynamic interaction of

cellular proliferation, differentiation and specialized cytokine induced changes
resulting in control of bleeding, wound debridement, and extracellular matrix
preparation setting the groundwork for the repair phase of wound healing, and
the ultimate closure of the defect. Interruption of any of these many intricate
cellular interactions will result in changes varying from exaggerated scarring to
delayed or non-healing of the wound.
FIG 1

INJURY
lymphocyte
HAEMORRHAGE complement
Interferon
bact\viral particles
oxygen Antigens
COAGULATION
THROMBOSIS INFLAMMATION
(PLATELETS) neutrophils prostaglandins helper T cells
monocytes lymphokines
cytokines cytokines
Epithelial Cell

cytokines MACROPHAGE
FIBROBLAST prostaglandins

Proteoglycans cytokines Endothelial Cell

Fibronectin
Collagen

Cytokines = TGFα, TGFβ, PDGF, EGF, FGF, TNFα

REPAIR

Fig 1: Wound Healing Sequence – Macrophage orchestrated

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b) PHYSIOLOGY OF WOUND HEALING: PART 2 – REPAIR

(It’s important to note that a knowledge of wound healing and repair enables the
clinician to design and implement treatment regimens based on scar biology.)
The inflammatory phase of wound repair prepares the groundwork for the
formation of granulation tissue (the name is derived from the granular
appearance of the newly forming blood vessels) and consists of a loose matrix of
fibrin, fibronectin, collagen, and glycosaminoglycans (especially hyaluronic acid)
containing macrophages, fibroblasts and developing blood vessels.This tissue
formation occurs between 4 and 21 days following wounding and serves as
scaffolding for new tissue ingrowth in deep wounds. Wound closure by
contraction, the inward movement of the wound edges of the injured tissue, is a
normal part of the healing process. Contraction begins 8 – 10 days following
injury. Fibroblasts and the extracellular matrix (ECM) orchestrate it, with
fibroblasts applying tension to the surrounding matrix. Fibroblasts align
themselves along the axis of the wound and form cell-to-cell links, which
contribute to contraction of the wound. Production of collagen remains a major
process in wound repair several weeks after wound closure, and the collagen
continues to undergo remodeling for 2 years or more, until stability of the process
occurs. Precise regulation of collagen metabolism during the repair process is
exerted by cytokines and by the interaction of the ECM with fibroblasts. Collagen
synthesis is maximal between 14 and 21 days. After 21 days the rate of
synthesis and the volume density of collagen in the wound return to normal
levels. However, the tensile strength of the tissue continues to increase for a
considerable time, up to 60 days or even 1 year.

In the adult, the normal repair of wounds occurs by the formation of granulation
tissue and its organization to a scar. Scar is a dynamic, metabolically active
tissue and tends to remain weaker than unwounded tissue. A scar tends to
contract abnormally, and overhealing may lead to a hypertrophic scar or keloid.
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The scar appears reddish at first but as the connective tissue grows tauter and
vascularisation slows, it gradually loses colour. Hair, sebaceous and sweat
glands are also absent, as is the ridged pattern of the epidermis. Thus the new
skin’s appearance is unusually smooth. The rate at which wounds gain tensile
strength is slow. For example, wounds have gained only about 20% of their final
strength by the third week. Wounded tissue fails to attain the same breaking
strength as uninjured skin. At maximum strength a scar is only 70% as strong as
intact skin.
c) WOUND ASSESSMENT
i) A full assessment of a problem wound is critical to successful management
and treatment and facilitates the choice of wound dressing required to
promote healing.
Factors include:
• the history of the wound
• the location of the wound
• the condition of the surrounding skin and the wound margins
• the extent and depth of the wound and the condition of the wound bed.
ii). Physiological assessment is also essential. This includes:
• general health status
• associated systemic disease
• associated vascular disease
• Neurosensory and neuromuscular status
• wound severity and tissue type involved
• factors affecting treatment option selection
• presence of foreign material

iii) Acute and chronic wounds. Acute wounds usually occur without an
underlying cause, usually trauma related. They are of short duration,
eliciting a normal inflammatory response, usually followed by healing
without subsequent breakdown.
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Chronic wounds usually result from underlying pathology, often vascular in

origin. They are of prolonged duration with a delayed and ongoing
inflammatory response, and liable to recurrence. Systemic factors
encouraging chronicity of wounds include varied disorders, the commonest
of which are the circulatory disorders. Other significant disorders that need
to be excluded include respiratory disorders, malabsorption syndromes
(Crohns etc), and disorders of mobility and sensation (spinal injuries,
diabetics, MS etc). Identifying local wound infection or systemic infection is
paramount.
vi). Wound Assessment Chart
This includes:
1. Wound edge – viable, rolled, fibrotic or flat and closed. (Rolled edges
could be an important clue to biopsy the edge to exclude malignancy).
2. Wound colour – red (granulating, protect it)
- yellow (sloughy, cleanse it)
- black (necrotic, debride it)
- pink (epithelializing, protect it)
3. Skin condition – macerated, intact, denuded, reddened.
4. Peri-wound colour – normal, white, bright red, dark red\purple, black, light
red\pink.
5. Oedema – mild, moderate, severe
6. Size – length, width, depth. In diabetic wounds it is extremely important
to assess whether the wound can be probed down to bone, signifying
more serious pathology and more aggressive management. Wound
measurement may be done by ruler, tracing the surface on dressings
particularly grid dressings (Flexigrid S&N etc), or with probes or fingered
gloves to document the depth of the wound.
7. Photographic documentation (especially digital) is being used more
commonly, with its added advantage of transmission via computer, when
necessary, for discussion.
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8. Undermining – extent, range.

9. Sinus tract – extent, direction
10. Drainage – absent, minimal, moderate, high.
11. Drainage type – serous, serosanguinous, purulent
12. Odour – pungent, foul, faecal, musty
13. Necrotic tissue – white macerated thick; yellow slough; black\brown
eschar
14. Granulation tissue – red, grainy, friable
15. Epithelial tissue – pink
16. Pain – burning, boring, throbbing, dull, intermittent, constant.
17. Doppler waveform, where applicable.
Aside from these local descriptions of the wound a full documented medical
history is noted, including allergies and sensitivities, previous treatments and
questioning related to the factors discussed above

d) SELECTION OF WOUND DRESSINGS

Wound care has developed into a distinct scientific field. There is no single
dressing that is ideal for all wound types. Many variables in patient factors,
product factors and the different stages of wound healing necessitate a wide
choice of dressings for different situations. The wound dressing function is to
provide the environment that will maximize the body’s potential to do this. Ideally
we need the dressing to provide mechanical protection, thermal insulation,
gaseous exchange, protection against infection and absorption of excess
exudates. We would also like as little sensitization potential as possible –
adhesive constituents may cause contact dermatitis. Provision of a moist
environment has been a prerequisite for healing in most wounds and with few
exceptions, the basis of wound management now involves the provision of this
high humidity at the wound dressing interface.
Additionally, occlusive dressings have been shown to decrease pain and
inflammation, to decrease wound infection in most wounds and to improve scar
formation.
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Essentially, the more difficult the wound is to heal, the more sophisticated the
dressing choice needs to be. Depending on their structure and composition,
dressings may be used to absorb exudate, combat infection or odour, relieve
pain, promote debridement, provide and maintain a moist environment
encouraging granulation tissue production and promoting epithelialisation. The
choice of dressings is made according to these different requirements unique to
each wound.

Dressing Categories
Transparent Film Dressings (examples Tegaderm, Op-Site)
Transparent films are semi-permeable membranes made of polyurethane. Most
are adhesive, although non-adhesive varieties do exist. The adhesives may have
the potential for sensitization. The film dressing serves as a non-absorptive
barrier. They provide moist healing, allow visualization of wounds and can serve
as a secondary dressing holding the primary dressings in place. They are also
excellent in protecting intact skin or in situations of superficial epidermal injury
such as burns and abrasions. They are contraindicated in deep, infected wounds,
or those with a macerated margin. Disadvantages include the fact that excessive
exudate may accumulate and adhesive trauma is possible.
Hydrogel Dressings (examples Intrasite, Granugel, Nugel)
Hydrogel dressings are available as a gel or as sheets. They are predominantly
composed of water, and thus are able to donate moisture to the wound.
Hydrogels can be packed into wounds to fill dead space - they provide a moist
protected environment, offer pain relief, encourage granulation and autolytic
debridement. They can be used on infected wounds.
The gels’ ability to donate moisture may be altered by combination with a
secondary dressing – thus combining with gauze will increase water loss,
combining with a film dressing will decrease water loss.
Hydrocolloid Dressing (examples Granuflex, Comfeel, Combiderm)
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These are water-impermeable, interactive dressings. They are usually composed

of three layers. The outer membrane layer is usually a film – this provides
occlusion.
The inner layer provides moisture - it is hydrophilic composed of gelatin or pectin
which converts to a gel when it contacts exudate (hence interactive). An
additional layer contains carboxymethylcellulose, which functions as an exudate
absorber. Hydrocolloids are available as wafers, as thicker or thinner sheets, or
as island combinations (Combiderm). These dressings are contraindicated in
infected wounds, but they do form a barrier to bacteria on the outside and they
encourage autolytic debridement. They can absorb small to moderate amounts of
exudate, but heavy exudate would require frequent dressing changes due to
leakage. These dressings maintain an acidic environment and promote
angiogenesis, granulation and re-epithelialisation. They are also available in
pastes and powder form.
Calcium Alginate Dressings (example Kaltostat)
These dressings are made from kelp, or seaweed, by injecting sodium alginate
into a calcium chloride bath. They are highly absorbent, and have a haemostatic
clotting effect produced by initiating a calcium - sodium exchange. They are used
in wounds with moderate to large amounts of exudate (not dry wounds) – on
contact with wound fluid a gel is formed (interactive). They are non-adhesive and
require a secondary dressing. They can be left in place up to 5 days.
Hydrophilic Foam Dressings (examples Allevyn, Tielle, Cavicare)
These dressings consist of hydrophilic foam chips for cavity dressings or flat
polyurethane combinations which are held together by a perforated film. The
foams have an open pore structure which make them highly absorbent. They
may be used in conjunction with hydrogels if the wound has excessive slough.
They are conformable and may be used in combination with films, pastes, or
compression bandages.
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Hydrophilic Fibre Dressings (example Aquacel)

These are non-adherent absorbent fibrous dressings, containing fillers of
carboxymethylcellulose. They form a cohesive gel sheet with exudate. They are
easy to apply and remove, are soft and absorbent and conformable.
Odour Absorbing Dressings (example Actsorb Plus)
These are highly absorbent dressings containing activated charcoal for
malodorous wounds. They are suitable for discharging, purulent, contaminated
wounds with offensive odour. They may need to be changed frequently initially.
Other classes of dressings include desloughers, topical antibacterials and the
like.
The Selection Process
The initial step in wound management and dressing selection is assessment of
the wound. Simplistically there are four categories of wound description to take
into account: black necrotic, yellow sloughy, red granulating and pink
epithelializing wounds.
Necrotic wounds: The most convenient way of rehydrating the necrotic wound
and encouraging separation is the use of hydrogels or hydrocolloids. These both
donate fluid to the wounds, acting as physical barriers, preventing the loss of
moisture vapour through the dead tissue to the external environment. As a result,
moisture accumulates within the necrotic layer causing it to become rehydrated.
To facilitate separation, debriding enzymes may be added as topical
preparations, if necessary. The necrotic layer separates, leaving behind it a
wound containing partially liquified yellow slough, the second category of wound
descriptions.
Sloughy wounds: The most effective way of removing this slough is by surgical
debridement. This is not always practical and alternatives may need to be used.
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Hypertonic saline gauze is excellent for mechanical debridement. Irrespective of

whether a topical preparation is used or not (Eusol and hydrogen peroxide soaks,
Aserbine, Betadine, Cicatrin or any of the newer more effective agents cleanse)
the class of dressing for the infected sloughy wound would be the foams,
hydrogels or hydrofibres.
Calcium alginates are effective in the sloughy bleeding wounds. If the wound is
infected it is best not to occlude the wound – hydrocolloids are contraindicated in
this situation.
Whatever technique is used, once the slough is removed, the formation of
granulation tissue can take place unhindered.
Granulating red wounds: Wounds with a narrow opening but large undermined
areas can be difficult to treat. One must not allow the opening to close before the
undermined areas have healed. If the wound is moist, it may be packed with
alginate ribbon (not too tightly); hydrocolloid granules or pastes are useful for the
smaller cavities, while hydrogels injected into the cavities are useful for the larger
ones, especially if slough is present. For more shallow chronic exuding wounds,
highly absorbent foams (Tielle, Allevyn, Combiderm [highly absorbent]) are
effective. If exudate production is not a problem hydrocolloids may be indicated.
Epithilialising pink wounds:
Superficial wounds which produce relatively little exudate may be dressed with
hydrocolloids or film dressings. Low adherent wound contact dressings have also
been recently introduced – these consist of a knitted viscose fabric impregnated
with silicone (Mepitel) which is very gentle on the skin. They are ideally used in
the final phases of wound healing. Highly exudative superficial wounds such as
donor sites and burns can be treated with alginates and hydrocolloids, which
have the advantage of faster healing times.
As with all medical treatment today, cost is a major factor in dressing choice.
Fortunately many controlled trials have been undertaken looking at unit costs and
more importantly treatment costs, the cost and effectiveness of the alternatives.
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Very often the individual cost of newer dressings is higher, but when compared
with the number of dressings that need to be done and the effective time taken to
full healing, patient comfort and out patient treatment, these dressings are
usually found to be more cost effective.

e) THE INFECTED WOUND

The presence of bacteria in our system does not denote infection. We live in
equilibrium with resident bacteria. But any breach of the skin or mucous
membrane barrier may disturb this equilibrium leaving us susceptible to wound
infection. Infection occurs when bacteria achieve penetration of the
subcutaneous tissue and reach significant numbers. The quantity of the bacteria
added to its virulence factors can result in the wound progressing to an infected
state, preventing healing from occurring.
No single recognized pathogen may always be the cause of delayed healing or
infection. The majority of the bacteria that contaminate wounds originate from
endogenous mucosal surfaces of the gut, the mouth and the genito-urinary tract
(the host’s own flora). At these sites anaerobic bacteria outnumber aerobic ones
by a factor of 1000:1. Co-existing aerobic and anaerobic bacteria are known to
work together to collectively enhance growth and virulence, and these synergistic
interactions may be a key factor in delayed wound healing.
Care needs to be taken to avoid either the under or over estimation of wound
infection. Only if infection is suspected should bacteriological sample be taken.
Many wounds are swabbed routinely if the presence of erythema and or oedema
are noted, despite the fact that these signs are normally seen during the
inflammatory phase of healing. However, failure of the wound to heal or sudden
unexplained deterioration may be indicative of ‘silent infection’.
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Other signs of infection include:

• increased wound\patient temperature;
• pain;
• pus;
• increased exudate production;
• change in exudate colour;
• offensive odour;
• discolouration of granulation tissue;
• wound breakdown
• accompanying oedema and erythema.
Infection is diagnosed by the host response to the invading pathogens. The
diagnosis is likely to be most accurate if based upon the presence or absence of
objective clinical signs, confirmed when possible, by bacteriological analysis.
Increased bacterial burden with decreased healing can produce signs of
infection, sometimes in subtle forms. Clinicians should examine wounds carefully
for local signs of infection. Bacterial balance is the central theme for local wound
care, along with debridement and moisture balance. If these steps have been
taken and healing is still not apparent, newer biological agents should be
considered. If an increased bacterial burden exists in the deep compartment and
there is failure to heal, systemic antimicrobial agents are probably necessary.
The patient as a whole should be considered and the underlying disease
processes treated.
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III. CLASSIFICATION OF WOUNDS

No single effective classification system exists which can optimally
define and describe all wounds. When assessing a wound it
becomes apparent what myriad of factors influence the wound and
complicate the classification.

Pathophysiologic Treatment
factors option

ouou
Description of wound
according to assessment outcome

General patient Wound life cycle

factors influencing

Improving Deteriorating

Fluctuating Static

a. ACUTE WOUNDS
Wounds may firstly be classified according to the mechanism of injury
and secondly to the amount of contamination (American Association
of Trauma Surgeons).

i) Lacerations, sharp penetrations, surgical incisions

Clean wounds, mostly superficial with minimal tissue damage and

contamination, requires suturing and heal by primary intention.
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ii) Abrasions

Involves the skin surface to a varying depth, caused by friction creating

heat (burn) necrosis, and if contaminants (tar, soil) get fixed may cause
infection. Effective treatment requires vigorous cleaning, enthusiastic
scrubbing, copious lavage and removal of tattooing by dermabrasion
mostly under general anaesthesia. Occlusive dressings promote moist
wound healing through secondary intention.

iii) Crushing, avulsion, degloving

These wounds are often hidden, the appearance is deceptive and of a

serious nature. Often present are underlying fractures and large spaces filled
with blood. The potential for life threatening infection is real. These injuries
require careful diagnosis and sometimes complicated treatment eg
replantation.

iv) High energy/velocity wounds

MVA and missile injuries cause widespread devascularized tissue damage.

The principles of treatment include multiple debridements, measures to
prevent infection, fasciotomies, reconstruction and rehabilitation.

v) Burns

vi) Bites

AATS classification

i) Clean wounds - incisional

ii) Clean contiminated - domestic
iii) Grossly contaminated - agricultural
iv) Infected – contamination may happen primarily or secondarily due to
inadequate or inappropriate treatment. Organisms flourish causing
suppuration.

b. CHRONIC WOUNDS

Acute wounds heal timely in an orderly fashion responsive to standard

therapy. The chronic healing process follows a delayed, incomplete,
uncoördinated course. The distinction between acute and chronic
relies on the timeliness of healing, but is arbitrary and varies with site,
cause, age and physical condition. Although a heterogenous group,
venous ulcers, diabetic ulcers and pressure sores constitute 70% of
cases.
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i) Classification according to cause:

1. Vascular insufficiency
- Chronic venous ulcers
- Artherosclerosis
- Lymphedema
2. Traumatic
- pressure ulcers (decubitus and neuropathic)
- burns, frostbite
- bites (insects, ticks, spiders, snakes)
- radiation injury

3. Metabolic
- diabetes
- gout
- calcinosis
- Gaucher’s disease

4. Inflammatory disorders
- pyoderma gangrenosum
- vasculitis – polyartheritis nodosa, granulomatoses
- panniculitis – necrobiosis lipoidica diabeticorum

5. Infections
- bacterial – TB, osteomyelitis
- other – fungal, treponemal, viral, protozoal

6. Connective tissue disease

- Sle, rumatoid arthritis, scleroderma, sclerosis
- Sjögren’s syndrome

7. Hematologic
- rbc (sickle cell anemia, thallassemia, spherocytosis, polycythemia
vera)
- wbc (leukemia)
- platelet (thrombocytosis, hypercoagulable states)
- dysproteinemia (amyloidosis, cryoglobulinemia)
8. Neoplastic
- marjolin’s ulcer
- primary and metastatic skin tumours
- lymphomas, sarcomas (kaposi)
- haemangiomas, vascular-, lymphatic malformations
9. Miscellaneous
- drugs (Coumadin – protein C deficiency)
- fictitious (malingering)
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ii) Pathophysiology (From Nwomeh et al: Clin in Plast Surg. Vol 25, no.
3, July 1998)

Tissue injury

Repeated Trauma, Infection

Hypoxia, Ischemia, Malnutrition

Chronic Inflammation

Activiation of Neutrophil
Macrophages Infiltration

Inflammatory Reactive
Cytokines Oxygen Species

Matrix Degrading Proteases

Protease Inhibitors

Excessive Matrix Degradation

Degradation of Growth Factors
Impaired Epithelialization

Chronic Wound

Local factors impairing wound healing include foreign bodies, smoking,

toxins (bites) and hyperthermia. Systemic factors are nutritional
deficiencies (protein, vitamins C, A, E, K, zinc, iron, copper, magnesium)
ageing, liver disease, alcoholism, jaundice, blood transfusion, uremia
and multiple drugs (Aspirin, povidone – iodine, colchicine, NSAID,
corticosteroids, retinoids).
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Although the association between cigarette smoking and delayed wound healing
is accepted in clinical practice, no controlled clinical studies have proved this
relationship (Burns).

iii) Management principles

Evaluation begins with adequate history and physical examination.

Special investigations include an arteriogram (vascular abnormalities),

arteriole Doppler studies including segmental and toe pressures (perfusion)
and transcutaneous oximetry (TcPO2)(oxygenation of the wound). If they
are abnormal, adjunctive therapy like HBO may be needed to aid in healing
the wound.

The foundation of treating a problem wound is the identification and correction

of the underlying etiology and risk factors that may hinder the healing
process. Some measures include bed rest, reduction of edema (stasis ulcers),
control of systemic medical conditions and infection, pharmacology
(vasodilators, steroids for vasculitis, blood transfusion for sickle cell) and
hyperbaric oxygen.

iv) Venous ulceration

Venous stasis ulcers make up 70% of vascular ulcers. They result from
chronic venous insufficiency. It is critical to differentiate venous from
arterial ulcers as the compression therapy used for venous ulceration
could have dire consequences if used in a patient with an arterial ulcer.
Venous malfunction initiates a series of events that result in increased
hydrostatic pressure, venous hypertension and, ultimately skin
ulceration.

Clinical Presentation

Lower limb ulcers are extremely common. A past history of DVT is a

good predictor of venous incompetence leading to ulceration. A full
clinical workup of the patient’s general health status and blood counts
should therefore be taken and all systems should be examined with
special emphasis on the appearance of the lower extremities. Ankle
oedema is the earliest sign of chronic venous insuffiency. (Oedema is
usually minimal or absent in arterial disease).
Leg pain relieved by elevation is consistent with venous disease (in
arterial disease pain is exacerbated with elevation) and the skin on the
lower limbs is usually hard and fibrotic.
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Other signs include:

• dilated superficial tissue veins;
• dermatitis;
• pigmentation due to extravasation of red blood cells into the skin –
purple in light skinned people, dark brown or dark purple in dark-
skinned people;
• dry flaky skin that has the appearance of fish scales;

Venous ulcers are also characterized by irregular wound margins; they are
non-tender, associated with eczema, covered with exudate and usually
located on the medial aspect of the lower leg or ankles. (Arterial ulcers occur
on toes, feet and unusual locations, are tender, gray and may contain necrotic
tissue) Palpation of peripheral pulses and temperature assessment
of lower limbs and hands is essential. Cold skin with diminished pulses suggest
arterial disease.

Chronic non-healing ulcers should be biopsied to exclude carcinoma or

vasculitis. Underlying osteomyelitits (x-ray confirmation), contact dermatitis
and soft tissue infections should be excluded or identified and treated. Once
diagnostic tests have ruled out arterial diesease, then compression therapy and
moist wound environment are the mainstays of venous ulcer management. High
compression (>35mmHg) is more effective than low
compression but should only be used in the absence of arterial disease. Non-
compliance with compression is, however, often a problem, hence the
importance of patient education. In post-thrombotic syndrome or if venous
insufficiency is still present, ulcers tend to recur. General or systemic risk factors
facilitating recurrence would be obesity, inadequate nutrition, lack of
exercise and smoking.

v. Arterial Ulcers

Peripheral ischaemia and reduced skin blood flow may lead to arterial
ulcers. Arterial insufficiency and occlusive disease is usually caused by
atherosclerosis of the extremities. The incidence of arterial insufficiency
and ulceration increases with age – the sixth and seventh decade
accounts for the highest incidence. Risk factors are also increased in
patients who are male, and those who have diabetes mellitus, hyper-
tension, Raynaud’s Disease, sickle cell anaemia, hypercholesterolaemia,
lead a sedentary lifestyle, suffer from obesity and smoke.

It is imperative to differentiate between venous ulceration and arterial

ulcers as treating these two disease processes is vastly different. The
diagnosis of each is vital to avoid inappropriate and dangerous treatment.
Venous ulcers occur slowly and are associated with oedema.
 22

Arterial ulcers occur in patients with the risk factors mentioned above and are
usually located on the lower leg over the toes, between the toes or on the
tips, on the heels or bony prominences of the foot and rarely over the
medial malleolus. They have deep pale wound beds with even wound
margins. The surrounding atrophic skin changes described previously are
present as well as the symptoms and signs of arterial insufficiency.
A history of intermittent claudication, coldness, numbness in the toes and
feet is typical. Resting pain in the lower limbs which improves when the
limb is dependent, is a sign of advanced atherosclerotic vascular
disease.

Examination reveals decreased or absent pulses, rubor with the foot in a

dependent position, pallor when elevated, cool dry skin and bruits over
the narrowed artery. As the disease progresses trophic skin changes are
seen, caynosis, thin shiny skin, loss of hair and thickened deformed
toenails.

Diagnosis is critical and this is usually apparent on history and

examination while Doppler flow studies provide useful additonal
information . Arterial ulcers are particularly difficult to treat as the cause,
arterial insufficiency, is progressive and in many cases, irreversible
with conservative means. The goal for treatment of patients with arterial
ulcers is to increase the blood supply to the affected area. Proper
maintenance of the feet is important – protect bony prominences, hygiene,
properly fitting shoes and socks. Elevating the head of the bed promotes
flow to the feet. Local treatment involves adequate debridement and
moist occlusive dressings once or twice a week. Operative intervention
such as aorta-bifemoral bypass, may be necessary in cases resistant to
conservative therapy. While the local treatment of the ulcer is important,
it is futile if the risk factors and underlying disease are not controlled. This
includes cessation of smoking, control of diabetes, obesity, cholesterol,
excercising and anti-coagulants where necessary.

vi. Wound healing in diabetes mellitus

Diabetic ulcers of the lower leg often present innocently but may progress rapidly
to fulminating infection and amputation. It has the highest lower limb
amputation rate of any chronic leg wound. Ulceration mainly affects the feet.
 23

Factors contributing to altered healing

1. Ischemia

a. Macrovascular atherosclerosis with emboli;

b. Microvascular disease with a pathologically thickened perivascular

capillary basement membrane. This abnormality may cause increased
vascular permeability resulting in edema and extracellular matrix
depositional “trapping” of inflammatory cells and suppression of
leucocyte function.

2. Neuropathy

Affects all nerve types with resultant:-

a. Loss of pain protection and protective reflexes. The foot muscles loose
their motor feedback causing the arch of the foot to collapse resulting in
deformed metatarsals and clawing of the toes. Painless repetitive
injuries from minor wounds like trimming of toe nails lead to chronic
ulceration and ill fitting shoes to pressure necrosis on the plantar
surface and tips of the toes. Protective calluses increase the chance of
pressure.

b. Loss of sympathetic nerve supply leads to a non-sweating foot, the lack

of moisture causes cracking of the skin, an altered bacterial flora and
invasion with colonization.

3. Uremia

Silent or overt renal failure causes loss of protein and edema but also
independantly alters wound healing.

4. Suppressed immunity

A reduced ability to deal with infection exists on a cellular and biochemical

level. Not only is there a break in the physical barrier through skin
cracking but lack of glucose control impair local leucocyte defences.
There is a decreased production and increased destruction of growth
factors present (Insulin-like GF I and II and Keratinocyte GF).
Hyperglycaemia contributes to the metabolic pathophysiology of diabetes
related complications (Greenhalgh). This occurs through intricate
pathways at molecular level.
 24

Clinically the classic chronic diabetic ulcer presents as a small punctate

wound over the plantar aspect of a deformed metatarsal head or toe tip.
The rim has a raised epithelial edge with pale granulation in the centre.

There may be surrounding cellulitis present and in a progressive fashion

the infection may invade along plantar fascial planes or cause failed
wound healing of gangrenous toes, metatarsal or eventually below knee
amputation. Ulcers secondary to necrobiosis lipoidica usually occur over
the pretibial region.

Management

1. Preventative foot maintenance include careful nail clipping, selection of

well fitting shoes and routine daily foot inspection.

2. Evaluation of proximal vascular status and sensory function. Calcification

makes the arteries inflexable and therefor palpable ankle pulses, toe blood
pressure and ankle – brachial (AB) index above 0,5 as predictors of
ulcer healing ability, is not reliable. Small ulcer size of short duration in non-
white patients and transcutaneous oxygen levels above 25-30 mm Hg are
reliable indicators of an increased ability to heal.

3. Tight control of blood sugar and infection is essential. Aggressive

debridements, removal of surrounding callus and broad-spectrum antibiotics
are indicated.

4. Dialysis for uremia or a kidney transplant is beneficial.

5. Meticulous protection and wound care will heal superficial shallow ulcers.
“Total contact” casts will “off-load” pressure and restricted activity should heal
moderately deep ulcers.

6. Reconstructive surgery includes vascular bypass, skin grafts, pedicled flaps

and free flaps for deep, extensive and bony defects. Limb salvage operations
require careful planning with full patient co-operation to prevent
early breakdown and failure.

7. Hyperbaric oxygen may theoretically be advantagous but lack of

randomised, prospective research evidence makes it controversial.

8. Natural or engineered growth factors show potential promise. The only

commercially available growth factor in the USA is for diabetic ulcer
treatment.
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vii. Radiated wounds

The effects of surgery are permanent – the effects of radiation are permanent,
continuous and progressive.

The effects of surgery are immediately obvious, while those of

radiation continue the patient’s entire life (Anon).

The exact incidence of clinical complications due to radiotherapy is not

known because they may develop many years after original exposure.
In the treatment of head and neck cancer it may be as high as 65%
(Harson).

In our efforts to achieve maximum long term cure for certain

cancers with combination therapy, we sometimes cause not only severe
physical deformity but also complicate difficult reconstructions due to
radiation sequelae. Radiation as a primary single modality of treatment
has as one of it’s aims the preservation of important functional and
esthetic structures. An example is the intra-oral reconstruction of a
functional tongue or soft palate after total surgical ablation for cancer.
As with breast conservation surgery and pelvo-perineal resection for
cancer, it is still not possible to perform a fully functional reconstruction.
At some centres radiation is favoured as primary treatment for these
conditions. Regrettably, fibrotic “frozen” tissue may result that could be
painful, and ulcerating with the potential of affecting quality of life
adversely.

Pathophysiology

The sequence of events following radiation continues to worsen long after

the noxious agent has been removed. Basically the gradual and progressive
obliterative endarteritis and cellular dysfunction leads to hypoxic, hypovascular
and hypocellular tissue (Marx). The area radiated is
characterized by loss of collagen and increased fibrosis with contraction.
Revascularization cannot occur in collagen deficient tissue because budding
capillaries do not have a soft collagenous matrix to invade. There is a
progressive loss of vascularity in a nearly linear fashion over time. This creates a
hypoxic wound bed. In radiated wounds, the oxygen gradient decreases from the
wound edge to the centre of the wound at such a gradual
rate that the hypoxic stimulus for angiogenesis is not initiated. This results in the
formation of poor granulation tissue and a wound of inferior quality that will
normally not heal on it’s own.
 26

Irradiation causes quantitative and qualitative suppression of fibroblasts and

formation of inferior quality collagen. Present is also decreased mitotic
activity and reduced numbers of epithelial cells causing thinning and complete
destruction of the epithelium.

Management
Basic management principles are used eg nutritional support, elimination of
causative agents, control of infection, debridement, pressure irrigation,
occlusive dressings and eventual reconstructive procedures. Promising
options for the future remain the therapeutic use of growth factors and
cytokines (transforming GF-beta, platelet derived GF, interleukin–3 and
granulocyte-macrophage GF).

Infection is often a difficult problem to handle and local antiseptics supported

by systemic antibiotics is often necessary for control. Complicated flap
reconstructions after repeated wide excisions can heal these often extensive
wounds.

When operating in irradiated tissue, some basic principles should be adhered to:

1. Primary closure of edematous wounds should be resisted.

2. Skin or muscle flaps must be used for tension free closure to prevent
exposure of vital structures.
3. Split skin grafts should be used preferably on immobile areas.
4. Incisions over vital structures eg carotid vessels in the neck should be
avoided. With breakdown of tissue, exposure of vessels create the life
threatening complication of a vascular “blow-out”.
5. Free grafts (eg bone) are rarely successful.

viii. Hyperbaric oxygen (HBO) therapy and wound healing

Problem wounds fail to heal in response to standard medical and
surgical therapy. Common risk factors impairing wound healing are hypoxia,
infection, vascular insufficiency, diabetes, poor nutrition, smoking, immuno-
suppression and advanced age.
 27

Pathophysiology:
1. Hypoxia
These wounds are hypoxic due to vascular damage, clotting, vaso-
constriction and increased cellular oxygen consumption.
A low O2 supply and increased oxygen demand causes
acidosis and the elevated lactate stimulates vascular growth factors.
2. Hypovascularity
Normal angiogenic capillary ingrowth occurs across a steep gradient
of high-O2- lactate towards low-O2- high- lactate levels (Niinikoski).
Severe hypoxia suppresses angiogenic and vascular endothelial
growth factor production (Gimbel).
3. Hypocellularity
Oxygen is essential for the normal collagen synthesis and maturation
from fibroblasts. Spontaneous wound break down may occur due to
an imbalance between cell death (collagen lysis) and cell replacement
(collagen formation). A non-healing wound thus results from metabolic
demands for healing and homeostasis that exceeds the vascular and
oxygen supply (Marx).
4. Infection
Neutrophils and macrophages normally kill micro-organisms via
O 2-dependant and O2-independant systems forming oxygen and
superoxide radicals that damage bacterial cell membranes. In hypoxic
cells the O2-dependant pathway is severely incapacitated, causing a
higher incidence of infection (Jonsson).

HBO therapy
The principles of managing problem wounds include correction of perfusion and
oxygenation insufficiencies, debridement, control of infection, wound care
and surgical reconstruction. If a patient suffers from deficient tissue
oxygenation due to nonreconstructable vascular disease, HBO as an adjunctive
therapy may be indicated. The best tool available to evaluate tissue hypoxia is
transcutaneous oxygen tension (TcPO2). A value greater than 50mm Hg
indicates spontaneous healing, whereas between 30-50mm is marginal and
below 30mm Hg requires HBO therapy. HBO therapy delivers 100% oxygen to
the patient at greater than two times the normal atmospheric pressure at sea
level.

This increases the partial pressure of oxygen in plasma resulting in hyperoxic

plasma” and tissue PO2 levels exceeding 600mm Hg. HBO creates a steep
tissue oxygenation gradiant forcing oxygen into injured and healing tissues by
diffusion. It is accomplished via different chambers accommodating single or
multiple patients. HBO therapy enhances wound healing by increasing
neutrophil bactericidal capacity (kills anaerobic bacteria and inhibits toxin
formation),stimulates fibroblasts and promotes angiogenesis.
 28

HBO is indicated for osteoradionecrosis, chronic osteomyelitis, necrotizing

infections, ischemic reperfusion and thermal injuries. Although double-blinded
prospective randomised research results do lack, some treatment results of
diabetic ulceration with HBO, seems to be very promising.

Problem wounds relate significantly to a patient’s productivity, disability and

premature death. Combined with other modalities, HBO treatment in selected
patients does improve healing and may improve the outcome.

xi. Reconstruction of tissue defects

After assessment of a wounded patient and classification of his wounds, the most
important action by the wound care team is to formulate and implement an
appropriate treatment plan. General factors influencing this are the patient’s age,
occupation, mobility, psychological tenacity, expectations and
cooperation. Added to this are the availability of expertise and logistical factors.
Although the famous sir Harold Gillies coined the phrase “Never do today what
can be better done tomorrow”, his intention was never to advocate postponement
of treatment for non-medical reasons. Undecisiveness and delegating important
wound management decisions to the most junior members of the team is
unethical and cause great injustice to the wounded patient.

Different options should follow the reconstructive ladder from simple to complex,
but often it will be necessary to travel by lift bypassing simpler options and
electing the best but complicated one:

Non-surgical treatment may consult with experts

Primary/delayed primary/secondary suturing

Excision of ulcer bed,

debridement(s)
Skin grafting (split or full-thickness)

Local/regional/distant pedicled flaps

Refer as soon as possible
to surgeon with necessary
expertise.

Free microvascular tissue transfers

Correction of arterial inflow and venous
incompetence.
 29

The pre-requisite for choosing a non-surgical option is the belief that the wounds
will heal with conservative treatment in a reasonable time. Allowing
full-thickness skin defects to heal by secondary intention leaves a poor
quality scar and should only happen if the patient’s general condition dictate.

Skin grafting requires an adequate bed for the graft to take. Five common
reasons why skin grafts fail are:

- poor quality bed (old granulation tissue)

- haematoma/seroma (between graft and bed)
- infection (streptococcus species)
- movement (apply post-op splints to extremeties)
- technical (thickness of graft)

Indications for flap reconstruction are:

- inadequate bed (exposed bone, cartilage, neuro-vascular bundles,
tendons).
-poor vascular bed
-exposed body cavities (chest wall and dura) and vital organs (heart, lungs,
brain)
- reconstruction of function and sensation (eg sole of foot)

IV. KELOIDS:
Clinical:
A keloid is descriptive of an uncontrollable growth of scar tissue. Keloids must be
differentiated from hypertrophic scars. A hypertrophic scar is confined to the area
of injury or incision and usually flattens with time.A keloid grows beyond the
boundaries of injury and does not usually improve with time. Keloids are
unpredictable in their behaviour. Despite all other things being equal, they
sometimes occur only in certain wounds and not in others in the same individual.
With multiple ear piercing in vogue at present, another intriguing phenomenon
has become apparent. One can get keloid formation at the second piercing and
not at the time of primary piercing. There is also the phenomenon of
spontaneous keloids. These are keloids that are usually multiple and occur on
most parts of the body. These patients do not give a preceding history of injury.
Animals do not form keloids and cannot be used as research models.
 30

Aetiology:
The precise aetiopathogenesis of keloids is unknown. Several associated
factors have been observed.
Genetic: Although there have been sporadic reports of keloids in families,
the majority of patients with keloids do not have a positive family history.
No gene markers have yet been identified.
Race: Keloids are more common in the Negroid and Asian population groups
and less common in people of Caucasian descent.
Melanocytes or melanin pigment may play a role in the aetiopathogenesis of
keloids because none have been reported in albinos.
Anatomical sites: There are certain areas of the body that have a
predilection for keloids. These include the ears, back, presternal, arms
and shoulder regions. It is rarely found in the upper eyelids, palms,
soles and genitalia.
Wound Factors: Factors in wound closure influencing the likelihood of
keloid formation.
· Tension
· Suppurative wounds or those that heal by secondary intention.
· Growth factors and cytokines. The ones most studied are the three
isoforms of transforming growth factor beta.
Immune theory: Some have likened the occurrence of a keloid to that of a
secondary immune response. The progression of initial keloid may be slow
(primary response), the recurrence is more florid (secondary response).
Biochemistry:
· Collagen type in normal skin - the dermis has approximately 85% of
collagen type I and 15% collagen type III. In keloids the collagen type
III is increased.
· Increased chrondoitin-4-sulphate.
· Collagenase activity normal or increased.
 31

· Increased alpha-2-macroglobulin.

· Increased alpha-1-antitrypsin.
Treatment
No single mode of therapy is effective for keloids. Because of the high
occurrence rates, a multimode therapy approach is recommended.
Pharmaceutical:
· Steroids. Intralesional injection of steroid can be used preoperatively
to soften the keloid and postoperatively to prevent, or treat early
recurrences. Injections are reapeated every 2 to 6 weeks.
· Bleomycin has been used intralesionally.
· Several other agents such as colchicine, D-penicillinamine and beta amino
propionitile.

Surgery: It is the most frequent mode of management and should be performed

at the appropriate time. If performed on a floridly developing keloid, the
chances of recurrence are much higher and the result may be more
disfiguring than the original keloid. After keloid excision, one must be
aware not to close the wound under tension.
Postoperative radiation: Usually performed for 3 consecutive days
immediately post surgery.
Pressure therapy and taping: Taping of a suture line certainly results in a
superior scar outcome. Pressure therapy in the form of pressure garments,
facial masks and clip-on earrings is recommended. This has to be used for a
protracted period of not less than 12 months.
Silicone Gel - sheets or topical ointment
Immunotherapy - intralesional interferon

Lasers
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