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 HAEMORRHAGE complement

Interferon bact\viral particles oxygen Antigens INFLAMMATION

neutrophils prostaglandins helper T cells monocytes lymphokines cytokines cytokines cytokines prostaglandins Proteoglycans cytokines Fibronectin Collagen Cytokines = TGFα, TGFβ, PDGF, EGF, FGF, TNFα

REPAIR Fig 1: Wound Healing Sequence – Macrophage orchestrated

MACROPHAGE

COAGULATION THROMBOSIS (PLATELETS)

FIBROBLAST

lymphocyte

Epithelial Cell

Endothelial Cell

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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 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.

Description of wound according to assessment

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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· 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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