In nature, life heals itself unless one or several of its systems fail. When the systemic failure is complete and irreversible, death ensues and healing is not possible.
Physiology of Wound Healing
1. The basic concept as to how wounds heal have not really changed over the last quarter century. What has changed exponentially however is the understanding of a variety of factors that control this process. The more important ones are mentioned towards the end of this chapter.
2. Wound healing begins with the formation of a blood clot, which both acts as a seal and is also a rich medium for bacteria to grow, a fact clinicians must bear in mind. Almost simultaneously starts an inflammatory response. The aggregated platelets in the clot stimulate fibroblasts and endothelial cells. Local vascular dilatation follows the inflammatory response. Clot formation also releases substances which increase permeability of vessels and white blood cells, mainly polymorphonuclear, pour out. They scavenge dead tissue and counteract bacteria. Monocytes follow the polymorphonuclear cells in two or three days, modify to become macrophages which continue to phagocytose tissues but also secrete factors stimulating the local endothelial cells, fibroblasts and keratinocytes to start the repair process. In the course of repair, the original fibrin platelet matrix is replaced by what is called ECM (extracellular matrix) which through a succession of initial ingredients ultimately lays down collagen. Initially called a tropocollagen, its molecules then form cross connections to form fibrils and then several fibrils forms a fibre. These fibres together form the fibrous tissue of a scar.
Factors influencing wound healing
3. A living thing can be a host to a variety of other living things and this coexistence is known to be mutually beneficial. But this rule is not universal and some organisms (viruses, bacteria and parasites) can be detrimental, even fatal to another life. These invaders can have local, regional or systemic effects which affect the healing processes as they colonise tissues.
4. A cancer cell is in a way also an alien creature and will grow at the expense of the host and create circumstances which will retard or completely inhibit the healing process.
5. The healing process depends upon the delivery of certain substances and cells to the affected area. The end products of the healing process also need to be cleared from the area.
6. The cells that arrive to heal, the local cells who help healing and the substances that are laid down in the process of healing are all dependent on a normal metabolism and circulation of blood.
7. It flows from the above that any arterial venous or lymphatic insufficiency will influence healing adversely. A disease like diabetes may have a two or three pronged effect via poor micro circulation, a high level of glucose available to the organisms but its poor utilization by host cells and may have had a deleterious effect on protein metabolism. The proteins constitute the basic building blocks throughout life. In modern times, morbid obesity and administration of corticosteroids have been incriminated in delayed healing.
8. The present state of our knowledge of embryology indicates that the nervous system is the master and leader of growth and development. Nothwithstanding the appearance of virtual autonomy of a variety of regions the nervous system is not a silent spectator to the events in these regions. The autonomic nervous system for example is closely linked to the way blood flows in and out of a given area. A curtailment of the nervous system either regional (a localized peripheral neuropathy) or more widespread (a paraplegia or quadriplegia) will harm the vasomotor function, reduce its flexible responses and create anaerobic conditions and retard healing.
9. Immune suppression not only reduces the healing process because the responses to the call for healing are meager but also because infection can occur with greater ease in an immunocompromised individual.
10. The psychological state of the patient may also influence wound healing. Though a variety of diseases have now been unequivocally linked to certain states of mind over a length of time, no substantive, verifiable work on the role of such states on wounds has been published though it stands to reason that the psychological state unlike everywhere else in the body cannot be a mute spectator to the process of healing.
11. Radiation either given as a therapy or received accidentally at work or in war can lead to death of cells and/or a variety of degrees of deprivation in the molecular function of a cell. The most conspicuous results of which are failure to grow and heal. Irradiated areas should therefore need close scrutiny by clinicians.
12. In general a clinician must therefore constantly seek reasons as to why a wound is not healing rather than seek avenues of hastening the natural healing process, which should be self sufficient. For example an ordinary wound on the ankle festering because of lack of rest and colonized by organisms can rapidly heal without any antibiotic or local ointments by way of a simple below knee rigid walking plaster cast which will give adequate rest to the part. All wounds need rest for healing.
Arun Bal who is a general surgeon and specialises in Diabetic Feet was invited to contribute to this blog in view of the almost epidemic increase in the incidence of Diabetes in India. He is attached to several hospitals in Mumbai and runs a centre dedicated to “foot care” in diabetics at the Amrita Institute in the southern state of Kerala. A summary of his communication is reproduced below:
While the theory of microvascular damage in diabetes has held sway for several years, the focus has now shifted to atherosclerotic mid-sized vessels in the lower half of the leg, atherosclerosis being more prevalent in diabetics. These vessels can now be mapped and their calibre can be measured under vision endoscopically, or by arteriograms as well as indirect methods (doppler). Arteriograms are contraindicated in the presence of renal failure because most radio opaque substances are excreted by the kidney. Equally important and a far simpler method is to measure the blood pressure in the arm and the calf and is called the ankle brachial index. To be able to feel the pedal pulse does not ensure a well vascularised foot because often the pulse may have been generated due to collateral blood flow in view of the chronicity of the condition. Reduced blood flow results in neuro ischaemia because the vasa nervosa are branches of local arteries. This is usually preceded by a myelopathy which is a direct effect of a high glucose level in the tissues. These high levels also cause stagnation of red blood cells, deterioration in polymorphonuclear cell function and inadequate production of collagen of poor quality. Combined with ischaemia the pathology progresses to an insensate foot, reduction in local trophicity, particularly in the fore foot leading to gradual “pressure ischaemic necrosis”, ulcerations and a feeble attempt locally to heal the wound resulting in a callus. Surgical endoscopic intervention (a thrombectomy and / or an atherectomy) or a bypass results in good wound healing even at levels around or below the ankles is feasible and can revascularise the limb leading to faster healing of wounds or in the least much better granulations more receptive to skin cover. In any event an effective debridement of the callus is a very important step in the treatment of these lesions. A callus is a mechanical barrier as also a biological hindrance to neoepithelialisation creates a favourable space for bacteria to grow and is subject to trauma in an insensate area leading to haemorrhage and production of oxygen free radicals which further damage or hinder local healing processes.
In addition to a proper skin cover and well designed foot wear, a surgeon can also help in changing the configuration of the foot (restore arches) by tendon / muscle transfer or deal with diseased bones (sequesterectomy) and effect more efficient joins within the small bones of the foot by way of arthodesis, arthroplasties. For further detailed scientific cellular information Dr. Bal is available at firstname.lastname@example.org
R. Ravindra Bharathi and S. Raja Sabapathy from Ganga Hospital, Coimbatore add the following:
Ulcerous disruptions in the feet, both on the plantar as well as the dorsal surface in diabetics pose a formidable challenge to surgeons. While the traditional teaching that diabetes leads to cellular deprivation and microvascular damage and this is compounded by a poor distal, vascular compliance due to neuritic changes which also causes loss of sensations and a vulnerability to injuries continues to hold forth, more attention is now being given to medium sized pulsatile vessels around the ankle which can be sourced for a free microvascular tissue transfer to bring fresh living tissue into an endemically moribund area. The earlier practice of repeated debridement, excision of osteomyelitic bone followed by skin grafting, an inferior choice particularly in the plantar area, as well as amputations can now be avoided at least in some cases to get a more reliable long term result. We present two examples one on the dorsum and the other on the plantar surface of the foot from our unit at the Ganga Hospital in Coimbatore.
Healing by primary and secondary intention, and scars
13. All wounds heal by formation of a scar. The scarring is less when the wound edges are joined together soon after the wounds are created (healing by primary intention). Wounds joined later, several hours after a proper debridement, also fall into the same category. However wounds which need to be secondarily excised after several days of their occurrence and then approximated might behave slightly differently because the process of healing by secondary intention is already begun and this process in the bed of the wound as well as the periphery of the wound means some additional scar formation.
14. When wound edges are not approximated during the process of healing the repair takes place by secondary intention. While the details of this process are described later, one of the more important components of this healing is the ability in the wound to pull the surrounding skin concentrically towards the centre of the wound. This contraction is facilitated if the surrounding skin in loose. For example, the large wounds left behind after excising a perianal fistula by the older method heal rapidly with surprisingly little scarring. Scrotal wounds also show this quality. Wounds along the anterior border of the tibia on the other hand, where there is no such loose skin, are therefore best treated with care lest scars form in this area which are vulnerable even to trivial injury.
15. The statement “all wounds heal with formation of scars” does not apply to foetal healing in early gestation. Here growth and development is occurring at a rapid pace and enough potential is available within the totipotent cells to build anew. The need to replace the lost tissue by scar is therefore not felt. This phase wanes off rather rapidly after the fourth month of gestation by which time the foetus is fully developed and only increases in dimensions over the remaining months. The scarless healing mentioned above is not determined by the environment of the foetus (for example the amniotic fluid) but is inherent in the foetus.
16. During secondary healing the bed of the wound is occupied by this developing collagen within a meshwork of blood vessels. This is called granulation tissue and has been dealt with in chapter 2, namely skin grafting.
17. This granulating bed, if not grafted with skin which carries dermis as well epidermis, can at best epithelialise across some distance and this gives the area only a tenuous cover without any proper established blood supply, which survives by imbibing oxygenated fluid from the bed. This invites repeated breakdowns following trivial insults.
18. Even in primary healing, the scar has only a thin layer of epithelium over it but the scar’s dimensions are small and, unlike the situation in a large area healed by secondary intention, no area is too far away from a properly established blood supply.
19. The dermal component of skin has elastic tissue allowing it a certain flexibility and this elastic tissue is laid in a manner that will allow ease of movement at the joints. In a classical example the direction of elastic tissue at the wrist crease is along or parallel to the crease and not across it. The nasolabial fold is another such example. Any incision along the wrist crease will create a very small defect as opposed to an incision across it. A simple one layer of suturing at the wrist crease and then immobilization for a short period in a neutral position will bring the elastic fibers together when the incision is parallel to it. As opposed to that, a vertical incision across the crease will retract the skin to a greater extent. The elastic recoil of this tissue continues for several weeks putting a retracting force on the healing process and in a way produces a secondary type of healing in the dermal zone creating a broader scar. To avoid this, the dermis needs to be approximated closely by a suture material which will retain its strength for several weeks or months to allow for a proper durable end to end opposition to produce primary healing of the dermis. The cross-hatch marks of the good old days, following interrupted vertical mattress sutures, resulted from dermal injury causing epidermo-dermal necrosis as a result of pressure of the suture material on post operative oedematous skin. This necrosis is also a traumatic wound which, like everything else, heals with a scar. A proper close closure of the dermal component of a wound avoids the need to take broad sutures across all layers of the skin and subcutaneous tissue. A close approximation of the subcutaneous fat with the superficial fascia is no substitute here because it cannot eliminate the elastic dermal recoil to any significant extent.
20. All scars start remodelling over a period of days and weeks and are usually fully stable at about one year. Notwithstanding the cross linking between fibers in a scar, the natural reticular pattern of normal fibrous tissues never gets replicated in a scar. As cross linking and remodelling progress, the blood supply to the area is withdrawn gradually and a red scar becomes whiter and may even get depigmented because the epithelial surface of the scar does not have the appendages of normal skin. In a majority of the Indian population however a depigmented scar is extremely uncommon and more often than not the scar might get darker, probably by migration of pigment from the surrounding skin, which is exposed to sunlight. Migration of pigment cells has been demonstrated in the treatment of vitiligo by very thin split thickness grafts and causes repigmentation of hair as well by this migration. In the Indian population the nature and the size of post-operative scars, except in some locations such as the wrist crease, the nasolabial fold or the eyelid along its fold, remain unpredictable.
21. During the process of healing some proprietary enzyme preparations have now become popular to hasten removal of slough. A variety of growth or other factors to hasten healing including the “platelet derived growth factor”, though available in the market, will require some time before a final judgment is passed about them.
22. However, incontrovertible evidence is now emerging that treatment with hyperbaric oxygen in a chamber definitely does have a beneficial effect on diabetic ulcers as well as ulcers due to peripheral vascular deficiency and may avoid amputations. A closed airtight dressing with some form of suction within it for several hours or days is also showing remarkable results in helping tardy wounds to heal. These two methods are only additional empirical aids at the present time.
“Dr. Hiren Bhatt from Vadodara adds that the application of the suction apparatus has been extended to wounds where skin grafting has been performed. He makes a valid point that hemostasis of the wounds on which the graft has been placed needs to be thorough in view of the suction principle.”
Keloids and hypertrophic scars.
23. A keloid is a broad and thickened scar which invades surrounding skin and does not settle spontaneously. It is genetically influenced and must be recognized as a distinct entity from a hypertrophic scar. The latter is raised but does not spread. A scar surrounded by close cross hatched marks appears like a keloid but careful inspection will reveal its true hypertrophic nature. In burn wounds, which heal with secondary intention, raised hypertrophic scars are common. Some donor areas used for skin grafting also behave unpredictably and get raised. Pressure garments are a popular but scientifically unproven remedy (because a proper controlled trial is not possible) for such scars.
24. The treatment for keloids continues to remain unsatisfactory. Preoperative corticosteroids followed by intrakeloidal excisions followed again with post operative corticosteroids and a variety of pressure splints applied soon after surgery are known to give relief and some improvement in appearance but a cure remains elusive.