Chapter Three

Rationale Foci of Local Treatment

of Burns Medicine and Therapy

Chapter Three

Rationale Foci of Local Treatment of Burns Therapy

Burns are systemic complex injuries following skin exposure to thermal energy. In this chapter, we focus on the local pathogenesis of burns when and after thermal injuries occur to disclose the pathogenic basis and rationale of local therapeutics.

I. Pathogenesis Focus of Burn Wound

Following thermal injury, skin undergoes three injury phases in pathogenic order: physical injury, biochemical injury, and rejection response of necrotic tissues.

1. Physical Injury Phase: This includes direct and indirect physical injury. Immediately following skin surface exposure to thermal source, the resultant direct injury leads to necrosis of interface skin, which is called “direct physical thermal injury”. Although the thermal source causing the direct injury is removed, the heat does not dissipate from the skin immediately. The residual heat continues to produce a cumulative thermal effect which causes secondary thermal injury to the skin. This secondary trauma usually persists for 6~12 h. This is called “indirect physical injury phase”.

2. Biochemical Injury Phase: Local biochemical injury begins within 1 hour of the thermal insult and lasts for up to 72 h post-burn. This persists through the thermal biochemical reaction phase and the biochemical inflammatory reaction phase on the time order. At 1~2 h post burn, there is a significant increase in capillary permeability occurring in the injured, though still viable tissues, contiguous with the necrosis caused by direct thermal injury. This results in exudation of intravascular fluid toward the wound surface and interstitial space while tissue ischemia is occurring. Simultaneously, the injured but viable tissues and cells in the area of lesion develop edema due to metabolic disorder. At this time, the permeable capillaries release plenty of chemical substances which not only locally aggravate the injury itself and damage the peripheral uninjured areas, but also may subsequently result in systemic injury. Although it is not quite clear what these chemical substances are, they appear to include histamine, 5-HT, hydrogen ion, kinin and bradykinin, etc. This phase is called the “thermal biochemical reaction phase”. About 2 h later, thermal biochemical reaction continues to affect the viable tissues in the injured area to cause a series of inflammatory reactions. The initiation of such an inflammatory pathological reaction in the injured area may result in the full spectrum of pathological injuries. For instance, inflammatory reaction activates the blood coagulation system to induce progressive thrombosis of the microcirculation, which may cause necrosis of the injured but viable tissues and may also result in ischemic and anoxic necrosis of the surrounding uninjured tissues. This process may last for 72 h postburn and is called the “biochemical inflammatory reaction phase”.

3. Reject Reaction of Necrotic Tissues: At 72 h postburn, the wound tissue comes into a phase of rejection reaction, which is a response of the viable tissues due to disintegration of necrotic tissues and cells in the interface of the lesion area. Usually mixed and extensive, this reaction process primarily includes three pathogeneses: (1) the disintegration of necrotic histiocytes in the injury interface; (2) the regeneration of viable histiocytes in the interface of the lesion area; (3) microbial infection in the injury interface. Besides an inflammatory reaction, disintegration of necrotic histiocytes may induce cell liquefaction in the injury interface and, more importantly, the accumulation of cell liquefied products continues the aggravation of the injured tissue. Meanwhile, the residual viable tissues in the injury interface begin instinctive regeneration when disintegrated tissues develop into a destructive substance unfavorable to the environment of cell regeneration, thereby inducing serious inflammation. The combination of the two above pathogeneses disturbs flora residing in the skin and causes the destruction of microbes in the injured area, both of which further aggravate damages and may result in systemic injury at any time. This process is called “rejection injury of necrotic tissues”, and is the last primary injury of a burn wound.

II. Pathological Focus of Burn Wound

Pathological changes after burns consist of injury pathology, repair pathology and physiology according to the changes of local wound. The injury pathological focus mainly refers to pathomorphological changes following thermal injury of skin while repair pathology and physiology refers to auto-repairing pathological and physiological changes of injured skin.

1. Characteristic of Morphological Changes of Injury Pathology: The injury area of burns skin is divided into necrotic and reaction layers from superficial to interior. The former results from physical injury, the latter from chemical reactions following thermal injury. In accordance with pathogenesis characteristic of burns, the tissue in the thermal chemical reaction layer is gradually transformed to the progressive necrosis and inflammatory reaction layers, thus the unique morphological appearance of local pathology following burns injury is formed. There are three concentric zones of thermal injury from superficial to internal which exist in burns wounds (excepting first-degree burns – see Fig. 4). The central “zone of necrosis” is directly injured by the heat source, causing immediate cell death. Outside this zone is the “zone of stasis” which is due to indirect thermal injury and chemical injury resulting from the circulatory stasis and tissue degeneration caused by progressive microcirculatory thrombosis. The outermost zone is the “zone of hyperemia” where skin tissue experiences an inflammatory reaction caused by local thermal and chemical injury. This zone is characterized by a series of fully reversible pathomorphological changes including tissue edema, hyperemia, anoxia and exudation.

The pathological injury changes within the three zones reveal the most complicated biodynamcis of all traumatic wounds. Apart from the natural changes among the three zones, their changes are also closely related to the administration of different clincal therapies. The application of a therapy which causes further injury to local wound may worsen the viability of all three zones. If no secondary injury is caused, the three zones may resolve in a natural process. However, if one uses a therapy which is protective and therapeutically effective to the tissue beneath the necrotic tissues, the progressive injury of the tissue in the zone of stasis may be prevented or reversed. Though the necrotic layer of the burns wound surface is impossible to rescue, the management of necrotic tissue of burns wounds affects viable tissue in the deep layer. If the necrotic layer is left alone, a nonphysiological pressure exerted upon the underlying tissue results due to tissue dehydration and lack of normal skin elasticity. The pressure and increased microcirculatory blood concentration may lead to pressure ischemia with consequent anoxia thus aggravating the progressive necrosis of the underlying tissue. Application of therapy characterized by dry, coagulation, formation of crust or eschar will cause lethal injury to stasis and hyperemia tissues, and thereby cause extension of the depth of the burn wound even to full-thickness necrosis. However, if measures for losing the necrotic layer or preventing pressure to the underlying tissue are adopted, this full-thickness necrosis can be prevented and reversible changes of underlying stasis and hyperemia tissue may be attained.

Fig. 4. Illustration of pathomorphological characteristic of burn wound

Besides the aforementioned indirect factors, treatment of the zone of stasis is also affected by various direct factors. For example, the application method of crust/eschar formation characterized by drying, dehydration and protein coagulation, or maceration method may speed up the microcirculatory progressive thrombosis. Alternatively, options exist for protecting the deep tissue which optimize the recovery of the tissue.

Repeated observation has taught the astute observer that the zone of hyperemia may recover naturally if no further injury occurs to the stasis tissues. Unfortunately, most typical burns treatments inadvertently allow progression of burn to necrotic tissue due to serious ischemia, anoxia and cell death.

2. Characteristic of Repairing Pathological and Physiological Changes. A revolutionary concept for the thorough repair of the aforementioned pathomorphological changes is put forward by the author after years of study of skin regeneration. The data derived from previous studies worldwide is marginally useful as it involved tissues treated by the standard treatment model of conventional burns surgery and burns care. Of note is that this treatment itself prevented people from understanding the natural repair mechanisms of burns wounds healing. A case in point is Dr. Jeckson who stated that he had never had a chance to observe how burns wounds heal in spite of his several decades of experience in the research and treatment of burns. What he had observed, admittedly, was either the burns wound covered by crust/eschar and thick dressing, reactive granulation tissue, or the absence of burn tissue due to surgical excision. His admission suggests that conventional burns therapy worldwide is limited to surgical excision and skin grafting therapy. Confirmation of that unfortunate fact is offered by the famous burn surgeon and chairman of the American Burn Association Dr. Deitch who stated in 1988: “Burn surgeons only know how to excise and graft skin instead of how to regenerate skin”. These remarks pinpoint the importance of evaluating innovations in burns regenerative medicine and therapy.

Following the separation, rejection or discharge of necrotic tissues, the residual viable skin tissue or information tissue (isogenous tissues and cells residing in subcutaneous tissue related to dermis and epidermis) remains in the injured area. The pathological change of natural burns repairing begins as follows.

(1) Superficial second-degree burns involve only the epidermis, so the repairing takes place in the epidermis tissue. The wound itself heals spontaneously without leaving a trace of scar whatever therapy is used since epidermis is formed by the layer-by-layer changes of basal cell layers.

(2) Deep second-degree burn involve part or most of the necrotic dermis. The pathology of repairing varies when different therapeutic techniques are applied. When treatment of dry and crust formation is applied, necrotic tissues are promoted to form a crust that is rejected from the underlying viable tissues along with the zone of leukocyte infiltration. If no infection and suppurative pathological change occur in the sub-crust, then the epithelial cells in residual dermis may grow along the zone of sub-crustal leukocyte infiltration. This then covers the wound under which dermis collagenous fibers and blood vessels proliferate in a disorderly manner. The wound closes pathologically via this epithelization and scar formation follows the shedding of crust. If subcrustal infection and suppurative pathological changes occur, the wound may be further injured and deep second-degree burns may progress into third-degree trauma followed by a full-thickness necrosis resulting in granulation of the wound. The wound resolves with permanent pathological healing even if it had a chance to close by skin grafting. However, suppose the necrotic tissues were to be discharged from the wound without causing any injury to the wound. Suppose also that the residual viable tissues were retained to the degree that a physiological environment is established sufficient to promote spontaneous residual tissue repair. In this case, we would witness wound healing without scar formation. By managing environment and local substances to optimize endogenous repair and regeneration, we facilitate healing of deep second-degree burns resulting in scar-free healing and recovery to normal tissue anatomy and physiology.

(3) Third-degree burns are equivalent to full-thickness burns and involve tissue beneath the dermis. They are defined according to the concept of skin burns. In terms of anatomy or histology or cytology, the skin consists of two layers: the epidermis derived from ectoderm and dermis (corium) from mesoblast. Full thickness refers to the combination of epidermis and dermis. As the conjunction area between the under-layer of dermis and subcutaneous tissue is an area like a rugged highland instead of a plane, full-thickness projects deep into the surface layer of subcutaneous tissue. In other words, full-thickness burn or third-degree burns involve tissue as deep as the surface layer of the subcutaneous tissue. Burn injuries involving most of the subcutaneous tissue and muscle layer extend beyond and should be excluded from the conception of skin burns. Diagnosis should be made in accordance with the injured tissue. For example, burns involving partial or major subcutaneous tissue should be termed subcutaneous tissue burns, burns involving full subcutaneous tissue and muscle layer should be termed muscle burns, burns involving full muscle layer and bone should be termed bone burns. It is same with the diagnosis of electric injury: burns caused by electricity are the ordinary skin burns while burns caused by electric current involve skin, subcutaneous, muscle, bone as well as other tissues which electric current penetrates. For a better and simpler understanding, the author has tried to classify third-degree burns into third superficial and third deep burns, of which the latter refers to non-skin burn involving the tissue under the subcutaneous layer. Thus, we might differentiate between skin and non-skin burns.

The pathological repairing of third-degree burns is characterized by the repairing of granulation tissue. There is no epithelial cell in subcutaneous tissue for closing the wound due to the full-thickness necrosis. It is conventionally recognized that a wound with a diameter of around 2 cm may close by migration of epithelial cells from the wound margin and heal spontaneously, while the larger wound should only be closed and healed by surgical skin grafting. Remarkably, despite this conventional wisdom, the author's studies proved that third-degree burns wounds therapy is possible through direct pathological or physiological healing without surgical intervention. The results of these studies indicated that: (1) Subsequent to burns, the adult tissue cells in residual viable subcutaneous and/or fat layer may be converted into adult skin stem cells. (2) Adult stem cells have the potential to regenerate and duplicate the organ of full-thickness skin. (3) The aforementioned regeneration and duplication was accomplished by the collaborative efforts of endogenous human regenerative potentials and control of localized tissue environmental conditions. (See relevant information below.)

III. Therapeutics Focus

Burn regenerative medicine and therapy refers to the medical management up to the complex pathogenesis of burns. Emphasis in this volume is made on the therapeutics focus of local burns wound, an especially conclusive description. Considering the management of the burns wound environment, two techniques are currently available worldwide for local burns treatment. One option is based upon the perceived benefit of maintaining the wound in a dry and dehydrated state while the other strives to maintain the wound in a physiologically moist state. Research clearly demonstrates that the former compromises while the latter encourages tissue regeneration. Simply stated, one is pathological and the other physiological as regards tissue repair. In clinical treatment, careful consideration is needed for choosing the appropriate burn therapy according to the depth of the burns wound. For superficial burns, as long as pain is relieved and further injury is prevented, any burn therapy may achieve successful results. For deep second-degree and/or third-degree burns, the choice of therapy is more critical since pathological healing may result in disablility and lifelong distress for the patients.

Due to differences of cultures and academic ideologies in the medical circles, two categories of burn therapy predominate in treating deep burns wounds. These are: (1) “surgical excision and skin grafting therapy” and (2) “conservative repairing therapy (burn regenerative medicine and therapy)”. The former is symbolized by the therapy established in the 1930s, with the characteristic of excision and skin grafting (a variety of autografts) for wound closure. As the main stream in the western medical circles, this therapy has been adopted in hospitals all over the world. The latter, burns regenerative medicine and therapy, involves two modalities: moist-exposed burns treatment (MEBT) and moist-exposed burn ointment (MEBO). This innovative and impressive modality was established by Dr. Rongxiang Xu in the late 20th century. It features the discharge of necrotic tissues by liquefaction in a manner that does not cause further secondary injury and also supports the establishment of a physiological environment sufficient to repair residual viable tissues while regenerating skin tissue. This therapy has been successfully exported to 48 countries and enjoys wide clinical application while attaining the predominant status for burns care in eastern medical circles. Herein to follow are the main points of the two categories of the burn therapies. 

1. Therapeutics focus of surgical excision and skin grafting therapy: Surgical excision and skin grafting therapy is established upon the premise that no effective method is available for treating a series of postburn illness. It is considered that the tissues in the zone of stasis of deep second-degree burns is doomed to a complicated and dangerous progressive necrosis. Additionally, it is assumed that wound with necrosis of full thickness dermis is unlikely to heal spontaneously. During the procedure of conservative repairing treatment for deep burn wounds, infection, inflammation and other serious complications may develop and become life threatening, and the treatment result will be pathological. Based upon the above consideration, a therapy was established: First transform the burns wound to a traumatic wound via surgical intervention and then perform the conventional burns treatment in an attempt to increase survival rate. In the clinic setting, the whole burned necrotic tissue together with some viable dermis or subcutaneous tissue are removed, creating a surgical wound of muscle layer over which a variety of autografts are placed to close the wound. Admittedly, this therapeutic option anticipates a compromised and suboptimal result while striving mostly to save the patient’s life. This therapy is a purely surgical technique and func