The process of repair in living tissue depends upon an inherent power possessed by vital cells of reacting to the irritation caused by injury or disease. The cells of the damaged tissues, under the influence of this irritation, undergo certain proliferative changes, which are designed to restore the normal structure and configuration of the part. The process by which this restoration is effected is essentially the same in all tissues, but the extent to which different tissues can carry the recuperative process varies. Simple structures, such as skin, cartilage, bone, periosteum, and tendon, for example, have a high power of regeneration, and in them the reparative process may result in almost perfect restitution to the normal. More complex structures, on the other hand, such as secreting glands, muscle, and the tissues of the central nervous system, are but imperfectly restored, simple cicatricial connective tissue taking the place of what has been lost or destroyed. Any given tissue can be replaced only by tissue of a similar kind, and in a damaged part each element takes its share in the reparative process by producing new material which approximates more or less closely to the normal according to the recuperative capacity of the particular tissue. The normal process of repair may be interfered with by various extraneous agencies, the most important of which are infection by disease-producing micro-organisms, the presence of foreign substances, undue movement of the affected part, and improper applications and dressings. The effect of these agencies is to delay repair or to prevent the individual tissues carrying the process to the furthest degree of which they are capable.
In the management of wounds and other diseased conditions the main object of the surgeon is to promote the natural reparative process by preventing or eliminating any factor by which it may be disturbed.
Healing by Primary Union.—The most favourable conditions for the progress of the reparative process are to be found in a clean-cut wound of the integument, which is uncomplicated by loss of tissue, by the presence of foreign substances, or by infection with disease-producing micro-organisms, and its edges are in contact. Such a wound in virtue of the absence of infection is said to be aseptic, and under these conditions healing takes place by what is called “primary union”—the “healing by first intention” of the older writers.
Granulation Tissue.—The essential and invariable medium of repair in all structures is an elementary form of new tissue known as granulation tissue, which is produced in the damaged area in response to the irritation caused by injury or disease. The vital reaction induced by such irritation results in dilatation of the vessels of the part, emigration of leucocytes, transudation of lymph, and certain proliferative changes in the fixed tissue cells. These changes are common to the processes of inflammation and repair; no hard-and-fast line can be drawn between these processes, and the two may go on together. It is, however, only when the proliferative changes have come to predominate that the reparative process is effectively established by the production of healthy granulation tissue.
Formation of Granulation Tissue.—When a wound is made in the integument under aseptic conditions, the passage of the knife through the tissues is immediately followed by an oozing of blood, which soon coagulates on the cut surfaces. In each of the divided vessels a clot forms, and extends as far as the nearest collateral branch; and on the surface of the wound there is a microscopic layer of bruised and devitalised tissue. If the wound is closed, the narrow space between its edges is occupied by blood-clot, which consists of red and white corpuscles mixed with a quantity of fibrin, and this forms a temporary uniting medium between the divided surfaces. During the first twelve hours, the minute vessels in the vicinity of the wound dilate, and from them lymph exudes and leucocytes migrate into the tissues. In from twenty-four to thirty-six hours, the capillaries of the part adjacent to the wound begin to throw out minute buds and fine processes, which bridge the gap and form a firmer, but still temporary, connection between the two sides. Each bud begins in the wall of the capillary as a small accumulation of granular protoplasm, which gradually elongates into a filament containing a nucleus. This filament either joins with a neighbouring capillary or with a similar filament, and in time these become hollow and are filled with blood from the vessels that gave them origin. In this way a series of young capillary loops is formed.
The spaces between these loops are filled by cells of various kinds, the most important being the fibroblasts, which are destined to form cicatricial fibrous tissue. These fibroblasts are large irregular nucleated cells derived mainly from the proliferation of the fixed connective-tissue cells of the part, and to a less extent from the lymphocytes and other mononuclear cells which have migrated from the vessels. Among the fibroblasts, larger multi-nucleated cells—giant cells—are sometimes found, particularly when resistant substances, such as silk ligatures or fragments of bone, are embedded in the tissues, and their function seems to be to soften such substances preliminary to their being removed by the phagocytes. Numerous polymorpho-nuclear leucocytes, which have wandered from the vessels, are also present in the spaces. These act as phagocytes, their function being to remove the red corpuscles and fibrin of the original clot, and this performed, they either pass back into the circulation in virtue of their amœboid movement, or are themselves eaten up by the growing fibroblasts. Beyond this phagocytic action, they do not appear to play any direct part in the reparative process. These young capillary loops, with their supporting cells and fluids, constitute granulation tissue, which is usually fully formed in from three to five days, after which it begins to be replaced by cicatricial or scar tissue.
Formation of Cicatricial Tissue.—The transformation of this temporary granulation tissue into scar tissue is effected by the fibroblasts, which become elongated and spindle-shaped, and produce in and around them a fine fibrillated material which gradually increases in quantity till it replaces the cell protoplasm. In this way white fibrous tissue is formed, the cells of which are arranged in parallel lines and eventually become grouped in bundles, constituting fully formed white fibrous tissue. In its growth it gradually obliterates the capillaries, until at the end of two, three, or four weeks both vessels and cells have almost entirely disappeared, and the original wound is occupied by cicatricial tissue. In course of time this tissue becomes consolidated, and the cicatrix undergoes a certain amount of contraction—cicatricial contraction.
Healing of Epidermis.—While these changes are taking place in the deeper parts of the wound, the surface is being covered over by epidermis growing in from the margins. Within twelve hours the cells of the rete Malpighii close to the cut edge begin to sprout on to the surface of the wound, and by their proliferation gradually cover the granulations with a thin pink pellicle. As the epithelium increases in thickness it assumes a bluish hue and eventually the cells become cornified and the epithelium assumes a greyish-white colour.
Clinical Aspects.—So long as the process of repair is not complicated by infection with micro-organisms, there is no interference with the general health of the patient. The temperature remains normal; the circulatory, gastro-intestinal, nervous, and other functions are undisturbed; locally, the part is cool, of natural colour and free from pain.
Modifications of the Process of Repair.—The process of repair by primary union, above described, is to be looked upon as the type of all reparative processes, such modifications as are met with depending merely upon incidental differences in the conditions present, such as loss of tissue, infection by micro-organisms, etc.
Repair after Loss or Destruction of Tissue.—When the edges of a wound cannot be approximated either because tissue has been lost, for example in excising a tumour or because a drainage tube or gauze packing has been necessary, a greater amount of granulation tissue is required to fill the gap, but the process is essentially the same as in the ideal method of repair.
The raw surface is first covered by a layer of coagulated blood and fibrin. An extensive new formation of capillary loops and fibroblasts takes place towards the free surface, and goes on until the gap is filled by a fine velvet-like mass of granulation tissue. This granulation tissue is gradually replaced by young cicatricial tissue, and the surface is covered by the ingrowth of epithelium from the edges.
This modification of the reparative process can be best studied clinically in a recent wound which has been packed with gauze. When the plug is introduced, the walls of the cavity consist of raw tissue with numerous oozing blood vessels. On removing the packing on the fifth or sixth day, the surface is found to be covered with minute, red, papillary granulations, which are beginning to fill up the cavity. At the edges the epithelium has proliferated and is covering over the newly formed granulation tissue. As lymph and leucocytes escape from the exposed surface there is a certain amount of serous or sero-purulent discharge. On examining the wound at intervals of a few days, it is found that the granulation tissue gradually increases in amount till the gap is completely filled up, and that coincidently the epithelium spreads in and covers over its surface. In course of time the epithelium thickens, and as the granulation tissue is slowly replaced by young cicatricial tissue, which has a peculiar tendency to contract and so to obliterate the blood vessels in it, the scar that is left becomes smooth, pale, and depressed. This method of healing is sometimes spoken of as “healing by granulation”—although, as we have seen, it is by granulation that all repair takes place.
Healing by Union of two Granulating Surfaces.—In gaping wounds union is sometimes obtained by bringing the two surfaces into apposition after each has become covered with healthy granulations. The exudate on the surfaces causes them to adhere, capillary loops pass from one to the other, and their final fusion takes place by the further development of granulation and cicatricial tissue.
Reunion of Parts entirely Separated from the Body.—Small portions of tissue, such as the end of a finger, the tip of the nose or a portion of the external ear, accidentally separated from the body, if accurately replaced and fixed in position, occasionally adhere by primary union.
In the course of operations also, portions of skin, fascia, or bone, or even a complete joint may be transplanted, and unite by primary union.
Healing under a Scab.—When a small superficial wound is exposed to the air, the blood and serum exuded on its surface may dry and form a hard crust or scab, which serves to protect the surface from external irritation in the same way as would a dry pad of sterilised gauze. Under this scab the formation of granulation tissue, its transformation into cicatricial tissue, and the growth of epithelium on the surface, go on until in the course of time the crust separates, leaving a scar.
Healing by Blood-clot.—In subcutaneous wounds, for example tenotomy, in amputation wounds, and in wounds made in excising tumours or in operating upon bones, the space left between the divided tissues becomes filled with blood-clot, which acts as a temporary scaffolding in which granulation tissue is built up. Capillary loops grow into the coagulum, and migrated leucocytes from the adjacent blood vessels destroy the red corpuscles, and are in turn disposed of by the developing fibroblasts, which by their growth and proliferation fill up the gap with young connective tissue. It will be evident that this process only differs from healing by primary union in the amount of blood-clot that is present.
Presence of a Foreign Body.—When an aseptic foreign body is present in the tissues, e.g. a piece of unabsorbable chromicised catgut, the healing process may be modified. After primary union has taken place the scar may broaden, become raised above the surface, and assume a bluish-brown colour; the epidermis gradually thins and gives way, revealing the softened portion of catgut, which can be pulled out in pieces, after which the wound rapidly heals and resumes a normal appearance.