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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.

Repair in Individual Tissues

Skin and Connective Tissue.—The mode of regeneration of these tissues under aseptic conditions has already been described as the type of ideal repair. In highly vascular parts, such as the face, the reparative process goes on with great rapidity, and even extensive wounds may be firmly united in from three to five days. Where the anastomosis is less free the process is more prolonged. The more highly organised elements of the skin, such as the hair follicles, the sweat and sebaceous glands, are imperfectly reproduced; hence the scar remains smooth, dry, and hairless.

Epithelium.—Epithelium is only reproduced from pre-existing epithelium, and, as a rule, from one of a similar type, although metaplastic transformation of cells of one kind of epithelium into another kind can take place. Thus a granulating surface may be covered entirely by the ingrowing of the cutaneous epithelium from the margins; or islets, originating in surviving cells of sebaceous glands or sweat glands, or of hair follicles, may spring up in the centre of the raw area. Such islets may also be due to the accidental transference of loose epithelial cells from the edges. Even the fluid from a blister, in virtue of the isolated cells of the rete Malpighii which it contains, is capable of starting epithelial growth on a granulating surface. Hairs and nails may be completely regenerated if a sufficient amount of the hair follicles or of the nail matrix has escaped destruction. The epithelium of a mucous membrane is regenerated in the same way as that on a cutaneous surface.

Epithelial cells have the power of living for some time after being separated from their normal surroundings, and of growing again when once more placed in favourable circumstances. On this fact the practice of skin grafting is based (p. 11).

Cartilage.—When an articular cartilage is divided by incision or by being implicated in a fracture involving the articular end of a bone, it is repaired by ordinary cicatricial fibrous tissue derived from the proliferating cells of the perichondrium. Cartilage being a non-vascular tissue, the reparative process goes on slowly, and it may be many weeks before it is complete.

It is possible for a metaplastic transformation of connective-tissue cells into cartilage cells to take place, the characteristic hyaline matrix being secreted by the new cells. This is sometimes observed as an intermediary stage in the healing of fractures, especially in young bones. It may also take place in the regeneration of lost portions of cartilage, provided the new tissue is so situated as to constitute part of a joint and to be subjected to pressure by an opposing cartilaginous surface. This is illustrated by what takes place after excision of joints where it is desired to restore the function of the articulation. By carrying out movements between the constituent parts, the fibrous tissue covering the ends of the bones becomes moulded into shape, its cells take on the characters of cartilage cells, and, forming a matrix, so develop a new cartilage.

Conversely, it is observed that when articular cartilage is no longer subjected to pressure by an opposing cartilage, it tends to be transformed into fibrous tissue, as may be seen in deformities attended with displacement of articular surfaces, such as hallux valgus and club-foot.

After fractures of costal cartilage or of the cartilages of the larynx the cicatricial tissue may be ultimately replaced by bone.

Tendons.—When a tendon is divided, for example by subcutaneous tenotomy, the end nearer the muscle fibres is drawn away from the other, leaving a gap which is speedily filled by blood-clot. In the course of a few days this clot becomes permeated by granulation tissue, the fibroblasts of which are derived from the sheath of the tendon, the surrounding connective tissue, and probably also from the divided ends of the tendon itself. These fibroblasts ultimately develop into typical tendon cells, and the fibres which they form constitute the new tendon fibres. Under aseptic conditions repair is complete in from two to three weeks. In the course of the reparative process the tendon and its sheath may become adherent, which leads to impaired movement and stiffness. If the ends of an accidentally divided tendon are at once brought into accurate apposition and secured by sutures, they unite directly with a minimum amount of scar tissue, and function is perfectly restored.

Muscle.—Unstriped muscle does not seem to be capable of being regenerated to any but a moderate degree. If the ends of a divided striped muscle are at once brought into apposition by stitches, primary union takes place with a minimum of intervening fibrous tissue. The nuclei of the muscle fibres in close proximity to this young cicatricial tissue proliferate, and a few new muscle fibres may be developed, but any gross loss of muscular tissue is replaced by a fibrous cicatrix. It would appear that portions of muscle transplanted from animals to fill up gaps in human muscle are similarly replaced by fibrous tissue. When a muscle is paralysed from loss of its nerve supply and undergoes complete degeneration, it is not capable of being regenerated, even should the integrity of the nerve be restored, and so its function is permanently lost.

Secretory Glands.—The regeneration of secretory glands is usually incomplete, cicatricial tissue taking the place of the glandular substance which has been destroyed. In wounds of the liver, for example, the gap is filled by fibrous tissue, but towards the periphery of the wound the liver cells proliferate and a certain amount of regeneration takes place. In the kidney also, repair mainly takes place by cicatricial tissue, and although a few collecting tubules may be reformed, no regeneration of secreting tissue takes place. After the operation of decapsulation of the kidney a new capsule is formed, and during the process young blood vessels permeate the superficial parts of the kidney and temporarily increase its blood supply, but in the consolidation of the new fibrous tissue these vessels are ultimately obliterated. This does not prove that the operation is useless, as the temporary improvement of the circulation in the kidney may serve to tide the patient over a critical period of renal insufficiency.

Stomach and Intestine.—Provided the peritoneal surfaces are accurately apposed, wounds of the stomach and intestine heal with great rapidity. Within a few hours the peritoneal surfaces are glued together by a thin layer of fibrin and leucocytes, which is speedily organised and replaced by fibrous tissue. Fibrous tissue takes the place of the muscular elements, which are not regenerated. The mucous lining is restored by ingrowth from the margins, and there is evidence that some of the secreting glands may be reproduced.

Hollow viscera, like the œsophagus and urinary bladder, in so far as they are not covered by peritoneum, heal less rapidly.

Nerve Tissues.—There is no trustworthy evidence that regeneration of the tissues

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