HEALING AND ADAPTATION

Injury to tissue may result in cell death and tissue destruction. Healing on the other hand, is the body response to injury in an attempt to restore normal structure and function. The process of healing involves 2 distinct processes:

1. Regeneration when healing takes place by proliferation of parenchymal cells and usually results in complete restoration of the original tissues.

2. Repair when healing takes place by proliferation of connective tissue elements resulting in fibrosis and scarring.

Some parenchymal cells are short-lived while others have a longer lifespan. In order to maintain proper structure of tissues, these cells are under constant regulatory control of their cell cycle. These include growth factors, e.g. brain, epidermis-, macrophage-, nerve-, and platelet, derived growth factors.

Depending upon their capacity to divide, the cells of the body can be divided into 3 groups: labile cells, stable cells and permanent cells.

1. Labile cells. These cells continue to multiply throughout life under normal physiologic conditions. These include surface epithelial cells of epidermis,

alimentary tract, respiratory tract, urinary tract, vagina, cervix, uterine endometrium, hemopoietic cells of bone marrow and cells of lymph nodes and spleen.

2. Stable cells. These cells decrease or lose their ability to proliferate after adolescence but retain the capacity to multiply in response to stimuli throughout adult life. These include parenchymal cells of kidneys, liver, adrenal glands; mesenchymal cells of smooth muscles.

3. Permanent cells. These cells lose their ability to proliferate around the time of birth. These include: neurons of nervous system, skeletal muscle and cardiac muscle cells.

Regeneration of any type of parenchymal cells involves the following 2 processes.

1. Proliferation of original cells from the margin of the injury with migration so as to cover the gap.

2. Proliferation of migrated cells with subsequent differentiation and maturation so as to reconstitute the original tissue.

There are 3 types of regeneration physiological, reparative and pathological.

Physiological regeneration is observed during the human life.

There are 2 types of reparative regeneration restitution and substitution. In restitution, reconstruction of the original tissue in the definite organ is observed. In substitution (so called «repair») connective tissue or fat appear instead of original tissue

(e.g. sclerosis develops in the area of the myocardial infarction).

The pathological regeneration may be of one of the following types: hyperregeneration, hyporegene-ration and metaplasia.

Contraction of Wounds. The wound starts contracting after 2—3 days and the process is completed by the 14th day. During this period, the wound is reduced by approximately 80% of its original size. Contracted wound results in rapid healing since lesser surface area of the injured tissue has to be replaced.

In order to explain the mechanism of wound contraction, a number of factors have been proposed. These are as follows:

1. Dehydration as a result of removal of fluid by drying of wound was first suggested but without being substantiated.

2. Contraction of collagen was thought to be responsible for contraction but wound contraction proceeds at a stage when the collagen content of granulation tissue is very small.

3. Discovery of myofibroblasts appearing in active granulation tissue has resolved the controversy surrounding the mechanism of wound contraction. These cells have features intermediate between those of fibroblasts and smooth muscle cells. Their migration into the wound area and their active contraction decreases the size of the defect.

Wound Healing

Healing of skin wounds provides a classical example of combination of regeneration and repair described above. This can be accomplished in one of the following two ways: healing by first intention (primary union) and healing by second intention (secondary union).

Healing by first intention (primary union).This is defined as healing of a wound which has the following characteristics: clean and uninfected, surgically incised, without much loss of cells and tissue, edges of wound are approximated by surgical sutures.

The sequence of events in primary union is described below.

Immediately after injury, the space between the approximated surfaces of incised wounds is filled with blood which then clots and seals the wound against dehydration and infection.

Acute inflammatory response occurs within 24 hours by appearance of polymorphs from the margins of incision. By the 3rd day, polymorphs are replaced by macrophages.

The basal cells of epidermis from both the cut margins start proliferating and migrating towards incisional space in the form of epithelial spurs. A well-approximated wound is covered by a layer of epithelium in 48 hours. The migrated epidermal cells separate

the underlying viable dermis from the overlying necrotic material and clot, forming scab which is cast off. The basal cells from the margins continue to divide. By 5th day, a multilayered new epidermis is formed which is differentiated into superficial and deeper layers.

By the 3rd day, fibroblasts also invade the wound area. By the 5th day, new collagen fibrils start forming which dominate till healing is completed. In 4 weeks, the scar tissue with scanty cellular and vascular elements, a few inflammatory cells and epithelialised surface is formed.

Each suture track is a separate wound and incites the same phenomena as in healing of the primary wound, i.e. filling the space with hemorrhage, some inflammatory cell reaction, epithelial cell proliferation along the suture track from both margins, fibroblastic proliferation and formation of young collagen. When sutures are removed around the 7th day, much of epithelialised suture track is avulsed and the remaining epithelial tissue in the track is absorbed. However, sometimes the suture track gets infected or the epithelial cells may persist in the track.

A sutured wound, thus takes a little longer to heal but the scar formed is neat due to close apposition of the margins of wounds. The use of adhesive tapes avoids this complication.

Healing by second intention (secondary union).This is defined as healing of a wound having

the following characteristics: open with a large tissue defect, at times infected; having extensive loss of cells and tissues; the wound is not approximated by surgical sutures but is left open.

The basic events in secondary union are similar to primary union but differ in having a larger tissue defect which has to be bridged. Hence healing takes place from the base upwards as well as from the margins inwards. The healing by second intention is slow and results in a large, at times ugly, scar as compared to rapid healing and neat scar of primary union.

The sequence of events in secondary union are as follows.

As a result of injury, the wound space is filled with blood and fibrin clot which dries.

There is an initial acute inflammatory response followed by appearance of macrophages which clear off the debris as in primary union.

As in primary healing, the epidermal cells from both the margins of wound proliferate and migrate into the wound in the form of epithelial spurs till they meet in the middle and re-epithelialise the gap completely. However, the proliferating epithelial cells do not cover the surface fully until granulation tissue from base has started filling the wound space. In this way, preexisting viable connective tissue is separated from necrotic material and clot on the surface, forming scab which is cast off. In time, the regenerated epidermis becomes stratified and keratinised.

The main bulk of secondary healing is by granulations. Granulation tissue is formed by proliferation of fibroblasts and neovascularisation from the adjoining viable elements. The newly-formed granulation tissue is deep red, granular and very fragile. With time, the scar on maturation becomes pale and white due to increase in collagen and decrease in vascularity. The specialized structures of skin like hair follicles and sweat glands are not replaced unless their viable residues remain which may regenerate.

Contraction of wound is an important feature of secondary healing, not seen in primary healing. Due to the action of myofibroblasts present in granulation tissue, the wound contracts to one-third to one-fourth of its original size. Wound contraction occurs at a time when active granulation tissue is being formed.

Bacterial contamination of an open wound delays the process of healing due to release of bacterial toxins that provoke necrosis, suppuration and thrombosis. Surgical removal of dead and necrosed tissue, debridement, helps in preventing the bacterial infection of open wounds.

During the course of healing, following complications may occur: infection of wound due to entry of bacteria delays the healing; implantation (epidermal) cyst formation may occur due to persistence of epithelial cells in the wound after healing; pigmentation, when healed wounds may at times have rust-like colour due to staining with

hemosiderin; deficient scar formation may occur due to inadequate formation of granulation tissue; incisional henia—a weak scar, especially after a laparotomy, may be site of bursting open of a wound (wound dehiscence) or an incisional hernia; hypertrophied scars and keloid formation; excessive contraction; rarely scar may be the site for development of carcinoma later, e.g. squamous cell carcinoma in scar.

Two types of factors influence the wound healing: those acting locally and those acting in general. Local factors: infection; poor blood supply to wound, foreign bodies including sutures interfere with healing and cause intense inflammatory reaction and infection; exposure to ionizing radiation; exposure to ultraviolet light; type, size and location of injury. Systemic factors: age, nutrition, systemic infection, uncontrolled diabetes, hematological abnormalities.