Healing

Physiological healing is the restoration of damaged living tissue to normal function. It is the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area. Healing incorporates both the removal of necrotic tissue (demolition), and the replacement of this tissue.

The replacement can happen in two ways:

by regeneration: the necrotic cells are replaced by the same tissue as was originally there.
by repair: injured tissue is replaced with scar tissue.

Most organs will heal using a mixture of both mechanisms.

Regeneration

In order for an injury to be healed by regeneration, the cell type that was destroyed must be able to replicate. Most cells have this ability, although it is believed that cardiac muscle cells and neurons are two important exceptions.

Cells also need a collagen framework along which to grow. Alongside most cells there is either a basement membrane or a collagenous network made by fibroblasts that will guide the cells' growth. Since ischaemia and most toxins do not destroy collagen, it will continue to exist even when the cells around it are dead.

Example

Acute tubular necrosis (ATN) in the kidney is a case in which cells heal completely by regeneration. ATN occurs when the epithelial cells that line the kidney are destroyed by either a lack of oxygen (such as in hypovolemic shock, when blood supply to the kidneys is dramatically reduced), or by toxins (such as some antibiotics, heavy metals or carbon tetrachloride).

Although many of these epithelial cells are dead, there is typically patchy necrosis, meaning that there are patches of epithelial cells still alive. In addition, the collagen framework of the tubules remains completely intact.

The existing epithelial cells can replicate, and, using the basement membrane as a guide, eventually bring the kidney back to normal. After regeneration is complete, the damage is undetectable, even microscopically.

Repair phases

Healing must happen by repair in the case of injury to cells that are unable to regenerate (e.g. cardiac muscle or neurons). Also, damage to the collagen network (e.g. by enzymes or physical destruction), or its total collapse (as can happen in an infarct) cause healing to take place by repair.

In response to an incision or wound, a wound healing cascade is unleashed. This cascade takes place in four phases: clot formation, inflammation, proliferative, and maturation.

Clotting phase

Healing of a wound begins with clot formation to stop bleeding and to reduce infection by bacteria, viruses and fungi. Clotting is followed by neutrophil invasion three to 24 hours after the wound has been incurred, with mitoses beginning in epithelial cells after 24 to 48 hours ^{[citation needed]}.

Inflammation phase

In the inflammatory phase, macrophages and other phagocytic cells kill bacteria, debride damaged tissue and release chemical factors such as growth hormones that encourage fibroblasts, epithelial cells and endothelial cells which make new capillaries to migrate to the area and divide.

Proliferative phase

In the proliferative phase, immature granulation tissue containing plump active fibroblasts forms. Fibroblasts quickly produce abundant type III collagen, which fills the defect left by an open wound. Granulation tissue moves, as a wave, from the border of the injury towards the center.

As granulation tissue matures, the fibroblasts produce less collagen and become more spindly in appearance. They begin to produce the much stronger type I collagen. Some of the fibroblasts mature into myofibroblasts which contain the same type of actin found in smooth muscle, which enables them to contract and reduce the size of the wound.

Maturation phase

During the maturation phase of wound healing, unnecessary vessels formed in granulation tissue are removed by apoptosis, and type III collagen is largely replaced by type I. Collagen which was originally disorganized is cross-linked and aligned along tension lines. This phase can last a year or longer. Ultimately a scar made of collagen, containing a small number of fibroblasts is left.

References

External links

How wounds heal and tumors form With this simple Flash demonstration, Harvard professor Donald Ingber explains how wounds heal, why scars form, and how tumors develop. Presented by Children's Hospital Boston.
Wound Healing and Repair
Lorenz H.P. and Longaker M.T. Wounds: Biology, Pathology, and Management. Stanford University Medical Center.
Romo T. and McLaughlin L.A. 2003. Wound Healing, Skin. Emedicine.com.
Rosenberg L. and de la Torre J. 2003. Wound Healing, Growth Factors. Emedicine.com.
After the Injury- Children's Hospital Of Philadelphia