CONTINUOUS PROCESS

Scars
Following tissue damage and/or loss from any cause, including damage due to the inflammatory process, there may be a number of different sequelae:

1. Resolution: Dead cellular material and debris are removed by phagocytosis and the tissue is left with its original architecture intact.
2. Regeneration. Lost tissue is replaced by proliferation of cells of the same type, which reconstruct the normal architecture.
3. Repair. Lost tissue is replaced by a fibrous scar which is produced from granulation tissue.

All of these processes may occur in the same tissue, and begin as soon as there is significant tissue damage; healing reactions do not wait for inflammation or other damaging mechanisms to subside, but take place at the same time. The outcome in any particular situation depends on which of the three processes of resolution, regeneration and repair predominates, and this in turn depends on a number of factors:

Resolution.
This tends to occur when there is little tissue destruction. A good example is lobar pneumonia: In the earlier stages of lobar pneumonia the alveolar spaces fill with pus but the alveolar walls remain intact. If the infecting organism is successfully destroyed at this stage (either naturally or with theraputic help) then the purulent material may be completely scavenged from the air spaces by macrophages, leaving the original lung structure intact.

Regeneration

Cell type: Cells are usually classified into three groups depending on their capacity for regeneration. Labile cells are those which normally have a high rate of loss and replacement (e.g. squamous and glandular epithelia, haemopoeitic cells in bone marrow) and therefore have a high capacity for regeneration. Stable cells do not normally proliferate to a significant extent but can be stimulated to do so after damage. Examples include renal tubular cells, hepatocytes, osteoblasts, endothelial cells, fibroblasts. Permanent cells are unable to divide after initial development and therefore cannot regenerate when some are lost. The best example here is neurons.

Tissue architecture: Simple structures are easier to reconstruct following damage than complex ones. For example a flat surface such as epidermis regenerates very successfully, but dermal sweat glands do not. An imperfect attempt at regeneration of tissue architecture may have important clinical consequences: for example, in some chronic inflammatory liver diseases regenerative proliferation of hepatocytes is very vigorous, but damage to the connective tissue framework of the liver tissue means that the regenerated tissue has an abnormal nodular architecture - cirrhosis. The abnormal architecture leads to haemodynamic abnormalities in the hepatic portal venous system - portal hypertension - which may culminate in death due to uncontrollable haemorrhage.

Amount of tissue loss: The idea of regeneration implies that there are cells left to regenerate. For example, if there is loss of a large area of epidermis then its central regions will heal by scar formation rather than regeneration, since the rate of migration of new epidermal cells from the eges of the wound is limited and scarring will proceed before they are able to cover the damaged area.

Repair
The process of repair results in formation of a fibrous scar from granulation tissue. The steps in this process (also termed organisation)are as follows:

1. Phagocytosis of necrotic debris and other foreign material by macrophages.
2. Proliferation of blood vessel endothelial cells and fibroblasts at the edges of the damaged area.
3. Endothelial cells grow into the damaged area, initially as solid buds from these adjacent blood vessels. The solid buds then canalise to form an abundant network of delicate, thin-walled capillaries.
4. Fibroblasts migrate into the damaged area along with the capillaries to form a loose connective tissue framework. This delicate fibrovascular tissue is granulation tissue.
5. The new capillary vessels anastomose to establish a blood circulation in the healing area and differentiate towards arterial and venous types as necessary. Fibroblasts produce collagen , giving the healing tissue mechanical strength.
6. Eventually a mature scar consisting almost entirely of dense collagen is produced. It is a general rule that the volume of scar tissue produced is always less than the bulk of the tissue it is replacing. This can have important clinical consequences where such scar contraction distorts the tissue enough to interfere with function. For example, scarring of tubular structures such as the intestines can produce stenosis of the lumen and obstruction; scarring of the skin around a joint can produce contractures and immobility.