Tissue injuries associated with inflammation are eventually followed by some form of healing. Removal of inflammatory and necrotic cellular debris must precede any such healing. Healing occurs rapidly after transitory injury such as a single minor traumatic episode. Healing is also rapid if the injurious agent is quickly inactivated by the host response, whether inflammatory or immune. With persistent low-grade injury, healing occurs concurrently with ongoing chronic inflammation.
The ideal result of healing is to restore the tissue to its normal (preinjury) state, a process termed resolution. Removal of debris associated with the inflammatory response is sufficient to restore a tissue to its normal state if injury has been minor (ie, if minimal parenchymal cell necrosis has occurred). After removal of cellular debris, any necrotic parenchymal cells may be replaced by new parenchymal cells of the same type in a process known as regeneration.
When resolution and regeneration are not possible, necrotic cells are replaced with collagen; this is termed organization, or repair by scar formation. In many instances, a combination of healing processes occurs.
The mechanism of healing depends on the type of inflammation, the extent of tissue necrosis, the types of cells involved, and the regenerative ability of damaged parenchymal cells.
Resolution after acute pneumococcal pneumonia. A and B: Lung, showing dilated alveolar capillaries and an exudate filling the alveoli. After the bacteria have been killed, resolution occurs by liquefaction of the exudate and phagocytosis by macrophages (C), resulting in a normal lung (D). Note that any alveolar epithelial cells undergoing necrosis in the acute phase regenerate. The amount of necrosis is small in an uncomplicated case.
Resolution is the ideal outcome of healing and occurs in acute inflammatory responses to minor injuries or those with minimal parenchymal cell necrosis. The tissue is in effect restored to the state it was in before injury occurred.
The fibrinous inflammatory exudate and tissue debris derived from the inactivated injurious agent or necrotic host cells (neutrophils, a few parenchymal cells) are liquefied by lysosomal enzymes liberated by neutrophils and then removed by the lymphatics. Any remaining particulate debris is phagocytosed by macrophages that enter the area during the later stages of the inflammatory response.
Replacement of lost parenchymal cells by division of adjacent surviving parenchymal cells (regeneration) can also restore injured tissue to normal. Whether regeneration occurs depends on (1) the regenerative capacity of involved cells (ie, their ability to divide), (2) the number of surviving viable cells, and (3) the presence of a connective tissue framework that will provide a base for restoration of normal tissue structure.
Before regeneration can occur, the necrotic cells must be removed. This involves an acute inflammatory response, liquefaction of cells by neutrophil enzymes, and ...