With physical trauma or disease suffered by an organism,healing involves the repairing of damagedtissue(s),organs and thebiological system as a whole and resumption of (normal) functioning. Medicine includes the process by which thecells in thebody regenerate and repair to reduce the size of a damaged ornecrotic area and replace it with new living tissue. The replacement can happen in two ways: byregeneration in which the necrotic cells are replaced by new cells that form "like" tissue as was originally there; or byrepair in which injured tissue is replaced withscar tissue. Mostorgans will heal using a mixture of both mechanisms.[1]
Withinsurgery, healing is more often referred to as recovery, and postoperative recovery has historically been viewed simply as restitution of function and readiness for discharge. More recently, it has been described as an energy‐requiring process to decrease physical symptoms, reach a level of emotional well‐being, regain functions, and re‐establish activities[2]
Healing is also referred to in the context of the grieving process.[3]
Inpsychiatry andpsychology, healing is the process by whichneuroses andpsychoses are resolved to the degree that the client is able to lead a normal or fulfilling existence without being overwhelmed bypsychopathological phenomena. This process may involvepsychotherapy,pharmaceutical treatment oralternative approaches such astraditional spiritual healing.[citation needed]
In order for aninjury to be healed by regeneration, the cell type that was destroyed must be able to replicate. Cells also need acollagen framework along which to grow. Alongside most cells there is either abasement membrane or acollagenous network made byfibroblasts that will guide the cells' growth. Sinceischaemia and mosttoxins do not destroy collagen, it will continue to exist even when the cells around it are dead.[citation needed]
Acute tubular necrosis (ATN) in thekidney is a case in which cells heal completely by regeneration. ATN occurs when theepithelial cells that line the kidney are destroyed by either a lack ofoxygen (such as inhypovolemic shock, when blood supply to the kidneys is dramatically reduced), or by toxins (such as someantibiotics,heavy metals orcarbon tetrachloride).[citation needed]
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.[citation needed]
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, evenmicroscopically.[citation needed]
Healing must happen by repair in the case of injury to cells that are unable to regenerate (e.g. neurons). Also, damage to the collagen network (e.g. byenzymes or physical destruction), or its total collapse (as can happen in aninfarct) cause healing to take place by repair.[citation needed]
Many genes play a role in healing.[4] For instance, in wound healing, P21 has been found to allow mammals to heal spontaneously. It even allows some mammals (like mice) to heal wounds without scars.[5][6] TheLIN28 gene also plays a role in wound healing. It is dormant in most mammals.[7] Also, the proteinsMG53 andTGF beta 1 play important roles in wound healing.[8]
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In response to an incision or wound, awound healing cascade is unleashed. This cascade takes place in four phases: clot formation, inflammation, proliferation, and maturation.
Healing of a wound begins withclot formation to stop bleeding and to reduce infection by bacteria,viruses andfungi. Clotting is followed byneutrophil invasion three to 24 hours after the wound has been incurred, withmitoses beginning inepithelial cells after 24 to 48 hours.[citation needed]
In the inflammatory phase,macrophages and otherphagocytic cells kill bacteria, debride damaged tissue and release chemical factors such asgrowth hormones that encourage fibroblasts,epithelial cells and endothelial cells which make newcapillaries to migrate to the area and divide.[citation needed]
In the proliferative phase, immaturegranulation tissue containing plump, active fibroblasts forms. Fibroblasts quickly produce abundant type IIIcollagen, which fills the defect left by an open wound. Granulation tissue moves, as a wave, from the border of the injury towards the center.[citation needed]
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 ofactin found insmooth muscle, which enables them to contract and reduce the size of the wound.[citation needed]
During the maturation phase of wound healing, unnecessary vessels formed in granulation tissue are removed byapoptosis, 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.[citation needed]
After inflammation has damaged tissue (when combatting bacterial infection for example) and pro-inflammatoryeicosanoids have completed their function, healing proceeds in 4 phases.[9]
In the recall phase theadrenal glands increase production ofcortisol which shuts down eicosanoid production and inflammation.[citation needed]
In the Resolution phase, pathogens and damaged tissue are removed bymacrophages (white blood cells). Red blood cells are also removed from the damaged tissue by macrophages. Failure to remove all of the damaged cells and pathogens may retrigger inflammation. The two subsets of macrophage M1 & M2 plays a crucial role in this phase, M1 macrophage being a pro inflammatory while as M2 is a regenerative and the plasticity between the two subsets determine the tissue inflammation or repair.[citation needed]
In the Regeneration phase, blood vessels are repaired and new cells form in the damaged site similar to the cells that were damaged and removed. Some cells such as neurons and muscle cells (especially in the heart) are slow to recover.[citation needed]
In the Repair phase, new tissue is generated which requires a balance of anti-inflammatory and pro-inflammatory eicosanoids. Anti-inflammatory eicosanoids includelipoxins,epi-lipoxins, andresolvins, which cause release of growth hormones.[citation needed]
