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With physical trauma or disease suffered by an organism, healing involves the repairing of damaged tissue(s), organs and the biological system as a whole and resumption of (normal) functioning. Medicine includes the process by which the
cells Cell most often refers to: * Cell (biology) The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclo ...
in the body regenerate and repair to reduce the size of a damaged or necrotic area and replace it with new living tissue. The replacement can happen in two ways: by ''regeneration'' in which the necrotic cells are replaced by new cells that form "like" tissue as was originally there; or by ''repair'' in which injured tissue is replaced with scar tissue. Most organs will heal using a mixture of both mechanisms. Within
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...
, 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 Healing is also referred to in the context of the grieving process. In
psychiatry Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry. Initial ...
and
psychology Psychology is the scientific study of mind and behavior. Psychology includes the study of conscious and unconscious phenomena, including feelings and thoughts. It is an academic discipline of immense scope, crossing the boundaries be ...
, healing is the process by which neuroses and psychoses are resolved to the degree that the client is able to lead a normal or fulfilling existence without being overwhelmed by psychopathological phenomena. This process may involve
psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...
,
pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field ...
treatment or alternative approaches such as traditional spiritual healing.


Regeneration

In order for an
injury An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intention Intentions are mental state A mental state, or a mental property, is a state of mind of a person. Mental states compr ...
to be healed by regeneration, the cell type that was destroyed must be able to replicate. Cells also need a
collagen Collagen () is the main structural protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalys ...
framework along which to grow. Alongside most cells there is either a
basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and min ...
or a collagenous network made by
fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and ...
s that will guide the cells' growth. Since ischaemia and most
toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organism In biology Biology is the scientific study of life. It is a natural science with a broad scope but has sever ...
s 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 The kidneys are two reddish-brown bean-shaped organs found in vertebrate Vertebrates () comprise all animal Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals con ...
is a case in which cells heal completely by regeneration. ATN occurs when the
epithelial cell Epithelium or epithelial tissue is one of the four basic types of animal Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, ...
s that line the kidney are destroyed by either a lack of
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal In chemistry, a nonmetal is a chemical element that generally la ...
(such as in
hypovolemic shock Hypovolemic shock is a form of shock caused by severe hypovolemia Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt ...
, when blood supply to the kidneys is dramatically reduced), or by toxins (such as some
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of pr ...
s,
heavy metals upright=1.2, Crystals of osmium, a heavy metal nearly twice as dense as lead">lead.html" ;"title="osmium, a heavy metal nearly twice as dense as lead">osmium, a heavy metal nearly twice as dense as lead Heavy metals are generally defined as ...
or
carbon tetrachloride Carbon tetrachloride, also known by many other names (such as tetrachloromethane, also recognised by the IUPAC, carbon tet in the cleaning industry, Halon-104 in firefighting, and Refrigerant-10 in HVACR) is an organic compound In chemist ...
). 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. 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. by
enzyme Enzymes () are protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic rea ...
s or physical destruction), or its total collapse (as can happen in an infarct) cause healing to take place by repair.


Genetics

Many genes play a role in healing. 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. The LIN28 gene also plays a role in wound healing. It is dormant in most mammals. Also, the proteins MG53 and
TGF beta 1 TGF may refer to: Medicine * Tubuloglomerular feedback, a reflex of the nephrons in the kidney * Transforming growth factor Transforming growth factor (, or TGF) is used to describe two classes of polypeptide growth factor A growth factor i ...
play important roles in wound healing.


Wound healing

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


Clotting phase

Healing of a wound begins with clot formation to stop bleeding and to reduce infection by bacteria,
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria Bacteria (; singular: bacte ...
es and
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold A mold () or mould () is one of the structures certain fungi can form. The dust-like, colored a ...
. Clotting is followed by
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cell White blood cells, also called leukocytes or leucocytes, are the cells of the immune system ...
invasion three to 24 hours after the wound has been incurred, with mitoses beginning in
epithelial Epithelium or epithelial tissue is one of the four basic types of animal Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, ...
cells after 24 to 48 hours.


Inflammation phase

In the inflammatory phase,
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer c ...
s and other
phagocytic Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis i ...
cells kill bacteria, debride damaged tissue and release chemical factors such as
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
s that encourage fibroblasts,
epithelial cell Epithelium or epithelial tissue is one of the four basic types of animal Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, ...
s and endothelial cells which make new
capillaries A capillary is a small blood vessel from 5 to 10 micrometre The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer ( American spelling), also commonly known a ...
to migrate to the area and divide.


Proliferative phase

In the proliferative phase, immature
granulation tissue Granulation tissue is new connective tissue Connective tissue is one of the four primary types of animal Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume org ...
containing plump, active fibroblasts forms. Fibroblasts quickly produce abundant type III
collagen Collagen () is the main structural protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalys ...
, 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 Actin is a family of globular multi-functional protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, incl ...
found in
smooth muscle Smooth muscle is an involuntary non-striated muscle Striations means a series of ridges, furrows or linear marks, and is used in several ways: * Glacial striation * Striation (fatigue), in material * Striation (geology), a ''striation'' as ...
, 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 Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
, 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.


Tissue damaged by inflammation

After inflammation has damaged tissue (when combatting bacterial infection for example) and pro-inflammatory eicosanoids have completed their function, healing proceeds in 4 phases.''The Anti-Inflammation Zone'', Barry Sears, pages 230-233, 2005.


Recall phase

In the recall phase the adrenal glands increase production of
cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the '' zona fasciculata'' of the adrenal cortex in the adrenal ...
which shuts down eicosanoid production and inflammation.


Resolution phase

In the Resolution phase, pathogens and damaged tissue are removed by
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer c ...
s (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.


Regeneration phase

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.


Repair phase

In the Repair phase, new tissue is generated which requires a balance of anti-inflammatory and pro-inflammatory eicosanoids. Anti-inflammatory eicosanoids include lipoxins, epi-lipoxins, and
resolvin Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is gi ...
s, which cause release of growth hormones.


See also

* Scar free healing *
Health Health, according to the World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations The United Nations (UN) is an intergovernmental organization Globalization is social chang ...


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.

* Lorenz H.P. and Longaker M.T.
Wounds: Biology, Pathology, and Management
Stanford University Medical Center. * Romo T. and McLaughlin L.A. 2003

Emedicine.com. * Rosenberg L. and de la Torre J. 2003

Emedicine.com.
After the Injury- Children's Hospital Of Philadelphia
{{Authority control Injuries Medical phenomena Physiology Therapy