Healing
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With physical trauma or disease suffered by an organism, healing involves the repairing of damaged tissue(s),
organs In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to a ...
and the
biological system A biological system is a complex Biological network inference, network which connects several biologically relevant entities. Biological organization spans several scales and are determined based different structures depending on what the system is ...
as a whole and resumption of (normal) functioning. Medicine includes the process by which the
cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...
in the
body Body may refer to: In science * Physical body, an object in physics that represents a large amount, has mass or takes up space * Body (biology), the physical material of an organism * Body plan, the physical features shared by a group of anim ...
regenerate and repair to reduce the size of a damaged or
necrotic Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is ...
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 "Scar Tissue" is the first single from American rock band Red Hot Chili Peppers' seventh studio album, ''Californication'' (1999). Released on May 25, 1999, the song spent a then-record 16 consecutive weeks atop the US ''Billboard'' Hot Modern R ...
. Most
organs In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to a ...
will heal using a mixture of both mechanisms. Within
surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
, 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, treatment, and prevention of deleterious mental disorder, mental conditions. These include matters related to cognition, perceptions, Mood (psychology), mood, emotion, and behavior. ...
and
psychology Psychology is the scientific study of mind and behavior. Its subject matter includes the behavior of humans and nonhumans, both consciousness, conscious and Unconscious mind, unconscious phenomena, and mental processes such as thoughts, feel ...
, healing is the process by which neuroses and
psychoses In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or incoher ...
are resolved to the degree that the client is able to lead a normal or fulfilling existence without being overwhelmed by
psychopathological Psychopathology is the study of mental illness. It includes the signs and symptoms of all mental disorders. The field includes abnormal cognition, maladaptive behavior, and experiences which differ according to social norms. This discipline is ...
phenomena. This process may involve
psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of Psychology, psychological methods, particularly when based on regular Conversation, personal interaction, to help a person change behavior, increase hap ...
,
pharmaceutical Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, 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 ...
treatment or
alternative Alternative or alternate may refer to: Arts, entertainment and media * Alternative (Kamen Rider), Alternative (''Kamen Rider''), a character in the Japanese TV series ''Kamen Rider Ryuki'' * Alternative comics, or independent comics are an altern ...
approaches such as traditional spiritual healing.


Regeneration

In order for an
injury Injury is physiological damage to the living tissue of any organism, whether in humans, in other animals, or in plants. Injuries can be caused in many ways, including mechanically with penetration by sharp objects such as teeth or with ...
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 in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
framework along which to grow. Alongside most cells there is either a
basement membrane The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...
or a collagenous network made by
fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...
s that will guide the cells' growth. Since
ischaemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
and most
toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...
s do not destroy collagen, it will continue to exist even when the cells around it are dead.


Example

Acute tubular necrosis Acute tubular necrosis (ATN) is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. Because necrosis is often not present, the term acute tubular injury (ATI) is preferred by pathologis ...
(ATN) in the
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
is a case in which cells heal completely by regeneration. ATN occurs when the
epithelial cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...
s that line the kidney are destroyed by either a lack of
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
(such as in
hypovolemic shock Hypovolemic shock is a form of Shock (circulatory), shock caused by severe hypovolemia (insufficient blood volume or extracellular fluid in the body). It can be caused by severe dehydration or blood loss. Hypovolemic shock is a medical emergency ...
, 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. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s,
heavy metals upright=1.2, Crystals of 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 is a controversial and ambiguous term for metallic elements with relatively h ...
or
carbon tetrachloride Carbon tetrachloride, also known by many other names (such as carbon tet for short and tetrachloromethane, also IUPAC nomenclature of inorganic chemistry, recognised by the IUPAC), is a chemical compound with the chemical formula CCl4. It is a n ...
). 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 Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical, e ...
. 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 An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s or physical destruction), or its total collapse (as can happen in an
infarct Infarction is tissue death (necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from the ...
) cause healing to take place by repair
Somatic psychology Somatic psychology or, more precisely, "somatic clinical psychotherapy" is a form of psychotherapy that focuses on somatic experience, including therapeutic and holistic approaches to the body. It seeks to explore and heal mental and physical inju ...
.


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 Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell prol ...
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 A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...
formation to stop bleeding and to reduce infection by bacteria,
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
es and
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
. Clotting is followed by
neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
invasion three to 24 hours after the wound has been incurred, with
mitoses Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the ...
beginning in
epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells after 24 to 48 hours.


Inflammation phase

In the inflammatory phase,
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s and other
phagocytic Phagocytosis () is the process by which a cell (biology), 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 ph ...
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 a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...
s and endothelial cells which make new
capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...
to migrate to the area and divide.


Proliferative phase

In the proliferative phase, immature
granulation tissue Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size ...
containing plump, active fibroblasts forms. Fibroblasts quickly produce abundant type III
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
, 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 proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
found in
smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
, 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 ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
, 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
eicosanoid Eicosanoids are lipid signaling, signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosa ...
s 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 gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...
s increase production of
cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...
which shuts down eicosanoid production and inflammation.


Resolution phase

In the Resolution phase, pathogens and damaged tissue are removed by
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
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
lipoxin A lipoxin (LX or Lx), an acronym for lipoxygenase interaction product, is a bioactive autacoid metabolite of arachidonic acid made by various cell types. They are categorized as nonclassic eicosanoids and members of the specialized pro-resolvi ...
s,
epi-lipoxin Epi-lipoxins are trihydroxy (i.e. containing 3 hydroxyl residues) metabolites of arachidonic acid. They are 15''R''-epimers of their lipoxin counterparts; that is, the epi-lipoxins, 15-epi-lipoxin A4 (15-epi-LxA4) and 15-epi-lipoxin B4 (15-epi-L ...
s, and
resolvin Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as from two isomers of docosapentaenoic acid (DPA), one omega-3 and one ...
s, which cause release of growth hormones.


See also

*
Health Health has a variety of definitions, which have been used for different purposes over time. In general, it refers to physical and emotional well-being, especially that associated with normal functioning of the human body, absent of disease, p ...


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