Fibrosis
   HOME

TheInfoList



OR:

Fibrosis, also known as fibrotic scarring, is the development of fibrous
connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease. Repeated injuries, chronic inflammation and repair are susceptible to fibrosis, where an accidental excessive accumulation of extracellular matrix components, such as the collagen, is produced by fibroblasts, leading to the formation of a permanent fibrotic scar. In response to injury, this is called
scar A scar (or scar tissue) is an area of fibrosis, fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other Organ (anatomy), organs, and biological tissue, t ...
ring, and if fibrosis arises from a single cell line, this is called a fibroma. Physiologically, fibrosis acts to deposit connective tissue, which can interfere with or totally inhibit the normal architecture and function of the underlying organ or tissue. Fibrosis can be used to describe the pathological state of excess deposition of fibrous tissue, as well as the process of connective tissue deposition in healing. Defined by the pathological accumulation of
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
(ECM) proteins, fibrosis results in scarring and thickening of the affected it is in essence a natural wound healing response which interferes with normal organ function.


Physiology

Fibrosis is similar to the process of scarring, in that both involve stimulated
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 laying down
connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
, including
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 ...
and glycosaminoglycans. The process is initiated when immune cells such as
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 release soluble factors that stimulate fibroblasts. The most well characterized pro-fibrotic mediator is
TGF beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the Transforming growth factor beta family, transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HUGO Gene Nomen ...
, which is released by macrophages as well as any damaged tissue between surfaces called interstitium. Other soluble mediators of fibrosis include CTGF,
platelet-derived growth factor Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing bloo ...
(PDGF), and interleukin 10 (IL-10). These initiate signal transduction pathways such as the AKT/mTOR and SMAD pathways that ultimately lead to the proliferation and activation of fibroblasts, which deposit extracellular matrix into the surrounding connective tissue. This process of tissue repair is a complex one, with tight regulation of
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
(ECM) synthesis and degradation ensuring maintenance of normal tissue architecture. However, the entire process, although necessary, can lead to a progressive irreversible fibrotic response if tissue injury is severe or repetitive, or if the wound healing response itself becomes deregulated.


Anatomical location

Fibrosis can occur in many tissues within the body, typically as a result of inflammation or damage. Common sites of fibrosis include the lungs, liver, kidneys, brain, and heart:


Lungs

* Fibrothorax * Pulmonary fibrosis **
Cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
** Idiopathic pulmonary fibrosis (''idiopathic'' meaning 'of unknown cause') * Radiation-induced lung injury (following radiation therapies commonly used to treat cancer)


Liver

* Bridging fibrosis – an advanced stage of liver fibrosis, seen in the progressive form of chronic liver diseases. The term ''bridging'' refers to the formation of a "bridge" by a band of mature and thick fibrous tissue from the portal area to the central vein. This form of fibrosis leads to the formation of pseudolobules. Long-term exposure to
hepatotoxins Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...
, such as thioacetamide,
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 ...
, and diethylnitrosamine, has been shown to cause bridging fibrosis in experimental animal models. * Senescence of hepatic stellate cells could prevent progression of liver fibrosis, although has not yet been implemented as a therapy due to risks associated with hepatic dysfunction. *
Cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...


Kidney

* CYR61 induction of
cellular senescence Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of appro ...
in the kidney has shown potential to limit renal fibrosis.


Brain

*
Glial scar A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and beg ...


Heart

Myocardial fibrosis has two forms: * Interstitial fibrosis, described in cases of congestive heart failure and hypertension, and as part of normal cellular aging. * Replacement fibrosis, indicating tissue damage from previous
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
. File:Histopathology of interstitial fibrosis in dilated cardiomyopathy.jpg, Healthy myocardium versus interstitial fibrosis in dilated cardiomyopathy. Alcian blue stain. File:Histopathology of dense fibrous scar replacing myocyte loss in myocardial infarction.jpg, Replacement fibrosis in myocardial infarction, being boundless and dense.


Other

* Arterial stiffness * Arthrofibrosis (knee, shoulder, other joints) *
Chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...
*
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
(intestine) * Dupuytren's contracture (hands, fingers) * Keloid (skin) *
Lipedema Lipedema is a condition that is almost exclusively found in women and results in enlargement of both legs due to deposits of fat under the skin. Women of any weight may be affected and the fat is resistant to traditional weight-loss methods. The ...
(fat cells, typically in lower limbs) * Mediastinal fibrosis (soft tissue of the mediastinum) *
Myelofibrosis Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in ...
(bone marrow) * Myofibrosis (skeletal muscle) * Peyronie's disease (penis) * Nephrogenic systemic fibrosis (skin) * Progressive massive fibrosis (lungs); a complication of pneumoconiosis * Retroperitoneal fibrosis (soft tissue of the retroperitoneum) *
Scleroderma Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas ...
/
systemic sclerosis Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are tw ...
(skin, lungs) * Some forms of adhesive capsulitis (shoulder) Fibrosis reversal Historically, fibrosis was considered an irreversible process. However, several recent studies have demonstrated reversal in liver and lung tissue, and in cases of renal, myocardial, and oral-submucosal fibrosis.


References


External links

* {{Connective tissue Symptoms and signs Medical terminology Rheumatology Scarring