Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

replaces normal

parenchymal tissue Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word π ...

to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue. 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 scarring, 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 (ECM) proteins, fibrosis results in scarring and thickening of the affected it is in essence an exaggerated 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 that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

s laying down

, including

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

and glycosaminoglycans. The process is initiated when immune cells such as

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 cel ...

s release soluble factors that stimulate fibroblasts. The most well characterized pro-fibrotic mediator is TGF beta, which is released by macrophages as well as any damaged tissue between surfaces called

interstitium The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. The fluid in this space is cal ...

. Other soluble mediators of fibrosis include CTGF, platelet-derived growth factor (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 (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, and examples include:

Lungs

* Fibrothorax * Pulmonary fibrosis **

Cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

** Idiopathic pulmonary fibrosis (idiopathic meaning the cause is unknown) * Radiation-induced lung injury (following treatment for cancer)

Liver

* Bridging fibrosis An advanced stage of liver fibrosis seen in the progressive form of chronic liver diseases. The term “bridging” means ‘the formation of “bridge” (by the band of mature & thick fibrous tissue) obliterating portal area to central vein’, leads to the formation of pseudolobules. Long-term exposure to hepatotoxin (e.g. thioacetamide, carbon tetrachloride, diethylnitrosamine) results in the bridging fibrosis in experimental animal models. * Senescence of hepatic stellate cells could prevent progression of liver fibrosis, although this has not been implemented as a therapy, and would carry the risk of hepatic dysfunction. Bridging fibrosis in rat liver exposed to thioacetamide

* Cirrhosis

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 approxi ...

in the kidney is a potential therapy to limit fibrosis.

Brain

* Glial scar

Heart

Myocardial fibrosis has mainly two forms: * ''Interstitial fibrosis'', which has been described in congestive heart failure, hypertension, and normal aging. * ''Replacement fibrosis'', which indicates an older myocardial infarction. 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 Arterial stiffness occurs as a consequence of biological aging and arteriosclerosis. Inflammation plays a major role in arteriosclerosis development, and consequently it is a major contributor in large arteries stiffening. Increased arterial stiff ...

Arthrofibrosis Arthrofibrosis (from Greek: ''arthro-'' joint, ''fibrosis'' – scar tissue formation) has been described in most joints like knee, hip, ankle, foot joints, shoulder (frozen shoulder, adhesive capsulitis), elbow (stiff elbow), wrist, hand joints as ...

(knee, shoulder, other joints) *

Chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

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 (which may be bloody if inflammation is severe), fever, abdominal distension ...

(intestine) * Dupuytren's contracture (hands, fingers) *

Keloid Keloid, also known as keloid disorder and keloidal scar, is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation t ...

(skin) *

Mediastinal fibrosis Mediastinal fibrosis most common cause is idiopathic mediastinal fibrosis; less commonly histoplasmosis tuberculosis or unknown. It is characterized by invasive, calcified fibrosis centered on lymph nodes that block major vessels and airways. In ...

(soft tissue of the mediastinum) * Myelofibrosis (bone marrow) * Peyronie's disease (penis) * Nephrogenic systemic fibrosis (skin) *

Progressive massive fibrosis Progressive massive fibrosis (PMF), characterized by the development of large conglomerate masses of dense fibrosis (usually in the upper lung zones), can complicate silicosis and coal worker's pneumoconiosis. Conglomerate masses may also occur in o ...

(lungs); a complication of coal workers'

pneumoconiosis Pneumoconiosis is the general term for a class of interstitial lung disease where inhalation of dust ( for example, ash dust, lead particles, pollen grains etc) has caused interstitial fibrosis. The three most common types are asbestosis, silicos ...

* Retroperitoneal fibrosis (soft tissue of the retroperitoneum) * Scleroderma/ systemic sclerosis (skin, lungs) * Some forms of adhesive capsulitis (shoulder)

References

External links

* {{Connective tissue Symptoms and signs Medical terminology Rheumatology