Fibrosis

Fibrosis as an abnormal proliferation of the connective tissue in human and animal tissues and organs is known, whose main component is collagen fibers. In this case, the tissue of the organ affected is hardened. It caused cicatricial changes that lead in advanced stage to limit the respective organ function. Substances that cause fibrosis, called fibrinogen; the related adjective is associated with fibrosis.

Etiology

There are so -called primary fibrosis, in which the cause of the change is unknown. This fibrotic the respective tissue without apparent external damage. An example of a primary retroperitoneal fibrosis is fibrosis Ormond's disease. More frequently, however, the formation of secondary fibrosis. In these, the tissue is initially caused by exogenous, that is acting from the outside, or endogenous, that is formed from the body itself damage, for example, inflammation or circulatory disorders. Such damage is called pollutant. Through these are within the destroyed Gewebsverbandes special cells within the connective tissue, called fibroblasts, activated, produce increased amounts of interstitial connective tissue. As interstitial is called the connective tissue that runs within the institutions between individual organ sections. Sitting blood vessels and nerves that supply the organs in it. Therefore, caused by fibrosis, ie the uncontrolled growth of these organs by pulling areas, scarring, affecting the functionality of the affected organs strong or in extreme cases, can destroy them.

In principle, this process is possible in each tissue. The best known example is the alcoholic toxic cirrhosis, fibrosis in the liver parenchyma, so the pollutant- degrading areas of the liver, destroyed by repeated and prolonged intoxication with alcohol. Other examples of diseases are caused by fibrosis as the final stage of various lung diseases, the pulmonary fibrosis, loss of function of the kidney after long-term chronic renal failure or diastolic dysfunction of the heart.

Eye

• Postoperative proliferation of connective tissue in surgical glaucoma or lens
• Endocrine ophthalmopathy

Dermatology / Urology

• Keloid
• Dupuytren's contracture
• Peyronie's disease
• Fibrous Nasenpapel

Heart

• Atrial fibrillation
• Cardiomyopathy
• Hypertensive heart disease
• Diastolic Dysfunction
• Myocardial infarction
• Remodeling

Lung

• Pulmonary fibrosis
• Scleroderma / CREST syndrome
• Asthma

Kidney

• Chronic renal failure
• Peritoneal dialysis: Ultrafiltration failure

Liver

• Steatohepatose
• Fibrosis
• Cirrhosis

Gastroenterology / retroperitoneum

• Collagen colitis
• Ormond's disease

Diabetes

• Diabetic nephropathy
• Diabetic cardiomyopathy

Oncology

• Promotes stroma, which local tumor growth
• Tumor growth supporting target tissue metastasis
• Myelofibrosis
• Radiation damage

Transplantation

• Chronic graft failure
• Chronic allograft
• Cyclosporine toxicity

Pathogenesis

The cells are differentiated in epithelial and mesenchymal cells. An epithelium is composed of a base forming the basement membrane and epithelial cells thereon.

Allen epithelial cells have in common is their polarity: You have an apical said outer side opposite the basal underside, facing the basement membrane. These have different functions. Epithelia are arranged close to each other to form a cover or glandular tissue in the form of an interface that performs specialized metabolic functions. In the kidney, for example, is the epithelium in the renal tubule, a fine tube in which the flowing urine is concentrated. The transporting epithelium here takes certain substances and secretes the rest. Revamped it is of dividing stem cells that sit isolated on the basement membrane.

A mesenchyme cell, however, is typically not tied to a basement membrane, but usually move freely like the cells of the immune system. You can move in the bloodstream and tissues happen.

The fibroblasts are a form of mesenchymal cells. Fill the space between the cells with the extracellular matrix of low structure and complement are also promising as a sort of scar tissue damaged areas of the epithelium.

In the development of fibrosis now assume differentiated epithelial characteristics of a mesenchymal cell. They transform into myofibroblasts. These are a special form of fibroblasts, which is normally responsible among other things for wound healing. This conversion process is called epithelial - mesenchymal transition.

The myofibroblasts are very productive, they produce much more matrix material than would be required and thus significantly affect the function of the surrounding cells.

The bone marrow mesenchymal progenitor cells forms, so-called fibrocytes, which may migrate to the organs and become fibroblasts.

Three factors affect this event: TGFbeta, p38 MAPK, and thrombospondin. The thrombospondin is antiangiogenic; it reduces the growth of blood vessels in the resulting scar tissue and thus causes a lack of energy of the adjacent epithelia. In the case of liver cirrhosis resulting from the reduced conductivity increased Perfusionswiderstand, so as to form bypass circuits.

Clinically, show organ-specific fibrosis of the liver, lung, kidney or heart that lead to functional limitation. In the field of rheumatic entities fibrosis can occur which affect several organs, such as scleroderma, which also changed the lungs and small renal vessel walls adjacent to a skin thickening.

Therapy

The most radical form of therapy is to destroy the myofibroblasts. This so-called NK cells are used. NK cells normally destroy body cells that are infected by viruses or other attackers. The most practical form of therapy, however, is somewhere to inhibit the signal transduction of the signal molecule TGFbeta. Similarly, many guidance and existing substances are known, for example, inhibit the p38 MAPK. Substances, of which it has been recognized that it would lead to TGFbeta activation, such as angiotensin or aldosterone are influenced with currently available drugs.

• Disease in internal medicine
• Pathology