Sclerosis and Fibrosis

In medicine, sclerosis (also spelled sclerosus in the names of a few disorders;

from Greek σκληρός "hard") is the stiffening of a structure, usually caused by a
replacement of the normal organ-specific tissue with connective tissue.
Types include:

 Amyotrophic lateral sclerosis, sometimes known as Lou Gehrig's disease, a

progressive, incurable, usually fatal disease of motor neurons.
 Atherosclerosis, a deposit of fatty materials, such as cholesterol, in the
arteries which causes hardening.
 Focal segmental glomerulosclerosis is a disease that attacks the kidney's
filtering system (glomeruli) causing serious scarring and thus a cause
of nephrotic syndrome in children and adolescents,[1] as well as an important
cause of kidney failure in adults.
 Hippocampal sclerosis, a brain damage often seen in individuals with
temporal lobe epilepsy.
 Lichen sclerosus, a disease that hardens the connective tissues of the vagina
and the penis. An autoimmune disorder.
 Liver sclerosis is a common misspelling of cirrhosis of the liver.
 Multiple sclerosis, or focal sclerosis,[2] is a central nervous system disease
which affects coordination.
 Osteosclerosis, a condition where the bone density is significantly increased.
 Otosclerosis, a disease of the ears.
 Systemic sclerosis (progressive systemic scleroderma), a rare, chronic
disease which affects the skin, and in some cases also blood vessels and
internal organs.
 Tuberous sclerosis, a rare genetic disease which affects multiple systems.
 Primary sclerosing cholangitis, a hardening of the bile duct by scarring and
repeated inflammation.
 Primary lateral sclerosis, progressive muscle weakness in the voluntary
muscles.
Micrograph of subepithelial sclerosus (middle third of image) in a case of lichen
sclerosus.H&E stain

Fibrosis is the formation of excess fibrous connective tissue in an organ or

tissue in a reparative or reactive process. This can be a reactive, benign, or
pathological state. 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 obliterate the 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 tissue, 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
fibroblasts laying down connective tissue,
including collagen and glycosaminoglycans. The process is initiated when
immune cells such as macrophages 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. Other soluble mediators of fibrosis
include CTGF, platelet-derived growth factor(PDGF), and Interleukin 4 (IL-4).
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 ECM synthesis
and degradation ensuring maintenance of normal tissue architecture. The entire
process however, 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.

Examples of fibrosis
Fibrosis can occur in many tissues within the body, typically as a result of
inflammation or damage, and examples include:

Micrograph showing cirrhosis of the liver. The tissue in this example is stained
with a trichrome stain, in which fibrosis is colored blue. The red areas are the
nodular liver tissue
Lungs

 Pulmonary fibrosis
 Cystic fibrosis
 Idiopathic pulmonary fibrosis (idiopathic meaning the cause is unknown)

Liver

 Cirrhosis
Heart

 Atrial Fibrosis
 Endomyocardial fibrosis
 Old myocardial infarction
Brain

 glial scar
Other

 Arthrofibrosis (knee, shoulder, other joints)

 Crohn's Disease (intestine)
 Dupuytren's contracture (hands,fingers)
 Keloid (skin)
 Mediastinal fibrosis (soft tissue of the mediastinum)
 Myelofibrosis (bone marrow)
 Peyronie's disease (penis)
 Nephrogenic systemic fibrosis (skin)
 Progressive massive fibrosis (lungs); a complication of coal
workers' pneumoconiosis
 Retroperitoneal fibrosis (soft tissue of the retroperitoneum)
 Scleroderma/systemic sclerosis (skin, lungs)
 Some forms of adhesive capsulitis (shoulder)