Systemic Scleroderma - Pathophysiology

Pathophysiology

The overproduction of collagen is thought to result from an autoimmune dysfunction, in which the immune system would start to attack the kinetochore of the chromosomes. This would lead to genetic malfunction of nearby genes. T cells accumulate in the skin; these are thought to secrete cytokines and other proteins that stimulate collagen deposition. Stimulation of the fibroblast, in particular, seems to be crucial to the disease process, and studies have converged on the potential factors that produce this effect.

A significant player in the process is transforming growth factor (TGFβ). This protein appears to be overproduced, and the fibroblast (possibly in response to other stimuli) also overexpresses the receptor for this mediator. An intracellular pathway (consisting of SMAD2/SMAD3, SMAD4 and the inhibitor SMAD7) is responsible for the secondary messenger system that induces transcription of the proteins and enzymes responsible for collagen deposition. Sp1 is a transcription factor most closely studied in this context. Apart from TGFβ, connective tissue growth factor (CTGF) has a possible role. Indeed, a common CTGF gene polymorphism is present at an increased rate in systemic sclerosis.

Damage to endothelium is an early abnormality in the development of scleroderma, and this too seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion and a type II hypersensitivity reaction have similarly been implicated. Increased endothelin and decreased vasodilation has been documented.

Jimenez & Derk describe three theories about the development of scleroderma:

  • The abnormalities are primarily due to a physical agent, and all other changes are secondary or reactive to this direct insult.
  • The initial event is fetomaternal cell transfer causing microchimerism, with a second summative cause (e.g. environmental) leading to the actual development of the disease.
  • Physical causes lead to phenotypic alterations in susceptible cells (e.g. due to genetic makeup), which then effectuate DNA changes which alter the cell's behavior.

Read more about this topic:  Systemic Scleroderma

Other articles related to "pathophysiology":

Pathophysiology - Uses
... Pathophysiology is a required area of study for nearly all healthcare professional school programs (medical, dental, physician assistant, occupational therapy, physical therapy, nurse practitioner ...
Tension Headache - Cause
... suggest that NO may play a key role in the pathophysiology of CTTH ... (in trigeminal spinal nucleus, thalamus, and cerebral cortex) is believed to be involved in the pathophysiology of chronic tension-type headache ... Moreover, a dysfunction in pain inhibitory systems may also play a role in the pathophysiology of chronic tension-type headache ...
University Of Ostrava - Faculties and Departments - Faculty of Medicine - Department of Physiology and Pathophysiology
... The Department of Physiology and Pathophysiology is divided into Institute of Physiology and Institute of Pathophysiology ... teaching, the Department of Physiology and Pathophysiology carries out scientific research and produces expert reports ...
Atrax Morgue - Partial Discography
... Slaughter Productions 1995 Homicidal Texture (Cass) Slaughter Productions 1995 Pathophysiology (Cass) Old Europa Cafe 1995 Untitled (Cass) Slaughter ... Finestre Che Ridono (CDr) Slaughter Productions 2002 Pathophysiology (CDr) Transf/Order 2002 Sweetly (CDr, Album) Spatter 2002 Death - Orgasm Connector (CD) Slaughter Productions 2003 ...