User:Nnoddy/sandbox
Pathophysiology
[edit]Proposed addtion.
Mechanisms
[edit]A Runaway Chemical Crystalisation
An acute attack occurs as a result of an inflammatory reaction to crystals of sodium urate that are deposited in the joint tissue. The inflammatory response involves the local infiltration of granulocytes which phagocytise the urate crystals. Lactate is high in synovial tissues and in the leucocytes that are associated with the inflammatory process which also favours the deposition of uric acid. [1]
B Kamikaze leucocytes
Self Perpetuating Fatal Phagocytosis
KT Rajan studied phagocytosis of urate crystals by polymorphonuclear leucocytes. From his investigations with specific reference to phagocytosis of urate crystals by polymorphonuclear leucocytes he proposed a sequence of events that may initiate the inflammatory reaction in acute gout. He concluded that :
(1) neutrophil leucocytes avidly ingest microcrystals of sodium monourate
(2) this causes the rapid degranulation and disintegration of the leucocytes
(3) fresh leucocytes ingest the debris and crystals liberated by the dead cells, and in their turn degranulate and die, thus possibly establishing a vicious circle in the system.
In support of his theory Rajan quoted research in the 1960’s where McCarty demonstrated that:
The severity of the inflammatory reaction is dependent on the number of neutrophils that are available at the time of invasion by the bacteria or toxic agent. In agranulocytosis the reaction to bacterial invaders by the host is functionally deficient and acute gouty effusions provoked by injecting crystals of uric acid into joints can be abolished by pretreating the host with drugs like vinblastine which reduce the total number of leucocytes available. (McCarty, 1965) [2].
C Matchstick Model
Theodore Fields Director, Rheumatology Faculty Practice Plan, Hospital for Special Surgery New York suggests that
Whatever the cause of elevated uric acid levels, the key event in gout is the movement of uric acid crystals into the joint fluid. Inflammatory chemicals are released when the body’s defense mechanisms, engulf the uric acid crystals. All the signs of inflammation, including heat, redness, swelling and pain are caused by these chemicals. (cytokines) The inflammation attracts more white blood cells to the joint, which increases the inflammation.[3]
Theodore stated
“When thinking of gout, a useful model has been proposed by Wortmann. Uric acid crystals can be thought of like matches, which can sit quietly or can be ignited. Crystals can be present for years in the cartilage, or even in the joint fluid, without causing inflammation. Then, at some point, due to increasing number of crystals or other inciting factor, the matches are “struck” and the inflammation begins. This analogy is important both for conceptualizing the uric acid crystals in the joint and for understanding the various types of gout treatment (see below) – some of which attack the inflammation (pour water on the flaming matches) and some of which remove the uric acid crystals (take away the matches).” [4]
D MicroTophi Grenades Urate Crystals in microtophi are normally covered with proteins that block the crystals from binding to cell receptors. When the coating is lost or the tophi burst the crystals suddenly bind to cells suddenly causing the inflammation.
E Crystalisation from Supersaturated Fluid Damaged cells release sodium urate resulting in a supersaturated microenvironment and crystalisation of sodium urate triggering the innate immune response.[5]
What Could End the Acute Symptoms of Gout?
[edit]Humans lack the uricase enzyme that converts urate to the more soluble and easily excreted compound allantoin in most mammals. The tangible presence of tophi is a fair indication that the human body does not have an effective means of eliminating monosodium urate monhydrate crystals once they have formed. The body's visible solution is to encapsulate the crystals and prevent interaction with the immune system.(hide the matches)
Anti-inflammatory drugs are effective in acute epsiodes and the body has a range of anti-inflammatory cytokines including, Interleukin 1 Receptor Antagonist, IL-10, and transforming growth factor (TGF)–beta that are produced.[6](pour water on the flaming matches)
This proposed contribution has been subjected to lengthy scrutiny. Any comments?Nnoddy (talk) 02:43, 10 March 2013 (UTC)
- Oppose Much of the text is not properly referenced. Google Knol is not a suitable source. Emedicine is sort of on the edge. References and headings are not formatted properly. Still needs a fair bit of work. Please see WP:MEDMOS for formatting and WP:MEDRS for reference requirements. Doc James (talk · contribs · email) (if I write on your page reply on mine) 15:48, 10 March 2013 (UTC)
58.111.90.234 (talk) 23:52, 15 March 2013 (UTC)
- Oppose Much of the text is not properly referenced. Google Knol is not a suitable source. Emedicine is sort of on the edge. References and headings are not formatted properly. Still needs a fair bit of work. Please see WP:MEDMOS for formatting and WP:MEDRS for reference requirements. Doc James (talk · contribs · email) (if I write on your page reply on mine) 15:48, 10 March 2013 (UTC)
- ^ Drug Houses of Australia Pty Ltd 1989 MIMS Annual p. 234
- ^ Observations on phagocytosis of urate crystals by polymorphonuclear leucocytes |url = [1] K. T. RAJAN Oxford Regional Rheumatic Diseases Research Centre, Stoke Mandeville Hospital, Aylesbury, Bucks. Rajan, K. T. (1975). Annals of the Rheumatic Diseases, 34, 54
- ^ Gout Risk Factors and Treatment | url = [2]
- ^ Wortmann RL. Effective management of gout: an analogy. Am J Med. 1998 Dec; 105(6):513-4. A review article that includes the "match" analogy
- ^ Gout and Pseudogout Bruce M Rothschild, MD Professor of Medicine, Northeast Ohio Medical University; Adjunct Professor, Department of Biomedical Engineering, University of Akron; Research Associate, University of Kansas Museum of Natural History; Research Associate, Carnegie Museum |url=[3]
- ^ Quench the Flames | url = [4]