Anatomy and Pathophysiology of Gout and Lupus

Anatomy and Pathophysiology of Gout and LupusIntroductionGout is an acute incitive arthritis with the potency to fully destroy the integrity of the conjugation star(p) to pixilated disability. It is termed as a true vitreous silica dethronement indisposition caused by formation of infectious mononucleosissodium urate crystals in joints and other tissues. It is the common cause of incitive arthritis that has change magnitude in prevalence in recent decades (Roddy and Doherty 2010). Gout normally results from the fundawork forcetal interaction of genetic, constitutional and environmental risk factors. It is more common in men and strongly age related. Both acute arthritis and chronic arthropathy (tophaceous gout) be considered on a lower floor the rubric of gout (Mikuls and Saag 2006 Roddy et al. 2007). In a broader term, it muckle be outlined as combination of events involving an increase in the serum urate assiduity, acute woebegone attacks with monosodium urate monoh ydrate crystals demonstrable in synovial fluid leukocytes, and tophi which unremarkably occurs in and close to joints of the extremities. These physio-chemical changes either occur separately or in combination (Terkeltaub 2003 Shai et al. 2010). sick arthritis accounts for millions of outpatient visits annually and the prevalence is rising. It affects 1-2% of adults in developed countries, where it is the virtually common inflammatory arthritis in men. Epidemiological data argon consistent with a everyplaceturn in prevalence of gout. Rates of gout have nigh(a)ly three-fold between 1990 and 2010. A number of factors have been erect to influence place of gout, including age, race, and the season of the year. In men over the age of 30 and women over the age of 50, prevalence is 2% (Eggebeen 2007).Anatomy and Pathophysiology ill arthritis is one of the most painful rheumatic diseases and its incidence increases promptly with advancing age. In 75% of the patients, ill arthriti s initially strikes a single joint which is most unremarkably the big toe. In women gout develop in increasing numbers racket after menopause eventually at an incidence rate represent to that of men (Hootman and Helmick 2006). In elderly patients, an occurrence of gout is usually slight spectacular than in middle age and often implies an upper finale poly or mono articular presentation rather than the classic mono articular lower extremity picture commonly displayed by middle-aged men. In older patients, gout give the sack be more probable the clinical picture of osteoarthritis or rheumatoid arthritis (Cassetta and Gorevic 2004). Gouty arthritis can be classified into four stages depending upon level of severity namely (i) asymptomatic Hyperuricemia In this stage, a person has elevated strain uric mordant levels but no other symptoms and therefore requires no treatment. (ii) Acute Gouty Arthritis In this stage, hyperuricemia leads to deposition of uric venomous crystals in joint spaces, leading to gouty attacks (iii) Interval / Intercritical This is the stage between acute gouty attacks with no symptoms and (iv) Chronic Tophaceous Gout where the disease leads to permanent damage (Bhansing et al. 2010).Pathogenesis of gouty arthritis is critically influenced by sodium urate crystals and inflammatory processes they induce (Wise and Agudelo 1996). An inefficient renal urate elimination which leads to the elevated levels of uric acid above the saturation point for urate crystal formation is a major determinant of the disease. Purine catabolism leads to the formation of metabolic by-product, uric acid. In most mammals like high primates, many birds and close to reptiles, the urate oxidase (uricase) enzyme converts uric acid (relatively insoluble) to allantoin (highly soluble), leading to very low serum uric acid levels. A series of parallel mutations in the genes of uricase in the Miocene degree results in the production of the dysfunctional form of uricase that leads to accumulation of relatively higher level of insoluble uric acid and subsequently the development of gouty arthritis (Liote and Ea 2006 Eggebeen 2007). Degradation of purines results in the endogenous production of uric acid that usually contributes about two-thirds of the body urate pool, the remainder being originated by dietry intake. Of the uric acid formed daily, about 70% is excreted through the kidney while the rest is eliminated into the livery tract and then converted to allantoin by colonic bacterial uricase. Therefore, in the vast majority gouty patients, hyperuricaemia occurs from reduced efficiency of renal urate clearance (Laubscher et al. 2009 Terkeltaub 2010).Development of the acute and chronic inflammatory gout is facilitated with the deposition of monosodium urate (MSU) crystals in joints. while MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a danger signal released from dyi ng cells, little is known about the molecular(a) mechanisms underlying MSU-induced inflammation (Martinon et al. 2006). For crystal formation n occurrence of gout, the dome product of sodium and uric acid must be at or above the saturation level at which MSU crystals can form. uric acid is a weak acid of pKa 5.75 and, it exists mainly in the ionised form as urate at physiological pH of 7.40. MSU has limited solubility under physiological conditions and the saturation level in plasma at a pH of 7.40 is 6.8 mg/dl (408 mol/l) and when the plasma concentration exceeds this level, crystals may form in the joints and tissues (Terkeltaub 2010).MSU crystals preferentially form within gristle and fibrous tissues, where they are relatively safer from contact with inflammatory mediators and may go for old age without causing any defects. However, if shed from these sites of origin into the joint space or bursa, they are highly phlogistic particles that are immediately phagocytosed by monoc ytes and macrophages, impact the NALP3 inflammasome, triggering the release of IL-1 and other cytokines and a subsequent infiltration of neutrophils. Here the blanched cells release a package of inflammatory mediator substances which, in assenting to destroying the crystals, also damage the surrounding tissues (Martinon et al. 2006). This acute inflammation defines the symptoms of an acute instant such as pain, swelling and redness and is typically self-limiting. Continual deposition of wide numbers of MSU crystals may also heading out the joint damage through mechanical effects on cartilage and wad (pressure erosion), and probably low-grade inflammation. However, these more chronic crystal-tissue interactions still remain knobbed and in need of further investigations (VanItallie 2010).Systematic Lupus Erythematosus (SLE)IntroductionLupus is an gondola repellent disease which leads to both acute and chronic inflammation of various tissues of the human body. Lupus can be clas sified into contrasting form depending upon the target tissues and organ system. delimitate as Type III hypersensitivity reaction, people with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than overseas infectious agents. Because the antibodies and accompanying cells of inflammation can affect tissues anywhere in the body, lupus has the potential to affect a variety of areas such as heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. When internal organs are involved, the condition is referred to as systemic lupus erythematosus (SLE). The disease may be mild or severe and life-threatening (Wallace 2010).The prevalence of lupus ranges from approximately 40 cases per 100,000 persons among Northern Europeans to more than 200 per 100,000 persons among blacks (Johnson et al. 1995). In the United States, the number of patients with lupus exceeds 250,000. The life expectancy of such patients has improved fro m an approximate 4-year survival rate of 50% in the 1950s to a 15-year survival rate of 80% today (Merrell and Shulman 1955 Abu-Shakra et al. 1995). Even so, a patient in whom lupus is diagnosed at 20 years of age still has a 1 in 6 chance of dying by 35 years of age, most often from lupus or infection. Later, myocardial infarction and stroke sire important causes of death (Cervera et al. 2003).Anatomy and PathophysiologySLE is an inflammatory and multi-systemic autoimmune rowdyism characterized by an uncontrolled auto-re use of B and T lymphocytes. This results in the production of auto antibodies (auto-Abs) against self-directed antigens and causes tissue last (Cuchacovich and Gedalia 2009). Pathogenesis of SLE is a multi-factorial event and the choose mechanism of disease development and progression is still unclear. Multiple factors are known to be associated with the development of the disease such as genetic, racial, hormonal, and environmental factors.Defects in apoptosis are one of the proposed mechanisms involved in patho-physiological events of SLE. unstableness in apoptotic machinery leads to the production of auto-antibodies. These antibodies lack the ability to differentiate between infectious and normal host cells and cause increase cell death and abnormalities in immune tolerance (Andrade et al. 2000 Rahman and Isenberg 2008). It is believed that all the major components of immune system are involved in SLE progression at various levels. broadly proteins present in cell nucleus are targeted by the immune system. The likely environmental triggers for SLE include ultraviolet light, drugs, and viruses. These stimuli cause the destruction of cells and expose their DNA, histones, and other proteins, particularly parts of the cell nucleus. It is observed that in patients suffering from SLE, there is increased cell death in monocytes and keratinocytes and hyper formula of Fas protein by B and T cells of the immune system. Tingible body macropha ges (TBMs) are large phagocytic cells present in the germinal centers of secondary lymph nodes. They express CD68 protein. These cells normally engulf B cells which have undergone apoptosis after somatic hypermutation. In some patients with SLE, significantly fewer TBMs can be found, and these cells rarely jibe stuff from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells (Gaipl et al. 2006).Monocytes separated from whole blood of SLE sufferers show reduced expression of CD44 step up molecules involved in the uptake of apoptotic cells. Most of the monocytes and tingible body macrophages (TBM), which are found in the germinal centres of lymph nodes, even show a definitely different morphology they are smaller or scarce and die earlier. serum components like complement factors, CRP, and some glycoproteins are, furthermore, decisively important for an efficiently operating( a) phagocytosis. With SLE, these components are often missing, diminished, or inefficient.ReferencesAbu-Shakra M, Urowitz MB, Gladman DD, Gough J (1995) Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality. J Rheumatol 221265-1270Andrade F, Casciola-Rosen L, Rosen A (2000) apoptosis in systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am 26215-227, vBhansing KJ, van Bon L, Janssen M, Radstake TR (2010) Gout a clinical syndrome illustrated and discussed. Neth J Med 68352-359Cassetta M, Gorevic PD (2004) Crystal arthritis. Gout and pseudogout in the geriatric patient. Geriatrics 5925-30 quiz 31Cervera R et al. (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82299-308 inside 10.1097/01.md.0000091181.93122.55Cuchacovich R, Gedalia A (2009) Pathophysiology and cli nical spectrum of infections in systemic lupus erythematosus. Rheum Dis Clin North Am 3575-93 inside S0889-857X(09)00004-0 pii10.1016/j.rdc.2009.03.003Eggebeen AT (2007) Gout an update. Am Fam Physician 76801-808Gaipl US et al. (2006) headway of apoptotic cells in human SLE. Curr Dir Autoimmun 9173-187 inside 10.1159/000090781 pii10.1159/000090781Hootman JM, Helmick CG (2006) Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum 54226-229 inside 10.1002/art.21562Johnson AE, Gordon C, Palmer RG, Bacon PA (1995) The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum 38551-558Laubscher T, Dumont Z, Regier L, Jensen B (2009) fetching the stress out of managing gout. Can Fam Physician 551209-1212 doi 55/12/1209 piiLiote F, Ea HK (2006) Gout update on some pathogenic and clinical aspects. Rheum Dis Clin North Am 32295-311, vi doi S0889-857X(06)00024-X pii 10.1016/j.rdc.2006.03.001Martinon F, Petrilli V, mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440237-241 doi nature04516 pii10.1038/nature04516Merrell M, Shulman LE (1955) Determination of prognosis in chronic disease, illustrated by systemic lupus erythematosus. J Chronic Dis 112-32Mikuls TR, Saag KG (2006) New insights into gout epidemiology. Curr Opin Rheumatol 18199-203 doi 10.1097/01.bor.0000209435.89720.7c00002281-200603000-00014 piiRahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358929-939 doi 358/9/929 pii10.1056/NEJMra071297Roddy E, Doherty M (2010) Gout. Epidemiology of gout. Arthritis Res Ther 12223 doi ar3199 pii10.1186/ar3199Roddy E, Zhang W, Doherty M (2007) The changing epidemiology of gout. Nat Clin Pract Rheumatol 3443-449 doi ncprheum0556 pii10.1038/ncprheum0556Shai A, Rimar D, Rozenbaum M, Wolfovitz E, Rosner I (2010) Gout in young migrant Filipino women in Israel a changi ng epidemiology. Case reports and review of the literature. Rheumatol Int 301685-1687 doi 10.1007/s00296-009-1198-7Terkeltaub R (2010) Update on gout new therapeutic strategies and options. Nat Rev Rheumatol 630-38 doi nrrheum.2009.236 pii10.1038/nrrheum.2009.236Terkeltaub RA (2003) Gout. New England Journal of Medicine 3491647-1655 doi doi10.1056/NEJMcp030733VanItallie TB (2010) Gout epitome of painful arthritis. Metabolism 59 Suppl 1S32-36 doi S0026-0495(10)00229-5 pii10.1016/j.metabol.2010.07.009Wallace DJ (2010) Advances in drug therapy for systemic lupus erythematosus. BMC Med 877 doi 1741-7015-8-77 pii10.1186/1741-7015-8-77Wise CM, Agudelo CA (1996) Gouty arthritis and uric acid metabolism. Curr Opin Rheumatol 8248-254