Monosodium urate

Abramson, S., Hofistein, S.T. and Weissmann, G. (1982). Superoxide anion generation by human neutrophils exposed to monosodium urate. Effect of protein adsorption and complement activation. Arth. Rheum. 25, 174-180. 

The solubility of uric acid depends on concentration and temperature. At high serum concentrations, lower body temperature causes the precipitation of monosodium urate crystals. Collections of these crystals (called micro tophi) can form in joint spaces in the distal extremities. 

FIGURE 56-1. Synovial fluid containing extracellular and intracellular monosodium urate crystals. (From Reginato AJ. Gout and other crystal arthropathies. In Braunwald E,... 

Aspiration of affected joint fluid is essential for a definitive diagnosis. Joint fluid containing negatively birefrin-gent monosodium urate crystals confirms the diagnosis. Joint fluid has an elevated WBC count with neutrophils predominating. 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

Gout A group of disorders of purine metabolism, manifested by various combinations of hyperuricemia recurrent acute inflammatory arthritis induced by crystals of monosodium urate monohydrate tophaceous deposits of monosodium urate monohydrate crystals in and around the joints of the extremities, which may lead to crippling destruction of joints and uric acid urolithiasis. 

Monosodium urate A crystallized form of uric acid that can deposit in joints leading to an inflammatory reaction and the symptoms of gout. 

The term gout describes a disease spectrum including hyperuricemia, recurrent attacks of acute arthritis associated with monosodium urate crystals in leukocytes found in synovial fluid, deposits of monosodium urate crystals in tissues (tophi), interstitial renal disease, and uric acid nephrolithiasis. 

The definitive diagnosis is accomplished by aspiration of synovial fluid from the affected joint and identification of intracellular crystals of monosodium urate monohydrate in synovial fluid leukocytes. 

Hyperuricemia may be produced by overproduction of uric acid or under-excretion of uric add by the kidneys. Kyperuricemia may progress to acute and chronic gouty arthritis if uric acid (monosodium urate) is deposited in joints and surrounding soft tissue, where it causes inflammation, Uric add is produced from excess endogenous purines as shown in Figure 1-18-5, and is also produced from dietary purines (digestion of nucleic acid in the intestine) by intestinal epithe-lia. Both sources of uric acid are transported in the blood to the kidneys for excretion in urine. 

Arthropathies associated with crystals deposition are acute gouty arthritis, chronic gout and chronic tophaceous gout due to monosodium urate crystals. Then there is acute pseudogout and chronic pyrophosphate arthropathy caused by calcium pyrophosphate dehydrate crystals. Acute calcific periarthritis, acute hydroxylapatite arthritis and chronic hydroxyapatite arthritis including Milwaukee-shoulder-knee syndrome are due to basic calcium-phosphate-hydroxyapatite crystals. 

Gouty arthritis is an inflammatory response to the deposition of monosodium urate monohydrate crystals secondary to hyperuricemia. It is called monosodium urate crystal deposition disease. Hyperuricemia is a serum urate concentration > 7 mg% in males and >6 mg% in females. Hyperuricemia results from overproduction (10-15% of individuals) or a renal excretion of urate lower than 400 mg uric acid/24 hours (85-90% of individuals). The urate under-excretors have a urate clearance of <6 ml/min or a urate to creatinine clearance ratio of <6%. The combination of a relative excess of dietary purine consumption together with urate under-excretion is often the basis for hyperuricemia. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Uric acid renal calculi, tophi, and interstitial nephritis may also occur. Gout is usually associated with hyperuricemia, high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism. In most mammals, uricase converts uric acid to the more soluble allantoin this enzyme is absent in humans. While clinical gouty episodes are associated with hyperuricemia, most individuals with hyperuricemia may never develop a clinical event from urate crystal deposition. 

Gout can be diagnosed by the presence of negatively birefringent monosodium urate crystals in aspirated synovial fluid examined by polarized-light microscopy. Here, crystals are within polymorphonuclear leukocytes. 

Gout is caused by the deposition of crystals of monosodium urate hydrate which are ingested by leucocyctes and trigger the inflammatory response. The biosynthesis of uric acid involves the oxidation of the more soluble compound xanthine (2,6-dihydroxypurine) by xanthine oxidase, and this enzyme is inhibited by allopurinol (187). The treatment of gout also relies on uricosuric drugs to accelerate urinary excretion of uric acid and antiinflammatory drugs to ease the pain and inflammation. 

Gout is a relatively common ( 3 per 1,000 persons) derangement of purine metabolism that is associated with elevated plasma levels of uric acid. The excessive uric acid leads to painful deposits of monosodium urate in the... 

Gout is a familial metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Formation of uric acid calculi in the kidneys... 

Yagnik DR, Hillyer P, Marshall D, Smythe CDW, Krausz T, Haskard DO, Landis RC. Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse macrophages. Implications for the control of joint inflammation in gout. Arthritis and Rheumatism 2000, 43, 1779-1789. 

Gout is a syndrome caused by an inflammatory response to the formation of monosodium urate crystals which develop secondary to hyperuricaemia (Johnstone, 2005). 

Weissman, G. and Rita, G.A., Molecular basis of gouty inflammation Interaction of monosodium urate crystals with lysosomes and liposomes, Nature New Biol., 240, 167, 1972. 

SYNS MONOSODIUM URATE IH-PURINE-2,6,8(3H)-TRIONE, 7,9-DIHYDRO-, MONOSODIUM SALT (9CI) URIC ACID, MONOSODIUM SALT... 

Underexcretion of urate is caused by all diuretics (except spironolactone), aspirin, ethambutol, pyr-azinamide, nicotinic acid, and alcohol (which increases urate synthesis and also causes a rise in blood lactic acid that inhibits tubular secretion of urate). The diagnosis of gout ideally requires the demonstration of negatively birefringent needle-shaped crystals in synovial fluid (monosodium urate monohydrate crystals), not just elevated serum urate. 

Other calcium-containing crystals Monosodium urate monohydrate Neuropathic disorders Intra-articular corticosteroid overuse Avascular necrosis Bone dysplasia... 

The anti-inflammatory effects of borage seed oil have been demonstrated in animal models. A diet enriched with borage seed oil (23% GLA) was compared to one with safflower oil (<1% GLA) with regard to effects on acute inflammation induced by monosodium urate crystals, subacute or chronic inflammation caused by Freund s adjuvant in a subcutaneous air pouch, or adjuvant-induced arthritis (Tate et al., 1989). Borage seed oil, but not safflower oil, decreased inflammation in all models. In addition, the ratio of DGLA to AA was five times that in the livers of animals fed safflower oil. 

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