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Gout Mechanisms |
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Alpha Health Education From the book Inflammatory Arthritis by Stephen Gislason MD Introduction to GoutAlpha Nutrition Products and Services
Alpha Nutrition Online. Alpha Nutrition ® is a registered trademark and a division of Environmed Research Inc., Sechelt, British Columbia, Canada. In business since 1984. Online since 1995.
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Uric Acid Crystals Cause Inflammation The pain and swelling of gout are caused by uric acid crystals that form in the joint. Uric acid is a waste product of purine metabolism. Uric acid is dissolved in the blood and is excreted through the kidneys into the urine. In people with gout, the uric acid level increases and uric acid crystals are deposited in joints and other tissues. These needle-shaped crystals trigger an immune response that produces intense local inflammation with severe pain, tenderness and swelling. After several years of increased serum uric acid, uric acid crystals can build up in the joint(s) and surrounding tissues. They form deposits that are sometimes apparent as firm lumps (tophi) under the skin. Tophi often are found in or near severely affected joints, on or near the elbow, over the fingers and toes, and in the outer edge of the ear. Uric acid crystals can also form stones in the kidneys, in the ureters and in the bladder. Stones form when the uric acid concentration in the urine is too high - this is cause by low water intake, diuretics, and overly acidic urine. A diet rich in purines may be the culprit. |
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Uric Acid Production Uric acid substance is a product of the chemical breakdown of the purine bases that compose the genetic material, DNA and RNA. As cells die and release DNA from their chromosomes, purines are converted into uric acid which is excreted in the urine and, to a lesser extent, the intestinal tract. The concentration of uric acid in the blood is related to the balance between uric acid production and excretion. The normal level in children is 4 ? 2 mg/dl. At puberty, the level increases in males by 1 mg/dl, but it does not increase in females; the normal range is 3 to 7 mg/dl in adult males and 2 to 6 mg/dl in adult females. At concentrations greater than 6.5 to 7.0 mg/dl in water, urate precipitates in the form of sodium urate crystals. When blood levels are above 10 mg/dl, the chance of an acute attack of gout is greater than 90 percent. Only 10% of people with hyperuricemia are over-producers of uric acid caused by diseases of the blood and bone marrow, inherited enzyme abnormalities and metabolic alterations due to obesity. In patients who overproduce uric acid because of a deficiency of hypoxanthine-guanine phosphoribosyltransferase, gout attacks may begin before puberty. Increased destruction of body cells leads to increased uric acid production; examples are malignancies, particularly lymphoreticular cancers, hemolytic anemia, polycythemia, leukemias and nonmalignant conditions of increased cellular proliferation (e.g., psoriasis). Uric acid production will also increase with the accelerated breakdown of adenosine triphosphate (ATP) in glucose-6-phosphatase deficiency, tissue ischemia and myophosphorylase deficiency. Kidney Excretion Decreased urinary excretion of urate most often contributes to hyperuricemia. Patients with urate clearances of 6 to 7 ml per minute are more likely to have hyperuricemia after a purine load than those with clearances of 12 to 14 ml per minute. The assessment of renal handling of urate may be part of medical investigation designed to provide information about urate production, renal function, urine flow and the contribution of dietary purine intake to serum and urine urate. |
