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.
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.
