Uric Acid Production and Elimination
Serum urate, produced when purines are metabolized, is eliminated from the body in the form of uric acid. The development of hyperuricemia is straightforward: uric acid builds up in the blood when the body increases its production of uric acid, or the kidneys do not eliminate it efficiently, or both. In a patient with hyperuricemia, urate can crystallize as monosodium urate monohydrate (MSUM) and may form tissue deposits. An acute gout attack can occur when there is a marked inflammatory response to the deposition of these crystals.
renal, diet, drugs >> excessive urate >> urate crystals >>
phagocyte activation >> inflammation
In most cases of primary gout, renal mechanisms are responsible for the imbalance that can lead to gout. Genetic factors may play a role for these individuals. Most subjects with gout have lower clearance rates for uric acid (which may be measured directly or as a ratio of urate to inulin clearance). The exact mechanism for this defect is not known, although 90% of primary gout cases are triggered by difficulties in urate elimination (underexcretors). Secondary gout can also be attributed to renal disorders or to medications that interfere with urate excretion such as diuretics.
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