The final breakdown product of purine nucleoside metabolism is uric acid. Gout, increased catabolism of nucleic acids, and renal disease are three main disease states associated with elevated plasma uric acid. Chemotherapy causes renal damage as well as increased nuclear catabolism, all of which lead to elevated serum uric acid levels.
Uric acid concentrations can be determined in heparinized plasma, serum, or urine. To avoid dilution by intracellular contents, serum should be separated from cells as soon as possible. Urinary acid concentrations can be influenced by diet. After RBCs are extracted, uric acid is stable in plasma or serum. Refrigerated serum samples can be held for 3 to 5 days.
Uric acid analysis techniques include enzymatic methods such as uricase, chemical methods such as phosphotungstic acid (PTA), and high-performance liquid chromatography (HPLC). The PTA method is based on the formation of a blue reaction in alkaline medium as PTA is reduced by urate. The color is read between 650 and 700nm. To isolate and measure uric acid, high-performance liquid chromatography (HPLC) with ion exchange or reversed-phase columns is used.
Uricase is a reaction that can be determined in either kinetic or equilibrium mode. At wavelengths ranging from 282 to 292nm, the decrease in absorbance as urate is transformed has been measured. The majority of existing enzymatic assays for uric acid in serum use a peroxidase mechanism in conjunction with one of several oxygen acceptors to generate a chromogen:
Uric Acid Reference Values (uricase method)
|Adult, female, plasma, serum||2.6-6.0mg/dL|
|Urine, 24 hour||250-750mg/day|
Uric acid levels in the blood are variable and higher in men than in women. Plasma urate is fully filterable, and it undergoes both proximal tubular resorption and distal tubular secretion. The plasma uric acid level rises gradually in advanced chronic renal failure. Uric acid is stored as renal failure progresses. The concentration of uric acid in the blood rises in advanced chronic renal failure, although this rarely results in classic gout. Uric acid levels are elevated in approximately 40% of patients with critical hypertension. Thiazide diuretics can also raise uric acid levels, which can lead to gout in some situations.