Uric acid estimation and gout

Uric acid

In humans approximately 75% of uric acid excreted is lost in the urine and most of the remained is secreted into GIT where it is degraded to allantoin by bacterial enzymes. Renal handling of uric acid is complex and involves four sequential steps: (1) glomerular filtration of virtually all the uric acid (2) reabsorption in PCT of about 98% of filtered UA, (3) subsequent secretion of UA into lumen in the distal portion of PCT about 50% (4) further reabsorption in distal tubule about 35-40%. The net urinary excretion of UA is 6-12% of the amount filtered. At pH <5.56 uric acid exist as urate ion, soluble than uric acid and at urine pH <5.75 uric acid is predominant form and is insoluble.

Clinical significance:

Hyperuricaemia: It is defined as plasma uric acid more than 7 mg/dl in men or >6 mg/dl in women. The major causes of hyperuricemia are due to increased formation like in excess dietary intake, tissue hypoxia, alcoholism, inherited metabolic disease, psoriasis, leukemia, myeloma, etc. and due to decreased excretion like in kidney disease, reduced secretion and increased absorption, lead poisoning, organic acids, salicylate, etc.

Measurement of plasma uric acid is predominantly used in the investigation of gout and it is also used in diagnosis and monitoring of pregnancy induced hypertension (preeclamptic toxemia). Primary gout occurs due to overproduction of uric acid and secondary gout occurs due to retention of uric acid. Patients excreting >600 mg uric acid/day are treated with allopurinol and secreting <600 mg/day are treated with uricosuric drugs.

Kidney disease associated with hyperuricemia may be gouty nephropathy with urate deposition in renal parenchyma or acute intratubular deposition or urate crystals and urate nephrolithiasis. Urate stone are formed during acidotic conditions where urinary pH is <6.

Preeclamptic toxemia is condition associated with increasing plasma uric acid concentration caused by uteroplacental tissue breakdown and decreased kidney perfusion.

Hypouricemia: Plasma urate concentrations <2 mg/dl. It may be seen during inadequate synthesis due to hepatic disease or mutation in Xanthine oxidase. There may be defective renal tubular reabsorption. Over treatment of hyperuricemia with allopurinol or uricosuric drugs.

Analytical methodology:

Chemical method: Phosphotungstic acid oxidizes uric acid to allantoin. The reduction product of phosphotungstate in an alkaline medium is blue and can be quantitated by measuring absorbance at approximately 700 nm.

Uricase method: Enzymatic end point.

The color formed is measured at 600 nm. Use of HESPT acts as electron acceptor and enhance molar absorptivity. Use of ferrocyanide is done to nullify bilirubin interference.

Dry chemistry system: It uses uricase as dry reagent. A multilayer film system employs uricase and peroxidase separated by semipermeable membrane from a leuco dye that is oxidized to form colored product. The quantitation of color is done by reflectance meter system. Another system incorporates separation of plasma from red cells and uricase peroxidase and substituted phenol to measure uric acid.

Reference interval:

Men = 3.5-7.2 mg/dl

Women = 2.6-6.0 mg/dl

Men with uric acid level exceeding 9.0 mg/dl are approximately 150 times more likely to have coexisting gouty arthritis.