Plasma urate

Dietary purines are not an important source of uric acid. Quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and derived from nucleic acid degradation are converted to xanthine or hypoxanthine and oxidized to uric acid (Figure 36-7). Allopurinol inhibits this last step, resulting in a fall in the plasma urate level and a decrease in the size of the urate pool. The more soluble xanthine and hypoxanthine are increased. 

Benefit from the lowered plasma urate will not be noticeable for some weeks. Medication should be adjusted to keep the plasma urate in the normal range. It can seldom be abandoned. 

Uric acid stones account for about 10% of all kidney stones in the United States. Most kidney stones consist of calcium phosphate or calcium oxalate. The risk for developing urate stones increases with increased levels of plasma urate and with... 

Fluid retention caused by nicotine causes a mild decrease in the plasma protein concentration but without demonstrable effect on the calcium concentration or on the activity of serum enzymes. The plasma urate concentration is less in smokers than in nonsmokers, probably as a result of lessened intake of food by smokers. Both the serum urea and creatinine concentrations tend to be less in smokers than in nonsmokers. 

The plasma urea nitrogen concentration decreases after birth as the infant synthesizes new protein, and the concentration does not begin to rise until tissue catabolism becomes prominent. The plasma amino acid concentration is low as a result of synthesis of tissue protein, although urinary excretion of amino acids may be quite high because of immaturity of the tubular reabsorptive mechanisms. The plasma urate concentration is high at birth, but the high clearance of urate soon reduces the plasma concentration below the adult value. 

Preeclamptic Toxemia. This condition is associated with increasing plasma uric acid concentration, probably caused by uteroplacental tissue breakdown and decreased kidney perfusion. Plasma urate measurement can be used as an indicator of the severity of preeclampsia. Redman et al noted that concentrations in excess of 6.0mg/dL (0.36mmol/L) at 32 weeks gestation are associated with a high perinatal mortality rate. 

Leary NO, Pembroke A, Duggan PF. Adapting the uricase/peroxidase procedure for plasma urate to reduce interference due to haemolysis, icterus or lipaemia. Ann Clin Biochem 1992 29 85-9. 

Redman CWG, Beilin LJ, Bonnar J, Wilkinson RH. Plasma urate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976 1 1370-3. 

The symptoms of acute gout respond to anli-innammatory drugs suchasindomelh-acin. but it should be noted that these drugs have no direct effect on the serum urate level. Low-dose aspirin should be avoided as it inhibits renal urate excretion. Treatment must also be directed at the hyperuricaemia. Drugs such as probenecid which promote urate excretion can be used prophylactically. A diet which is low in purines and alcohol may be prescribed in an effort to reduce the plasma urate concentration. Allopurinol, a specific inhibitor of the enzyme xanthine oxidase which catalyzes the oxidation... 

Gout is a condition in which excess plasma urate precipitates in joints, forming uric acid crystals. These crystals precipitate an inflammatory response, which involves the migration of neutrophils into the affected area, and release of inflammatory mediators. 

Low doses (1 or 2 g/day) can decrease urate excretion and elevate plasma urate concentrations intermediate doses (2 or 3 g/day) may not alter urate excretion large doses (more than 5 g/day) induce uricosuria and lower plasma urate levels. However, such large doses are tolerated poorly. Even small doses of salicylate can block the effects 0/probenecid and other uricosuric agents that decrease tubular reabsorption of uric acid. 

Man excretes urate very inefficiently. The major fraction of the plasma urate is not protein bound and is freely filtrable (Steele, 1978, review). However 90% of the filtrable amount is transported back to the plasma by the reabsorptive mechanism (D J <... 

The proximal and distal convoluted tubules of tliese nephrons reach the surface of the cortex. The pars recta of proximal tubules is not accessible. Progress in the micropuncture field was slow because a very sensitive method for the determination of urate was needed, the volume of tubular fluid collected being small (0.1 //liter) and the plasma urate concentration being low (table 1). Furthermore, all mammalian species have uricase activity... 

The initial plasma urate concentration (Table 1) was disproportionately high levels greater than 0.6-0.9mmol/l in cases of acute renal failure are rare. The plasma urate concentration remained high when renal function had returned to normal 115 ml/min) However, the urinary uric acid, hypoxanthine and xanthine were nomnal for age, as was the excretion of total oxypurines in relation to creatinine excretion on a millimolar basis. Only after clinical gout appeared two years later was purine overproduction demonstrated, with plasma and urinary urate increased, as were hypoxanthine and xanthine excretion. The oxypurine/creatinine ratio was raised. 

He was referred to Guy s for assessment and treatment of his gouty arthritis in 1980, and was admitted with swelling and tenderness of the left knee, the right elbow and MTP joint of the left foot. Urate crystals were identified in synovial fluid. He had no evidence of gouty tophi. Plasma urate was 0.60 and climbed to O.95mmol/1 (Vickers method). Liver biopsy to investigate persistently raised alkaline phosphatase, SCOT and 5 nucleotidase was normal. 

Mean fractional uric acid excretion (C /C x lOO) was low and decreased even further on allopurinol ai ail doses (Fig. lb) indicating that the increase in plasma urate was due to a decrease in uric acid clearance in both studies. Creatinine clearance (uncorrected), was not considered abnormal for age (Study 1 87-97ml/min Study 2 72-90ml/min). The patient showed the characteristic fixed urine pH of the gouty but was unable to concentrate t e urine to the degree noted for controls or primary gout patients (not shown). 

The correlation between uricemia and uricosuria, for the range of plasma urate studied, showed an excellent statistical significance (r=0.90 p<0.0l). 

When plasma urate concentrations increase to around 10 mg/dl, tubular secretion and postsecretory reabsorption modulate serum uric acid levels by a slight increment of the first and a marked diminution of the second, thus increasing uricosuria and lowering uricemia. The inverse mechanism was not evident in the hypouricemia state, possibly because low urate filtrable load is undoubtedly less pernicious than hyperuricemia. 

The experimental data of plasma and urine radioactivities were analyzed by the non-compartmental approach (Rescigno and Gurpide, 1973), as described in details previously (Bianchi et al., 1979). The formulas utilized in this approach allow to determine the following parameters of uric acid kinetics total metabolic clearance rate (MCR), mean residence time of the tracer, total distribution volume (TDV, plasma equivalent), fractional catabolic rate (FCR, relative to TDV), and clearance rate of C-uric acid via the renal route (MCR] ). The total turnover rate (TR) and the total pool of exchangeable uric acid are then obtained as the product of, respectively MCR or TDV by the plasma urate concentration. The extrarenal disposal of uric acid (bacterial uricolysis in the gut, skin desquamation) is determined as the difference between the total metabolic clearance rate and the clearance rate of uric acid through the kidney route. 

NONGOUTY SUBJECTS, NONE EXCEEDED kO YEARS OF AGE. ALL HAD RELATIVELY LOWER URINE PH. THE CREATININE AND TOTAL NITROGEN EXCRETIONS WERE also quite COMPARABLE FOR BOTH GROUPS. In 19 NONGOUTY SUBJECTS, THE MEAN PLASMA URATE WAS 5 5 0.8 MGJ, AND THE MEAN URINE PH WAS 5 + 0.2, TITRATABLE ACID WAS 24.8 + 6.1 A E q/ MIN, NHh WAS 35 0 + 7 3 N, URINARY URIC ACID WAS 0 5 MG +... 

ENT FROM THE CORRESPONDING VALUES FOR THE NONGOUTY CONTROLS. IN 10 OTHER gouty SUBJECTS, WHOSE MEAN PLASMA URATE WAS 9 6 + 0., ... 

FURTHER decreased WHEN THE MEAN PLASMA URATE OF ANOTHER GROUP OF k GOUTY SUBJECTS WERE UP TO I I -7 + I.3 MGJ. AS THE URINARY NH4+ EXCRETION BECAME STEADILY LOWER, THE URINARY URIC ACID WAS STEADILY HIGHER. (Table 3) The total metabolic acid was lower in the... 

GOUTY, PARTICULARLY WHEN THE PLASMA URATE BECAME HIGHER, NH4 /TA RATIOS CORRESPONDINGLY FELL FROM I. 5 + O.5 TO. 0 + 0.2. AS THE NH][ /TN ratios fell, an inverse RELATIONSHIP IN UA-N/TN WAS NOTED. TA WAS NOT DIFFERENT IN VARIOUS GROUPS. 

Fig. 4. Relation o erythrocyte PP-ribose-P production to plasma urate after 120 minutes incubation.

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