Uric acid in gout

B15. Benedict, J. D., Forsham, P. H., Rocke, M., Soloway, S., and Stetten, D., Jr., The effect of salicylates and adrenocorticotropic hormone upon the miscible pool of uric acid in gout. J. Clin. Invest. 29, 1104-1111 (1950). 

INOORPORmCN OF FI04 GLyciNE INTO URIC ACID IN GOUT A FOLLOW-UP STUD5T... 

RENAL HANDLING OF URIC ACID IN GOUT BY BffiANS OF THE PYRAZINAMIDE AND PROBENECID TESTS... 

THE EFFECT OF BEER INGESTION ON PLASMA AND URINE URIC ACID IN GOUT AND NORMOURICAEMIC SUBJECTS... 

Phase diagram for uric acid in gout. Old Ma Kettle has gout. Gout is a disease of crystallization of uric acid in the blood. Figure 25.23 is the phase diagram. 

Deficiency or Toxicity in Humans. Molybdenum deficiency in humans results in deranged metaboHsm of sulfur and purines and symptoms of mental disturbances (130). Toxic levels produce elevated uric acid in blood, gout, anemia, and growth depression. Faulty utiH2ation results in sulfite oxidase deficiency, a lethal inborn error. 

The active principle of the autumn crocus (Colchicum autumnale), colchicine (48), is one of the very few drugs that have remained in reputable medical use since ancient times. This drug was the only useful treatment available for the excruciating pain associated with crystallization of uric acid in the joints characteristic of gout until the advent of allopurinol. Although the precise mechanism by which colchicine gives this dramatic relief remains undefined, the antimitotic activity of this agent is... 

Anti-gout Drugs. Figure 2 Reabsorption and secretion of uric acid in the proximal renal tubulus. (a) Normal situation. Uric acid is completely reabsorbed in the proximal segment of the renal tubulus and secreted more distally. (b) Situation in untreated hyperuricemia. 

Consider briefly the disease gout, which is characterized by the precipitation of urates in tissues and by the presence of hyperuricemia. Bauer and Klemperer state, 11 "The etiology of the disease is unknown." As has been pointed out by other writers, the presence of high concentrations of uric acid in the blood may be due to (1) overproduction, (2) lowered excretion, (3) lowered destruction, or, of course, any combination of the three. Let us consider two hypothetical individuals, A and B, 30 years of age who have exactly the same uric acid blood level (4 mg. per cent) and exactly the same amount of blood (8 liters). The total uric acid in their respective bloods is 320 mg. Let us suppose further that the rate of production of uric acid in the two individuals is continuously exactly the same, the rate of destruction in the two is continuously the same, and that they consume exactly the same food. One hypothetical individual, A, however, continuously excretes on the average 0.1 mg. less uric acid per day than the other. This is very little, compared with the usual total excretion of 700 mg. per day. In the course of 10 years, A s uric acid blood level will, however, have more than doubled, due to this increased retention, and he will be in the range of "gouty" as contrasted with "normal" individuals. This could happen by a very gradual increase, in one individual, of the renal threshold for uric acid. Whether excretion, production, or destruction is responsible for the difference between individuals, the total accumulation of uric acid in hyperuricemia is small. 

The low solubility of uric acid has unfortunate consequences since at higher than normal concentrations it can crystallise in the body. For example, when the urine is unusually acid, calcium urate stones can form in the kidney and bladder. High levels of uric acid in the blood can result in the formation of urate crystals in the joints, which causes a very painful condition, since it results in inflammation in these joints. Gout is unlikely to develop if the urate concentration remains low (<0.4 mmol/L) but any factor that increases the rate of production or decreases that of elimination by the... 

In the proximal tubule probenecid, sulfinpyrazone and benzbromarone enhance the excretion of uric acid Although they compete with uric acid for active secretion by the proximal tubules, resorption of uric acid in the proximal tubules is also inhibited with as a net effect the promotion of uric acid excretion. Indications for the use of uricosurics are repeated attacks of gout, the presence of renal impairment associated with hyperuricaemia and the presence of chronic gouty arthropathy or tophi. 

Correct answer = E. The patient s pain is caused by gout, resulting from the crystallization of excess uric acid in his joints. The cell death caused by radiation therapy leads to the degradation of nucleic acids from those cells. The degradation of purines from these nucleic acids results in excess production of uric acid—a relatively insoluble compound that can cause kidney stones, as well as gout. The end products of pyrimidine degradation do not cause these problems, because they are all soluble compounds that can be more easily excreted in the urine. 

Conversion of lactose into edible protein for animal or human consumption has appeal because of trends in nutrition which emphasize the importance of protein in diets. The high content of purines and pyrimidines in yeast cells is a limitation in consumption of yeasts by humans. These materials in the diet can lead to high levels of uric acid in blood, which may then lead to gout. Principles underlying microbiological conversion of sugars to protein have been available for many years. 

Pyrimidines and purines derivatives act as bases and can be acquired through the diet. In particular, organ meats such as liver are a rich source of DNA and RNA. Most dietary purines are oxidized by enzymes to uric acid in the intestinal mucosa that is their excretory product in humans. The desease known as gout is related to high levels of uric acid in serum and the result of deposition of urate salts in various tissues. 

Blood urate concentrations can be increased because of reduced excretion of uric acid in patients taking ethambutol (390). This is probably enhanced by combined treatment with isoniazid and pyridoxine. Special attention should be paid when tuberculostatic drug combinations include pyrazinamide. However, severe untoward clinical effects are rare, except in patients with gout or renal insufficiency (391,392). 

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