Uric acid precipitation

Gout is caused either by an overproduction of purines, which leads to the overproduction of uric acid, or to a failure of the kidneys to excrete uric acid. Because of its insolubility, uric acid precipitates in the joints and causes inflammation. 

Thiazide diuretics cause hjrperuricemia and can occasionally precipitate gout (21). They can also cause renal stones (22). Uric acid precipitation is not normally a problem, although it was with the uricosuric drug tieniUc acid. Renal vasculitis due to thiazides is rare (SEDA-18,234). 

Two mechanisms responsible for phenylbutazone-induced acute oligo-anuric renal failure include 1) inhibition of uric acid reabsorption, leading to hyperu-ricosuria and, ultimately, bilateral ureteral obstruction due to uric acid stones [112] 2) an idiosyncratic reaction has been reported that results in acute tubular injury without uric acid precipitation [113]. 

Probenecid and benzbromarone increase the renal excretion of oxipurinol, the active metabolite of allopurinol, but this probably does not alter clinical efficacy. Theoretically, the use of uricosuric drugs with allopurinol could lead to uric acid precipitation in the kidneys and therefore maintenance of a high urine output is recommended when allopurinol is given by injection. Probenecid markedly increases the serum levels of allopurinol riboside, which may be advantageous in some circumstances. 

Reduction of Fehling s solution. Dissolve o i g. of uric acid in NajCOs solution, and to the clear solution add Fehling s solution drop by drop. Note the formation of a white precipitate of copper... 

Reduction of potassium permanganate. To a solution of uric acid in aqueous NajCO add KMnO solution drop by drop a brown precipitate of MnOj is produced immediately in the cold. 

Add dil. H2SO4 until the solution is acid to litmus. Cool, and scratch the sides of the vessel with a glass rod a white precipitate indicates an aromatic carboxylic acid or uric acid, or a solid phenol insoluble in water (e.g., i- or 2-naphthol). If a precipitate is obtained, filter off through a Buchner funnel, wash with water, recrystallise if necessary and identify. 

Uric acid first gives white precipitate of copper urate and then reduces. 

Formation of silver mirror or precipitate of silver indicates reducing agent. (This is often a more sensitive test than I (a) above, and some compounds reduce ammoniacal silver nitrate but are without effect on Fehling s solution.) Given by aldehydes and chloral hydrate formates, lactates and tartrates reducing sugars benzoquinone many amines uric acid. 

The presence of nucleic acids ia yeast is oae of the maia problems with their use ia human foods. Other animals metabolize uric acid to aHantoia, which is excreted ia the uriae. Purines iagested by humans and some other primates are metabolized to uric acid, which may precipitate out ia tissue to cause gout (37). The daily human diet should contain no more than about 2 g of nucleic acid, which limits yeast iatake to a maximum of 20 g. Thus, the use of higher concentrations of yeast proteia ia human food requires removal of the nucleic acids. Unfortunately, yields of proteia from extracts treated as described are low, and the cost of the proteia may more than double. 

In figure 7 a procedure was described for aspirating a sample from a capillary tube and simultaneously adding zinc sulfate and barium hydroxide solutions in order to produce a Somogyi filtrate. Aliquots of the supernatant are suitable for assay for glucose and urea by various procedures. The reason for this is the fact that zinc hydroxide precipitates uric acid, creatinine and other substances, such as low molecular polypeptides, along with the proteins, so that there results a solution which is clear with relatively few components. 

Another procedure which has adequate sensitivity for determining the glucose in 1 microliter of serum of filtrate, is the method which uses copper reduction, and subsequently determination of the cuprous ion with a suitable reagent (15) However, one must be careful that one has obtained complete precipitation, for, if uric acid or any other impurities remain, false high values will be obtained. This would result in disaster for the hypoglycemic infant. To uncover this condition is often one of the major reasons for doing this test. 

The solubility of uric acid depends on concentration and temperature. At high serum concentrations, lower body temperature causes the precipitation of monosodium urate crystals. Collections of these crystals (called micro tophi) can form in joint spaces in the distal extremities. 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

Patients with tumor lysis syndrome experience a wide range of metabolic abnormalities. The massive cell lysis that occurs leads to the release of intracellular electrolytes, resulting in hyperkalemia and hyperphosphatemia. High concentrations of phosphate bind to calcium, leading to hypocalcemia and calcium phosphate precipitation in the renal tubule. Purine nucleic acids are also released that are subsequently metabolized to uric acid... 

In acute uric acid nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of uric acid crystals in the collecting ducts and ureters. This syndrome is a well-recognized complication in patients with myeloproliferative or lymphopro-liferative disorders and results from massive malignant cell turnover, particularly after initiation of chemotherapy. Chronic urate nephropathy is caused by the long-term deposition of urate crystals in the renal parenchyma. 

The major side effects associated with uricosuric therapy are GI irritation, rash and hypersensitivity, precipitation of acute gouty arthritis, and stone formation. These drugs are contraindicated in patients who are allergic to them and in patients with impaired renal function (CLcr <50 mL/min) or a history of renal calculi, and in patients who are overproducers of uric acid. 

In Goiffon s method (G3) peptides are precipitated with phospho-tungstic acid from a trichloroacetic acid filtrate. The precipitate is dissolved and color is developed by a reaction with Folins phenol reagent. This method, however, is not only specific for peptides and a separate assay of uric acid has to be made since this substance also reacts with Folin s reagent. 

In that test tube, he now saw, the poison uric acid could exist in solution or as a precipitate. Its condition depended on pH and temperature, just as in an ordinary test tube, and in either event, whether in the blood or tissues, it produced disease. That deposits in the tissues would cause irritation was obvious enough, but the mechanism by which dissolved uric acid worked its havoc required some logical analysis. Since his migraine pain was aggravated by stooping and alleviated by applying pressure to the arteries of the neck, Haig deduced the immediate cause of the headache had to be elevated blood pressure. 

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. 

Adverse reactions may include anaphylactoid reactions, dermatitis, pruritus, decreases in visual acuity, anorexia, nausea, vomiting, Gl upset, abdominal pain, fever, malaise, headache, dizziness, mental confusion, disorientation, possible hallucinations, peripheral neuritis, elevated serum uric acid levels, precipitation of acute gout, transient impairment of liver function, and joint pain. 

Uric acid is minimally water-soluble and most cases of gout arise from inadequate excretion by the kidneys (souric acid and precipitation of urate stones In the kidneys and extremities. 

Gout results from hyperuricemia i.e. increased serum uric acid levels. Normal serum uric acid level is 1-5 mg/dl. Uric acid is formed in the metabolism of purine. When the blood levels of uric acid are high, it precipitates in joints, cartilage, kidney and subcutaneous tissues and leads to various signs and symptoms. Hyperuricemia is also seen in various leukemias, lymphomas... 

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