Pathogenesis Of Gout Research Articles

An abnormality of glutamine metabolism in primary gout

Six gouty and four nongouty men were given a standard oral dose of glycine-N 15, and the incorporation of isotope into the urinary uric acid, urea, ammonia and creatinine was determined, in most instances in four hourly urine collections on day 1, thereafter in twenty-four hour urine samples to day 7. The measurements included not only the total uric acid-N 15 enrichment but also the N 15 abundance of each of the four uric acid nitrogens. Two noteworthy abnormalities were found in the patients with primary gout. One was in the initial intramolecular distribution of uric acid-N 15, characterized by consistently disproportionate isotope enrichment of N-9 and N-3, both derived from the amide nitrogen of glutamine. The other was in the urinary total N 16 partition, characterized by a deficiency in urinary ammonium-N 15 excretion due to a defect in renal production of ammonia from glutamine. An abnormality of glutamine metabolism in primary gout is implied. It is suggested that the abnormality in glutamine metabolism described may have significance for the pathogenesis of primary gout. A defect in utilization of glutamine for renal production of ammonia (? glutaminase deficiency) might enhance uric acid production by recycling extra glutamine into the first and apparently rate-determining reaction of de novo purine biosynthesis, and moreover would predispose to uric acid stone formation.

URICOSURIC AGENTS AND PHENOLSULFONPHTHALEIN EXCRETION.

Introduction At the time of his historic discovery of hyperuricemia in gout, A. B. Garrod stated that Gout would thus appear, at least partly, to depend on a loss of power (temporary or permanent) in the uric acid-excreting function of the kidneys.1Thus began a century of interest and controversy over the role of the kidney in the pathogenesis of gout. The fact that renal mechanisms, as well as metabolic considerations, are important in some cases of gout has been demonstrated by several investigators and accepted by most workers in the field.2In addition, the kidney is one of the major sites for the deposition of uric acid crystals.3-6Nonspecific findings such as proteinuria, a decrease in the ability of the kidney to concentrate the urine, and a decrease of phenolsulfonphthalein (PSP) excretion by the kidney are the early manifestations of this derangement. In recent years uricosuric

The pathogenesis of gout.

Since Garrod's original observation1in 1848 that excessive amounts of serum uric acid were present in gouty patients, there has been widespread agreement that gout is attributable to a sustained accumulation of uric acid in the body. I believe that if a patient has a sufficient degree of hyperuricemia for a long enough period he will eventually develop gout, irrespective of the nature of the hyperuricemia. This, then, implies that the clinical syndrome of gout comprises several distinct entities. The accumulation of uric acid must result from a disturbance in the normal equilibrium between the production of uric acid on one hand and the elimination of urate on the other. As a consequence, hyperuricemia will occur in the following circumstances: When the production of urate is so great that, even though the routes of elimination are of normal capacity, they are inadequate to handle the excessive load.

The Pathogenesis of Gout

The Pathogenesis of Gout

Identification of urate crystals in gouty synovial fluid.

Excerpt Urate crystals have been noted in synovial fluid from gouty patients in the past, but this finding was believed to be infrequent and of little assistance to the clinician in his attempt to ...

The role of the kidney in the pathogenesis and treatment of gout.

AbstractThe author presents a comprehensive review of experimental observations and changing concepts concerning the relationship of renal function to gout. Recent knowledge of the role of the kidney in the pathogenesis and treatment of this disease has been summarized. Topics that are discussed include urate excretion in normal and gouty individuals, renal dysfunction in patients with gout, primary renal gout and the pharmacology of uricosuric agents. Le autor presenta un revista comprehensive del observationes experimental e del cambiante conceptos in re le relation inter function renal e gutta. Le cognoscentias currente in re le rolo del ren in le pathogenese e le tractamento de iste morbo es summarisate. Le themas discutite include le excretion de urato in individuos normal e guttose, le dysfunction renal in guttosos, primari gutta renal, e le pharmacologia de agentes uricosuric.

Renal function in gout: With a commentary on the renal regulation of urate excretion, and the role of the kidney in the pathogenesis of gout

1. 1. A study was made of renal function in some 300 gouty subjects. Standard renal clearance technics were employed in approximately 160 cases, including some asymptomatic hyperuricemic relatives of these gouty subjects. 2. 2. C inulin, C PAH and Tm PAH were for the most part consonant with the values found in normal subjects of equivalent age, but impairment of renal hemodynamics was not infrequent particularly in those of advanced age or with overt renal disease. 3. 3. Determinations of urinary urate excretion, whether measured as UV urate in short clearance experiments or in twenty-four-hour urine collections, gave values within the normal range in most cases. In a significant minority of instances, however, the urinary urate excretion was unequivocally in excess of the limits of normal variation. 4. 4. The filtered urate load was found to be increased in most gouty subjects. The presumptive tubular reabsorption of urate was correspondingly increased but, so far as could be determined, not disproportionately so in relation to the percentage of urate reabsorbed by the tubules at equivalent filtered urate loads in normal man. 5. 5. The results thus indicate essentially normal discrete renal functions in most gouty subjects. With advancing years and disease, however, the glomerular filtration rate progressively declines and some tubules apparently deteriorate. Secondary renal retention of urate then becomes apparent. 6. 6. The data fail to disclose any primary defect in tubular function, specifically of abnormally enhanced tubular reabsorption of urate. On the contrary, the clearance data imply overproduction of urate in gout. This interpretation is supported by reference to metabolic data. 7. 7. The question of tubular excretion of urate is reviewed. The available clearance data are not incompatible with the view that the filtered urate load, assuming complete filtrability of plasma urate, normally is wholly or in very large part reabsorbed by the tubules, and that the excreted urate derives entirely, or for the greater part, from tubular secretion; the analogy with potassium excretion is pointed out. Indirect but not direct support of this postulation is presented. 8. 8. It is concluded that the pathogenesis of hyperuricemia and of the other manifestations of gout cannot be ascribed to any hypothetic primary renal defect, whether of abnormally great tubular reabsorption or deficient tubular secretion of urate.

Uric acid production in normal and gouty subjects, determined by N15 labeled glycine.

Summary1. Glycine was synthesized by the Schoenheimer and Ratner method with a modification (ion exchange resins) which in our hands gave better yields. 2. N15 tagged glycine was fed to a normal and to a gouty subject while they were on the same constant, low protein, low purine, 2000-calorie diet. Daily urine samples were analyzed for total nitrogen and uric acid, as well as for isotope concentration in these 2 fractions. 3. No significant difference could be found between the 2 subjects in the isotope distribution of the total nitrogen or uric acid. The percentage of N15 excreted as uric acid was no greater in the gouty than in the normal subject. The significance of this finding in relation to the pathogenesis of gout is discussed.

Effects of adrenocorticotropic hormone (ACTH) in gout

1. 1. ACTH effected a very rapid and satisfactory response in the local and systemic manifestations of acute gout in seven of eleven cases treated, including one patient refractory to colchicine. ACTH therefore appears to be a useful agent in the therapy of acute gout. In many of these patients, however, ACTH was not convincingly superior to colchicine, and in four instances colchicine terminated attacks responding unsatisfactorily to ACTH. Unlike colchicine, ACTH is not suitable for prophylactic use in the prevention of acute gouty attacks. 2. 2. Exacerbation of symptoms occurred in four patients following discontinuance of ACTH therapy after a satisfactory response. Such exacerbations usually suggested re-exhibition of the underlying disease upon termination of the suppressive effects of ACTH rather than initiation of a new attack of acute gout. The conjoint and continued prophylactic use of colchicine seems rational in patients subject to frequent recurrences. 3. 3. Acute gouty arthritis developed only once in eight cases of interval gout when ACTH was given in full dosage and then abruptly discontinued. 4. 4. In the prevention and treatment of chronic tophaceous gout, the use of ACTH is neither feasible nor desirable at present. Salicylates and carinamide are at least as effective uricosuric agents, are readily available and orally administered. 5. 5. The available evidence does not appear to justify the view that the pituitary and/or adrenal glands play a central role in the pathogenesis of gout.

THE PATHOGENESIS AND TREATMENT OF GOUT.

Since the classical investigations of Garrod we know that gout is characterized by the presence of uric acid in the serum and that the gouty attacks are caused by the precipitation of this acid into the joints. Every theory of gout must explain these characteristic features, and every pathogenic conception of the disease is based on these facts. Before we enter the discussion of the different theories which attempt to explain the pathogenesis of gout, I should like to give a short review of the formation of uric acid in physiologic conditions. While till about ten years ago uric acid was considered to be a product of imperfect oxidation of albuminous bodies, it has been proved since that uric acid has nothing whatever to do with albumin, but must be looked on as a specific oxidation product of the purin bodies derived either from the nucleic acid of the food or from the breaking down of the cell nuclei in the catabolism.

The Pathogenesis of Gout

The Pathogenesis of Gout

The Pathogenesis of Gout

The Pathogenesis of Gout

The Pathogenesis of Gout

The Pathogenesis of Gout

Observations on the Pathogenesis of Gout

Observations on the Pathogenesis of Gout