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Gout has been defined as one of the most painful rheumatic diseases. It results from the deposition of crystals of uric acid in connective tissue, joint spaces, or both, and is due to a disorder of uric acid metabolism. It is caused by either an overproduction, or under excretion of uric acid and is manifested by hyperuricemia, acute or chronic recurrent arthritis, and deposits of monosodium urates.
Uric acid serves no physiologic purpose and is the end product of purine metabolism. In lower animals, the enzyme uricase breaks down uric acid to the more soluble allanotoin, thus uric acid does not accumulate. Gout occurs only in humans where there is a miscible pool of uric acid. Under normal conditions, uric acid is dissolved in the blood and passes through the kidney and into the urine for elimination. The amount of cumulated uric acid in men is about 1,200mg and in women, about 600mg. These values are increased several-fold in individuals with gout.
Population studies have shown that serum urate concentrations (and consequently risk of gout) correlates with age, serum creatinine, blood urea nitrogen, male gender, blood pressure, body weight, and alcohol intake. Prevalence increases with age, especially in men.(1) Men are affected by gout approximately 10 times more often than women. Although no genetic marker has been isolated for gout, the familial nature of gout strongly suggests an interaction between genetic and environmental factors.(2)
Hyperuricemia may result when a patient eats too many high-purine foods such as liver, dried beans and peas, anchovies, and gravies. However, dietary purines play an unimportant role in the generation of hyperuricemia in the absence of some derangement in purine metabolism or excretion. Hyperuricemia is not a disease and by itself is not dangerous.
The purines from which uric acid is produced come from three sources: dietary purines, conversion of tissue nucleic acids to purine nucleotides, and de novo synthesis of purine bases. The purines derived from these three sources enter a common metabolic pathway, leading to either the production of nucleic acid or uric acid. Uric acid may accumulate excessively if production exceeds excretion.(2) Several enzyme systems regulate the metabolism of purines, and a partial deficiency of one or more enzymes may be responsible for marked hyperuricemia in otherwise normal individuals. Uric acid may also be overproduced as a consequence of increased breakdown of tissue nucleic acids, as with myeloproliferative and lymphoproliferative disorders.
Uric acid does not accumulate as long as production is balanced with elimination. About two thirds of uric acid is eliminated through the kidneys. The remaining one third is eliminated through the GI tract after enzymatic degradation by colonic bacteria. Almost all the urate in plasma is freely filtered across the glomeruli. Multiple renal tubular transport processes, in addition to the filtered load, determine the concentration of uric acid in the urine. Evidence favors a four-component model including glomerular filtration, tubular reabsorption, tubular secretion, and postsecretory reabsorption.(3) In addition, there appears to be a close linkage between uric acid reabsorption and sodium reabsorption, so there will be an elevated uric acid level in conditions that enhance sodium reabsorption.
There are a number of conditions that affect either uric acid clearance or increase its production. Therefore, a patient with these conditions has a greater risk of developing gout. Some of the conditions associated with hyperuricemia include:
| diabetic ketoacidosis |
obesity |
myeloproliferative disorders |
| sarcoidosis |
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| Footnotes |
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1 Kelley WN, Worthman RL. Gout and hyperuricemia. In: Kelley WN, Harris EP, Ruddy S, Sledge CB, eds. Textbook of Rheumatology. Philadelphia: Saunders; 1997:1313-1351.
2 Hawkins DW, Rahn DW. Gout and Hyperuricemia. In: DiPiro JT, et al, eds. Pharmacotherapy, A Pathophysiologic Approach, 4th ed. Stamford, CT: Appleton & Lange; 1999.
3 Levinson DJ, Becker MA. Clinical gout and the pathogenesis of hyperuricemia. In: Koopman WJ, ed. Arthritis and Allied Conditions, 13th ed. Baltimore: Williams & Wilkins; 1997:2041-2071.
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