Gout is characterized biochemically as a disorder of uric acid metabolism and clinically by hyperuricemia and recurrent attacks of acute arthritis. Gouty arthritis is most frequently seen as an acute inflammation primarily in the large toe, instep, ankle, or heel. Less often the initial symptoms appear in the knee or elbow; occasionally they are seen in the wrist. If the condition remains untreated over years, sodium urate crystals may form in the subcutaneous tissue, joints, renal parenchyma, and renal pelvis. Uric acid stones may form in the lumen of the urinary tract, and progressive renal failure often occurs in the later stages of untreated gout. Also, microcrystalline deposits of sodium urate frequently result in inflammatory bulges or bumps, termed tophi, appearing in the subcutaneous tissue of the earlobes, elbows, and hands and at the base of the large toe.
The elevated blood uric acid concentration in gout is an easily identified and readily treated abnormality. However, it is essential to identify the condition and institute therapy early to avoid the complications that result from a prolonged elevated uricemia. Complications include arthritis, tophi, urinary calculi, and gouty nephropathy.
Although all forms of gout have the common trait of hyperuricemia, their causes can be manifold. Primary, or genetic, gout results from either increased synthesis of uric acid or decreased renal excretion of the substance. Some gout patients have an unusual shunt mechanism that converts glycine directly to uric acid rather than to its normal metabolic products. Secondary gout may result from either overproduction or impaired elimination of uric acid. Overproduction is usually secondary to some other disorder, most frequently of hematological origin. For instance, in leukemia, myeloid metaplasia, lymphoma, polycythemia vera, and rapid weight loss (dieting), breakdown of cellular nucleoprotein is increased, which can lead to excess formation of uric acid.
In secondary gout, diminished elimination of uric acid can be due to lead nephropathy, glycogen storage disease, or sickle cell anemia. In addition, several drugs, including salicylates, pyrazinamide, alcohol, ethambu-tol, nicotinic acid, cyclosporine, fructose, cytotoxic agents, and certain diuretics (e.g., thiazides, furosemide, bumetanide) will impair the renal elimination of uric acid. These drugs competitively inhibit the active secretion of uric acid (see Chapter 4) into the urine, with resulting hyperuricemia.
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