also result in overproduction of ur

also result in overproduction of uric acid due to lysis and breakdown of
cellular matter.
• Dietary purines play an unimportant role in the generation of hyperuricemia
in the absence of some derangement in purine metabolism or
elimination.
• About two-thirds of the uric acid produced each day is excreted in the
urine. The remainder is eliminated through the GI tract after enzymatic
degradation by colonic bacteria. A decline in the urinary excretion of uric
acid to a level below the rate of production leads to hyperuricemia and an
increased miscible pool of sodium urate.
• Drugs that decrease renal clearance of uric acid through modification of
filtered load or one of the tubular transport processes include diuretics,
nicotinic acid, salicylates (less than 2 g/day), ethanol, pyrazinamide,
levodopa, ethambutol, cyclosporine, and cytotoxic drugs.
• The average human produces 600 to 800 mg of uric acid daily and excretes
less than 600 mg in urine. Individuals who excrete more than 600 mg after
being on a purine-free diet for 3 to 5 days are considered overproducers.
Hyperuricemic individuals who excrete less than 600 mg of uric acid per
24 hours on a purine-free diet are defined as underexcretors of uric acid.
On a regular diet, excretion of more than 1,000 mg per 24 hours reflects
overproduction; less than this is probably normal.
• Deposition of urate crystals in synovial fluid results in an inflammatory
process involving chemical mediators that cause vasodilation, increased
vascular permeability, complement activation, and chemotactic activity for
polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes
results in rapid lysis of cells and a discharge of proteolytic enzymes
into the cytoplasm. The ensuing inflammatory reaction is associated with
intense joint pain, erythema, warmth, and swelling.
• Uric acid nephrolithiasis occurs in 10% to 25% of patients with gout.
Predisposing factors include excessive urinary excretion of uric acid, acidic
urine, and highly concentrated urine.
• 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 wellrecognized
complication in patients with myeloproliferative or lymphoproliferative
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.
• Tophi (urate deposits) are uncommon in gouty subjects and are a late
complication of hyperuricemia. The most common sites of tophaceous
deposits in patients with recurrent acute gouty arthritis are the base of the
great toe, helix of the ear, olecranon bursae, Achilles tendon, knees, wrists,
and hands