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INTRODUCTION

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  • Gout involves hyperuricemia, recurrent attacks of acute arthritis with mono-sodium urate (MSU) crystals in synovial fluid leukocytes, deposits of MSU crystals in tissues in and around joints (tophi), interstitial renal disease, and uric acid nephrolithiasis.

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PATHOPHYSIOLOGY

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  • Uric acid is the end product of purine degradation. An increased urate pool in individuals with gout may result from overproduction or underexcretion.

  • Purines originate from dietary purine, conversion of tissue nucleic acid to purine nucleotides, and de novo synthesis of purine bases.

  • Overproduction of uric acid may result from abnormalities in enzyme systems that regulate purine metabolism (eg, increased activity of phosphoribosyl pyrophosphate [PRPP] synthetase or deficiency of hypoxanthine-guanine phosphoribosyl transferase [HGPRT]).

  • Uric acid may be overproduced because of increased breakdown of tissue nucleic acids, as with myeloproliferative and lymphoproliferative disorders. Cytotoxic drugs can result in overproduction of uric acid due to lysis and the breakdown of cellular matter.

  • Dietary purines are insignificant in generation of hyperuricemia without some derangement in purine metabolism or elimination.

  • Two thirds of uric acid produced daily is excreted in urine. The remainder is eliminated through gastrointestinal (GI) tract after degradation by colonic bacteria. Decline in urinary excretion to a level below rate of production leads to hyperuricemia and increased pool of sodium urate.

  • Drugs that decrease renal uric acid clearance include diuretics, nicotinic acid, salicylates (<2 g/day), ethanol, pyrazinamide, levodopa, ethambutol, cyclosporine, and cytotoxic drugs.

  • Deposition of urate crystals in synovial fluid results in inflammation, 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 discharge of proteolytic enzymes into cytoplasm. The ensuing inflammatory reaction causes 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 because of blockage of urine flow from massive precipitation of uric acid crystals in collecting ducts and ureters. Chronic urate nephropathy is caused by long-term deposition of urate crystals in the renal parenchyma.

  • Tophi (urate deposits) are uncommon and are a late complication of hyperuricemia. Most common sites are the base of the fingers, olecranon bursae, ulnar aspect of forearm, Achilles tendon, knees, wrists, and hands.

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CLINICAL PRESENTATION

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  • Acute gout attacks are characterized by rapid onset of excruciating pain, swelling, and inflammation. The attack is typically monoarticular, most often affecting the first metatarsophalangeal joint (podagra), and then, in order of frequency, the insteps, ankles, heels, knees, wrists, fingers, and elbows. Attacks commonly begin at night, with the patient awakening with excruciating pain. Affected joints are erythematous, warm, and swollen. Fever and leukocytosis are common. Untreated attacks last from 3 to 14 days before spontaneous recovery.

  • Acute attacks may occur without provocation or be precipitated by stress, trauma, alcohol ingestion, infection, surgery, rapid lowering of serum uric acid by uric acid–lowering ...

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