Urate crystals

Thus, the presence of uric acid crystals in joints triggers a vicious cycle, resulting in an extremely painful inflammation. A typical localization of acute gouty arthritis is the first metatarsal joint of the foot (podagra). The diagnosis of acute gouty arthritis is confirmed by the detection of urate crystals in the joint or tophus. 

Host-derived (e.g., antigen-antibody complexes, activated complement fragments, inflammatory bile acids, urate crystals, certain androgenic steroid metabolites [e.g., etiocholanolone], certain lymphocyte products)... 

Gout is a form of arthritis in which uric acid accumulates in increased amounts in the blood and often is deposited in the joints. The deposit or collection of urate crystals in the joints causes the symptoms (pain, redness, swelling, joint deformity). 

Allopurinol (Zyloprim) reduces the production of uric acid, thus decreasing serum uric acid levels and the deposit of urate crystals in joints. The exact mechanism of action of colchicine is unknown, but it does reduce the inflammation associated with the deposit of urate crystals in the joints. This probably accounts for its ability to relieve the severe pain of acute gout. Colchicine has no effect on uric acid metabolism. 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

Humans catabolize purines to uric acid (pA 5.8), present as the relatively insoluble acid at acidic pH or as its more soluble sodium urate salt at a pH near neutrality. Urate crystals are diagnostic of gout. Other disorders of purine catabolism include Lesch-Nyhan syndrome, von Gierke s disease, and hypo-uricemias. 

The solubility of uric acid depends on concentration and temperature. At high serum concentrations, lower body temperature causes the precipitation of monosodium urate crystals. Collections of these crystals (called micro tophi) can form in joint spaces in the distal extremities. 

FIGURE 56-1. Synovial fluid containing extracellular and intracellular monosodium urate crystals. (From Reginato AJ. Gout and other crystal arthropathies. In Braunwald E,... 

Aspiration of affected joint fluid is essential for a definitive diagnosis. Joint fluid containing negatively birefrin-gent monosodium urate crystals confirms the diagnosis. Joint fluid has an elevated WBC count with neutrophils predominating. 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

The term gout describes a disease spectrum including hyperuricemia, recurrent attacks of acute arthritis associated with monosodium urate crystals in leukocytes found in synovial fluid, deposits of monosodium urate crystals in tissues (tophi), interstitial renal disease, and uric acid nephrolithiasis. 

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. 

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 well-recognized complication in patients with myeloproliferative or lymphopro-liferative 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. 

The goals in the treatment of gout are to terminate the acute attack, prevent recurrent attacks of gouty arthritis, and prevent complications associated with chronic deposition of urate crystals in tissues. 

The low solubility of uric acid has unfortunate consequences since at higher than normal concentrations it can crystallise in the body. For example, when the urine is unusually acid, calcium urate stones can form in the kidney and bladder. High levels of uric acid in the blood can result in the formation of urate crystals in the joints, which causes a very painful condition, since it results in inflammation in these joints. Gout is unlikely to develop if the urate concentration remains low (<0.4 mmol/L) but any factor that increases the rate of production or decreases that of elimination by the... 

Gout increased uric acid resulting in sodium urate crystals deposited in the joints... 

Pharmacoiogy The exact mechanism of action of colchicine in gout is not known. Colchicine apparently exerts its effect by reducing the inflammatory response to the deposited crystals and also by diminishing phagocytosis. Colchicine diminishes lactic acid production by leukocytes directly and by diminishing phagocytosis and thereby interrupts the cycle of urate crystal deposition and inflammatory response that sustains the acute attack. 

Hyperuricemia and chronic or episodic joint pain due to deposition of sodium urate crystals and consequent inflammation (gouty arthritis) are the hallmarks of gout. 

Arthropathies associated with crystals deposition are acute gouty arthritis, chronic gout and chronic tophaceous gout due to monosodium urate crystals. Then there is acute pseudogout and chronic pyrophosphate arthropathy caused by calcium pyrophosphate dehydrate crystals. Acute calcific periarthritis, acute hydroxylapatite arthritis and chronic hydroxyapatite arthritis including Milwaukee-shoulder-knee syndrome are due to basic calcium-phosphate-hydroxyapatite crystals. 

Gouty arthritis is an inflammatory response to the deposition of monosodium urate monohydrate crystals secondary to hyperuricemia. It is called monosodium urate crystal deposition disease. Hyperuricemia is a serum urate concentration > 7 mg% in males and >6 mg% in females. Hyperuricemia results from overproduction (10-15% of individuals) or a renal excretion of urate lower than 400 mg uric acid/24 hours (85-90% of individuals). The urate under-excretors have a urate clearance of <6 ml/min or a urate to creatinine clearance ratio of <6%. The combination of a relative excess of dietary purine consumption together with urate under-excretion is often the basis for hyperuricemia. 

Mechanism of Action An alkaloid that decreases leukocyte motility, phagocytosis, and lactic acid production. Therapeutic Effect Decreases urate crystal deposits and reduces inflammatory process. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Uric acid renal calculi, tophi, and interstitial nephritis may also occur. Gout is usually associated with hyperuricemia, high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism. In most mammals, uricase converts uric acid to the more soluble allantoin this enzyme is absent in humans. While clinical gouty episodes are associated with hyperuricemia, most individuals with hyperuricemia may never develop a clinical event from urate crystal deposition. 

An alternative to thiazides is allopurinol. Some studies indicate that hyperuricosuria is associated with idiopathic hypercalcemia and that a small nidus of urate crystals could lead to the calcium oxalate stone formation characteristic of idiopathic hypercalcemia. Allopurinol, 300 mg daily, may reduce stone formation by reducing uric acid excretion. 

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