musculoskeletal and connective tissue disorders
Gout
Pathophysiology of Gout
The greater the degree and duration of hyperuricemia, the greater is the likelihood that gout will develop. Urate levels can be elevated because of Decreased renal (most common) or gastrointestinal excretion Increased production (rare) Increased purine intake (usually in combination with decreased excretion) Why only some people with elevated serum uric acid (urate) levels develop gout flares is not known. Decreased renal excretionis by far the most common cause of hyperuricemia. It may be hereditary (eg, due to variations in uric acid transporter efficiency) and also occurs in patients receiving diuretics and in those with diseases that decrease the glomerular filtration rate (GFR).Ethanolincreases purine catabolism in the liver and increases the formation of lactic acid, which blocks urate secretion by the renal tubules, andethanolmay also stimulate liver urate synthesis. Lead poisoning andcyclosporine, usually in the higher doses given to transplant patients, alter renal tubular function leading to urate retention. of urate may be caused by increased nucleoprotein turnover in hematologic conditions (eg, lymphoma, leukemia, hemolytic anemia) and in conditions with increased rates of cellular proliferation and cell death (eg, psoriasis, cytotoxic cancer therapy, radiation therapy). Increased urate production may also occur as a primary hereditary abnormality and in obesity, because urate production correlates with body surface area. In most cases, the cause of urate overproduction is unknown, but rarely can be attributable to enzyme abnormalities; deficiency of hypoxanthine-guanine phosphoribosyltransferase (complete deficiency is Lesch-Nyhan syndrome ) is a possible cause, as is overactivity of phosphoribosylpyrophosphate synthetase. Increased intakeof purine-rich foods (eg, liver, kidney, anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, sardines, sweetbreads) can contribute to hyperuricemia. Beer, including nonalcoholic beer, is particularly rich in guanosine, a purine nucleoside. However, a strict low-purine diet lowers serum urate by only about 1 mg/dL (0.1 mmol/L) and thus is rarely sufficient therapy for patients with gout. Urate precipitates as needle-shaped monosodium urate (MSU) crystals, which are deposited extracellularly in avascular tissues (eg, cartilage) or in relatively avascular tissues (eg, tendons, tendon sheaths, ligaments, walls of bursae) and skin around cooler distal joints and tissues (eg, ears, finger pads). In severe, long-standing hyperuricemia, MSU crystals may be deposited in larger central joints and in the parenchyma of organs such as the kidney. At the acid pH of urine, urate precipitates readily as small platelike or diamond-shaped uric acid crystals that may aggregate to form gravel or stones, which may obstruct urine outflow. Tophi are MSU crystal aggregates that most often develop in joint and cutaneous tissue. They are usually encased in a fibrous granulomatous matrix, which prevents them from causing acute inflammation. ), or indulgence in purine-rich food or alcohol. Flares are often precipitated by a sudden increase or, more commonly, a sudden decrease in serum urate levels. Why acute flares follow some of these precipitating conditions is unknown. Tophi in and around joints can limit motion and cause deformities, called chronic tophaceous gouty arthritis. Gout increases the risk of developing Classification . 