Chapter 169 Gout

image General Considerations

Gout is a common type of arthritis caused by an increased concentration of uric acid (the final breakdown product of purine metabolism) in biological fluids. In gout, uric acid crystals (monosodium urate) are deposited in joints, tendons, kidneys, and other tissues, where they cause considerable inflammation and damage.1 Gout is a condition characterized biochemically by increased serum uric acid levels, leukotriene levels, and neutrophil accumulation. Gout may lead to debilitation owing to the tophaceous deposits around the joints and tendons; renal involvement may result in kidney failure due to either parenchymal disease or urinary tract obstruction.

Gout is associated with affluence and is often called the “rich man’s disease.” Throughout history, the sufferer of gout has been depicted as a portly, middle-aged man sitting in a comfortable chair with one foot resting painfully on a soft cushion as he consumes great quantities of meat and wine. In fact, the traditional picture does have some basis in reality, as meats, particularly organ meats, are high-purine foods, whereas alcohol inhibits uric acid secretion by the kidneys. Furthermore, even today, gout is primarily a disease of adult men; more than 95% of sufferers of gout are men older than age 30. The incidence of diagnosed gout cases has been estimated at 2.13% of the 2009 U.S. population, although 10% to 20% of the adult population has hyperuricemia. Gout is a strong predictor of the metabolic syndrome and an increased risk for type 2 diabetes.14

Causes of Gout

Gout is classified into two major categories: primary and secondary. Primary gout accounts for about 90% of all cases, whereas secondary gout accounts for only 10%. Primary gout is usually idiopathic (i.e., the underlying metabolic defect is unknown). However, there are several genetic defects in which the exact cause of the elevated uric acid is known.1 The synthesis and degradation of purines are summarized in Figure 169-1.

The term secondary gout refers to those cases in which the elevated uric acid level is secondary to some other disorder such as excessive breakdown of cells or some form of renal disease. Diuretic therapy for hypertension and low-dose aspirin therapy are also important causes of secondary gout because they cause decreased uric acid excretion.

The increased serum uric acid level observed in primary idiopathic gout can be divided into three categories:

Although the exact metabolic defect in gout is unknown in the majority of cases, gout is one of the most controllable metabolic diseases. Box 169-1 summarizes the causes of gout.

About 200 to 600 mg of uric acid are excreted daily in the urine of an adult male. This is two thirds of the amount produced, the rest being excreted in the bile and other gastrointestinal tract secretions. The dietary component of uric acid is usually 10% to 20%, but in an individual with significant hyperuricemia, 1 mg/100 mL may be added to the serum concentration of uric acid through the diet, enough to increase precipitation into the tissues if the individual is near the saturation threshold.

Almost all of the plasma urate is filtered at the glomerulus: only the small amount bound to protein is not filtered. Renal excretion is peculiar in that about 80% of the filtered uric acid is reabsorbed in the proximal tubule of the nephron. Actually, the distal tubule secretes most of the uric acid found in the urine. Distal to this site, some postsecondary reabsorption occurs. These events are summarized in Figure 169-2.

Uric acid is a highly insoluble molecule; at pH 7.4 and body temperature, the serum is saturated at 6.4 to 7 mg/100 mL. Although higher concentrations do not necessarily result in urate deposition (some unknown factor in serum appears to inhibit urate precipitation), the chance of an acute attack is greater than 90% when the level is above 9 mg/100 mL (Table 169-1). Lower temperatures decrease the saturation point of uric acid, which may explain why urate deposits tend to form in areas such as the pinna of the ear, where the temperature is lower than the mean body temperature (Table 169-2). Uric acid is insoluble below pH 6 and can precipitate as the urine is concentrated in the collecting ducts and passed to the renal pelvis.

TABLE 169-1 Prevalence of Gouty Arthritis by Maximum Urate Level

SERUM URATE (mg/100 mL) MEN (%) WOMEN (%)
<6 0.6 0.08
6-6.9 1.9 3.3
7-7.9 16.7 17.4
8-8.9 25 0
9+ 90 0

Data from Faller J, Fox IH. Ethanol-induced hyperuricemia: evidence for increased urate production by activation of adenine nucleotide turnover. N Engl J Med 1982;307:1598-1602.

TABLE 169-2 Solubility of Urate Ion as a Function of Temperature in 140 mM Na+

37 6.8
35 6
30 4.5
25 3.3
20 2.5
15 1.8
10 1.2

Data from Faller J, Fox IH. Ethanol-induced hyperuricemia: evidence for increased urate production by activation of adenine nucleotide turnover. N Engl J Med 1982;307:1598-1602.

Sep 12, 2016 | Posted by in MANUAL THERAPIST | Comments Off on Gout
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