Porth's Essentials of Pathophysiology, 4e

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Disorders of the Skeletal System: Metabolic and Rheumatic Disorders

C h a p t e r 4 4

the hips and knees are involved. Muscle-strengthening exercises may help protect the joint and decrease pain. Several dietary supplements are available and adver- tised as beneficial for OA, but few have undergone rigor- ous testing. The most widely used supplements for OA are glucosamine and chondroitin sulfate. A recent mul- ticenter trial funded by the National Institutes of Health found that glucosamine and chondroitin (alone or in combination) were no better than placebo in reducing pain in the total group of persons with knee pain, but that the combination may be effective in those with mod- erate to severe pain. 63 Topical capsaicin may have some pain-relieving effect in osteoarthritic knees and hands. Oral medications are aimed at reducing inflammation or providing analgesia. The mainstay of treatment for mild osteoarthritis is acetaminophen. When acetamino- phen fails to control symptoms , or if the symptoms are moderate to severe, NSAID therapy is recommended. Intra-articular corticosteroid injections may be used when other treatment measures have been unsuccessful in adequately relieving symptoms. 60,61 They are espe- cially helpful in persons who have an effusion of the joint. Injections usually are limited to no more than three times a year in the same joint because their use is thought to accelerate joint destruction. Viscosupplementation is based on the hypothesis that joint lubrication is abnor- mal in OA. 64 Hyaluronate is injected into the joint weekly for 3 to 5 weeks. Surgery is considered when the person is having severe pain and joint function is severely reduced. 60 Procedures include arthroscopic lavage and débridement, bunion resections, osteotomies to change alignment of the knee and hip joints, and decompression of the spinal roots in osteoarthritic vertebral stenosis. Total hip replace- ments have provided effective relief of symptoms and improved range of motion for many persons, as have total knee replacements, although the latter procedure has produced less-consistent results. Joint replacement is available for the first carpometacarpal joint. Arthrodesis (surgical stiffening of a joint) is used in advanced disease to reduce pain; however, this results in loss of motion. Crystal-Induced Arthropathies Crystal deposition in joints produces arthritis. In gout, monosodium urate or uric acid crystals are found in the joint cavity. Another condition in which calcium pyro- phosphate dihydrate crystals are found in the joints sometimes is referred to as pseudogout or chondrocal- cinosis. A brief discussion of pseudogout is found in the section on rheumatic diseases in the elderly. Gout Gout is actually a group of diseases known as the gout syndrome. 66–68 It includes acute gouty arthritis with recurrent attacks of severe articular and periarticular inflammation; tophi or the accumulation of crystalline deposits in articular surfaces, bones, soft tissue, and cartilage; gouty nephropathy or renal impairment; and uric acid kidney stones.

The term primary gout is used to designate cases in which the cause of the disorder is unknown or an inborn error in metabolism and is characterized primarily by hyperuricemia and gout. Primary gout is predominantly a disease of men, with a peak incidence in the fourth to sixth decade. In secondary gout, the cause of the hyper- uricemia is known but the gout is not the main disorder. Asymptomatic hyperuricemia is a laboratory finding and not a disease. Most persons with hyperuricemia do not develop gout. Pathogenesis. The pathogenesis of gout resides in an elevation of serum uric acid levels. Uric acid is the end product of purine (adenine and guanine from DNA and RNA) metabolism. 3,4 The elevation of uric acid and the subsequent development of gout can result from over- production of purines, decreased salvage of free purine bases, augmented breakdown of nucleic acids as a result of increased cell turnover, or decreased urinary excre- tion of uric acid. Primary gout, which constitutes 90% of cases, 3 may be a consequence of enzyme defects that result in an overproduction of uric acid, inadequate elimination of uric acid by the kidney, or a combina- tion of the two. In most cases, the reason is unknown. In secondary gout, hyperuricemia may be caused by increased breakdown of nucleic acids, as occurs with rapid tumor cell lysis during treatment for lymphoma or leukemia. Other cases of secondary gout result from chronic kidney disease. Some of the diuretics, including the thiazides, can interfere with the excretion of uric acid. An attack of gout occurs when monosodium urate crystals precipitate in the joint and initiate an inflam- matory response. Synovial fluid is a poorer solvent for uric acid than plasma. Moreover, uric acid crys- tals are even less soluble at temperatures below 37°C, and typically are deposited in peripheral areas of the body, such as the great toe, where the temperatures are cooler than other parts of the body. 3 With prolonged hyperuricemia, crystals and microtophi (i.e., small, hard nodules with irregular surfaces that contain crys- talline deposits of monosodium urate) accumulate in the synovial lining cells and in the joint cartilage. The released crystals are chemotactic to leukocytes and also activate complement. Phagocytosis of urate crystals by polymorphonuclear leukocytes occurs and leads to polymorphonuclear cell death with the release of lysosomal enzymes. As this process continues, the inflammation causes destruction of the cartilage and subchondral bone. Repeated attacks of acute arthritis eventually lead to chronic arthritis and the formation of the large, hard nodules called tophi 3,4 (Fig. 44-13). They are found most commonly in the synovium, olecranon bursa, Achilles tendon, subchondral bone, and extensor sur- face of the forearm and may be mistaken for rheu- matoid nodules. Tophi usually do not appear until 10 years or more after the first gout attack. This stage of gout, called chronic tophaceous gout, is characterized by more frequent and prolonged attacks, which often are polyarticular. 67