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372 Chapter 8: Musculoskeletal system

Calcium hydroxyapatite crystals are involved in the

Guanine Adenine
pathogenesis of osteoarthritis.
The crystals deposited in the joint are phagocytosed by
neutrophils. Typically pyrosphosphate crystals are seen Xanthine Hypoxanthine
within a phagolysosomal sac, whereas urate crystals are
Xanthine Oxidase
not confined. Phagolysosomal lysis results in the release
of enzymes into the cell cytoplasm. Phagocytosis induces Uric Acid
cytokine release leading to chemotaxis and further in-
flammation. Figure 8.5 Uric acid formation.

Gout Decreased renal excretion may be idiopathic or sec-
ondary to renal failure or drugs such as thiazides or
Definition low-dose aspirin.
An acute inflammatory arthritis resulting from urate Anacuteepisodeofgoutmaybeprecipitatedbyasudden
crystal deposition secondary to hyperuricaemia. increase or decrease in urate concentration. Risk factors
include surgery, infection, dehydration, severe illness,
Prevalence/incidence starvation, diuretics and alcohol.
Hyperuricaemiaoccursin5%,goutaffects1–20per1000
males.
Pathophysiology
Injointsanacutesynovitismayoccurwhenuratecrys-

Age tals have been phagocytosed. The crystals cause dis-
Peak incidence at the age of 40–50 years. ruption of lysosomal membranes and hence release of
inflammatory mediators.
Sex If chronic, the crystals accumulate in the synovium
10M:1F and sites such as the ear cartilage forming lumps
termed tophi.
Geography In the kidney, urate crystals may precipitate in the
Mainly a disease of developed countries. collectingductsorcausestoneformation.Theresultof
urate damage is either tubulointerstitial disease (urate
nephropathy) or acute tubular necrosis.
Aetiology
High levels of uric acid cause gout but not all individuals
with hyperuricaemia will develop gout. Hyperuricaemia Clinical features
is associated with increasing age, male sex and obesity, In 70–90% the initial attack of gout affects the big toe. It
and in females urate levels rise after the menopause. is known as podagra if it first affects the metatarsopha-
Uric acid is formed from the breakdown of purines (see langeal joint. The joint is red, hot, swollen and very ten-
Fig. 8.5). Hyperuricaemia may occur due to increased der. There may be an associated fever. These features
ratesofuricacid production or decreased uric acid make it difficult to distinguish from a septic arthritis.
excretion. Other joints affected include ankles, knees, fingers, el-
Increased uric acid production may be idiopathic or bowsandwrists.Chronicgoutisunusualbutmaycausea

secondary to excessive intake or high turnover as seen chronic polyarthritis with destructive joint damage with
in malignancy (especially with chemotherapy). large erosions on X-ray and deformity. Tophi (smooth
Decreased salvage of purines may occur; in Lesch– whiteskinandjointdeposits)occuratcartilagenoussites

Nyhan syndrome a defect in HGPRT results in im- particularly in the Achilles tendon and the helix of the
paired salvage and hence high uric acid levels. ear. This usually reflects severe untreated gout.