X]VeiZg-/ DISORDERS OF WATER, ELECTROLYTES AND URATE BALANCES
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Figure 8.21 (A) Crystals of monosodium urate
viewed using polarized light. (B) Gout of the right
big toe showing diffuse swelling and inflammation
centered where the toes join the foot but also
extending over much of the foot. Courtesy of Charlie
Goldberg, M.D., medicine.ucsd.edu/clinicalmed.Urate has low solubility and the ECF easily becomes saturated at
concentrations just above the upper limit of the reference range. There
is a tendency for crystalline monosodium urate to form in people with
hyperuricemia, giving rise to gout. Crystals of monosodium urate (Figure
8.21(A)) tend to form in cartilage and synovial fluid of joints and particularly
those of the big toe causing gout (Figure 8.21(B)). The crystals are phagocytosed
by neutrophil leukocytes and may cause damage to lysosomal membranes
within these cells (Chapter 16). As a consequence, lysosomal contents are
released, causing damage to both leukocytes and surrounding tissues with
an associated inflammatory response (Chapter 4). Gout may be primary,
with no known cause, or secondary, as a consequence of another disorder.
Primary gout is characterized by recurrent attacks of arthritis. It is more
common in men than women. The metabolic defect in patients is unknown
but a number of abnormalities may be responsible for the overproduction of
urate and therefore increased urinary urate output. In many patients there is
a combined defect of urate overproduction together with its impaired renal
excretion. Patients with primary gout often have deposits of urate in their soft
tissues and some can develop renal stones composed of urate salts. The risk
that a normal person will develop gout varies with their urate concentration.
The annual incidence of gout in men is low, about 0.1%, when the urate
concentration is less than 0.42 mmol dm–3. This increases to 0.6% when the
concentration is 0.42–0.54 mmol dm–3 and 5% when urate concentrations
are greater than 0.54 mmol dm–3. The reason for the onset of acute attacks in
gout is unclear since a sharp rise in the concentration of urate is not usually
demonstrable.Secondary gout is rare but can arise from a number of other disorders including
myeloproliferative disor ders (Chapter 17) such as polycythemia vera, where
the hyperuricemia is due to an increased cell turnover, the use of cytotoxic
drug therapy that increases cell destruction and the breakdown of nucleic
acids, and psoriasis with its increased turnover of skin cells.