Page 260 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Gout
Gout is the result of chronically elevated uric since the digits are cooler than the body core,
acid/urate concentration in plasma (hyperuri- urate crystals are often formed in the acral
cemia: > 7 mg/dL). joints of the foot (microtophi). Alcohol, which
Uric acid formation. Uric acid (UA) is the increases adenine nucleotide metabolism, fa-
end-product of purine metabolism (→ A1). vors crystal deposition as does obesity, certain
However, normally 90% of the resulting nu- drugs (e.g., diuretics), and a high lead load. The
cleotide metabolites adenine, guanine, and hy- often increased urinary concentration of UA/
poxanthine are reused in that they are re- urate in hyperuricemia results in the forma-
formed to AMP, IMP, and GMP by adenine tion of urinary stones (→ A5 and p.120).
phosphoribosyltransferase (APRT) and hypo- An attack of gout (→ A4) occurs when the
xanthine guanine phosphoribosyltransferase urate crystals (possibly as a result of trauma)
(HGPRT), respectively. Only the remainder is are suddenly released from the microtophi
converted to xanthine and further to uric acid and are recognized by the immune system as
by xanthine oxidase (XO) (→ A1). The low solu- foreign bodies. An aseptic inflammation of the
bility of urate and especially of uric acid, which joint develops (arthritis, → A4; see also
decreases even further in the cold and at low
p. 48ff.), attracting neutrophils which phago-
Metabolism pH (pK a ′ of urate/uric acid ≈ 5.4), is the reason cytize the urate crystals. When the neutrophils
subsequently break down, the phagocytized
why gout develops from hyperuricema.
urate crystals are released again, which main-
The renal excretion of uric acid (→ A2) is ca.
joint swelling occurs, in 70–90% of first at-
concentration in the final urine is 10–20 times
8 10% of the filtered amount, i.e., the UA/urate tains the process. A very painful, deep-red
higher than in plasma. Drugs with uricosuric tacks affecting one of the proximal toe joints.
activity (e.g., benzbromarone) can increase Acute urate nephropathies (→ A5). If the UA
UA/urate excretion and thus lower their plas- concentration in plasma and primary urine
ma concentration. suddenly rises markedly (usually in secondary
Hyperuricemia occurs in ca. 10% of the pop- gout; see below) and/or (because of low fluid
ulation in western industrialized countries; intake), the urine is highly concentrated and
one in 20 develops gout (men > women). 90% the urine pH low (e.g., in protein-rich diet),
of patients with the condition have primary large amounts of UA/urate may be precipitated
gout (→ A3) with a genetic disposition. The in the collecting duct with plugging of the lu-
underlying primary hyperuricemia is due to men. Acute renal failure may result (→ p.108).
the fact that the renal excretion of UA can Repeated attacks of gout (chronic gout) can
match normal UA production only when the damage the joints (also hands, knees, etc.) to
UA concentration in plasma, and thus in the such an extent that, under constant pain,
glomerular filtrate, is raised (asymptomatic hy- marked joint deformities with destruction of
peruricemia). If there is a higher purine intake cartilage and bone atrophy will occur (→ A4,
(especially in innards, meat extract, fish, mus- photograph). There may also be circumscribed
sels, etc.), this is even more the case, and thus deposits of urates (tophi) around the joint or at
in the long term sodium urate crystals are pre- the edge of the auricles as well as in the kid-
cipitated again and again. On rare occasions neys (chronic gouty nephropathy).
the hyperuricemia is caused by a partial lack So-called secondary hyperuricemia or gout
of HGPRT, in which case the proportion of re- is initiated by, for example, leukemia, tumor
utilized nucleotide metabolites (see above) treatment (raised nucleotide metabolism) or
falls, and thus more UA is formed (→ A1). (In by renal failure with other causes (reduced UA
the Lesch–Nyhan syndrome there is a complete excretion).
absence of HGPRT. In this disease childhood
gout is paralleled by severe central nervous
system abnormalities.)
250 As the solubility of urate is especially low in
synovial fluid and at low temperature, and
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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