Gout
Gout is a tissue in which tissue deposition of monosodium urate (MSU) crystals occurs due to hyperuricemia (MSU supersaturation of extracellular fluids), resulting in one or more of the following manifestations:
Gouty arthritis
Tophi; aggregate deposits of MSU occuring in articular, osseous, cartilaginous, and soft tissue)
Gouty nephropathy
Uric acid nephrolithiasis
The term gout is derived from the Latin gutta, which means a drop - it comes from the 13th century when it thought that gout resulted from a drop of evil humour affecting a vulnerable joint.
Etiology
Patients suffering with hyperuricemia can either be:
Overproduction of urate (endogenous or exogenous dietary purine precursors)
Underexcretion of urate (abnormal renal handling of urate)
A combination of both processes
Most patients with hyperuricemia and primary gout (90%) are underexcretion of uric acid.
There are two inherited enzyme abnormalities in the urate biosynthesis pathway that can cause urate overproduction:
Superactivity of phosphoribosylpyrophosphate (PRPP) synthetase
Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT): Kelley-Seegmiller syndrome
Epidemiology
Serum uric acid concentrations are both age- and sex-dependent. For this reason, gout is rare in males under age of 30 and in premenopausal women. The peak age of onset of gout in males is 40-50 years and in females. Overall, the prevalence increases with age and increasing serum urate concentrations. It is 5-28/1000 for males and 1-6/1000 for females.
Pathophysiology
Uric acid is the end product of the degradation of purines. Humans lack the enzyme - uricase - which oxidises uric acid to the highly soluble compound allantoin. The lack of this enzyme subjects human to potential risks of tissue deposition of uric acid crystals.
Presentation and History
Investigations and Diagnosis
Serum uric acid concentrations are both age- and sex-dependent. Hyperuricemia is defined as serum uric acid concentration >7.0mg/dl in males and >6.0mg/dl in females. Hyperuricemia is not the same as Uremia; Uremia is raised urea in the blood; secondary to kidney disease or acute GI bleeds.
To determine if a patient with gout is an overproducer or an underexcretor of uric acid, we can do a 24-hour urine collection for the determination of uric acid and creatinine excretion (the creatinine ensures that it was an adequate 24-hour collection).