Gout can arise from metabolic deficits that cause uric acid overproduction or from renal underexcretion of urates, or it may be secondary to hyperuricemia induced by coexisting disease or medications. The most characteristic lesion of gout is the tophus, a deposit of crystals of monosodium urate that triggers a severe inflammatory reaction in the surrounding tissue. Although the first metatarsophalangeal joint (big toe) is the most common site of initial inflammatory disease (podagra), visible tophi can also develop on the helix of the ear, elbow, Achilles tendon, extensor surface of the forearm, knee, fingertips and toes.
Other factors that may contribute to the development of gout include alcohol use, hypertension, obesity, insulin resistance, high-purine diet or lead exposure. Secondary hyperuricemia may be due to myeloproliferative disease or renal insufficiency. Severe psoriasis and other diseases with high tissue nucleic acid turnover may also lead to hyperuricemia.
Uric acid is the terminal product of purine metabolism in humans; other mammals express uricase, which metabolizes uric acid to allantoin, a significantly more water-soluble product. The only other mammal prone to uric acid kidney stones is the Dalmatian dog, which suffers from these due to increased fractional excretion of uric acid.