Gout
Gout is an inflammatory arthritis caused by crystallization of monosodium urate crystals within joints as a result of hyperuricemia (high levels of uric acid in the blood). Levels of uric acid greater than 6.8mg/dL can cause gout, although only 20% of those with values above this will actually go on to develop gout. Gout is typically an acute monoarthropathy and most commonly affects the metatarsophalangeal joint of the big toe (podagra). The main differentials include septic arthritis, haemarthrosis, calcium pyrophosphate deposition and palindromic RA.
Gout has a high incident rate in western cultures, up to 20%, due to the increased longevity, increased prevalence of hypertension, obesity and the increased consumption of high-fructose corn syrup and meat heavy diets.
Uric acid is the end product of purine metabolism in humans, an over consumption of purines or the inability to properly excrete uric acid through the kidneys are therefore the two pathogenic mechanisms of hyperuricemia. Through either mechanism, supersaturation of urate ions in the blood occurs, leading to the precipitation of monosodium urate crystals in synovial fluid, soft tissues, and organs.
In 90% of cases the imbalance in uric acid occurs due to renal underexcretion, the remaining 10% are due to purine overproduction or a combination of overproduction and underexcretion. Some important causes include, reduced GFR, hypertension, obesity, use of (Thiazide) diuretics, overconsumption of alcohol, red meat and high fructose corn syrup.
Additionally there are some genetic causes of hyperuricemia, these include inborn errors of purine metabolism, and excessive cell death and urate generation (e.g. the Glycogen storage diseases). These should be suspected in young people with recurrent gout.
Monosodium urate crystals will precipitate and deposit in tissue in hyperuricemic patients. They deposit in small lattices known as microtophi on the surface of cartilage and synovial lining. These grow gradually within the tissue, at the point in which flares occur there is a change in this microtophi lattice (generally a change in the environment) which causes the crystal lattice to break apart and shed crystals into the joint space which are then phagocytized leading to the production of interleukin-1 which is responsible for all the cardinal features of acute gout.