Gout

Gout is a type of inflammatory arthritis caused by the deposition of needle-like uric acid crystals in the joint membranes. It often involves just a single joint, usually the metatarsal-phalangeal joint of the big toe. The cause is the over production of uric acid, which is a breakdown product of DNA. A large proportion of DNA consists of purines, and it is the breakdown of purines that lead to uric acid.

Most animals have an enzyme called uricase that turns uric acid into the more water soluble allantoin, but humans (and the great apes and bizarrely Dalmatian dogs) lack uricase and therefore have problems with uric acid.

Where does the uric acid come from? It comes from the breakdown of purines in the diet, especially from meats, but it also comes from the body's own cells as they are broken down. Therefore anybody who hemolytic anemia, cancer, leukemia, lymphoma, or even pregnancy will make more uric acid than usual. This excess is increased following chemotherapy.

Finally some people are better at handling uric acid than others. this is probably a genetic thing, though except in a few rare inherited cases, it has not been worked out.

As well as causing gout, uric acid can cause kidney stones and kidney failure.

Treatment of gout is twofold. First the inflammation needs to be dealt with. An anti-inflammatory drug like Indomethacin or Diclofenac needs to be used. Then the amount of uric acid produced needs to be reduced. This is usually dealt with a drug called allopurinol. Allopurinol is a xanthine oxidase inhibitor. Xamthine oxidaseis the enzyme that turns the purine degradation products, xanthine and hypoxanthine into uric acid.

Allopurinol is a pretty safe drug. It does cause a rash in about 20% of users and in people with impaired renal function it can make things worse. It is often given as a preventative in patients receiving chemotherapy.

Pseudo-gout is a condition with the physical symptoms of gout without the raised uric acid levels. It is caused by deposits of calcium pyrophosphate dihydrate crystals in a joint. Nobody really knows why these crystals form. It is treated by anti-inflammatory drugs. Allopurinol is not indicated.

Pseudo-gout occurs when there is increased cell turnover due to the increased amount of nucleic acid metabolism. Two of the four bases that make up the genetic code of DNA are purines and uric acid is the waste product of purine metabolism. This elevates the uric acid in the blood and allows for the crystalization of phosphates in the joints.

Uric acid can be increased through a high purine diet (organ meats for example) or decrease mobilization of calcium phosphates (dehydration or anti-hypertension medications) or through an increased turnover of cells.

Treatment can be as easy as taking medication such as allopurinol or colchicine or as difficult as changing your diet.