Gout is an inflammatory disease that usually affects middle aged males who have a high level of red meat and beer within their diet. The pathophysiology behind this condition is the depositing of monosodium urate crystals within joints, most commonly affecting the 1st metatarsal phalangeal (MTP) joint, aka the base of the big toe. This can happen in any joint however and results in a red, hot, swollen and tender joint, often causing difficulty and pain to walk; this is commonly known as a gouty attack and can last days to weeks. Repeated gouty attacks can cause destruction of the joint tissue and lead to arthritis within that joint. This chronic gout can also result in tophi which are permanent deposits of urate crystals along the bone just deep to the skin. Chronic gout also puts individuals at an increased risk of kidney stones that are made of uric acid.
The high levels of uric acid within the blood of individuals with gout causes sharp needle like crystals to form in areas that have a slow blood supply, like a joint and the kidneys. So where does this high level of uric acid come from? Well uric acid comes from purines. Purines are components of nucleic acid within DNA and form the bases adenine and guanine. When DNA is broken down, the purines are converted to uric acid so they can be excreted by the kidneys into the urine. Uric acid is soluble, however only up to a certain concentration within the blood, therefore when the uric acid level is over this threshold; the uric acid loses a proton and gains a sodium ion which results in the formation of these monosodium urate crystals. This increased level of uric acid can be due to increased consumption of purines, from foods such as shellfish, red meat and anchovies. It could also be due to decreased clearance of uric acid from dehydration, either caused by not drinking enough water or by a high level of alcohol consumption; but usually a combination of the two.
The monosodium urate crystals result in inflammation due to the body’s immune system attacking the crystals within the joint. This is done by neutrophils which try to phagocytoses the crystals, until there are so many crystals within the neutrophils that thy burst open releasing the crystals back into the synovial fluid (fluid within the joint) as well as lysosomal enzymes. Monocytes also phagocytose the crystals and release cytokines in response, this draws more neutrophils to the area and also causes the release of proteases, both this and the neutrophils reaction result in injury to the joint tissues and inflammation.
Diagnosis of his condition is based on analysis of the synovial fluid that is found in joints. Under a microscope the monosodium urate crystals can be seen. These are examined under polarised light to differentiate them from calcium crystal deposits, where monosodium urate crystals are negatively birefringent. This fluid is also sent for culture to check that it is not a bacterial infection of the joint causing the inflammation (septic arthritis). Blood tests can show an increased white cell count in the acute attacks and an increased level of uric acid. Imaging of the joint is not useful in acute attacks as early changes aren’t detectable on an x-ray, however in chronic gout, there are punches –out lytic bone lesions with spiky periosteal appositions.
Treatment of gouty attacks and prevention of these attacks is different. During acute attacks the treatment focuses on symptom management, including non-steroidal anti-inflammatory (NSAID) treatment eg ibuprofen, corticosteroids and colchicine. Colchicine works by inhibiting the migration of white blood cells into the joint as it is this process of the white blood cells that attack the urate crystals that causes the inflammation. Allopurinol is used as prevention for gouty attacks, but cannot be used in the acute phase as it has been shown to make the attack worse. Allopurinol works by decreasing the uric acid levels. Allopurinol is a xanthine oxidase inhibitor; xanthine oxidase is an enzyme within the body that is used in the pathway for converting purines into uric acid. Therefore allopurinol inhibits this enzyme and reduces the breakdown of purines into uric acid.
Join us for our next blog post where we discuss pseudogout, an important differential for gout.