Gout is a complex form of arthritis that is characterized by sudden and severe attacks of pain, redness and tenderness in the joints. Gout most commonly affects the metatarsophalangeal joint at the base of the big toe. The cause occurs when urate crystals accumulate in the joint and cause inflammation.
The body naturally produces uric acid when it breaks down purines. Purines are naturally found in the body but can also be ingested by foods like steak, seafood, and beverages that contain fructose. Normally, uric acid is dissolved in the bloodstream where it passes through the kidneys and is excreted from the body as urine. In an individual with gout, the body either produces too much uric acid or too little uric acid. When this happens, uric acid can build up, forming sharp, needle-like urate crystals in a joint or surrounding tissue that cause pain, inflammation and swelling. Chronic gout can also lead to deposits of hard lumps of uric acid in the tissues, particularly in and around the joints and may cause joint destruction, decreased kidney function, and kidney stones.
There are risk factors that can lead to the development of gout when combined with high serum urate levels. These include irritation, low temperatures, and previous disease.
1 Patients with gout tend to have urate crystal deposition at sites of trauma or irritation, and the metatarsophalangeal joint is a common site for mechanical stress. Low temperatures favor crystal deposition which may explain why the foot is most susceptible.
2 It is likely that it is the combination of trauma and low temperatures that contribute to disease onset.
In the joint space, the synovial lining cells are the first to be phagocytized by the crystals.
3 The phagocytosis of these cells causes IL-1 beta to be realized which is the most important mediator of an acute gout attack. IL-1 beta stimulates the release of chemokines, other cytokines, and a variety of proinflammatory molecules.
4 The chemokines attract neutrophils into the synovial tissue and fluid which is a key feature in an acute attack.
References:
1. Mandell, Brian F., et al. "The Pathogenesis of Gout." Cleveland Clinic Journal of Medicine, 25 Sept. 2018, www.mdedge.com/ccjm/article/94990/pathogenesis-gout/page/0/1.
2. Loeb JN. The influence of temperature on the solubility of monosodium urate. Arthritis Rheum 1972; 15:189-192.
3. Schumacher HR Jr, Wortmann RL. The pathology of crystal-induced arthropathies. In: Wortman RL, Schumacher HR Jr, Becker MA, Ryan LM, eds. Crystal-Induced Arthropathies. New York, NY: Taylor & Francis Group; 2006:291-319.
4. Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 2006; 116:2262-2271.
