The triggers that cause uric acid to build up in the blood are not well understood. While it may crystallize at normal levels, it is more likely to do so as uric acid levels increase. Other factors believed to be important in triggering an acute episode of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrixproteins, such as proteoglycans, collagens, and chondroitin sulfate. The increased critilization at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to a number of factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting the medication allopurinol.