Leukemia (Blood Cancer)

 Gout is an inflammatory disease in which monosodium urate crystals deposit into a joint, making it red, hot, tender, and swollen within hours. When this happens, it’s called a gouty attack. The underlying cause is hyperuricemia—too much uric acid in the blood, which results in the formation of sharp, needle-like crystals, in areas with slow blood flow like the joints and the kidney tubules.

Over time, repeated gouty attacks can cause destruction of the joint tissue which results in arthritis. To understand where the uric acid comes from, let’s start with urines, which, together with pyrimidines, are nature’s most common nitrogen-containing heterocycles. A heterocycle is any molecular ring or cycle with different types of atoms. Purines, as well as pyrimidines, are key components of nucleic acids like DNA and RNA, and when cells, along with the nucleic acids in those cells, are broken down throughout the body, those purines are converted into uric acid—a molecule that can be filtered out of the blood and excreted in the urine.

Uric acid has limited solubility in body fluids, though. Hyperuricemia occurs when levels of uric acid exceed the rate of its solubility, which is about 6.8mg/dL. At a physiologic pH of about 7.4, uric acid loses a proton and becomes a urate ion, which then binds sodium and forms monosodium urate crystals. These crystals can form as a result of increased consumption of purines, like from consuming purine-rich foods like shellfish, anchovies, red meat, or organ meat. Also, though, they can result from increased production of purines, for example, high-fructose corn syrup containing beverages could contribute to the formation of uric acid by increasing purine synthesis. Another way crystals could form is from decreased clearance of uric acid, which can result from dehydration from not drinking enough water or from consumption of alcoholic beverages, both allowing uric acid to precipitate out.

Regularly eating these kinds of foods can also lead to obesity and diabetes, both of which are risk factors for gout. Hyperuricemia can also develop as a result of chemotherapy or radiation treatment since cells die at a faster-than-normal rate. Also, some individuals have a genetic predisposition to overproduction of uric acid while others with chronic kidney disease may be unable to excrete the uric acid. Finally, there are some medications like Thiazide diuretics and aspirin which can also increase the levels of uric acid and therefore the risk of gout. Now gout most often affects the first metatarsal joint of the foot—or the base of the big toe, and when it does, this condition is called podagra.

Classically in podagra, a person will wake up from sleep feeling like their big toe is on fire; even the weight of the sheets can be painful. The pain is most severe in the hours immediately following the attack and then generally lessens over time, but that discomfort and swelling can last for days or weeks. Gout can affect other joints as well like those in the ankles, knees, wrists, and elbows. This inflammation and local pain are ultimately caused by white blood cells, or leukocytes, which migrate to the site to help eliminate uric acid and release pro-inflammatory chemicals, including cytokines.

Treatment of a gouty attack is typically focused on decreasing the pain and swelling, most often with non-steroidal anti-inflammatory medications, or NSAIDs, like ibuprofen or naproxen sodium, but occasionally with corticosteroids as well. Colchicine which has anti-inflammatory effects by inhibiting white blood cell migration has also been used for a long time to treat gouty attacks. To treat the underlying cause of increased uric acid, though, it’s important to modify the diet, doing things like staying well hydrated (with water), reducing or eliminating soda, alcohol, red meat, and seafood, and staying active to ward off obesity.

There are also medications that help to decrease uric acid levels, which include xanthine oxidase inhibitors like allopurinol. Xanthine oxidase is an enzyme involved in the breakdown of purines to uric acid, so inhibiting this enzyme results in less uric acid production. Uricosuric medications, like probenecid, increase the excretion of uric acid by the kidneys. Over time, repeated gouty attacks can develop into chronic gout, which is a type of arthritis with joint tissue destruction and permanent joint deformity. Chronic gout can eventually lead to permanent deposits of urate crystals—called tophi, which form along with the bones just beneath the skin. Individuals with chronic gout are also at an increased risk for developing kidney stones made of uric acid, as well as urate nephropathy, which is when urate crystals deposit in the interstitium of the kidney.

Alright, as a quick recap, gout is a type of inflammatory disease that typically affects the first metatarsal joint, which is the base of the big toe, where uric acid precipitates to form monosodium urate crystals, which deposit in the joint and lead to inflammation and pain.

Thank you