Gout – causes, symptoms, diagnosis, treatment, pathology

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 purines, which, together with pyrimidines, are nature’s most common
nitrogen-containing heterocycles. A heterocycle being 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 of 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’s ultimately
caused by white blood cells, or leukocytes, which migrate to the site to help eliminate
uric acid and release proinflammatory chemicals, including cytokines. Treatment of a gouty attack is typically focused
on decreasing the pain and swelling, most often with nonsteroidal 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
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 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. Okay, 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 lead to inflammation and pain. Thanks for watching, you can help support
us by donating on patreon, or subscribing to our channel, or telling your friends about
us on social media.