Saturday, December 16

Gout: An Overview of The Pathophysiology, Symptoms And Treatment

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Gout is an acutely painful rheumatic condition associated with serum uric acid (urate). It is caused by disorders of purine metabolism in the body resulting in elevated levels of uric acid. Urate crystals can deposit in the synovial fluid in joints, in the kidneys or other tissues in the body, where it can exert unwanted effects.

The prevalence of gout increases with age, especially in men. Men are affected approximately 10 times more often than women; however, this difference is less pronounced when compared with women after menopause. The familial nature of gout suggests an interaction between genetic and environmental factors.

Uric acid is the end product of purine degradation. Uric acid has no physiological function and is purely a waste product to be eliminated from the body. Hyperuricaemia is a term that is used to describe an increased concentration of urate in the blood. Gout is usually caused by an overproduction or underexcretion of uric acid from the body. Hyperuricaemia is a known risk factor for gout; however, the exact relationship is unclear because there has been incidences where patients have acute gouty arthritis with normal serum urate levels, and patients with hyperuricaemia but no gout.

So how is uric acid overproduced? Uric acid is derived from three sources of purines, namely dietary intake, conversion of tissue nucleic acids to purine nucleotides, and de novo purine synthesis (ie. synthesis from precursor molecules). Uric acid accumulates if production exceeds excretion. This may result from abnormalities in the enzyme systems which produce uric acid, excess production from increased tissue breakdown (especially with people on chemotherapy), and from dietary sources.

On the other hand, how is uric acid underexcreted? Uric acid is eliminated via two mechanisms: two-thirds are excreted in the urine, and the remainder are excreted via the gastrointestinal tract. Hyperuricaemia occurs when excretion becomes slower than the production of uric acid. Studies have shown that the renal handling of uric acid is defective in more than 98% of patients with primary hyperuricaemia and gout.

Acute gout normally presents as a monoarthritic condition, which means that normally only one joint is affected. More than 75% of incidences occur in the lower extremities, and the podagra (big toe) accounts for more than 50% of acute attacks and is hence the most common location to be affected. Other locations that can be affected include the instep/forefoot, ankles, heels, knees, wrists, fingers and elbows. Crystal deposits of uric acid leads to inflammation with concomitant pain, erythema, warmth and swelling. Patients normally wake up with excruciating pain as the urate settles and forms the deposits while they are sleeping. A fever can also accompany an episode of acute gout. If left untreated, it takes around 3 to 14 days before an acute gout spontaneously recovers. The definitive diagnosis of gout is via joint aspiration for urate crystals.

Treatment of gout is necessary to terminate an acute attack, prevent recurrent attacks of gouty arthritis, and to prevent or reverse complications associated with chronic deposition of urate crystals in tissues. Dietary and lifestyle changes can sometimes help. Weight reduction, decreased alcohol ingestion (especially beer), decreased ingestion of food with high purine content, increased water consumption, and good control of cholesterol levels and hypertension are among ways that can be implemented. However, these are usually insufficient alone and symptomatic patients normally require medications.

To terminate acute attacks, non-steroidal anti-inflammatory drugs (NSAIDS), corticosteroids and colchicine are frequently used. For the prevention of gout, NSAIDs, colchicine and allopurinol are the cornerstone of therapy. Uricosuric agents such as probenecid and sulfinpyrazone can be used for prevention too although they are less commonly used as compared to allopurinol.

In conclusion, gout is a medical condition not to be taken lightly as it can cause quite debilitating pain and affect day to day activities. Thus, if you experience any excruciating pain, especially in the big toe, consult your doctor or physician as soon as possible to get the condition checked out.


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