Serum Uric Acid

Date: 22/02/2011


Lavoro svolto da Elena Asteggiano ed Elena Banino



-Reduced excretion by the kidneys or high intake of dietary purine.
-Hereditary reasons.
-Diet: fructose can cause increased levels of uric acid. Eating large amounts of sea salt can cause increased levels of uric acid.
- Iron (Fe) activates xanthine oxidase (XO) and copper (Cu) deactivates it, so as men accumulate Fe with age (ferritin levels rise above 45 ng/dl) and Cu levels decline as testosterone levels drop with age (testosterone increases Cu half life), eventually the high Fe/Cu results in more active XO and higher urate levels. Excess Fe can be eliminated through phlebotomy (blood donation) and low Cu can be corrected through daily intake of 2 mg Cu per day, reducing urate levels.

Iron regulates xanthine oxidase activity in the lung, 2002
Functional and structural alterations induced by copper in xanthine oxidase, 2009


Gout and Hyperuricemia
Markedly elevated levels of urate in the blood (3-7 mg/dl normal) can lead to a type of arthritis known as gout.

Hyperuricemia (elevated serum uric acid) is not always symptomatic, but, in certain individuals, something triggers the deposition of sodium urate crystals in joints and tissues. In addition to the extreme pain accompanying acute attacks, repeated attacks lead to destruction of tissues and severe arthritic-like malformations. The term gout should be restricted to hyperuricemia with the presence of these tophaceous deposits.

Urate in the blood could accumulate either through an overproduction and/or an underexcretion of uric acid by the kidneys. In gouts caused by an overproduction of uric acid, the defects are in the control mechanisms governing the production of the nucleotide precursors or from high intake of purine-rich foods.

Gout can occur where serum uric acid levels are as low as 6 mg/dL (~357┬Ámol/L), but an individual can have serum values as high as 9.6 mg/dL (~565┬Ámol/L) and not have gout.

Gout and Its Comorbidities,2010

Lesch-Nyhan syndrome
Lesch-Nyhan syndrome, an inherited disorder, associated with very high serum uric acid levels. Spasticity, involuntary movement and cognitive retardation as well as manifestations of gout are seen in cases of this syndrome.

Lesch-Nyhan syndrome

Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis, 2009

Cardiovascular disease
Excess serum accumulation of uric acid is associated with cardiovascular disease. This is supported by the causative role of Xanthine oxidoreductase in cardiac oxidative stress. There is substantial evidence supporting the involvement of oxidative stress in a variety of pathophysiological states such as atherogenesis , systemic hypertension , myocardial IR injury , atrial fibrillation, pulmonary hypertension ventricular hypertrophy, cardiomyopathy, and heart failure.

Xanthine Oxidoreductase in Respiratory and Cardiovascular Disorders. 2008

Metabolic syndrome and diabetes
The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, fructose-induced hyperuricemia has a pathogenic role in metabolic syndrome(hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) Moreover uric acid dose dependently inhibited endothelial function as manifested in some studies by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function.
High serum uric acid is associated with higher risk of type 2 diabetes, independent of obesity, dyslipidemia, and hypertension.

A Causal Role for Uric Acid in Fructose-Induced Metabolic Syndrome. Am J Renal Physiol, 2005.

Uric acid stone formation
Uric acid stones are felt to be secondary to obesity and insulin resistance seen in metabolic syndrome.
Increased dietary acid leads to increased endogenous acid production in the liver and muscles, which in turn leads to an increased acid load to the kidneys. The urine is therefore quite acidic, and uric acid becomes insoluble, crystallizes and stones form. In addition, naturally present promotor and inhibitor factors may be affected. This explains the high prevalence of uric stones and unusually acidic urine seen in patients with type 2 diabetes. Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed crystals" (heterogeneous nucleation).
These uric acid stones are radiolucent and so do not appear on an abdominal plain X-ray or CT scan. Their presence must be diagnosed by ultrasound for this reason. Very large stones may be detected on X-ray by their displacement of the surrounding kidney tissues.

Uric acid crystals form kidney stones

Nephrolithiasis: Treatment, causes, and prevention, 2009
The role of hyperuricemia and gout in kidney and cardiovascular disease,2008
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?,2003


Precipitation of uric acid crystals, and conversely their dissolution, is known to be dependent on the concentration of uric acid in solution, pH , sodium concentration, and temperature. Established treatments address these parameters.

Maintaining a lower blood concentration of uric acid similarly should reduce the formation of new crystals. If the person has chronic gout or known tophi, then large quantities of uric acid crystals may have accumulated in joints and other tissues, and aggressive and/or long duration use of medications may be needed.
Medications most often used to treat hyperuricemia are of two kinds: xanthine oxidase inhibitors and uricosurics. Xanthine oxidase inhibitors decrease the production of uric acid, by interfering with xanthine oxidase. Uricosurics increase the excretion of uric acid, by reducing the reabsorption of uric acid once the kidneys have filtered it out of the blood. Several other kinds of medications have potential for use in treating hyperuricemia. In people receiving hemodialysis, sevelamer can significantly reduce serum uric acid, apparently by adsorbing urate in the gut. In women, use of combined oral contraceptive pills is significantly associated with lower serum uric acid.
Non-medication treatments for hyperuricemia include a low purine diet and a variety of dietary supplements. These treatments are regarded by many physicians as having little or no efficacy. Treatment with lithium salts has been used as lithium improves uric acid solubility.

Serum pH is neither safely or easily altered. Therapies that alter pH principally alter the pH of urine, to discourage a possible complication of uricosuric therapy: formation of uric acid kidney stones due to increased uric acid in the urine. Dietary supplements that can be used to make the urine more alkaline include sodium bicarbonate, potassium citrate, magnesium citrate. Medications that have a similar effect include acetazolamide.

Low temperature is a commonly reported trigger of acute gout. This is believed to be due to temperature-dependent precipitation of uric acid crystals in tissues at below normal temperature. Thus, one aim of prevention is to keep the hands and feet warm, and soaking in hot water may be therapeutic.

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