Uric acid

Uric acid is a product of the metabolic breakdown of purine nucleotides. The presence of an excess amount of uric acid in the body may lead to various diseases. Read this article to know about the medical conditions associated with either high or low levels of uric acid and methods to increase or decrease it!

Introduction

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Uric acid is an end-product of the purine degradation in humans. Purines are produced as an end product in the digestion of certain proteins in the diet, but some are synthesized in the body.

In normal conditions, it is eliminated via urine (R). Changes in normal blood levels may lead to a number of diseases.

Production in the Body

Uric acid is the last step in the breakdown pathway of purines. Purines convert to hypoxanthine, then to xanthine and xanthine converts to uric acid.

For the last two steps in conversion, we need the enzyme xanthine oxidase (uricase). Humans have less amount of the enzyme uricase (R). The ability to further metabolize uric acid is lost due to two mutations that silence the gene coding for the enzyme uricase (R).

Disposition of the Body

Uric acid is removed from kidney and gut routes. It is almost completely filtered by the glomerulus, 98 – 100% is then reabsorbed in the proximal tubule and 50% is secreted by the distal tubule (R).

About 70% is removed from the urine and 30% is removed from the gut route (R).

Normal Range of Uric Acid in the Body

Humans have a higher uric acid level because they lack a functional Uricase gene. Levels start to rise after puberty. Men have slightly higher levels than women until the female menopause (R).

Normal blood level for women: 2.6 – 5.7 mg/dl, and for men: 3.5 – 7 mg/dl.

These levels depend on the balance between purine production and the ingestion of dietary purines, and the elimination of urates by the kidney and intestine. Too high or too low levels are not good (R).

High Level of Uric Acid and Diseases Associated with it

High level of uric acid in the body is known as Hyperuricemia. High level of uric acid in the blood usually forms urates and acid urates in blood. Acid urates are any salt of uric acid such as sodium urate.

Urates are found in urine, blood and in tissue. Urate deposits can lead to oxidative stress (R), inflammation and endothelial dysfunction (R).

Most people with hyperuricemia are asymptomatic and don’t need any clinical treatment. However, hyperuricemia can lead to several diseases.

Gout 

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Gout is inflammatory arthritis associated with hyperuricemia. It is a different form of other form arthritis because it occurs when there are high levels of uric acid in the circulating blood.  That can cause urate crystals to settle in the tissues of the joints.

The symptoms appear suddenly, overnight. It comes with agonizing pain, swelling and redness of the joint. The attack may be precipitated by too much food, alcohol, by starting a diuretic or by dehydration.

Symptoms go away after 10-15 days and can keep recurring. Eventually, stone-like deposits known as tophi may build up in joints, ligaments, and tendons and therefore can lead to joint deformation (R).

Kidney stone formation

If your urine contains more calcium, oxalate and uric acid you are more likely to developed kidney stone formation (R).

Hypertension and Chronic Kidney Diseases

High level of uric acid in the blood is associated with hypertension (HTN) and chronic kidney disease (CKD).

HTN and CKD are associated with higher risk of cardiovascular events (RR) like Atherosclerosis, heart failure, stroke, type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease and others (R).

What Causes High Uric Acid Levels?

Kidney problems

Higher levels of uric acid can occur when your kidneys don’t eliminate it efficiently due to kidney dysfunction and/or influence by certain metabolites and medications (R).

Food Consumption

Studies have shown that each additional intake of meat portion per day increases the risk of gout by 21% (R).

In a crossover study design, the effect of ingesting some purine-rich foods like beef liver, haddock fillets and soybean was investigated. Results showed that the ingestion of all the test meals caused an increase in serum uric acid levels (R).

High dietary intake of fructose

High dietary intake of fructose in foods and drinks increase production of inosine and purines. Also, fructose competes with uric acid for the secretion in the kidney (R).

Diuretics

Diuretics are one of the most important causes of secondary hyperuricemia. Drugs increase blood uric acid levels by an increase of uric acid reabsorption and/or decrease uric acid secretion (R).

Alcohol

According to a population-based cohort study, Alcohol-related diseases were significantly associated with a gout risk. Also, severe alcohol-dependent patients were associated with an increased risk of gout (R).

Obesity

According to a population-based epidemiological study, Obesity resulted in an increased risk of developing hyperuricemia. If you are overweight your body produces more uric acid. As a result, the kidney has a more difficult time eliminating uric acid (R).

Genetics

According to one study, the gene UCP2 influenced the serum urate concentration and the risk of hyperuricemia and the degree of association varies with gender and BMI levels (R).

Psoriasis

Serum uric acid levels were significantly increased in patients with psoriasis compared with controls (R). But these levels did not modulate the inflammation seen in these patients.

Others

Niacin, hypothyroidism (R), renal insufficiency, immune-suppressing drugs, tumor lysis syndrome (R).

Low Levels of Uric Acid and Diseases Associated with it

Hypouricemia occurs when you have a low level of uric acid in your blood (2mg/dl or less) (R).

It is not considered to be a medical condition, but a useful medical sign.

What Causes Low Uric Acid Levels?

Medication/Treatments

Hypouricemia can be found in 1% of hospitalized patients. In most cases, the cause is related to drugs like salicylates, allopurinol, x-ray contrast agents and glyceryl guaiacholate (R).

Also, drugs like losartan  (an angiotensin II receptor antagonist drug), fenofibrate (drug of the fibrate class, mainly used to reduce cholesterol levels) and some non-steroidal anti-inflammatory drugs (NSAIDs) reduce the serum uric acid (SUA) levels (R).

Forced diuresis used mainly in the treatment of suicide-attempt patients renal colic may result in hypouricemia (R).

Genetics

The human urate transporter 1 (URAT 1) and human glucose transporter-like protein 9 (GLUT 9) are two kidney urate transporters.

A genetic mutation in these two transporters is responsible for idiopathic hypouricemia (R).

Nervous system Disorders

Lower blood values have been associated with several nervous system disorders such as multiple sclerosis (MS)(R), Alzheimer’s disease (AD) (R), Huntington’s disease (HD), Parkinson’s disease (PD) (R).

Malignant Diseases

Several malignant diseases including Hodgkin’s disease, sarcoma, glioblastoma and a variety of carcinomas have been associated with hypouricemia (R).

Diet

By following a low purine diet, uric acid levels are lowered by only 15% at the most (R).

Mineral intake/deficiency

In a case study of molybdenum deficiency serum hypouricemia was present (R).

Low dietary Zinc intake causes lower uric acid levels. This effect is more common in women taking oral contraceptives (R).

Patients with high copper/Fe levels experience hypouricemia (R).

Hormones

Estrogen suppresses proximal tubule epithelial cell OAT (organic anion transporter) expression which explains the lower serum urate levels in postmenopausal women as opposed to men (R).

Investigations

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Blood test

Most common test that is used to monitor people with gout, check kidney function, disorder or stones if you are under chemotherapy or radiation treatment.

Urine test

24hours urine is collected.

Treatment

Treatment With Agents that Reduce Uric Acid Level

Non-steroidal anti-inflammatory drugs

Uricosuric drugs (R) – These drugs increase the secretion of uric acid in urine – probenecid or sulfinpyrazone

Xanthine oxidase inhibitors – allopurinol because it prevents gout but it also can be given to you when you have a certain form of leukemia or lymphoma, to prevent a complication of chemotherapy or tumor lysis syndrome.

Also due to its adverse effect allopurinol is currently not indicated in asymptomatic hyperuricemia and its related cardiovascular disease or in the diseases other than gout (R).

Febuxostat – a selective xanthine oxidase/xanthine dehydrogenase inhibitor (R).

Weight loss – research suggests that losing weight may help reducing high levels.

Purine – restricted diet – you should avoid alcohol, red meat, seafood, sugary beverages. Avoid/ limit refined carbs. The foods lowest in purine content include eggs, fruit, cheese, nuts and vegetables other than legumes. (R).

Water – keep yourself hydrated.

Treatment with Agents that Increase Uric Acid Levels

Inosine is the most powerful way to increase the uric acid levels (R).

Zinc increases uric acid level if you are deficient.

Animal products increase levels in general.

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