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Uric acid

Uric acid is a product of the metabolic breakdown of purine nucleotides. The presence of an excess amount of this heterocyclic compound 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 of Uric Acid 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

Disposition of uric acid by 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 urate by the kidney and intestine. Too high or too low levels are not good (R).

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High Level of Uric Acid and Diseases Associated with it

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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. Urates are any salt 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).

Others

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

Hypertension (high blood pressure) 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).

Causes

  • 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).
  • Consumption of liver, game meat, anchovies, dried beans and peas and others (R).
  • 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 increase uric acid reabsorption and/or decrease uric acid secretion (R).
  • Alcohol – Alcohol-related diseases and alcohol dependence syndrome have a great impact on the development of  gout (R).
  • Obesity – 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 – inherited tendencies (R).
  • Others: psoriasis (R), Niacin, hypothyroidism (R), renal insufficiency, immune-suppressing drugs, tumor lysis syndrome (R).

Low Level of Uric Acid – Hypouricemia

Hypouricemia occurs when you have a low level of uric acid in your blood. It is not considered to be a medical condition, but a useful medical sign.

Causes 

  • Medication – there are two types of medication that can reduce the level of uric acid – one that provides higher excretion in the blood while the other which reduces its production.
  • Diet – if you are having low purine diet you are more likely to develop hypouricemia.
  • Genetics mutation of URAT1 and GLUT9 and genetics mutation of XOR (R).
  • Kidney reabsorption problem
  • Low dietary Zinc intakes
  • Molybdenum deficiency
  • High Cu level
  • High estrogen
  • Liver failure and others.
  • Lower blood values have been associated with several nervous system disorders such as multiple sclerosis (MS), Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) (R).
  • Low levels might lead to oxidative stress.

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

  • Zinc increases uric acid level if you are deficient.
  • Animal products increase levels in general.
  • Inosine is the most powerful way to increase the uric acid levels (R).

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