Cause of Gout

To understand the cause of gout it is essential to know how uric acid formation occurs in the body. All the DNA in our body is made of two types of molecules, these are

• Purines
1. Adenine
2. Guanine
• Pyrimidines
1. cytosine
2. guanine
3. uracil

Uric acid is the final end product of purine metabolism. The formation of uric acid depends upon two factors

• the quantity of purines ingested in the diet
• the formation of purines in the body

Uric Acid Metabolism

• Adenine is converted into adenine monophosphate under the effect of the enzyme adenine phospho-ribosyl-pyrophosphate synthetase.
• Adenine monophosphate is then converted to Adenosine under the effect of the enzyme nucleotidase.
• Adenosine is then converted to Inosine under the effect of the enzyme adenosine deaminase.
• Inosine is then converted to Hypoxanthine under the effect of the enzyme nucleoside phosphorylase.
• Hypoxanthine is then converted to Xanthine by the enzyme xanthine oxidase.
• Xanthine is converted into uric acid again under the effect of enzyme xanthine oxidase.

The level of uric acid in the body depends upon two factors

1. The rate of formation of uric acid.
2. The rate of excretion of uric acid by the kidneys

A increase in formation or a decrease in the excretion of uric acid will result in the accumulation of uric acid in the blood. When the blood levels of uric acid cross the normal values then that condition is called Hyperuricemia. This is the precursor stage of gout.

The normal value of uric acid in the blood of adults is about 360 to 415 micro mole/litre or 6 to 6.8 milligram/decilitre. At this level the blood is saturated with uric acid. When the uric acid concentration crosses this level then blood becomes supersaturated solution. Now precipitation and uric acid crystal formation can occur at any time.

Crystal precipitation causes irritation of the synovial membrane of the joint and results in inflammation, pain and swelling.

Factors that cause a increase in formation of uric acid in the body include the following and these account for 10% cases of hyperuricemia as a cause of gout

• dietary consumption of liver, pancreas, kidney and anchovy
• diseases that cause a increase in turn over and destruction of cells in the body
1. blood cancers
2. hemolytic anaemia caused from snake bite, poisoning, malaria
3. destruction of muscle tissue (rhabdomyolysis) by extreme physical activity or a continuous epileptic fit or a heart attack
• deficiency of enzymes hypoxanthine-phosphoribosyl-transfrase
• increased activity of enzyme phospho-ribosyl-pyrophosphate synthetase
• psoriasis
• pagets disease
• alcoholism
• obesity

Factors that cause a decrease in excretion of uric acid by the kidneys include the following and these account for 90% cases of hyperuricemia as a cause of gout.

• failure of the kidneys
• lead toxicity
• high blood pressure
• hypothyroidism
• eclampsia in pregnancy
• Down syndrome
• sarcoidosis
• berylliosis
• Drugs such as
1. aspirin
2. levodopa
3. cyclosporine
4. ethambutol
5. pyrizinamide
6. diuretics (increase urine formation)

Hyperuricemia is seen in 2 to 13% of the normal population. The prevalence of gout is between 1.3 tp 3.7%. This means that many people with hyperuricemia never develop gout. If it is detected in routine testing then the cause of hyperuricemia should be found out and factors such as high blood pressure, obesity, alcoholism should be controlled.

This page was created on 14th November 2008

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