Uric Acid

Komar University of
Science and technology

Clinical Biochemistry Experiment 3
(uric Acid)
By Dr. Yassin Ahmadi
Introduction
• Purines are a group of aromatic, heterocyclic,

nitrogenous bases. They consist of a five-membered
imidazole ring fused to a six-membered pyrimidine
ring forming a double- ring structure.
• All purines are derived from and are structurally

related to the parent compound of that name, and
include caffeine, xanthine, hypoxanthine, adenine,
guanine, and uric acid.
• Uric acid is the excretory end product of purine

metabolism in humans. It is removed from the blood
by filtration through the kidneys and excreted in urine.
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• The excretion and poor solubility of uric acid ensure that it is normally
present in only small concentrations in the plasma.
• However, some conditions can lead to decreased or increased

concentrations, which are called hypouricaemia and hyperuricaemia
respectively. Hyperuricaemia is the commoner of the two.
• Several disorders associated with purine metabolism are predominantly the

result of an abnormal catabolism.
• This either increases the amount of uric acid formed or decreases its
excretion
• The clinical outcome ranges from relatively mild, for example gout, to
severe symptoms such as mental retardation and even death
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Sources of pourins
The three sources of purines in humans are:

v Dietary intake
vDe novo synthesis from small molecules present in the body
v Salvage pathway
Dietary intake of purines:
• Dietary intake of purines accounts for about 30% of excreted uric acid. Red meat, game,
shellfish, and yeast containing foodstuffs, such as Marmite and beer have high purine content and
intake should be limited in patients with clinical gout.
De novo synthesis of purines
• The de novo synthesis of purine occurs mainly in the liver.
Salvage pathway for purine nucleotides
• The synthesis of purine nucleotides is expensive in terms of the metabolic energy required.
Strategies have evolved where free purine bases obtained in the diet or from the metabolic
turnover of nucleotides can be reused or salvaged. 4
Purine catabolism and excretion
• Nucleotides are eventually converted by a variety of enzyme catalysed

reactions into xanthine. In turn, xanthine is oxidized to uric acid.
• Uric acid is sparingly soluble but, despite this, the kidneys play the major
role in removing it from the blood.
• This is possible because it can ionize in the presence of sodium, giving the
salt, monosodium urate.
• Approximately 98% of the uric acid filtered by the glomeruli is
reabsorbed by the proximal tubules.
• About 60-70% of the uric acid is eliminated by the kidneys.
• A smaller proportion of uric acid is secreted in the intestine, and is further
metabolized by resident gut bacteria in a process termed intestinal
uricolysis to form carbon dioxide and ammonia:
• Uric acid + 4 H2O + → 4 NH4+ + 3 CO2 + glyoxylic acid
5
6
• The concentrations of uric acid in blood are normally determined in samples of serum.
• Concentrations are generally higher in males than females, with a usual reference range for
males of 0.1–0.42 and for females 0.1–0.36 mmol/L.
• Values below or above these limits are called hypouricaemia and hyperuricaemia respectively.
Hypouricemia:
• Hypouricemia is uric acid below its reference ranges.
• It is rare, being associated with relatively few clinical conditions.
• The primary metabolic cause is an autosomal recessive disorder in which there is a deficiency
of xanthine oxidase activity in the liver.
• This results in increased excretions of xanthine and hypoxanthine and the formation of
xanthine stones. This condition is called xanthinuria.
• Hypouricemia can be caused by treatment with the drug allopurinol that inhibits xanthine
oxidase, thus reducing the synthesis of uric acid.
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Hyperuricemia
• Hyperuricemia is defined as an increase in the concentration of uric acid in samples of serum from patients to values above
the reference ranges.
• Given, the concentration of uric acid in plasma reflects an equilibrium between the amount ingested and produced, and the
quantity excreted, then hyperuricemia may be due to an increase in its formation or a reduction in its excretion, or a
combination of both.
• The causes of hyperuricemia are divided into primary disorders due to inherited metabolic diseases involving purine
metabolism, or secondary ones caused by a co-existing clinical condition. Both, of course, lead to an accumulation of uric
acid in the body.
• More than 99% of causes of primary gout are idiopathic, that is there is no known cause, although contributory factors such
as hormones, family history, and dietary causes are implicated.
• The X-linked recessive disorder, Lesch-Nyhan syndrome is characterized by an increase in the de novo synthesis of purines
and is a major cause of primary hyperuricemias.
• The increase in the amount of purines synthesized occurs because of an impaired feedback mechanism that severely reduces
the activity of HGPRT (Hypoxanthine-guanine phosphoribosyltransferase) and so impairs the salvage pathways for reusing purine
nucleotides.
•
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Secondary causes of hyperuricemia
• An increase in the concentration

of uric acid in plasma may be
secondary to an increase in the
uric acid formed in the body.
• Thus, secondary hyperuricaemia

may result from several factors
such as a high dietary intake,
increased metabolism of ATP, or
an increase in the turnover of
nucleic acids.
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Secondary causes of hyperuricemia
• Other causes include a reduced excretion of uric acid by the kidneys.

• This may be due to renal disease or the stimulating effects of drugs, such as thiazide diuretics and low doses of
salicylate, on its reabsorption from the kidney tubules, or to prolonged metabolic acidosis.
• Irrespective of whether the hyperuricaemia is primary or secondary in origin, the build-up in the concentration of
uric acid in the blood leads to the deposition of crystals of monosodium urate in the joints and tendons, a condition
called gout.
Clinical features of gout
• Gout is an inflammatory disease caused by accumulation of monosodium urate crystals in the joints particularly
those of the big toe.
• It affects approximately 1% of the population; 7% of male patients are over 65 years in age.
• The likelihood of developing gout and the onset of pain correlates with the amount of uric acid in the blood.
• Gout can be divided into four main phases:
1) asymptomatic, 2)acute, 3) intercritical 4) chronic tophaceaous gout
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Gout phases:
• As the term suggests, a patient at the asymptomatic stage of gout does not experience pain or swelling of the joints although
samples of serum have concentrations of uric acid above reference ranges.
• However, acute gout is characterized by a sudden onset of pain with swelling of the affected joint. The peak incidence of
acute gout occurs between 30 to 50 years of age. In 60% of cases, it affects the first metatarsal joint of the big toe or
metacarpal of a finger.
• Until the menopause, the incidence of gout in women is far less than that seen in men but following menopause the
numbers become greater although never equal to that seen in men.
• Intercritical gout occurs when these initial symptoms resolve within one to two weeks. During this phase, the patient
appears asymptomatic.
• In chronic tophaceous gout, the frequency of acute attacks of gout increases over time with symptoms like polyarthritis.
Approximately 60% of patients have a second attack within one year and only 7% do not have recurrence within ten years.
• Tophi are chalky deposits of monosodium urate crystals that can be detected by radiological examination and are visible
around the joints of the hands or feet.
• The duration of time between a first gouty attack and the development of tophi is highly variable, varying from 3 to 40
years.
• There is a correlation between the rate of tophi formation and the duration and increasing concentrations of uric acid in the
plasma of the patient.
• Renal urate stones (urolithiosis) develop in patients who have prolonged increased levels of uric acid, They are produced in
the kidney when the urinary uric acid concentration is increased. The most common urate stone is composed of ammonium
urate.
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Diagnosis of gout
• A diagnosis of gout usually begins with a review of the family medical history and a physical examination. A
swollen joint and red shiny skin above the affected area can indicate gout.
• However, a thorough medical examination is required to exclude other conditions such as pseudogout,
psoriatic arthritis, rheumatoid arthritis, or infection.
• Most patients with gout have concentrations of uric acid in samples of their serum above their reference
ranges. Thus, this is a useful index to measure at the time the patient has symptoms.
• However, an increased uric acid concentration is not universal in all patients with gout and, indeed,
concentrations may fall in the acute phase.
• Thus, confirmation of an initial diagnosis of gout requires that synovial fluid be aspirated from the affected
joint and examined using a microscope for the presence of monosodium urate crystals.
• Urine analysis and radiology may also be used.
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Pseudogout
• Pseudogout is a common inflammatory arthritis that results from an accumulation of
calcium pyrophosphate crystals in synovial fluid surrounding the joint.
• It typically affects the knee joint and is often misdiagnosed as gout, whose clinical
symptoms it resembles.
• Pseudogout is not a disorder of purine metabolism and concentrations of uric acid in

serum samples are within reference ranges.
• There is evidence of calcification of the cartilage of the knee joint seen by radiological
examination
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Komar University of

Science and technology

• Purines are a group of aromatic, heterocyclic,

• All purines are derived from and are structurally

• Uric acid is the excretory end product of purine

• However, some conditions can lead to decreased or increased

• Several disorders associated with purine metabolism are predominantly the

The three sources of purines in humans are:

• Nucleotides are eventually converted by a variety of enzyme catalysed

• An increase in the concentration

• Thus, secondary hyperuricaemia

• Other causes include a reduced excretion of uric acid by the kidneys.

• Urine analysis and radiology may also be used.

• Pseudogout is not a disorder of purine metabolism and concentrations of uric acid in

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