Uric acid

Uric acid is produced by xanthine oxidase from xanthine

and hypoxanthine, which in turn are produced from purine.
Mainly in liver, kidney, intestine.
Uric acid
In human blood plasma, the reference range of uric
acid is

Male: 237.9～356.9μmol/L(4～6mg/dL),
Female: 178. 4～297.4μmol(3～5mg/dL).

This range is considered normal by the American

Medical Association.

Uric acid concentrations in blood plasma above

( >6mg/dL) and below (<3mg/dL) the normal range are
known, respectively, as hyperuricemia and hypouricemia.
The reasons of hyperuricemia

● Produce too much uric acid

(about 10% of cases)

● unable to excrect enough uric acid into

the urine (about 90% of cases)
Produce too much uric acid
About 10% of cases of gout are due to overproduction of
uric acid. When uric acid is overproduced, it is high not only in
the blood but in the urine.
● Some people overproduce uric acid due to a genetic defect in
an enzyme in the purine breakdown pathway which leads to
overactivity of this pathway.
● Since cells contain DNA, and DNA contains purines, anything
that increases the breakdown of cells in the body can lead to
more uric acid .
For example, if a patient is receiving chemotherapy for a tumor, as
the treatment kills the tumor cells, hyperuricemia can develop as a result
of the breakdown of the purines from those cells.
● Foods can also lead to overproduction of uric acid, such as
meats and beans and beer, which contain high levels of purines.
unable to excrect enough uric acid
into the urine
● The most common is a genetic defect in substances
referred to as organic anion transporters in the kidney,
which leads to an excessive reabsorption of uric acid from
the kidney—and thus too much uric acid in the blood.
● However, a defect in excretion of uric acid can also
occur due to medications, such as diuretics, low dose
aspirin, or alcohol.
● Defective uric acid excretion also occurs when the
kidneys are functioning poorly.
 Clinical Significance
 Disease states with increased plasma uric acid
 Gout
 Increased catabolism of nucleic acids
 And renal disease
 In Gout increased serum levels of uric acid lead to
formation of monosodium urate crystals around
the joints.
 Uric acid test is useful to assess for gout and to
monitor patients with renal failure
 Clinical Significance
• To monitor if uric acid levels are too high after
chemotherapy or radiation.

• Hypouricemia is seldom observed and associated

with rare hereditary metabolic disorders.(e.g.
Wilson’s disease , Fanconi’s Syndrome)
 Specimen
• Serum or plasma may be used
• Stability in serum / plasma:
– 6 months at -20°C
– 7 days at 4-8°C
– 3 days at 20-25°C
ANALYTIC METHODS—
URIC ACID
• Chemical Method (old) :
– Phosphotungstic Acid, read the absorbance(Ab) at
700nm (UV). blue Colored product
• Enzymatic Method: is More specific
– By using Couple reaction of uricase and Peroxidase. Pink
solution (Ab at 500nm spectrophotometric) Pink color
solution.
 Gout
Excess serum accumulation of uric acid can lead to a
type of arthritis known as gout. This painful condition is
the result of needle-like crystals of uric acid precipitating
in joints and capillaries.
Gout can occur where serum uric acid levels are as low
as 6 mg/dL (~357µmol/L).

Man get gout more than women, and at younger ages,

the male to female ratio is 9:1. The most common age
of onset is from age 40- 60 years.
 Uric Acid Crystals Under
Polarizing Light Microscopy

urate crystal
gouty arthritis
Toe with Acute Attack of Gout
 uric kidney stones

Saturation levels of uric acid in blood may result in one form of

kidney stones when the urate crystallizes in the kidney.
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. Some
patients with gout eventually get uric kidney stones
 GOUT: THE PROTOTYPICAL CRYSTAL
DEPOSITION ARTHROPATHY
Monosodium
Urate
Crystal
Diet and Alcohol-Related Trends Influencing
Incident Gout
in the “Health Professionals Follow-Up
Study”
Relative risk of incident gout :
•Meat 1.41
•Seafood 1.51
Highest intake quintiles
•Dairy 0.56
•Any Alcohol 2.53
•Five 12 oz Beers/Wk To One Beer Daily 1.75
•Two or More Beers Daily 2.51
•Per Shot of Spirits daily 1.15
•Per Glass of Wine Daily 1.04

n = 47,150 men without gout aged 40-75,

12 year follow-up with 730 cases of new gout
Choi H et al, NE JM and Lancet 2004
EMERGING EPIDEMIOLOGY IN GOUT:
MORE FEMALES, ++ RISE IN 70-80 AGE GROUP
 GOUT IN OLDER WOMEN
• INCREASING PREVALENCE ALONG WITH INCREASED
LONGEVITY

• LINKED TO COMMON USE OF DIURETICS (>25% after age

65)

• WILL DECREASED USE OF ESTROGENS RAISE URIC

ACID&GOUT PREVALENCE ?

• MAY BE CLINICALLY SUBTLE AND MASQUERADE AS

INFLAMMATORY HAND OSTEOARTHRITIS
• The prevalence of asymptomatic
hyperuricemia is 5 to 8%.
• The prevalence of gout is 13 cases
per 1000 men and 6.4 cases per 1000
women.
• The higher the uric acid, the higher
the risk to develop gout.
• 90% of patients with primary gout
are men.
• Women rarely develop gout before
the menopause, because estrogens
are thought to be uricosuric.
• Peak incidence in men is in the fifth
decade.
• Primary gout is associated with:
obesity, hyperlipidemia, diabetes
mellitus, hypertension and
atherosclerosis.
 Diagnostic Tests
• 24 urine collection for uric acid
determination is useful in assessing
the risk of renal stones and planning
for therapy.
• Radiological examination is helpful to
exclude other kinds of arthritis. Long
term gout shows erosive arthritis
with the characteristic “punched-
out” erosions.
• TERIMA KASIHHH