GOUT
PRESENTED BY
SINDHU VARMA-131
SHAILAJA-125
INTRODUCTION
• Gout is a systemic disease caused by excess uric acid as the result of deficient
purine metabolism. Clinically, gout is marked by peripheral arthritis and painful
inflammation in joints resulting from deposition of uric acid in joint synovia as
monosodium urate crystals. Although gout is the most common crystal-induced
arthritis, a condition known as pseudogout can commonly be mistaken for gout
in the clinic. Pseudogout results from deposition of calcium pyrophosphatase
(CPP) crystals in synovial spaces, but causes nearly identical clinical
presentation.
CAUSE OF GOUT
• The normal serum level of gout is 3-7mg/dl.
uric acid When
is 3-7mg/dL. this
When level
this levelexceeds
exceedsover 7
mg/dl, it precipitates and gets deposited in the joints and this causes
inflammation.
• Alcohol and non-vegetarian food precipitates gout.
• As the consumption of alcohol leads to the accumulation of ethanol. The
conversion of ethanol to acetaldehyde and then to acetic acid releases NADH.
• This NADH is used in the formation of uric acid by converting monosodium
urate to uric acid.
DEGREDATION OF PURINE
NUCLEOTIDES TO URIC ACID
PRIMARY GOUT
• It is an inborn error of metabolism due to overproduction of uric acid. This is
mostly related to increased synthesis of Purine Nucleotides.
• METABOLIC DEFECTS ASSOCIATED WITH PRIMARY GOUT
• PRPP
PRP SYNTHETASE
SYNTHETASE
• PRPP GLUTAMIDOTRANSFERASE
GLUTAMYLAMIDOTRANSFERASE
• HGPRT DEFICIENCY( ALSO CAUSES LESCH-NYHAN SYNDROME)
• GLUCOSE
GLUCOSE-6-PHOSPHATE DEFICIENCY
6-PHOSPHATASE DEFICIENCY
• ELEVATION OF GLUTATHIONE REDUCTASE
• Among the five enzymes mentioned above , the first three enzymes are directly
linked to purine synthesis. The remaining two indirectly regulate purine
production.
SECONDARY GOUT
• Secondary hyperuricemia is due to various diseases causing increased synthesis
or decreased excretion of uric acid. Increased degradation of nucleic acids
(hence more uric acid formation) is observed in various cancers (leukemias,
polycythemia, lymphomas, etc.) psoriasis and increased tissue breakdown
(trauma, starvation etc.). The disorders associated with impairment in renal
function cause accumulation of uric acid which may lead to gout.
PSEUDOGOUT
• The clinical manifestations of pseudogout are similar to gout. But this disorder is
caused by the deposition of calcium pyrophosphate crystals in joints. Further,
serum uric acid concentration is normal in pseudogout.
SYMPTOMS OF GOUT
• The most common symptom of gout is pain in the affected joint. Many people
have their first flare of gout in one of their big toes, but it can also affect other
joints in your body. Gout flares often start suddenly at night, and the intense
pain may be bad enough to wake you up. In addition, your joint may feel
swollen, red, and warm.
• Hypertension (high blood pressure).
• Chronic kidney disease.
• Obesity.
• Diabetes.
• Nephrolithiasis (kidney stones).
• Myocardial Infarction (heart attack).
• Congestive heart failure.
TREATMENT OF GOUT
• The drug of choice of the treatment of gout is
allopurinol. This is a structural analog of
hypoxanthine that competitively inhibits the
enzyme xanthine oxidase.
• Further, allopurinol is oxidized to alloxanthine
by xanthine oxidase Alloxanthine, in turn, is a
more effective inhibitor of xanthine oxidase.
• Inhibition of xanthine oxidase by allopurinol
leads to the accumulation of hypoxanthine and
xanthine. These two compounds are more
soluble than uric acid, hence easily excreted.
