The term Gout is a clinical Spectrum of diseases including elevated serum urate (hyperuricemia), recurrent attacks of acute arthritis associated with monosodium urate crystals in synovial fluid leukocytes, deposits of monosodium urate crystals, in tissues in and around joints, interstitial renal disease, and uric acid nephrolithiasis

1. GOUT AND HYPERURICEMIA
PATHOGENESIS AND THERAPY
Dr. S P Srinvas Nayak,
Assistant Professor, SUCP
Hyderabad

2. GOUT
• The core metabolic disorder of gout is
hyperuricemia
• hyperuricemia is defined as serum urate
concentrations greater than 7.0 mg/dL for
men and 6.0 mg/dL for women.
• This excess accumulation may result from
either overproduction or underexcretion of
uric acid
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3. GOUT DEFINITION
• The term Gout is a clinical Spectrum of
diseases including elevated serum urate
(hyperuricemia), recurrent attacks of acute
arthritis associated with monosodium urate
crystals in synovial fluid leukocytes, deposits
of monosodium urate crystals, in tissues in
and around joints, interstitial renal disease,
and uric acid nephrolithiasis
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4. EPIDEMIOLOGY
• Gout has been referred to as both the “king of
diseases” and the “disease of kings ”
• Hippocrates described it as ‘arthritis of the rich’
• Gout affects men about seven to nine times more
often than women.
• Gout in men younger than 30 years of age, or in
premenopausal women may indicate an
inherited enzyme defect or the presence of renal
disease
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5. AETIOLOGY AND PATHOPHYSIOLOGY
OVER PRODUCTION OF URIC ACID
• The purines from which uric acid is produced
originate from three sources:
1. dietary purine,
2. conversion of tissue nucleic acid to purine
nucleotides, and
3. de novo synthesis of purine bases
The average human produces about 600 to 800 mg
of uric acid each day
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6. ENZYME ABNORMALITIES IN GOUT
• Over activity of phosphoribosyl pyrophosphate
(PRPP) synthetase,
• Deficiency of hypoxanthine-guanine
phosphoribosyltransferase (HGPRT)
• Complete absence of HGPRT results in the
childhood Lesch-Nyhan syndrome, characterized
by choreoathetosis, spasticity, mental
retardation, and markedly excessive production
of uric acid. A partial deficiency of the enzyme
may be responsible for marked hyperuricemia in
otherwise normal, healthy individuals.
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8. REDUCED EXCRETION OF URIC ACID
• Uric acid is eliminated in two ways.
• About two-thirds of the uric acid produced each
day is excreted in the urine. The rest one-third is
eliminated through the gastrointestinal tract after
enzymatic degradation by colonic bacteria
• DEHYDRATION promotes reabsorbtion as sodium.
• Kidney impairement, some drugs reduces
excretion
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9. RISK FACTORS FOR GOUT
• Genetics
• Renal disease
• Co-morbidities, for example, obesity,
dyslipidaemia, glucose intolerance, hypertension
• Diet
• Medication: Diuretics, Nicotinic acid, Salicylates
(<2 g/day) Ethanol, Pyrazinamide, Levodopa,
Ethambutol, Cytotoxic drugs, Cyclosporine.
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Chronic tophaceous
gout.

13. TREATMENT
NONPHARMACOLOGIC THERAPY
• Pharmacological measures should be
combined with non-pharmacological
measures such as weight loss, changes in diet,
increased exercise and reduced alcohol
consumption..
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14. PHARMACOTHERAPY
• ACUTE TREATMENT
• Drugs used in the management of an acute
attack include NSAIDs, colchicine and
corticosteroids.
• Anakinra, an IL-1 receptor antagonist, has
complete resolution by day 3 in the
majority of patients after a course of three
100-mg subcutaneous injections
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15. Chronic prophylactic therapy
• Uricostatic agents: allopurinol, febuxostat
• Uricosuric agents: benzbromarone,
probenecid, sulphinpyrazone
• Uricolytic agents: rasburicase, polyethylene
glycol-uricase
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17. Glucocorticoids
• Glucocorticoids can be given via the oral,
intramuscular or intraarticular routes. They act by
inhibiting cytokine release and give rapid relief of
symptoms and decrease inflammation.
• Prednisolone is the most commonly used oral
steroid.
• Intra-articular injections, such as triamcinolone or
methylprednisolone, are administered into
inflamed joints for local anti-inflammatory action,
pain relief and to reduce deformity.
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19. Case discussion
• Mr TH is a 50-year-old, slightly over-weight (95kg) male who
presents with an extremely painful big toe. He states that the pain
started suddenly in the early hours of the morning and that he
cannot even bear to put a sock over his foot. no recent trauma to
his foot. He has no other symptoms and there is no previous
significant medical history apart from high blood pressure for
which he takes bendroflumethiazide (2.5mg in the morning). On
examination, the toe is red, hot, swollen and extremely painful on
palpation. The patient also has an elevated blood pressure of
150mm/95mmHg. On questioning about his weekly alcohol
intake, he states that he usually does not exceed 21 units/week,
but that it was a friend's 50th birthday party recently and he
might have had considerably more to drink than usual. Blood
results show a slightly raised C-reactive protein, other parameters
are normal including renal function; however, his serum urate is
slightly raised (390μmol/L). A diagnosis of acute gout is made.
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20. QUESTIONS
• 1. What initial therapy would you
recommend to treat the patient's acute
attack of gout?
• 2. What risk factors could have contributed to
the acute attack?
• 3. What lifestyle and dietary advice would you
give to the patient to assist in preventing
further attacks?
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21. ANSWER 1
• Initial therapy should be directed at promptly
and safely resolving the pain. Drugs used in
the management of an acute attack include
NSAIDs, colchicine and corticosteroids
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22. ANSWER 2
• Hyperuricaemia (raised serum uric acid levels) is
one of the main risk factors for the development
of gout; however, not all patients with a raised
serum uric acid level will go on to develop gout.
Studies have shown obesity, weight gain and
hypertension all to be independent risk factors
for the development of gout. Mr TH is slightly
over-weight and has a history of hypertension.
Measurement of his serum lipid levels should be
considered as dyslipidaemia is commonly
associated with gout.
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23. ANSWER 3
• Patient councilling,
• Diet
• Alcohol restriction
• Reduce weight
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24. THANK YOU
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