2.
Define
Discuss the epidemiology
Identify the age groups and gender differences
Explain the pathology and pathogenesis
LEARNING OUTCOMES
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Derived from the latin word gutta, meaning "a drop" (of liquid).
Gout
A rheumatic disease resulting from deposition of uric acid crystals (monosodium
urate) in the joints or soft tissues,
caused by elevated level of serum uric acid (hyperuricemia).
Hyperuricemia
serum uric acid concentration > 7 mg per dL (420 μmol per L),
caused by an imbalance in the production and excretion of urate
DEFINE GOUT
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Gout has a worldwide distribution. The prevalence varies widely from country to country. Regional
differences may reflect environmental, dietary, and genetic influences.
EPIDEMIOLOGY
The predominant age range 30-60 years.
Men:
uric acid levels rise at puberty
peak age of onset 4th to 6th decade of life.
Women:
uric acid levels rise at menopause
peak age of onset 6th to 8th decade of life.
Male predominance
Estimated prevalence 5.9% in men and 2% in women.
Estrogenic hormones have a mild uricosuric effect gout unusual in premenopausal
women
Earlier onset of gout occurs in patients with renal insufficiency or a genetic abnormality of purine metabolism (eg, hypoxanthine-guanine
phosphoribosyltransferase deficiency or phosphoribosylpyrophosphate synthetase superactivity). Cyclosporine A can cause an accelerated
form of gout, even in premenopausal women, that can present after only a few years of hyperuricemia, particularly if the patient is also
receiving diuretics.
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The prevalence of gout is higher in developed countries and in Oceanic populations compared with
other areas of the world despite no data being available for a large part of the developing world.
Global epidemiology of gout: prevalence, incidence and risk factors
•Chang-Fu Kuo,
•Matthew J. Grainge,
•Weiya Zhang
•& Michael Doherty
Nature Reviews Rheumatology
11,
649–662
(2015)
doi:10.1038/nrrheum.2015.91
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AGE GROUP & GENDER DIFFERENCES
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8. Hyperuricemia
PATHOGENESIS
↑ PRODUCTION URIC ACID
Increased purine synthesis de novo due to:
- HGPRT reduction
- hosphoribosyl-pyrophosphate synthase
overactivity
- Glucose-6-phosphatase deficiency with
glycogen storage disease type 1
↓ EXCRETION URIC ACID
Chronic renal disease
Drug therapy
Hypertension
Lead toxicity
Primary hyperthyroidism
Hypothyroidism
Glucose-6-phosphatase deficiency
↑ TURNOVER OF PURINES
Myeloproliferative disorder
Lymphoproliferative disorder
Others; carcinoma
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9.
Image taken from : Robbins Basic Pathology, 9th ed.
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10. Raised serum urate Increase risk of gout
Genetics Mutations in genes for urate transporter URAT1 & fructose transporter GLUT9
Age 2% of 45-64y/o men
6% men >75y/o have gout
Gender Men:women ratio is 3:1 respectively
Osteoarthritis Gout attacks more likely in joints affected by OA
RA is protective
Diet & alcohol
Hypertension
RISK FACTOR
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Usually, uric acid levels are elevated for 10-20 years before the onset of gout.
The higher prevalence of gout in elderly persons may also reflect an increased prevalence of metabolic syndrome, high rates of diuretic treatment for hypertension and chronic heart failure, and the use of low-dose aspirin.