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Gout

 Define
 Discuss the epidemiology
 Identify the age groups and gender differences
 Explain the pathology and pathogenesis
LEARNING OUTCOMES
Izatty Lim (0308188) 2

 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
Izatty Lim (0308188)
3

 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.
Izatty Lim (0308188)
4

 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
Izatty Lim (0308188)
5

AGE GROUP & GENDER DIFFERENCES
Izatty Lim (0308188) 6

 Idiopathic
 Major determinant  Hyperuricemia
 Hyperuricemia
 ↑ production uric acid
 ↓ excretion uric acid
PATHOGENESIS
Izatty Lim (0308188) 7
 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
Izatty Lim (0308188) 9

Image taken from : Robbins Basic Pathology, 9th ed.
Izatty Lim (0308188)
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
Izatty Lim (0308188) 12

Thank You!
Izatty Lim (0308188)
13

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Gout

  • 2.   Define  Discuss the epidemiology  Identify the age groups and gender differences  Explain the pathology and pathogenesis LEARNING OUTCOMES Izatty Lim (0308188) 2
  • 3.   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 Izatty Lim (0308188) 3
  • 4.   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. Izatty Lim (0308188) 4
  • 5.   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 Izatty Lim (0308188) 5
  • 6.  AGE GROUP & GENDER DIFFERENCES Izatty Lim (0308188) 6
  • 7.   Idiopathic  Major determinant  Hyperuricemia  Hyperuricemia  ↑ production uric acid  ↓ excretion uric acid PATHOGENESIS Izatty Lim (0308188) 7
  • 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 Izatty Lim (0308188) 9
  • 9.  Image taken from : Robbins Basic Pathology, 9th ed. Izatty Lim (0308188) 10
  • 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 Izatty Lim (0308188) 12

Editor's Notes

  1. 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.