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Gout

Gout. Dr. Wael H.Mansy , MD Assistant Professor College of Pharmacy King Saud University. Gout. Gout is defined as a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints. Uric Acid.

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Gout

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  1. Gout Dr. WaelH.Mansy, MD Assistant Professor College of Pharmacy King Saud University

  2. Gout • Gout is defined as a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints.

  3. Uric Acid • URIC ACID: Isthe final breakdownproduct of purinedegradation in humans • URATE: Theionizedforms of uricacid, predominante in plasma, extracellular fluid and synovial fluid. • Approximately 98% existing as monosodiumurate at pH 7.4

  4. Uric Acid • Plasma issaturatedwithmonosodiumurate at a concentration of 6.8 mg/dl. • At higerconcentrations, plasma istherforesupersaturated, creatingthepotentialforuratecrystalprecipitation. • Urateproductionvarieswiththepurinecontent of thediet and therates of purinebiosyntesis, degradation and salvage. • 2/3 to¾ of urateisexcretedbykidneys, and most of theremaineriseliminatedthroughtheintestines.

  5. Uric Acid • Uricacidis more soluble in urinethan in water. • The pH of urinegreatlyinfluencesitssolubility. • pH 5 urineissaturatedwithuricacid at concentrationsrangingfrom 6 to 15 mg/dl. • At pH 7 saturationisreached at concentrationbetween 158 and 200mg/dl.

  6. Uric Acid • Serumuratelevelsvarywithage and sex. • Children: 3 to 4 mg/dl • Adultmen: 6 to 6.8 mg/dl

  7. Epidemiology • Prevalence of hyperuricemia • 2.3 – 41.4% in various populations. • Corresponds with serum creatinine /BUN levels, body weight, height, age, blood pressure, and alcohol intake. (Taiwan) • Body bulk (as estimated by body weight, surface area, or body mass index) has proved to be one of the most important predictors of hyperuricemia in people of widely differing races and cultures. • Incidence of Gout • Varies depending on population studied – 1.8 /1000 – 3.2/1000 • RR for blacks slightly higher (1.3)

  8. Hyperuricemia • Defined as a plasma urate concentration > 7.0 mg/dl

  9. Hyperuricemia • Can result from: • Increased production of uric acid • Decreased excretion of uric acid • Combination of the two processes.

  10. Increased Urate Production • Dietprovidesanexogenoussource of purines and, accordingly, contributestotheserumurate in proportiontoitspurinecontent. • Foodshigh in nucleicacid: liver, red meat and anchovy. • Restrictionintake: reduces: 1 mg/dl

  11. Endogenoussources: • De novopurinebiosynthesis.Increasedphosphoribosylpyrophosphatase (PRPP) synthetaseactivity and Hypoxanthinephosphoribosyltransferase (HPRT) deficiency are associatedwithoverproduction of purine, hyperuricemia and hyperuricaciduria.

  12. Decreased Uric Acid Excretion • Alterateduricacidexcretioncouldresultfrom: • Decreased glomerular filtration. • Decreased tubular secretion. • Enhanced tubular reabsorption.

  13. Decreased tubular secretion of urate causes the secondary hyperuricemia of acidosis. • Diabetic ketoacidosis, starvation, ethanol intoxication, lactic acidosis, and salicylate intoxication are accompanied by accumulations of organic acids (B-hydroxybutyrate, acetoacetate, lactate or salicylates) that compete with urate for tubular secretion.

  14. Combined Mechanisms • Alcohol intake promotes hyperuricemia: • Fast hepatic breakdown of ATP and increases urate production. • Can induce hyperlacticacidemia, and inhibition of uric acid secretion. • The higher purine content in some alcoholic beverages such as beer may also be a factor.

  15. Evaluation of Hyperuricemia • Hyperuricemiadoesnotrepresent a disease. • Isnotanspecificindicationfortherapy. • Thefinding of hyperuricemiaisanindicationto determine its cause.

  16. Thehyperuricemia of individualswho excrete highuricacidamountswhileon a purine-free dietisduetopurineoverproduction • Whereasitisduetodecreasedexcretion in thosewho excrete loweramountsonthepurine-free diet.

  17. Complications of Hyperuricemia • Themostrecognizedcomplication of hyperuricemiaisgoutyarthritis • Nephrolithiasis • UrateNephropathy • UricAcidNephropathy

  18. Gout = Crystal-inducedarthritis • MSU (monosodiumurate) • CPPD (calciumpyrophosphatedihydrate) • HA (calciumhydroxyapatite) • Calciumoxalate (CaOx)

  19. Monosodiumurate Gout

  20. Monosodiumurate Gout • Affecting middle-aged to elderly men. • Women represent only 5 to 17% of all patients.

  21. Monosodiumurate Gout • Associatedwithanincreaseduricacid, hyperuricemia, episodicacute and chronicarthritis, and deposition of MSU crystals in connectivetissuetophi and kidneys.

  22. Acute and chronicarthritis • Acutearthritisisthemostfrequentearlyclinicalmanifestation of MSU gout. • Usuallyonlyonejointisaffectedinitially • Polyarticularacutegoutisalsoseen in malehypertensivepatientswithethanol abuse as well as in postmenopausalwomen.

  23. Acute and chronicarthritis • The metatarso phalangealjoint of thefirst toe isofteninvolved. • Ankles, and knees are alsocommonlyaffected. • In elderlypatients, fingerjointsmaybeinflamed.

  24. Acute and chronicarthritis

  25. Acute and chronicarthritis • Thefirstepisode of acutegoutyarthritisfrequentlybegins at night. • Withdramaticjointpain and swelling. • Earlyattackstendtosubsidespontaneouslywithin 3 to 10 days. • Most of thepatients do nothave residual symptomsuntilnextepisode.

  26. Signs and Symptoms • Chronic: • Destructive tophacous gout. • Much greater chance if untreated • Rarely presents as a chronic

  27. Nephrolithiasis • The prevalence of nephrolithiasis correlates with the serum and urinary uric acid levels. • Serum urate levels 13 mg/dl • Urinary uric acid excretion > 1100 mg/d

  28. Diagnosis • Based on history and physical • Confirmed by arthrocentesis • Urate crystals: needle-shaped negatively birefringent either free floating or within neutrophils & macrophages. • Uric acid level non specific. • 30% may show normal level • Urine collection: • <800 mg dl/d underexcertor (<600 purine-free diet)

  29. X-ray • Acute • Soft tissue swelling • Chronic • chronic tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones

  30. Prognosis • Generally good • More severe course when Sx present < 30 y/o • Up to 50% progress to chronic disease if untreated. • Surgical intervention may be required for tophi.

  31. Treatment • Acute: • NSAID’s anti-inflammatory doses • Colchicine 0.5 mg po q2 hours, may require 6 mg. • Stop with response or side effect (diarrhea) • Can be used for chronic disease, increased risk for BM suppression • Aspirate followed by administration of corticosteroids • Prednisone • ACTH 40-80 IM/IV

  32. Treatment • Chronic: • Diet will decrease uric acid 1 mg/dL at best • Weight loss • Modification of medications • Avoid low dose ASA, diuretics, etc.

  33. Treatment • Chronic • Uricosuric: for under-excretors • Probenicid: • Sulfinpyrazone: toxic side effects • Avoid with renal disease • Consider NSAIDs to avoid exacerbation of gout.

  34. Treatment • Chronic • Indications for Allopurinol • Tophaceousdeposites • Uric acid consistently >9 mg/dl. • Persistent Sx with moderate UA levels • Impaired renal function • Prophylaxis for tumor-lysis syndrome • Consider NSAID’s to avoid exacerbation

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