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KUSHAGRA,MSIV,MAMC,DELHIDR.GILLIANLIEBERMAN,M.D.AUGUST23,2010DefinitionEpidemiologyPathophysiology,EtiologyandRiskFactorsStagesandClinicalFeaturesAssociatedCo-MorbiditiesCommonSitesandDistributionPatientDiscussionClassicalFindingsDifferentialDiagnosisMenuofImagingStudiesManagementandPreventiveMeasuresKushagra,MAMCMSIVGillianLieberman,MDGOUTisaformofperipheralarthritisresultingfromthedepositionofmonosodiumuratecrystalssecondarytohyperuricemia.Themetatarsal-phalangealjointatthebaseofthebigtoeisthemostcommonaffected.(AlsoknownasPODAGRA).Kushagra,MAMCMSIVGillianLieberman,MDemedicine.medscape.comGoutisacommonsystemicmetabolicdisease,affectingmorethan1%ofthepopulation.Itisthemostcommoninflammatoryarthritis,afflicting1ormorejointsinmenolderthan40yearsofage.Typicallyoccursinmiddleagedorelderlymales(90%ofcasesareinmales).PrevalenceintheUnitedStates:1.6to13.6per1000.Kushagra,MAMCMSIVGillianLieberman,MDGoutcanbebroadlyclassifiedinto2types:PRIMARYSECONDARYGoutiscalledPrimarywhennoidentifiablediseasecausingthehyperuricemiacanbefound.PrimaryGoutoccursinMajorityofthecases.SecondaryGout,whichislesscommon,occursduetosomeunderlyingdisease.Kushagra,MAMCMSIVGillianLieberman,MDCausescanbebroadlyclassifiedinto:INCREASEDURICACIDPRODUCTION(5%-10%ofpatients)DECREASEDURICACIDEXCRETION(90%-100%ofpatients)Kushagra,MAMCMSIVGillianLieberman,MDINCREASEDURICACIDPRODUCTION(5%-10%ofpatients)GeneticenzymaticdefectsHypoxanthine-guaninephosphoribosyltransferasedeficiencyglucose-6-phosphatasedeficiency5-phosphoribosyl-1-pyrophosphatesynthetaseoveractivityKushagra,MAMCMSIVGillianLieberman,MDINCREASEDURICACIDPRODUCTION(5%-10%ofpatients)AcquiredcausesDietaryindiscretions:excessivepurinedietObesityIncreasedtissueturnover—tumors,lympho-proliferativedisordersVigorousmuscleexertioncausingincreasedturnoverofATPAlcohol-inducedturnoverofATPChemotherapyKushagra,MAMCMSIVGillianLieberman,MDDECREASEDURICACIDEXCRETION(90%-100%ofpatients)GeneticcausesDownsyndromePolycystickidneydiseasesAcquiredcausesDiminishedrenalfunctionInhibitionoftubularuratesecretion:competitiveanions(keto-acidosisandlacticacidosis)Kushagra,MAMCMSIVGillianLieberman,MDDECREASEDURICACIDEXCRETION(90%-100%ofpatients)AcquiredcausesEnhancedtubularuratereabsorption:DehydrationStarvationInsulinresistance(metabolicsyndrome)Medications:Low-doseaspirinThiazideanddiureticsEthambutolNiacinLeadnephropathyKushagra,MAMCMSIVGillianLieberman,MDHumansdonotexpresstheenzymeurateoxidase(uricase),becauseofamutationduringevolutionoftheuricasegene,whichconvertsuratetothemoresolubleandeasilyexcretedcompoundallantoin.LessSolubleMoreSolubleKushagra,MAMCMSIVGillianLieberman,MDAmongmammals,onlyhumansandotherprimatespeciesexcreteuricacidastheendproductofpurinemetabolism.UricacidisaweakorganicacidthatexistsmainlyastheurateionatpH5.75andastheun-ionizeduricacidformatmoreacidic(lower)pHlevels.Thus,theurateformpredominatesinallextracellularfluids,includingserum,inwhichphysiologicalpHis7.4.Inurine,whichisusuallyacidic,theun-ionizeduricacidformpredominates.Kushagra,MAMCMSIVGillianLieberman,MDWhenoverproductionorunderexcretionofuricacidoccurs,theserumurate(SU)concentrationmayexceedthesolubilityofurate(aconcentrationapproximately6.8mg/dl),andsupersaturationofurateintheserum(andotherextracellularspacesresults.Thisstate,calledhyperuricemia,impartsariskofcrystaldepositionofurateintissuesfromthesupersaturatedfluids.Kushagra,MAMCMSIVGillianLieberman,MD1.ASYMPTOMATICSTAGE2.ACUTEGOUTYARTHRITIS3.INTER-CRITICALGOUT4.CHRONICTOPHACEOUSGOUTKushagra,MAMCMSIVGillianLieberman,MDACUTEGOUTYARTHRITIS90%ofattacksinvolveasinglejointwithseverepain,rednessandswelling.Mostlyinvolvingthelowerextremity,usuallythefirstmetatarsal-phalangealjoint.(50%)Kushagra,MAMCMSIVGillianLieberman,MDbeliefnet.comqwickstep.comINTER-CRITICALGOUTTheseareasymptomaticintervalsbetweenacuteattacksmostcommonearlyindiseaseprogression.Thispatternisquiteuncommoninotherarthriticdisordersandaloneisverysuggestiveofgout.Kushagra,MAMCMSIVGillianLieberman,MDCHRONICTOPHACEOUSGOUTThetophusisthepathognomoniclesionofgoutandisessentiallyaforeignbodygranuloma.Seenintheexternalearandpressurepointsovertheelbows,hands,feet,knees,andforearms.Kushagra,MAMCMSIVGillianLieberman,MDcedar-sinai.eduhopkins-arthritis.orgPAINRapidonsetandprogression.Worstpainthatthepersonhaseverendured.Associatedwithwarmth,redness,andswellingoftheaffectedjoint.Systemicsymptomsandsignsoffatigue,feverandchillsmayaccompany.Thefirstepisodeofgoutyarthritisoftenbeginsatnight.Kushagra,MAMCMSIVGillianLieberman,MDGOUTYNEPHROPATHYTworenalsyndromesareassociatedwithhyperuricemia:acuteuratenephropathyanduricacidurolithiasis..UricacidstoneCalciumoxalatestonesKushagra,MAMCMSIVGillianLieberman,MDkidney-stone-treatment.blogspot.comlithostat.comPatientsalsohaveanincreasedincidenceofcalciumoxalatestonesbecauseuratecrystalsserveasnidusforcalciumstoneformation.Isosthenuria(inabilitytoconcentrateurine),pyelonephritisandproteinuriaareotherrenalmanifestations.Kushagr