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GOUTGOUT
Case Case
A 45y/o obese male with h/o painfull A 45y/o obese male with h/o painfull ankle associated with hottness and ankle associated with hottness and redness since 2 days agoredness since 2 days ago
PMH: HTN, DMPMH: HTN, DMP/E: Signs of severe ankle arthritisP/E: Signs of severe ankle arthritis
GoutGout(monosodium urate crystal (monosodium urate crystal
deposition disease)deposition disease) is characterized biochemically by is characterized biochemically by
extracellular urate supersaturation extracellular urate supersaturation
GoutGoutRecurrent attacks of acute Recurrent attacks of acute
inflammatory arthritis inflammatory arthritis Accumulation of urate crystals in the Accumulation of urate crystals in the
form of tophaceous deposits form of tophaceous deposits Uric acid nephrolithiasis Uric acid nephrolithiasis NephropathyNephropathy
EpidemiologyEpidemiology incidence = 0.2-0.35/1000 incidence = 0.2-0.35/1000 Prevalence = 1.6-13.6/1000Prevalence = 1.6-13.6/1000Prevalance increased with age and Prevalance increased with age and
uric acid leveluric acid levelThe incidence rate of gout is 4.9% for The incidence rate of gout is 4.9% for
urate greater than 9mg/dl and 0.5% urate greater than 9mg/dl and 0.5% for 7-8.9 and 0.1% for less than for 7-8.9 and 0.1% for less than 7mg/dl7mg/dl
Familial incidence range from 11-Familial incidence range from 11-80%80%
hyperuricemiahyperuricemia
Hyperurecemia: Overproduction or underexcretion of uric acid,the byproduct of purine metabolism in humans can result in hyperurecemia
The upper limit = at 7 mg/dl in men and 6 mg/dl in women
Decreased efficiency of renal uric Decreased efficiency of renal uric acid excretion is responsible for acid excretion is responsible for about 85 to 90 percent of primary or about 85 to 90 percent of primary or secondary hyperuricemia .secondary hyperuricemia .
Supersaturated concentration of urate (> or= 6/8mg/dl)
cause crystalization and deposition in joints and other connective tissues
DNADNARNARNA
PyrimidinesPurines
Uric acid Energy
APRT
PRPP.Syn
IMP.DXMP
GTP & ATP &
AMP.SAS.S
5’NAMP. D
5’N
GuanaseXantine oxidase
Xantine oxidase
5’N
PNP
Aden.PRT
PNP
HGPRT
Ribose-5 phosphate + ATP
PRPP + AMP
PRPP Synthetases
IMPUric Acid
Uric acid productionUric acid production
SalvageSalvageSometime free purine base are Sometime free purine base are
salvaged and reused instead of salvaged and reused instead of degrading them all the way to uric degrading them all the way to uric acid.acid.
Salvage of purine BasesSalvage of purine Bases
AdenineAdenineGuanine Guanine HypoxanthineHypoxanthine
PhosphoribosylationPrimary nuclotides
Hyperuricemia cascadeHyperuricemia cascade
Hyperuricemia
Urate
UnderexcretionOverproduction
Endogenous purinesynthesis
Dietary purines
Tissuenucleicacids
Uric acid overproductionUric acid overproduction
• Primary hyperurecimiaPrimary hyperurecimia
•Secondary hyperuricemia Secondary hyperuricemia
·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity
·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis ·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy
Uric acid overproductionUric acid overproduction
• Primary hyperurecimiaPrimary hyperurecimia
•Secondary hyperuricemia Secondary hyperuricemia
·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity
·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis ·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy
Uric acid overproductionUric acid overproduction
• Primary hyperurecimiaPrimary hyperurecimia
•Secondary hyperuricemia Secondary hyperuricemia
·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity
·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis
·Accelerated ATP degradationAccelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy
Uric acid overproductionUric acid overproduction
• Primary hyperurecimiaPrimary hyperurecimia
•Secondary hyperuricemia Secondary hyperuricemia
·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity
·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis
·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy
Uric acid overproductionUric acid overproduction
• Primary hyperurecimiaPrimary hyperurecimia
•Secondary hyperuricemia Secondary hyperuricemia
·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity
·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious secondary polycytemia,pernicious anemia,hemoglobinopathyanemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis ·Accelerated ATP degradation Accelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy
Uric acid overproductionUric acid overproduction
• Primary hyperurecimiaPrimary hyperurecimia
•Secondary hyperuricemia Secondary hyperuricemia
·IdiopathicIdiopathic·HGPRT deficiencyHGPRT deficiency·PRPP synthetase superactivityPRPP synthetase superactivity
·Excessive dietary purine intakeExcessive dietary purine intake·Increased nucleotide turnoverIncreased nucleotide turnover myelo & lymphoproliferative dis. ,multiple myelomamyelo & lymphoproliferative dis. ,multiple myeloma secondary polycytemia,pernicious anemia,hemoglobinopathysecondary polycytemia,pernicious anemia,hemoglobinopathy hemolysis,infectious mononucleosis hemolysis,infectious mononucleosis
·Accelerated ATP degradationAccelerated ATP degradation Glycogen storage dis( type3,5,7) ,G6PDGlycogen storage dis( type3,5,7) ,G6PD Fruoctose intolerance(F1P.aldolase)Fruoctose intolerance(F1P.aldolase) Hypoxemia & tissue underperfusionHypoxemia & tissue underperfusion Sever muscle exertion ,acutly ill patient,MI, epilepsySever muscle exertion ,acutly ill patient,MI, epilepsy
Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia
Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic
•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption•Mechanism incompletely definedMechanism incompletely defined
Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia
Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic
•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption•Mechanism incompletely definedMechanism incompletely defined
Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia
Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic
•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption•Mechanism incompletely definedMechanism incompletely defined
Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia
Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic
•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion Competitive anions ( keto & lactic acidosis ) Competitive anions ( keto & lactic acidosis ) Polycyctic kidney, Lead nephropathy?Polycyctic kidney, Lead nephropathy?
Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia
Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic
•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption Dehydration : diuretics,adrenal insufficency, Dehydration : diuretics,adrenal insufficency, nephrogenic DInephrogenic DI Insulin resistance SyndromeInsulin resistance Syndrome
Uric acid UnderexcretionUric acid Underexcretion Primary hyperurecimiaPrimary hyperurecimia
Secondary hyperuricemiaSecondary hyperuricemia•IdiopathicIdiopathic
•Diminished renal function ( GFR)Diminished renal function ( GFR)• Inhibition of tubular urate secretionInhibition of tubular urate secretion•Enhanced tubular urate reabsorptionEnhanced tubular urate reabsorption•Mechanism incompletely definedMechanism incompletely defined Hypertension,Hyperparathyroidism,hypoparathyroidismHypertension,Hyperparathyroidism,hypoparathyroidism
.hypothyroidism, Drugs (cyclosporine, pyrazinamide , .hypothyroidism, Drugs (cyclosporine, pyrazinamide , ethambutol , salicylate, nicotinic acid) , ethambutol , salicylate, nicotinic acid) , Chronic lead nephropathyChronic lead nephropathy
Classification of hyperuricemiaClassification of hyperuricemia3- Combined Overproduction & Underexcretion3- Combined Overproduction & Underexcretion
• Alcohol consumptionAlcohol consumption• Inborn errors of metabolismInborn errors of metabolism
Glucose - 6 - phosphatase deficiencyGlucose - 6 - phosphatase deficiencyFructose -1- phosphate aldolase deficienccyFructose -1- phosphate aldolase deficienccy
Conditions influencing the Conditions influencing the deposition deposition of urate crystalsof urate crystals
Decreased solubility of urate Decreased solubility of urate Low temperatureLow temperature Low PHLow PH
Disturbance to the joint or soft tissueDisturbance to the joint or soft tissue Trauma or tissue injury or altered connective Trauma or tissue injury or altered connective
tissue matrixtissue matrix
Reabsorbtion of water resulting in Reabsorbtion of water resulting in supersaturation supersaturation
Lack of joint activity during sleepLack of joint activity during sleep
OthersOthers Gammaglobulin, insoluble collagen, proteoglycansGammaglobulin, insoluble collagen, proteoglycans
Urate crystal phagocytosis leads to Urate crystal phagocytosis leads to an inflammatory cascade and acute an inflammatory cascade and acute gouty arthritisgouty arthritis
Pathogenesis of acute gouty Pathogenesis of acute gouty inflammationinflammationHyperurecimia
Urate crystals
Activation of mast cellsActivation of endothelium
Chemotactic factor
SynovitisNeutrophil influx
Amplification of synovitis by neutrophil activation
Synovial liningCell activation
Complementactivation
Extracellular urateExtracellular urate
Urate-cell contactUrate-cell contact
Entrance of uric acidEntrance of uric acid
Phagocytosis of uratePhagocytosis of urate
Late phagocytosisLate phagocytosis
Intracellular urateIntracellular urate
CLINICAL SYNDROMESCLINICAL SYNDROMES
1- Asymptomatic 1- Asymptomatic hyperurecemiahyperurecemia
2- Acute flare2- Acute flare
3- Intercritical segments3- Intercritical segments
4- Advanced gout4- Advanced gout
Silent hyperurecemiaSilent hyperurecemia
Silent deposition of urate crystalsSilent deposition of urate crystalsElevated serum urate with no clinical Elevated serum urate with no clinical
manifestation of goutmanifestation of gout
Acute flareAcute flare
Acute inflammation in the joint caused Acute inflammation in the joint caused by urate crystallization ,often at nightby urate crystallization ,often at night
erythema. Swelling ,warmth in a jointerythema. Swelling ,warmth in a jointFever , chills and malaise may occureFever , chills and malaise may occureUntreated initial attach subside over Untreated initial attach subside over
3-10 days3-10 days90% first attack monoarticular( 50% 90% first attack monoarticular( 50%
podagra)podagra)
Acute arthritisAcute arthritis
initial or early attacksinitial or early attacks
Lower extremity and distal joint Lower extremity and distal joint involvement usually predominatesinvolvement usually predominates
however, the shoulders, hips, however, the shoulders, hips, sternoclavicular joints, and even the sternoclavicular joints, and even the spine and sacroiliac joints may spine and sacroiliac joints may become inflamed and cause become inflamed and cause diagnostic confusion. diagnostic confusion.
Polyarticular gouty arthritisPolyarticular gouty arthritis
(less than 20 percent of instances), (less than 20 percent of instances), uncommon as an initial manifestation), uncommon as an initial manifestation),
may be more frequent in patients with may be more frequent in patients with secondary to a secondary to a myeloproliferativemyeloproliferative or or lymphoproliferativelymphoproliferative disorder, or in organ disorder, or in organ transplant recipients who are receiving transplant recipients who are receiving cyclosporine Acyclosporine A. “. “
. Polyarticular symptoms are particularly . Polyarticular symptoms are particularly common late in the course of common late in the course of untreated untreated goutgout, when multiple recurrences, short or , when multiple recurrences, short or absent symptom free intervals, and absent symptom free intervals, and tophaceous deposits are common. tophaceous deposits are common.
Acute arthritisAcute arthritis
Acute arthritisAcute arthritis
Precipitating factors in acute Precipitating factors in acute flareflare
Local traumaLocal traumaBinges of alcoholBinges of alcoholOvereating or fastingOvereating or fastingConcurrent acute medical or surgical Concurrent acute medical or surgical
illnessillnessMarked rise or fall in serum uric acidMarked rise or fall in serum uric acidSeasonal factorsSeasonal factors
Gouty handGouty hand
Gouty burcitisGouty burcitis
Diagnosing GoutDiagnosing Gout
Serum urate( may be normal)Serum urate( may be normal)History and physical examHistory and physical examSynovial fluid analysisSynovial fluid analysisDiff is very importantDiff is very important
Fluid analysisFluid analysis
microscope with crossed microscope with crossed polarizing filterspolarizing filters
Birefringence phenomenon Birefringence phenomenon
when light enters a non-equivalent when light enters a non-equivalent axis, it is refracted into two rays, axis, it is refracted into two rays, each polarized with the vibration each polarized with the vibration directions oriented at perpendicular directions oriented at perpendicular to one another and traveling at to one another and traveling at different velocities. different velocities.
Birefringent CrystalsBirefringent Crystals
Birefringent CrystalsBirefringent Crystals
Crystals bend light and become visible in Crystals bend light and become visible in joint fluid when viewed through a joint fluid when viewed through a microscope with crossed microscope with crossed polarizing filterspolarizing filters
When a compensator plate is used on the When a compensator plate is used on the microscope’,monosodium urate crystals microscope’,monosodium urate crystals parallel to the axis of the compensator parallel to the axis of the compensator appear yellow (appear yellow (negatively birefringentnegatively birefringent) and ) and calcium pyrophosphate dihydrate crystals calcium pyrophosphate dihydrate crystals parallel to the axis of the compensator parallel to the axis of the compensator appear blue (positively birefringent appear blue (positively birefringent
Birefringent CrystalsBirefringent Crystals
negative birefringent negative birefringent CrystalsCrystals
Positive birefringent Positive birefringent CrystalsCrystals
Criteria for clinical Criteria for clinical diagnosisdiagnosis
A classic history of one or more episodes of A classic history of one or more episodes of monoarticular arthritis followed by intercritical monoarticular arthritis followed by intercritical periods completely free of symptoms periods completely free of symptoms
Maximum inflammation within 24 hours Maximum inflammation within 24 hours Rapid resolution of synovitis after colchicine Rapid resolution of synovitis after colchicine
therapy therapy Unilateral first metatarsophalangeal joint attack Unilateral first metatarsophalangeal joint attack Hyperuricemia Hyperuricemia Subcortical bone cysts apparent on plain Subcortical bone cysts apparent on plain
radiograph radiograph Sterile joint fluid obtained from an affected joint Sterile joint fluid obtained from an affected joint
during an attack during an attack identify urate crystals, or in the presence of a identify urate crystals, or in the presence of a
negative polarized light microscopic studynegative polarized light microscopic study
DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS
PseudogoutPseudogoutSeptic arthritisSeptic arthritisHydroxyapatite calcific tendinitisHydroxyapatite calcific tendinitisSarcoid arthritisSarcoid arthritisErythema nodusumErythema nodusumRheumatoid arthritisRheumatoid arthritisFamilial mediterranian feverFamilial mediterranian fever
Etiology ofEtiology of spontaneous resolutionspontaneous resolution
TNF induced PMN apoptosisTNF induced PMN apoptosisMembranolysis due to crystal ingestionMembranolysis due to crystal ingestion Increased crystal coated by Increased crystal coated by
apolipoprotein apolipoprotein Production of IL1 antagonist Production of IL1 antagonist Increased tempreture and solubilityIncreased tempreture and solubilityACTH secretionACTH secretion Increased circulation and moved crystalIncreased circulation and moved crystal
ASSOSIATED CONDITIONASSOSIATED CONDITION
ObesityObesity Diabetes mellitusDiabetes mellitus HypertriglyceridemiaHypertriglyceridemia HypertentionHypertention Athrosclerosis Athrosclerosis HypothyroidismHypothyroidism Ethanol consumptionEthanol consumption PregnancyPregnancy Syndrome XSyndrome X
NEGATIVE NEGATIVE ASSOCIATION CONDITIONASSOCIATION CONDITION
Rheumatoid arthritisRheumatoid arthritisSystemic lupus erythmatosisSystemic lupus erythmatosisAnkylosing spondylitisAnkylosing spondylitisLong-term use of NSAIDLong-term use of NSAID
Intercritical SegmentsIntercritical SegmentsClinically silent gout without crystal Clinically silent gout without crystal
deposition and potential hidden deposition and potential hidden damagedamage
The intervals between acute flaresThe intervals between acute flaresThe patient hasn’t any symptom but The patient hasn’t any symptom but
Joint fluid revealed crystal in 12.5-Joint fluid revealed crystal in 12.5-58% with mild leukocytosis58% with mild leukocytosis
In 78% , second attack occur within In 78% , second attack occur within 6month to 2years6month to 2years
Synovial analysis during Synovial analysis during intercritical period intercritical period
extracellular urate crystals are extracellular urate crystals are identifiable in synovial fluid from identifiable in synovial fluid from previously affected joints in virtually previously affected joints in virtually all untreated gouty patients all untreated gouty patients
CHRONIC TOPHACEOUS GOUTCHRONIC TOPHACEOUS GOUT
collections of solid urate in connective collections of solid urate in connective tissues (which may be calcified). tissues (which may be calcified).
a a chronic granulomatouschronic granulomatous inflammatory inflammatory response is identifiable on histological response is identifiable on histological examination of the lesions, and, on examination of the lesions, and, on occasion, acute inflammation occasion, acute inflammation mimicking that of gouty arthritis occurs mimicking that of gouty arthritis occurs in one or several tophiin one or several tophi
CHRONIC ARTHRITISCHRONIC ARTHRITIS
The average interval between the first The average interval between the first attack and chronic arthritis is 11.6 yattack and chronic arthritis is 11.6 y
2% gouty patients has crippling disease2% gouty patients has crippling diseaseMay polyarticularMay polyarticular History of intermittent attacks, additive& ascendingHistory of intermittent attacks, additive& ascending
Gouty handGouty hand
Chronic taphusChronic taphus
Chronic goutChronic gout
Gouty handGouty hand
Advanced goutAdvanced gout
Advanced goutAdvanced gout
Erosion in both Erosion in both destructive and destructive and hypertrophic leads to hypertrophic leads to overhanging edgeoverhanging edge
Joint space is often Joint space is often preserved untile very preserved untile very late in the disease late in the disease processprocess
TaphousTaphous
Over hangingOver hanging
TaphousTaphous
Crystal precipitate in joint and Crystal precipitate in joint and soft tissuessoft tissues
RENAL COMPLICATIONS OF RENAL COMPLICATIONS OF CHRONIC HYPERURICEMIACHRONIC HYPERURICEMIA
nephrolithiasisnephrolithiasis;(only5 to 10 percent ;(only5 to 10 percent of all urinary tract stones in the of all urinary tract stones in the United States and Europe)United States and Europe)
chronic urate nephropathychronic urate nephropathy
three major risk factors for uric three major risk factors for uric acid nephrolithiasis acid nephrolithiasis
Increased uric acid excretion Increased uric acid excretion Reduced urine volume Reduced urine volume Low urine pH, a setting in which most Low urine pH, a setting in which most
of the uric acid exists as the intact of the uric acid exists as the intact insoluble acid. insoluble acid.
Uric acid stoneUric acid stone
Chronic urate Chronic urate nephropathynephropathy
urate may deposit in the renal urate may deposit in the renal medullary interstitium.medullary interstitium.
Deposition in this area induces a Deposition in this area induces a modest chronic inflammatory modest chronic inflammatory ((tophaceoustophaceous) reaction, and varying ) reaction, and varying degrees of degrees of fibrosis fibrosis
Treatment of GoutTreatment of Gout
• The therapeutic aim in gout :The therapeutic aim in gout :1- To terminate the acute attack1- To terminate the acute attack2- To prevent recurrence of acute gouty 2- To prevent recurrence of acute gouty arthritisarthritis3- To prevent or reverse complications of 3- To prevent or reverse complications of the diseasesthe diseases4 - To prevent or reverse associated feature 4 - To prevent or reverse associated feature ( Obesity , hypertriglyceridemia and( Obesity , hypertriglyceridemia and hypertension ) hypertension )
TreatmentTreatment
Anti-inflammatory therapy — prompt Anti-inflammatory therapy — prompt and safe termination of the acute and safe termination of the acute arthritic attack arthritic attack
Prophylaxis — prevention of Prophylaxis — prevention of recurrences of acute gouty arthritis recurrences of acute gouty arthritis
Antihyperuricemic therapy Antihyperuricemic therapy
Treatment of GoutTreatment of Gout
• Acute Gouty arthritisAcute Gouty arthritis
• ProphyProphyllaxisaxis
• ControControl l of hyperuricemia of hyperuricemia
· ColchicineColchicine· NSAIDNSAID· CorticosteroidCorticosteroid
· ·ColchicineColchicine· NSAIDNSAID
· AAllllopurinoopurinoll · Uricosuric agents ( Probenecid, suUricosuric agents ( Probenecid, sullfinpyrazone )finpyrazone )
The recommended duration of The recommended duration of prophylactic colchicine or NSAIDs prophylactic colchicine or NSAIDs during the initiation of during the initiation of uric acid uric acid
lowering therapylowering therapy
In patients without evident tophi, In patients without evident tophi, prophylaxis can be safely prophylaxis can be safely discontinued 6 months after normal discontinued 6 months after normal serum urate values have been serum urate values have been obtained. obtained.
The optimal duration of prophylactic The optimal duration of prophylactic therapy for patients with tophi is therapy for patients with tophi is uncertain. uncertain.
COMORBID RISK COMORBID RISK REDUCTIONREDUCTION
Nutritional strategies (eg, Nutritional strategies (eg, achievement of ideal body weight, achievement of ideal body weight, reduction of dietary protein intake, reduction of dietary protein intake, and limitation of ethanol and limitation of ethanol consumption) can treat both the consumption) can treat both the associated conditions and associated conditions and hyperuricemia hyperuricemia
general goal of general goal of antihyperuricemic therapy antihyperuricemic therapy
is a serum urate concentration of 5 is a serum urate concentration of 5 to 6 mg/dL [297 to 357 µmol/L], a to 6 mg/dL [297 to 357 µmol/L], a level substantially below that at level substantially below that at which monosodium urate is which monosodium urate is saturating in extracellular fluids.saturating in extracellular fluids.
Indication of Indication of antihyperurecemic therapyantihyperurecemic therapy
Frequent and disabling Frequent and disabling attacksattacks of gouty of gouty arthritis (three or more per year) arthritis (three or more per year)
Clinical or radiographic signs of chronic Clinical or radiographic signs of chronic gouty gouty jointjoint disease disease
TophaceousTophaceous deposits in soft tissues or deposits in soft tissues or subchondral bone subchondral bone
Gout with Gout with renal insufficiencyrenal insufficiency Recurrent Recurrent nephrolithiasisnephrolithiasis Urinary uric acid excretion exceeding Urinary uric acid excretion exceeding 11001100
mg/day (when determined in men < 30 mg/day (when determined in men < 30 years of age and premenopausal women) years of age and premenopausal women)
Xanthine oxidase Xanthine oxidase inhibitorsinhibitors
xanthine oxidase inhibitors are likely xanthine oxidase inhibitors are likely to be effective in virtually all to be effective in virtually all circumstances warranting therapy for circumstances warranting therapy for gout ( gout ( AllopurionlAllopurionl))
Uricase (urate oxidase) Uricase (urate oxidase)
Uricase, an enzyme that converts urate Uricase, an enzyme that converts urate to a more soluble molecule ( allantoin). to a more soluble molecule ( allantoin).
uricase can reduce the size of tophi in uricase can reduce the size of tophi in patients with tophaceous disease, patients with tophaceous disease,
Conversion of urate to allantoin by Conversion of urate to allantoin by uricase action thus has the potential to uricase action thus has the potential to be helpful in patients who are allergic or be helpful in patients who are allergic or refractory to treatment with allopurinol. refractory to treatment with allopurinol.
Other drugs that enhance Other drugs that enhance uric acid excretionuric acid excretion
LLosartan osartan FenofibrateFenofibrate