GOUTGOUT

GOUTGOUT

Common medical problem, Male: female ratio 7:1 to 9:1.

GOUTGOUT

Humans do not express the enzyme uricaseuricase, which degrades uric acid, an end product of purine nucleotide catabolism.

Consequently, statistically normal uric acid levels in men and premenopausal women are close to the limits of urate solubility in vitro, imposing a delicate physiologic urate balance.

Uric Acid ProductionUric Acid Production

Uric Acid OverproductionUric Acid Overproduction

Secondary causesSecondary causesExcessive dietary purine intakeIncreased nucleotide turnover

Myeloproliferative diseaseLymphoproliferative diseaseHemolytic anemiaPsoriasis

Accelerated ATP degradationHereditary fructose intolerance Glycogen storage diseaseSevere muscle exertionEthanol abuse

Primary causesPrimary causes

Idiopathic HGPRT deficiency Increased PRPP activity

Uric Acid underexcretionUric Acid underexcretion

Renal insufficiency

Inhibition of tubular urate secretion:

Keto- and lactoacidosis

Enhanced tubular urate reabsorption:

Diuretics,Insulin resistance,Dehydration

Undefined mechanism:

Hypertension, HyperparathyroidisLow-dose salicylates, Pyrazinamide, EthambutolLead nephropathy

GOUTGOUT

Clinical & Laboratory FeaturesClinical & Laboratory Features

Stages of classical goutStages of classical gout

1. Asymptomatic Hyperuricemia1. Asymptomatic Hyperuricemia::

Very common biochemical abnormality

Epidemiological definition: Serum urate level above the mean.

The upper normal value is 8.0-8.5mg/dl

StagesStages - Asymptomatic Asymptomatic HyperuricemiaHyperuricemia

In physiological terms any level above 6.8 mg/dl is hyperuricemia, since it exceeds the soluble concentration of MSU in body fluids.Vast majority of people with hyperuricemia will never develop symptoms.

Stages Stages -- Acute intermittent gout Acute intermittent gout

Characteristic gout attack:rapid development of warmth, swelling,

erythema and pain in the affected joint.

The initial attack is monoarticular and in 50% of cases involves the 1st metatarsal joint, which will finally be affected in 90% of patients.

Acute PodagraAcute Podagra

StagesStages - Acute intermittent goutAcute intermittent gout

Other joints: MT, ankle, heels and knees.Systemic symptoms: Fever, chills and malaise.Early in the disease the episodes are infrequent Between the attacks the previously affected joints are free of pain,

despite this, MSU crystals can be identified in the synovial fluid.

Stages Stages –– Chronic Chronic TophaceousTophaceous GoutGout

Usually develops after 10 years of acute intermittent gout.

In this stage the affected joints become persistently uncomfortable and swollen.

The intensity of these symptoms is much less than the acute attacks.

Stages Stages –– Chronic Chronic TophaceousTophaceous GoutGout

• Characterized by: • tophi formation and • polyarticular involvement, including the

small joints of the hands .

• Subcutaneous gouty tophi can be found in the fingers, wrists, ears, knees, olecranon bursa and pressure points

Tophi

Tophi

GOUTY TOPHUS FORMATIONGOUTY TOPHUS FORMATION

Macrophage acinusMacrophage acinus is the first structure, it has a core of noncrystalline material surrounded by mononuclear phagocyte.

MSU crystals start forming in the corecore..

Macrophages proliferate forming a coronacoronawhich will be replaced by fibrous material.

Finally nearby structures will coalesce to form multilobulated tophimultilobulated tophi

Provocative factorsProvocative factors

The degree of decrease or increasedecrease or increase in the concentration of synovial-fluid urate is more related to acute attack than the degree of hyperuricemia .

TraumaTrauma is frequently reported as an initiating event for an acute gouty attack:

the attack sometimes occurs when the joint is allowed to rest,there is a rapid efflux of water from the joint fluid and the result is sudden increase in urate concentration.

Provocative factorsProvocative factors

Alcohol ingestionAlcohol ingestion: By accelerating the breakdown of intracellular ATPAlcohol contains large quantities of guanosine.

DrugsDrugs: thiazides

Clinical association Clinical association –– Renal involvementRenal involvement

Chronic urate nephropathyChronic urate nephropathy:Deposition of MSU in the renal medulla Associated with mild microalbuminuria.

Acute uric acid nephropathyAcute uric acid nephropathy:ARF caused by hyperuricemia in tumor lysis syndrome or post chemotherapy.

Uric acid renal stonesUric acid renal stones: 10-25% of all people with gout, the incidence correlate with the serum urate levels.

Radiological featuresRadiological features

In early stages :In early stages :Soft tissue swelling around the affected jointsPreserved joint space

Later:Later:Bony erosions that are both atrophic and hypertrophic, Erosions with overhanging edges

Radiological featuresRadiological features

Radiological featuresRadiological features

Laboratory Features and DiagnosisLaboratory Features and Diagnosis

Uric acid level in serum is of limited value in establishing the diagnosis:

The majority of hyperuricemic subjects will not develop gout.Normal level of uric acid during gouty attack is frequent.

DiagnosisDiagnosis

Definitive diagnosis is possible only by aspiration and inspection of the synovial fluidsynovial fluidor tophaceous materialtophaceous material.

Crystals are needle or rod-shaped. On polarized microscopy, they appear as a bright, birefringent crystalsbirefringent crystals (usually intracellular) that are yellow in color

Crystals

DiagnosisDiagnosis

The synovial fluid finding consistent with moderate to severe inflammation.

TreatmentTreatment

The management of gout involvestreating acute arthritic inflammation and urolithiasis lowering urate levels with the goal of preventing recurrent disease and progression.

Treatment of Acute Gouty ArthritisTreatment of Acute Gouty Arthritis

NSAIDsNSAIDs are considered first-line therapy.Selective Cox-2 inhibitors are an alternative in patients with GI contraindications.

CorticosteroidsCorticosteroids or subcutaneous injections of corticotropin are additional alternatives.

Because colchicinecolchicine adverse effects can be serious, IV colchicine should not be used.

LongLong--Term or Prophylactic TherapyTerm or Prophylactic Therapy

NSAIDsNSAIDs and colchicinecolchicine are frequently used as prophylaxis against recurrent acute gout, since such episodes are common during the initiation of uric acid–lowering treatment.AllopurinolAllopurinol and ProbenecidProbenecid - a potent uricosuric agents equally acceptable as first-line drug in the absence of documented urate overproduction or renal failure.

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