hyperuricemia and gout

Hyperuricemia and gout

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Uric Acid


Uric Acid Is the final breakdown product of

purine degradation in humans


Urates The ionized forms of uric acid,

predominante in plasma, extracellular fluid and synovial fluid.

Approximately 98% existing as monosodium urate at pH 7.4


Plasma is saturated with monosodium urate at a concentration of 6.8 mg/dl.

At higer concentrations, plasma is therfore supersaturated, creating the potential for urate crystal precipitation.


Urate production varies with the purine content of the diet and the rates of purine biosyntesis, degradation and salvage.


2/3 to ¾ of urate is excreted by kidneys, and most of the remainer is eliminated through the intestines.


Renal handling Glomerular filtration Tubular reabsorption Secretion Postsecretory reabsorption


Uric acid is more soluble in urine than in

water. The pH of urine greatly influences its

solubility. pH 5 urine is saturated with uric acid at

concentrations ranging from 6 to 15 mg/dl. At pH 7 saturation is reached at

concentration between 158 and 200mg/dl


Serum urate levels vary with age and sex.

Children: 3 to 4 mg/dl Adult men: 6 to 6.8 mg/dl


Hyperuricemia


Hyperuricemia

Defined as a plasma urate concentration > 7.0 mg/dl


Hyperuricemia Can result from:

Increased production of uric acid Decreased excretion of uric acid Combination of the two processes.


Increased Urate Production Diet provides an exogenous source

of purines and, accordingly, contributes to the serum urate in proportion to its purine content.


Hyperuricemia

Foods high in nucleic acid: liver, thymus and pancreas, kidney and anchovy.

Restriction intake: reduces: 1 mg/dl


Endogenous sources: De novo purine biosynthesis: 11 step Increased PRPP synthetase activity

and HPRT deficiency are associated with overproduction of purine, hyperuricemia and hyperuricaciduria.


Decreased Uric Acid Excretion Alterated uric acid excretion could

result from decreased glomerular filtration, decreased tubular secretion or enhanced tubular reabsorption.


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.


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.


Prevalence

2 and 13.2%


Causes of hyperuricemia Primary No recognized cause Hypoxanthine

phosphoribosyltransferase deficiency

Increased phosphoribosyl pyrophosphatase activity.

Secundary Hereditary fructose

intolerance Mieloproliferative

disease Linfoproliferative

disease Hemolitic anemia Drugs: Low-doses

salicylate, diuretis, pyrazinamide, ethambutol, nicotinamide, etanol


Evaluation of Hyperuricemia Hyperuricemia does not represent

a disease. Is not an specific indication for

therapy. The finding of hyperuricemia is an

indication to determine its cause.


The hyperuricemia of individuals who excrete uric acid above this level while on a purine-free diet is due to purine overproduction, whereas it is due to decreased excretion in those who excrete lower amounts on the purine-free diet.


Complications of Hyperuricemia The most recognized complication

of hyperuricemia is gouty arthritis

Nephrolithiasis Urate Nephropathy Uric Acid Nephropathy


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


Urate Nephropathy Deposits of monosodium urate

crystals surrounded by a giant cell inflammatory reaction in the medullary intrerstitium and pyramids.

Clinically: silent or cause proteinuria, hypertension and renal insufficiency.


Uric acid nephropaty Precipitation in renal tubules and

collecting ducts cause obstruction to urine flow.

Following sudden urate overproduction and marked hyperuricaciduria:

Dehydration and acidosis Lymphoma Cytolytic therapy


Treatment


Asymptomatic Hyperuricemia Treatment with anthyperuricemic

agents entails inconvenience, cost and potential toxicity.

“Routine” treatment of asymptomatic hyperuricemia cannot be justified.


Treatment with anthyperuricemic agents in asymptomatic hyperuricemia is not recommended.

“Treatment in special conditions” like patients during cytolytic therapy for neoplastic disease.

Justification:prevent uric acid nephropathy.


Nephrolithiasis Prevention Fluid ingestion (urine >2 L/d) Alcalinization of the urine (sodium

bicarbonate or acetazolamide) to increase the solubility of uric acid.

Allopurinol (Decrease the serum urate concentration) 300 mg/d


Uric Acid Nephropathy Vigorous intravenous hydration

and diuresis with furosemide. Acetazolamide and sodium

bicarbonate (urine pH >7) Allopurinol


GOUT


Crystal-induced arthritides MSU (monosodium urate) CPPD (calcium pyrophosphate

dihydrate) HA (calcium hydroxyapatite) Calcium oxalate (CaOx)


Monosodiumurate Gout


Monosodiumurate Gout Affecting middle-aged to elderly

men.

Women represent only 5 to 17% of all patients.


Monosodiumurate Gout

Associated with an increased uric acid, hyperuricemia, episodic acute and chronic arthritis, and deposition of MSU crystals in connective tissue tophi and kidneys.


Acute and chronic arthritis Acute arthritis is the most frequent

early clinical manifestation of MSU gout.

Usually only one joint is affected initially

Polyarticular acute gout is also seen in male hypertensive patients with ethanol abuse as well as in postmenopausal women.


The metatarso phalangeal joint of the first toe is often involved.

Ankles, and knees are also commonly affected.

In elderly patients, finger joints may be inflamed.


The first episode of acute gouty arthritis frequently begins at night.

With dramatic joint pain and swelling.


Joints rapidly become warm, red, and tender, and the clinical appearence often mimics a cellulitis.


Early attacks tend to subside spontaneously within 3 to 10 days.

Most of the patients do not have residual symptoms until next episode.


Several events may precipitate acute gouty arthritis: Dietary excess Trauma Surgery Excessive ethanol ingestion Glucocorticoid withdrawal


After many acute attacks, a portion of gouty patients may presents with a chronic nonsymmetric synovitis.

Causing potential confusion with rheumatoid arthritis.


More rarely, the disease will manifest as inflamed or noninflamed periarticular tophaceous deposits in the absence of chronic synovitis.


Laboratory Diagnosis Even the clinical appearance

strongly suggests gout. The diagnosis should be confirmed by needle aspiration of acute or chronically inflamed joints or tophaceous deposits.


Acute septic arthritis several of the other crystalline – associated arthropathies, and psoriatic arthritis may present with similar clinical features.


Effusion appear cloudy due to leukocytes and a large amounts crystals ocassionally produce a thick pasty or chalky joint fluid.


Radiographic Features Cystic changes, well-defined

erosions described as punched-out lytic lesion.

Soft tissue calcified masses (chronic tophaceous gout)


Treatment Acute attack: Anti-inflammatory drug:

Colchicine Nonsteroidal anti-inflamtory drugs Glucocorticoids

Depending on the age of the patient and comorbid conditions.


Colchicine and NSAIDs may be quiet toxic in the elderly, particularly in the presence of renal insufficiency and gastrointestinal disorders.


In elderly patients : Intraarticular glucocorticoid injections Cool aplications along with lower oral

doses of colchicine.


Colchicine 0.6 mg tablet every hour until relief of

symptoms Gastrointestinal toxicity occurs

( never excede 4 mg)


Uricosuric agents Probenecid 2oo mg twice Allopurinol 300 mg


hyperuricemia and gout

Documents

urinary uric acid levels

hyperuricemia primary

complications of hyperuricemia

hyperuricemia of individuals

finding of hyperuricemia

tubular secretion of

nucleic acid

ionized forms of uric