1. Definition
Hyperuricemia refers to an elevated concentration of uric acid in the blood, exceeding 6.7 mg/dl (women) or 7.4 mg/dl (men).
2. Physiology of Uric Acid
Uric acid is the final breakdown product of purine metabolism in humans. It is primarily excreted through the kidneys (~70%) and intestines. Normal levels are maintained by a balance between production and excretion.
3. Etiology
Hyperuricemia occurs due to increased production or decreased renal clearance of uric acid.
In general, the causes are classified into:
3.1 Primary Hyperuricemia
Linked to genetic enzyme defects such as:
- Lesch-Nyhan syndrome
- Increased activity of the glutamine phosphoribosylpyrophosphate amidotransferase (GPAT)
- Increased activity of the xanthine oxidase (XO)
3.2 Secondary Hyperuricemia
Linked to different diseases or therapies with certain medications such as:
- Increased uric acid production
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- Polycythemia vera
- Chronic myeloid leukemia (CML)
- Acute lymphoblastic leukemia (ALL)
- Cytostatics
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- Reduced renal uric acid excretion
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- Alcoholism
- Kidney disease
- Diuretics
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4. Symptoms
Many cases are asymptomatic. Symptomatic hyperuricemia manifests as:
- Acute Gout: Painful joint inflammation due to crystal deposition
- Chronic Gout: Development of tophi (urate crystal aggregates) in tissues
- Nephrolithiasis: Uric acid kidney stones
5. Differential diagnosis
- Pseudogout: Calcium pyrophosphate deposition disease
- Septic Arthritis: Differentiated via synovial fluid culture
- Rheumatoid Arthritis: Autoantibodies (e.g., RF, anti-CCP) assist in distinction
6. Therapy
6.1 Lifestyle Modifications
- Low-purine diet (avoidance of red meat, seafood)
- Reduced alcohol intake
6.2 Pharmacological Treatment
- Xanthine Oxidase Inhibitors (Allopurinol, Febuxostat): Reduce uric acid production
- Uricosurics (Probenecid, Lesinurad): Enhance uric acid excretion
- Colchicine or NSAIDs for acute gout attacks