Foundations · Year 1 · from Foundations
Case 1: Gout (Hyperuricemia and Urate Crystal Deposition)
Clinical Image
Source: Wikipedia - Gout - CC BY-SA 3.0
Case Presentation
A 55-year-old man presents to the emergency department at 3 AM with excruciating pain, swelling, and redness of his right great toe. The pain awakened him from sleep and is so severe he cannot tolerate even a bedsheet touching his foot. He attended a work dinner last night with rich food and several alcoholic drinks. He has a history of hypertension treated with hydrochlorothiazide. Physical examination reveals an erythematous, swollen, exquisitely tender first metatarsophalangeal joint (podagra). Laboratory studies show serum uric acid of 10.2 mg/dL (elevated). Arthrocentesis yields cloudy synovial fluid with WBC count of 42,000/mm3 and negatively birefringent needle-shaped crystals under polarized microscopy, confirming monosodium urate crystals. He is diagnosed with acute gouty arthritis. The biochemistry is explained: uric acid is the end product of purine degradation in humans; we lack uricase, which converts uric acid to the more soluble allantoin in most other mammals. When serum urate exceeds solubility (~6.8 mg/dL), crystals precipitate in joints and trigger intense inflammation. He is treated with colchicine and NSAIDs for acute relief, and allopurinol (a xanthine oxidase inhibitor) is later started for long-term urate lowering. Thiazide diuretics are changed as they decrease uric acid excretion.
Key Learning Points
- Uric acid is the final product of purine catabolism in humans; xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid
- Hyperuricemia results from either overproduction (increased purine synthesis or turnover) or underexcretion (the more common cause); thiazides, alcohol, and high-purine foods can elevate urate levels
- Allopurinol and febuxostat inhibit xanthine oxidase, reducing uric acid production; uricosurics (probenecid) increase renal excretion; newer agents like pegloticase provide recombinant uricase