Hyperuricemia and Gout
(Etiology, Pathogenesis, and Clinical Manifestations)
Definition
- Hyperuricemia = Increased levels of uric acid in the blood (>6.8 mg/dL).
- Gout = A chronic metabolic disease caused by monosodium urate crystal deposition in joints and tissues, due to persistent hyperuricemia.
Etiology
- Hyperuricemia
Caused by either:
- Overproduction of uric acid.
- Decreased excretion of uric acid.
- Or both.
Pathogenesis
- ↑ Uric acid in blood → supersaturation → forms monosodium urate (MSU) crystals.
- MSU crystals deposit in:
- Joints → activate innate immune response (especially neutrophils).
- Tendons, bursae, cartilage → chronic inflammation.
- Crystals are phagocytosed by macrophages → release of IL-1, TNF-α, IL-6.
- This causes:
- Acute inflammation: vasodilation, pain, swelling.
- Chronic inflammation: joint destruction, tophi formation.
- Crystals may also deposit in kidneys → uric acid nephropathy or stones.
Clinical Manifestations
Acute Gout Attack (Monoarticular arthritis)
- Sudden, severe joint pain (usually 1st metatarsophalangeal joint – podagra ).
- Red, swollen, warm, very tender joint.
- Fever may be present.
- Often triggered by alcohol, trauma, large meal, or dehydration.
Chronic Gout
- Recurrent attacks.
- Tophi: nodular urate deposits in soft tissues (ear, fingers, elbows).
- Joint deformity and erosion (seen on X- ray).
- Renal complications:
- Uric acid nephrolithiasis (kidney stones).
- Chronic urate nephropathy.