Gouty Arthritis Pathophysiology

Pathophysiology of Gouty Arthritis

• Gouty arthritis is a metabolic inflammatory joint disease
• Hyperuricemia, or elevated uric acid in the blood, is the primary cause of gout
• Uric acid is the final product of purine metabolism
• When serum urate levels surpass 6–7 mg/dL, monosodium urate (MSU) crystals form and deposit in joints and tissues
• The deposition of MSU crystals in synovial fluid and connective tissues results in an intense inflammatory response

Role of Immune Cells and Cytokines

• Neutrophils and macrophages attempt to phagocytize the crystals
• Phagocytosis leads to the release of inflammatory cytokines like IL-1 and TNF-α, amplifying the inflammatory cascade

Genetic and Risk Factors

• Genetic factors, like variants in urate transporter genes (SLC2A9, URAT1), and epigenetics, influence serum urate levels and gout development
• Risk factors include obesity, metabolic syndrome, hypertension, type 2 diabetes, and renal disease
• Diets rich in purines (red meats, seafood), alcohol (especially beer), and fructose are risk factors
• Using medications affecting serum urate levels like diuretics increases risk

Impact of Kidney Dysfunction

• Kidney dysfunction reduces uric acid excretion, contributing to hyperuricemia

Development of Chronic Gout

• A chronic state may develop, leading to chronic gouty arthritis, tophi formation (MSU crystal aggregates in soft tissues), and joint erosion and deformity

Clinical Manifestations of Gout

• Acute gout attacks usually occur suddenly, often at night
• Acute gout is characterized by severe joint pain, warmth, redness, swelling, and tenderness
• The first metatarsophalangeal joint (big toe) is commonly affected in a condition known as podagra
• Lower extremities are more vulnerable due to cooler temperatures, decreasing MSU solubility

Commonly Affected Joints and Tophi Formation

• Other commonly affected joints include the ankles, knees, wrists, fingers, and elbows
• Tophi, or firm, yellowish-white nodules of MSU crystals, may form under the skin in chronic gout, around joints, bursae, or cartilage

Risk and Complications

• Men are at higher risk, especially with urate levels >420 μmol/L
• Women rarely experience gout before menopause
• Attacks are recurrent
• Without proper treatment, joint destruction and disability can occur
• Patients may have a history of urolithiasis (kidney stones), especially if uric acid levels are persistently elevated

Summary Table: Gouty Arthritis

• Gout is a metabolic inflammatory arthritis caused by hyperuricemia and monosodium urate (MSU) crystal deposition in joints
• Elevated serum uric acid levels can be caused by increased production, decreased excretion, or both
• Pathophysiology involves hyperuricemia leading to MSU crystal formation, followed by crystal deposition in joints, activation of the innate immune system (neutrophils), and an inflammatory cascade triggered by cytokines (IL-1, TNF-α, etc.)
• Lifestyle-related risk factors: high-purine diet, alcohol (esp. beer), fructose. Medical risk factors: obesity, metabolic syndrome, hypertension, and renal disease. Medication risk factors: diuretics, low-dose ASA
• Genetic/environmental factors include urate transporter gene variants (e.g., SLC2A9, URAT1), cell death, lactic acidosis, chemotherapy, and psoriasis
• Common sites affected: first metatarsophalangeal joint (big toe, podagra), ankles, knees, elbows, wrists, fingers
• Clinical manifestations include acute attacks with severe joint pain, redness, swelling, and warmth (usually at night) and tophi (firm nodules from chronic MSU crystal deposits)
• Men are six times more likely to develop gout, while women are usually affected post-menopause Progression:
• Initial stage involves asymptomatic hyperuricemia progressing to acute intermittent gout, which later develops into chronic tophaceous gout with joint damage
• Management involves treating acute attacks with NSAIDs, corticosteroids, or colchicine, and preventing further attacks through lifestyle changes and serum urate-lowering therapy such as allopurinol
• Comorbidities include metabolic syndrome, type 2 diabetes, cardiovascular disease, and urolithiasis