Gout
- Lesion
Too much uric acid crystallizes in and around joints; neutrophils attack the crystals and the big toe swells, red and very painful.
What it is
Gout is caused by deposition of monosodium urate crystals in joints and soft tissue in people with long-standing hyperuricaemia. Most patients underexcrete urate through the kidney; a minority overproduce it, as with inherited enzyme defects or high cell turnover. Crystals shed into the joint are taken up by macrophages, which activate the NLRP3 inflammasome and release IL-1β, bringing an intense neutrophilic attack. Repeated attacks lead to chronic arthritis and tophi, and urate also harms the kidney.
Structure
- Acute arthritis: dense neutrophilic synovitis; crystals inside neutrophils in the fluid.
- Tophus: chalky white deposit; under the microscope, amorphous or feathery urate masses (dissolved by aqueous fixatives, kept by alcohol) ringed by foreign-body giant cells.
- Chronic tophaceous gout: synovial hyperplasia, fibrosis and punched-out erosions with overhanging edges.
- Kidney: tophi in the medulla and intratubular urate crystals.
Step by step
- Uric acid, the end product of purine breakdown, rises from underexcretion or overproduction.
- Above its solubility limit, especially in cool distal joints, it crystallizes as monosodium urate.
- Crystals shed into the joint are phagocytosed by macrophages and activate the NLRP3 inflammasome.
- IL-1β and chemokines recruit neutrophils that release enzymes and form NETs; the joint becomes red, hot and swollen.
- Attacks subside, but persistent hyperuricaemia lets tophi grow and erode bone.
Stages of gout
| Stage | What happens |
|---|---|
| Asymptomatic hyperuricaemia | High urate for years; most people never develop gout |
| Acute gouty arthritis | Sudden, very painful monoarthritis that resolves in days to weeks |
| Intercritical gout | Symptom-free intervals that shorten over time |
| Chronic tophaceous gout | Tophi, erosions and persistent arthritis after years of attacks |
Clinical notes
- Diagnosis by aspiration: needle-shaped negatively birefringent crystals in neutrophils; serum urate can be normal during an attack.
- Acute attacks are treated with anti-inflammatory drugs, colchicine or glucocorticoids; long term, urate-lowering drugs such as xanthine oxidase inhibitors.
- Gout is linked to obesity, metabolic syndrome, hypertension and kidney disease.
Test yourself
Think of the answer, then tap the question to see it.
How do gout crystals look under polarized light?
Needle-shaped and negatively birefringent.
Which innate immune complex is activated by urate crystals?
The NLRP3 inflammasome, leading to IL-1β release.
What is a tophus?
A deposit of urate crystals surrounded by foreign-body giant cells and macrophages.
Is serum urate always high during an acute attack?
No, it can be normal; joint fluid crystals make the diagnosis.
Elsewhere in DurgiPedia
- Uric acid
- Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
- Interleukin-1
- Innate immunity (overview, barriers)
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Gout (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.