Why does hyperuricemia occur? (Etiology)
By origin, the pathology is divided into primary (genetically determined defect in purine metabolism enzymes) and secondary. Regardless of the form, excess uric acid in the blood develops according to two main scenarios.
1. Hyperproduction (too much is synthesized):
- Heredity: endogenous metabolic abnormalities.
- Dietary factor: abundance of purines in the diet (meat, fish) and alcohol.
- Enhanced cell breakdown: observed in hemolysis, leukemias, myeloproliferative disorders, psoriasis, and during antineoplastic chemotherapy (tumor lysis syndrome).
- Obesity: acts as a mixed risk factor.
2. Impaired excretion (too little is eliminated):
- Renal pathologies: chronic kidney disease.
- Endocrine and systemic shifts: hypothyroidism, hyperparathyroidism, acidosis, arterial hypertension.
- Toxic exposure: lead poisoning, alcohol.
- Drug iatrogenesis: use of diuretics, cyclosporine, levodopa, and low-dose acetylsalicylic acid.
From hyperuricemia to inflammation (Pathogenesis)
Prolonged circulation of high concentrations of uric acid leads to the deposition of its crystals in peripheral tissues. Clusters—microtophi—gradually form in the articular cartilage and synovial membrane.
The attack itself starts at the moment of destabilization of these microclusters. A trigger can be physical trauma, hypothermia, or a sudden hyperuricemic crisis. The crystals burst directly into the joint cavity, which instantly triggers a cascade of pronounced intra-articular inflammation.
Clinical presentation and evolution of the disease
The classic onset of the disease is acute arthritis of the first metatarsophalangeal joint (the big toe).
- Acute attack: Begins suddenly, most often at night or early morning. The joint rapidly turns red, becomes hot to the touch, and massive edema of the periarticular tissues develops. The pain is intense and agonizing. Sometimes the local inflammation is so pronounced that it mimics phlegmon, cellulitis, or phlebitis. In severe cases, fever joins.
- Course: Even without treatment, the attack resolves spontaneously within a few days. An intercritical period ensues, during which the patient has no complaints.
- Progression: If left untreated, the disease progresses. In 60% of patients, a relapse occurs within the first year. Over time, the symptom-free intervals shorten, attacks become more severe, and the knees, ankles, and small joints of the hands become involved.
- Chronization: After 3–5 years, gouty nodules—tophi—form under the skin (especially on the auricles, elbows, and fingers).
Visceral targets and diagnostics
Gout extremely rarely occurs in isolation. It is firmly associated with metabolic syndrome (obesity, type II diabetes mellitus, atherosclerosis) and cardiovascular pathology (arterial hypertension, CHD).
The main visceral target of the disease is the kidneys. Urate nephropathy develops, which can manifest in three forms:
- Acute renal failure — due to massive tubular obstruction by crystals at the peak of the attack.
- Chronic renal failure — as an outcome of urate interstitial nephritis.
- Urolithiasis — urate nephrolithiasis.
Diagnostic evaluation includes the assessment of laboratory markers: persistent hyperuricemia (above 6.5 mg%) is recorded in blood serum, and during an acute attack, signs of inflammation appear—elevated ESR, leukocytosis, and a positive C-reactive protein. In later stages, X-ray is informative: narrowing of the joint space and specific bone defects due to intraosseous tophi ("punch-out" lesions) are visualized.
Briefly: answers to topical questions
What is the mechanism of action of allopurinol in the treatment of gout?
Allopurinol is a structural analogue of hypoxanthine and an inhibitor of the enzyme xanthine oxidase, disrupting the synthesis of uric acid.
Mechanism of action:
- xanthine oxidase oxidizes allopurinol to oxypurinol;
- oxypurinol binds tightly to the active center of the enzyme;
- purine catabolism is inhibited at the hypoxanthine stage, reducing the formation of uric acid.
As a result, instead of uric acid, hypoxanthine and xanthine are excreted, which are more water-soluble and easier for the kidneys to eliminate.
To remember the characteristics of the attack onset, use the "night rooster" rule: pain in gout traditionally wakes the patient in the second half of the night or early morning—this is a characteristic symptom of the "cock's crow."
Class and exam questions
What most frequently provokes an acute gouty attack?
Classic triggers of an attack are a gross dietary violation (overeating purine-rich foods) and alcohol consumption. Trauma, temperature changes, or a sharp spike in uric acid levels can also provoke an attack.
Can the attack go away on its own without pills?
Yes, an acute attack can resolve on its own within a few days or weeks. However, this does not mean recovery: the disease progresses in a latent form, and the risk of an early relapse remains extremely high.
What diseases can gout be confused with at the beginning?
In the early stages, gouty arthritis is often mistaken for post-traumatic arthritis or suspected rheumatoid arthritis, especially when the inflammation becomes chronic and involves new joints.
What else to study on this topic
- Differential diagnosis of gout and rheumatoid arthritis
- Principles of pharmacotherapy and drug classes for treatment
- Specifics of the diet in gout and lifestyle modification
- Pathogenetic connection between gout and metabolic syndrome
- Mechanisms of tumor lysis syndrome development
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