Hyperuricemia : Causes, Symptoms, Diagnosis & Treatment

• Classification
• The Reasons
• Physiological Causes
• Gout
• Overproduction Of Uric Acid
• Slow Excretion Of Uric Acid
• Other Reasons
• Diagnostics
• Correction
• Medical Treatment
• Experimental Therapy
• Forecast

Hyperuricemia is a laboratory symptom characterized by an increase in the level of uric acid in the blood serum of more than 400 µmol / l. This condition indicates a violation of purine metabolism. The causes of hyperuricemia can be excessive consumption of meat food, medication, metabolic disorders, etc. In some cases, symptoms such as pain, redness and swelling of the joints, the formation of tophi are observed. The concentration of uric acid is measured in a biochemical blood test. To correct hyperuricemia, a diet, urate-lowering therapy is prescribed.

Classification

According to the etiology, there are 2 main types of hyperuricemia:

• Primary - occurs due to a genetically determined defect in the enzymes involved in the metabolism of uric acid.
• Secondary - develops against the background of certain diseases, the action of toxins, drugs, etc.

According to the pathogenesis, 3 types of hyperuricemia are distinguished:

• Metabolic ( hyperproductive ) - associated with increased formation of uric acid.
• Renal ( hypoexcretory ) - due to a slowdown in the excretion of uric acid from the body with urine.
• Mixed.

According to clinical manifestations, there are:

• asymptomatic hyperuricemia;
• acute/intermittent arthritis;
• interictal period;
• chronic tophi gout.

The reasons

Physiological causes

In healthy people, there may be a short-term or slight increase in the concentration of uric acid (UA) without any clinical symptoms. Most often, hyperuricemia is observed when eating meat food, since meat products are rich in purine bases (adenine, guanine), which are a substrate for the synthesis of UA. Also, hyperuricemia occurs with dehydration, intense physical activity, alcohol intake.

Gout

This rheumatological disease can be considered a clinical manifestation of hyperuricemia. Gout develops as a result of a genetically determined defect in the enzymes that regulate UA metabolism. Such defects include deficiency of hypoxanthine-guanine phosphoribosyltransferase, increased activity of 5-phosphoribosyl-1-synthetase. Violation of the functional activity of these enzymes leads to an increase in the synthesis of UA.

In peripheral tissues, especially in the articular bags, cartilage, crystallization of uric acid salts and their deposition occurs. As a result, the following symptoms appear: acute, intense pain in the joints (often in the I metatarsophalangeal joint), swelling of the joint with reddening of the skin. A rather specific symptom of gout is the formation of nodules - tophi, localized mainly on the auricles, the back surface of the elbow joints. Also, gout can develop against the background of diseases that affect purine metabolism.

Hyperuricemia

Overproduction of uric acid

With intensive destruction of cells and their nuclei, nucleotides are released, from which a large amount of UA is subsequently formed, which leads to an increase in the level of UA. The presence of clinical symptoms of hyperuricemia that has arisen is determined by the degree of tissue destruction. Enhanced catabolism is observed in the following diseases and pathological conditions:

• Myeloproliferative and lymphoproliferative diseases (leukemias, lymphomas).
• Tumor lysis syndrome after chemotherapy courses.
• Congenital and acquired hemolytic anemias.
• Severe generalized psoriasis.
• Storage diseases: Gaucher disease, glycogenoses.

Slow excretion of uric acid

Approximately 2/3 of the total amount of UA is excreted in the urine. Therefore, any violation of the excretory function of the kidneys due to their organic damage can lead to hyperuricemia. The same often happens with a decrease in the effective volume of blood, which disrupts the blood supply to the kidneys. The following are the main reasons for the suppression of MK clearance:

• Glomerulonephritis.
• Interstitial nephritis.
• Chronic renal failure.
• Massive bleeding.
• Congestive heart failure.
• Lead poisoning (lead nephropathy).
• Taking thiazide diuretics.

Other reasons

• Endocrine disorders: hypoparathyroidism, hypothyroidism.
• Diabetic ketoacidosis.
• lactic acidosis.
• Preeclampsia.
• Sarcoidosis.
• Taking medications: acetylsalicylic acid, cytotoxic drugs (cyclosporine, sodium mycophenolate), anti-tuberculosis drugs (ethambutol, pyrazinamide), nicotinic acid.

Diagnostics

If hyperuricemia is detected, it is necessary to consult a general practitioner to find out the cause of its occurrence. At the reception, the presence of symptoms characteristic of this condition is clarified. The joints disturbing the patient are carefully examined for swelling or redness. It is found out whether the patient has any chronic diseases, whether he is registered with the dispensary, what medicines he takes. An additional examination is scheduled, including:

• Blood tests. During a gouty attack with severe symptoms in the general blood test, an increase in ESR, neutrophilic leukocytosis is noted. In the biochemical analysis, in addition to hyperuricemia, inflammatory markers are detected (an increase in C-reactive protein, ferritin), in patients with renal pathology, an increase in the concentration of creatinine, uric acid is detected.
• General urine analysis. Microscopic examination of the urine sediment reveals a large number of UA (urate) crystals. In nephrological patients, a chemical analysis of urine can detect protein, erythrocytes, and a change in its relative density.
• Examination of joint fluid. To obtain synovial fluid, a puncture of the affected joint is performed. In a native unstained preparation, polarizing microscopy reveals needle-shaped crystals of sodium monourate. This is the "gold standard" for diagnosing gout. These crystals can also be found in the contents of tophi.
• X-ray of the joints. X-ray changes in patients with gout appear only after a few years from the onset of the disease. Typical radiographic findings include well-defined bone defects in the epiphyses of the bones of the feet and hands.

Diet for hyperuricemia

Correction

Medical treatment

To correct hyperuricemia, it is necessary to eliminate the etiological factor. If, in the process of collecting anamnesis, it turns out that the patient is taking a drug that causes hyperuricemia, either reducing the dosage or replacing the drug with an alternative drug that does not have such a side effect should be considered. The tactics of treatment is largely determined by the presence of clinical symptoms, as well as their severity.

• Diet. People suffering from gout should definitely stop drinking alcohol and exclude high-purine foods (red meat, liver, smoked meats) from the diet, as they can provoke an increase in symptoms.
• Colchicine alkaloids. The main group of drugs for the relief of acute gouty attacks. Reduction of symptoms occurs within 12 hours after the first dose.
• NSAIDs. They are prescribed in addition to colchicine alkaloids to relieve the symptoms of arthritis. Preference is given to drugs with the most pronounced analgesic and anti-inflammatory effect.
• Glucocorticosteroids. Hormonal agents are used to eliminate symptoms in case of individual intolerance to colchicine and NSAIDs or if the patient has strict contraindications to taking them.
• Uricodepressors. The drugs of this group reduce the content of UA by suppressing the activity of the enzyme involved in the synthesis of UA (xanthine oxidase). Long-term use helps to reduce the incidence of gout symptoms, slow down the deposition of crystals and the formation of tophi.
• Selective xanthine oxidase inhibitors. The main difference from uricodepressors is a lower incidence of adverse reactions, such as upper and lower respiratory tract infections, hepatotoxicity, and hypersensitivity reactions.
• Uricosuric drugs. These drugs inhibit the reabsorption of sUA in the tubules of the kidneys, thereby increasing the excretion of sUA.
• Antigout drugs of mixed action. There are also combined drugs that simultaneously act on 2 links of UA metabolism. They contain a uricodepressive component and a uricosuric agent.
• Alkalizing drugs. To prevent the development of urate nephropathy and the deposition of urate stones, the main urate-lowering therapy should be supplemented by taking drugs for alkalinizing urine - sodium citrate, sodium bicarbonate.

Experimental Therapy

Development and clinical trials of new drugs to combat hyperuricemia are ongoing. Rasburicase, a drug containing recombinant uricase (an enzyme that destroys uric acid), has shown high efficacy in the treatment of tumor lysis syndrome. Also, this drug is distinguished by the possibility of resorption of deposited crystals of sodium monourate.

Promising is the use of genetically engineered biological preparations - an antagonist of interleukin-1 receptors (anakinra), fully humanized monoclonal antibodies to IL-1-beta (canakinumab), soluble IL-1 protein (rilonacept). Their use has demonstrated sufficient efficacy in the prevention of exacerbations of symptoms of chronic gouty arthritis.

Forecast

Long-term hyperuricemia is associated with a higher incidence of cardiovascular complications - heart attacks, strokes. This condition also negatively affects carbohydrate and lipid metabolism - it increases the level of low-density lipoproteins, increases insulin resistance and aggravates the course of already existing type 2 diabetes mellitus. Therefore, the detection of hyperuricemia requires a thorough examination of the patient and the timely appointment of therapy.