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Giới thiệu
Gout is a condition wherein there is increased urate in the body, also called hyperuricemia, that leads to deposition of monosodium urate (MSU) monohydrate crystals in various tissues (eg joints, connective tissue, kidney). Hyperuricemia is a necessary precondition for the development of monosodium urate crystal deposition, but this has to be distinguished from gout, the clinical syndrome. This results in acute and chronic inflammation associated with changes in articular and periarticular structures. It is the most common inflammatory arthritis in men.
Dịch tễ học
In the US and Europe, the estimated prevalence of gout is 3% of the adult population. The prevalence of gout in the Asia-Pacific region varies. Ethnic groups in China and Malaysia (eg Malays, Tamils) were found to have higher uric levels as compared to the Japanese and Thai. Taiwan is one of the countries in the world with the highest prevalence of gout.
Younger males and patients of Malay ethnicity are more likely to have poorly controlled gout. Male patients were more likely to have gout due to diet (eg beef, pork, seafood, alcohol). In females, estrogen is presumed to have a protective effect through renal uric acid excretion. Thus, the level of uric acid increases in women after menopause. The prevalence of gout increases with advancing age.
Sinh lý bệnh
Gout develops due to the accumulation and crystallization of uric acid,
forming monosodium urate (MSU) crystals. Uric acid itself is a byproduct of
purine metabolism, originating from three main sources: cell turnover, dietary
purine intake, and internal (de novo) synthesis. These monosodium urate
crystals tend to deposit in joints and surrounding tissues, most commonly
affecting the first metatarsophalangeal (MTP) joint of the big toe. The
likelihood of gout developing in a joint is influenced not only by the amount
of urate present in the tissue but also by factors such as the joint fluid’s pH
level, temperature, macromolecular composition, and the concentrations of
sodium ions and proteins.
The concentration of serum uric acid is the main determinant of MSU
crystal formation and gout development. This urate level depends on the balance
between production (from purines and metabolism) and excretion (mainly via the
kidneys). Thus, hyperuricemia may result from either increased uric acid
production or decreased elimination from the body.
Nguyên nhân
The causes of hyperuricemia are excessive uric acid production and decreased renal clearance. Excessive uric acid production is seen in inherited enzyme defects (eg hypoxanthine-guanine phosphoribosyltransferase deficiency, phosphoribosyl pyrophosphate synthetase overactivity, glycogen storage diseases, fructose-1-phosphate aldolase deficiency, myoadenylate deaminase deficiency, carnitine palmitoyltransferase II deficiency); clinical disorders (eg myeloproliferative and lymphoproliferative disorders, malignancies, psoriasis, Down syndrome); and induced by diet, drugs, or toxins (eg Ethanol, excessive purine in diet, fructose, vitamin B12 deficiency, Nicotinic acid, cytotoxic drugs, Warfarin).
A decrease in the renal clearance, on the other hand, is noted in genetic disorders such as medullary cystic kidney disease, familial juvenile hyperuricemic nephropathy and uric acid transportasome mutations; chronic renal insufficiency, volume depletion (eg heart failure, volume loss), obesity, diabetic or starvation ketoacidosis, lactic acidosis, hyperparathyroidism, hypothyroidism, sarcoidosis; and induced by diet or drugs (eg Aspirin, diuretics, Ciclosporin, Tacrolimus, Ethambutol, Pyrazinamide, Ethanol, Levodopa). Saturnine gout is a rare form of gout that is due to chronic lead exposure and is commonly seen in plumbers and those exposed to lead-based paints.
Yếu tố nguy cơ
Risk factors for gout and associated comorbidity should be assessed. The risk factors associated with gout include: Hyperuricemia, which is the single most important risk factor for developing gout; male sex; menopausal women; age; purine-rich diet (eg meat, seafood); alcohol intake; drug use (eg diuretics, low-dose Aspirin, Ciclosporin); lead exposure; obesity; and renal insufficiency.
The metabolic abnormalities/comorbidities associated with gout are hypertension, obesity, dyslipidemia, hyperglycemia and insulin resistance, coronary artery disease, type 2 diabetes mellitus (DM), renal insufficiency, metabolic syndrome, and kidney stones.