Gout

Gout is outlined with a group of genetic purine metabolism rate of chaos caused by the disease. The clinical features of recurrent acute and chronic arthritis of the performance of tophi, joint stiffness, or deformity, renal parenchymal damage, urolithiasis, hyperuricemia. Gout is not a single disease but a syndrome, there are many diseases can cause increased blood uric acid, and calmly in the joints, connective tissue and lead to kidney damage sites. Cause pathogenesis of gout classification and pathogenesis of Hyperuricemia is an important characteristic of gout. Uric acid in the blood uric acid level decided to produce and the balance between excretion. Normal male serum uric acid high limit of 417 μmol L-1. 98% Clinical gout patients serum uric acid ≥ 417μmol L-1, 3-and 4% of female patients with gout. serum uric acid between 357 ~ 417μmol L-1, So women's sexual serum uric acid in patients with gout limited to a high of 357 μmol L-1. Uric acid influenced by the race, eating habits, age, physical condition (obesity), and other factors. Hyperuricemia men at puberty, women in menopause in the future. Special enzyme defect exceptions can play in infancy. Male child testosterone treatment, the blood uric acid increased significantly, and the child or castrated and reproductive women have not been found in patients with gout. Hyperuricemia may have excessive uric acid (75%), it can also be too low uric acid excretion (25%). Uric acid is a product of purine metabolism final. DNA purine exist, in the DNA and protein synthesis. Purine from : ① endogenous purine synthesis increased, primarily in the liver glutamate synthesis; ② endogenous nucleic acid metabolism constantly update and the final decomposition of uric acid; ③ exogenous nucleic acid decomposition, All proteins are purine sources. In etiological gout can be divided into primary and secondary categories. Gout is a primary congenital genetic, rather than secondary to other diseases or other congenital a secondary clinical performance; Secondary gout and hyperuricemia, or is secondary to other diseases in the process of a clinical manifestations, As can also be caused by certain drugs. Primary gout (1) removal of uric acid in patients with gout low of about 90%. the basis of the total urinary uric acid "600mg d-1. Remove uric acid were significantly lower. The results show that the patients with gout renal clearance of uric acid / inulin clearance ratio decreased to achieve than normal clearance, then blood uric acid value higher than the normal 119-179μmol L-1, 75 ~ 80% gout patients showed renal clearance of uric acid deficient. Its mechanism may be as follows : ① reduced glomerular filtration : gout patients in the uric acid salt and protein. Some combination of urate not out glomerular filtration; ② increased tubular reabsorption. Absorption filtration may exceed the amount of uric acid. Therefore uric acid reabsorption may Hyperuricemia is an important factor; ③ tubular secretion decreased. This may well be the high urinary uric acid in patients with gout and hyperuricemia reasons. Some organic acids such as lactic acid and beta-hydroxybutyric acid and uric acid secretion in the same location, when the blood increased organic acids, excretion of uric acid that is competitive inhibition. It was assumed that such gout patients have mild organic acid metabolism disorders. (2) excessive production of uric acid in the main basis for 24 h uric acid emission. In the absence of purine diet and the impact of service is not yet uric acid excretion of the drug situation, urinary uric acid 600 mg d-1 as normal; Fresh in Pristina, urinary uric acid 1,000 mg d-1 is too high. 800 ~ 1000 d-1 for the upper limit of normal. Primary gout patients about 10% is due to produce high uric acid. These patients purine synthesis to accelerate, as HGPRT lack of PRPP synthase activity increased, or glucose-6-phosphatase lack. Recently it was discovered that ATP deaminase abnormalities can lead to accelerated nucleotide catabolism, have increased uric acid caused gout. Furthermore, in cell culture, found adenine acid synthase, the product of purine metabolism high purine synthesis. These observations suggest that human phenomenon may be similar. HGPRT found in the lack of adolescence or adulthood, the main clinical manifestations of hyperuricemia and high uric acid in urine, no significant neurological damage. HGPRT part of the typical lack is a high uric acid in urine. its scope toxicity ranged from 10 ~ d-1 d-1 [normal children and adults ceiling of 18 and 10m g d-1 d-1]. Thus urinary uric acid crystals are, was mostly kidney stones, kidney stones often as initial symptoms and treatment. Due to the high uric acid in urine, can lead to confrontation diuretic hormone (ADH) and the confrontation was polyuria. Serum uric acid between 417 ~ 883μmol L-1. Most patients with acute gouty arthritis history, a majority of tophi, minorities are not typical of nerve damage, lower intelligence. RBC HGPRT activity with the family of the other, about the normal 0.01 ~ 30%. HGPRT part of the lack of hyperuricemia mechanism of three. As IMP or GMP decline purine synthesis, because IMP and GMP is important purine synthesis inhibitor; Secondly PRPP concentration increased, that the increased synthesis of matrix; the third is to reduce the hypoxanthine reuse, and the final oxidized into uric acid. Genetic characteristics of the X-linkable recessive inheritance. Female carriers, male incidence. Heterozygous females can be mild biochemical changes that higher serum uric acid concentrations, but no clinical symptoms. Some amenorrhea after gout, and may lack the HGPRT the heterozygous. PRPP synthase activity increased, PRPP result of the increased purine synthesis, So obviously hyperuricemia and high uric acid in urine. The clinical manifestations of gout, age 20 ~ 39 years of age. Secondary gout (1) reduce the excretion of uric acid kidney : based on the 24 h urinary uric acid "600mg d-1. Some secondary gout is due to decreased renal excretion of uric acid, when the glomerular filtration rate is associated with lower urinary uric acid excretion decreased. Glomerular lesions induced hyperuricemia with this. Polycystic kidney disease, lead poisoning can cause renal tubular secretion decreased excretion of uric acid reduction. Because of renal failure caused hyperuricemia in gout rare. Tubular reabsorption of uric acid reduction, but also have hyperuricemia. Diuretics, especially thiazide diuretics can increase blood uric acid, the medication about 75%. In the United States, hyperuricemia patients 20% is attributed to the use of diuretics. Because diuretics sodium, reduced blood volume, making the uric acid tubular sodium reabsorption, resulting in reduced secretion. If additional blood volume can be avoided hyperuricemia. Other drugs such as aspirin, pyrazinamide, ethambutol, ethanol, such as nicotinic acid can also be induced hyperuricemia. However, the mechanism has not yet entirely clear. Dietary protein content excessive : hyperuricemia in patients with gout and rich styles. During World War II, in Western Europe the crowd gout and hyperuricemia were rare. After the war, the gradual increase. Obesity serum uric acid than the same age, sex in the control group, by the control of uric acid diet can be lowered. This is because ① excessive intake of protein, nucleic acid decomposition excessive; ② rich in carbohydrate, 5 '--ribose, PRPP thus increased (such as synthesis of purine substrate); ③ blood fats increase blood ketone concentration increased, inhibition in renal excretion of uric acid; ④ alcohol can be induced hyperuricemia. When blood alcohol concentration nearly 0.00220 mmol L-1, can lead to hyperuricemia. Organic acids increase : competitive inhibition may tubular uric acid secretion caused hyperuricemia. If diabetic ketoacidosis, any reasons for the high lactic acidosis, lactic acidosis (infection, shock, etc.). (2) have too much uric acid in many secondary hyperuricemia and gout is due to the decomposition of nucleic acid metabolism speed up. More common in bone marrow and lymph node hyperplasia diseases. Such as multiple myeloma, acute leukemia, lymphoma, erythrocytosis, hemolytic anemia. Especially leukemia and lymphoma patients treated with chemotherapy and / or radiotherapy process, because of the substantial damage cells, nucleic acid metabolism speed up, lead to hyperuricemia and compensatory purine synthesis. ATP excessive decomposition may have excessive uric acid is an important reason. Such as acute myocardial infarction, a lot of smoking status epilepticus not commensurate with the strength of strenuous exercise ATP can make substantial break down into uric acid. HGPRT complete lack of innate genetic disease before mentioned, But HGPRT complete lack of the major clinical manifestations of central nervous system lesions. Hyperuricemia and gout was to be followed by clinical manifestations. Therefore can be seen as secondary gout. Glycogen deposition disease type I (von Gierke's disease) due to the lack of hepatic glucose-6-phosphatase, make 6-phosphate glucose can change glucose, and participation in metabolic pathway, in vivo 5 '- ribose phosphate increased. 5'-phosphate ribose is the matrix synthesis PRPP, the increase in the synthesis of purine. But its main performance of low blood sugar, high blood cholesterol, high lactic acidosis, and hyperuricemia and gout only minor performance. Gouty arthritis : uric acid crystals in acute attack of arthritis appear to have confirmed. Acute stage, within the synovial fluid leukocyte see a large number of double refraction crystal. These can be crystallization of uric acid enzyme digestion. Experiment shows uric acid crystals of sodium can lead to human and animal skin, subcutaneous tissue reaction and arthritis. Symptoms very similar to gout, colchicine may be easing. Also found that the acute gouty first attack, a day after the synovial on uric acid salts and uric acid-rock, These crystals can be peeled off on the synovium, or synovial neutrophil phagocytosis, cause acute inflammation. Synovial fluid uric acid is saturated acute attack of gout conditions. Hyperuricemia and gouty arthritis attack there is a certain relationship, but not at all. Some hyperuricemia no gout attack. Instead, some have normal blood uric acid acute gout attacks, there is a note of precipitation prompted factor. If gout synovial fluid of patients by adding saturated acid solution, can significantly increase the crystallization. And the relationship between rheumatoid patients with the synovial fluid is not. Glycoprotein role : Urate number of organizations, with great glycoprotein. When glycoprotein accelerating decomposition, synovial fluid concentrations of uric acid sodium increased, and because the joint cavity vascular small, poor circulation, right uric acid sodium absorption slow to promote gout attack. Temperature role : the solubility of sodium acid at 37 ° C is 357 μmol L-1, At 30 ° C is 268 μmol L-1. Human internal and peripheral environment of temperature. Knee for the rest of the state temperature of 32 ° C, the movement will rise. So acute arthritis attack at night when the rest, often in acromegaly (especially the lower extremity end) and ear. These were poor circulation, the lower temperatures. Traumatic arthritis is the trigger, the big toe metatarsophalangeal joints particularly vulnerable involved. This was most vulnerable, because the unit area under pressure capacity, the connective tissue injury, make urate crystals release into the articular synovial fluid within the cavity. The elderly are prone because the elderly poor blood circulation, local temperature lower than that of young people, local urate difficult to absorb. PH : The impact of injuries increased leukocyte anaerobic yeast solution, lactate increased, and local pH decrease. Because uric acid solubility of sodium in pH6 ~ 6.5 hours compared to 7.4 hours, Therefore, the lower the pH value can only increase uric acid precipitation, and the attack for the WBC uric acid sodium, Therefore, the local pH change of acute gout attack less affected. WBC role : uric acid sodium dependent on the response of polymorphonuclear leukocytes. Give the dog or vancomycin resistant polymorphonuclear leukocytes serum interleukin deficiency caused, uric acid salt that is not induced inflammatory response; if the supplementary WBC, inflammatory response resume. Crystal in leukocyte phagocytosis can release right after the other leukocyte chemotactic factor. If we give the colchicine RNA synthesis, chemokines noticeably reduced. Note chemotactic factor is a protein. These chemokines to attract more leukocytes into the joint cavity and lead to inflammation. Lysosomal enzyme role : the acute inflammatory response and gout destructive changes, the release of lysosomal enzymes play a key role. Leukocytes of lysosomes containing cationic protein, the latter causing rupture of mast cell granules induce inflammatory reaction, will also contain changes in capillary permeability-cartilage and decomposition of the acid glycoprotein protease. Cartilage glycoprotein decomposition leads to further increase uric acid salt crystallization. Of course, lysosomes can be seen as all the other factors articular lesions injury of last resort. In the joint, the inner layer of synovial cells, cartilage cells, and the migration of fixed phagocytic cells, vascular cells in the adventitia. Neutrophils are within lysosomes.