Gout and Hyperuricemia
Introduction
Introduction to gout and hyperuricemia Gout is a disease caused by a disorder of hernia caused by hereditary or acquired causes. Its clinical features are hyperuricemia and the resulting recurrent attacks of gouty acute arthritis, tophi deposits, tophus chronic arthritis and joint deformities, often involving the formation of chronic interstitial nephritis and uric acid kidney stones Acute renal failure can also be caused by uric acid stones. At present, the clinical treatment of gout is still no cure for the following four purposes: 1 to stop the onset of acute arthritis as soon as possible; 2 to prevent recurrence of arthritis; 3 to correct hyperuricemia, to prevent urate deposition in the kidneys, joints, etc. Complications; 4 specific treatment measures to prevent the formation of uric acid kidney stones should be determined according to the stage of disease development. basic knowledge The proportion of illness: 0.073% Susceptible people: no specific population Mode of infection: non-infectious Complications: Hypertension Arteriosclerosis Coronary heart disease Type II diabetes
Cause
Causes of gout and hyperuricemia
Genetic factors (45%):
Gout has been found to have a familial incidence in ancient times. Among patients with primary gout, 10% to 25% have a positive family history of gout, and 15% to 25% of gout patients have hyperuricemia. Primary gout is a dominant chromosomal inheritance, but the penetrance is incomplete. The genetic status of hyperuricemia varies greatly. It may be polygenic. Many factors can affect the manifestation of gout inheritance, such as age and gender. Diet and kidney function, etc., it has been determined that two congenital ankle metabolic disorders are sexually linked inheritance, namely hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency and 5-phosphate ribose-1-pyrophosphate Synthetic enzyme (PRPP synthetase) is too active, female is a carrier, and male is ill. In secondary gout, glycogen storage disease type I (von Gierke disease) is cryptic recessive. In short, it is necessary to find each A more specific phenotype of gout can be used to clarify the genetic pattern.
Related disease factors (20%):
Gout is often accompanied by hypertension, hypertriglyceridemia, arteriosclerosis, coronary heart disease and type 2 diabetes (NIDDM). In the cause of death in elderly gout patients, cardiovascular factors exceed renal insufficiency, but gout and cardiovascular disease There is no direct causal relationship, but both are related to obesity and dietary factors. Limiting diet or reducing body weight can improve the condition, other diseases associated with gout, such as myeloproliferative diseases and hemolytic anemia, chronic kidney disease, kidney Diabetes insipidus, lead poisoning, sputum poisoning, sarcoma-like, hyperparathyroidism, Down syndrome and psoriasis are caused by excessive decomposition of nucleic acids leading to excessive uric acid and/or decreased uric acid excretion by the kidneys.
Endocrine factors (15%):
The study found that the uric acid in the uric acid pool in normal people is 1200mg, which produces 750mg per day, about 2/3 is cleared by the kidney, and 1/3 is excreted by the intestine. Most of the uric acid is excreted by the kidney in the form of free sodium urate. A small part of uric acid can be destroyed, mainly because the uric acid secreting the human intestine is decomposed by bacteria into allantoin and carbon dioxide. In the case of gout, no decomposition of uric acid is found. In fact, in hyperuricemia, special After renal failure occurs, the uric acid that enters the intestinal cavity will only increase and become an important second-line defense. Therefore, increased anabolic metabolism and/or decreased uric acid excretion are important mechanisms for the increase of serum uric acid value in patients with gout.
After eating for 5 days, it was found that 90% of patients with gout belonged to uric acid exclusion, but their renal function was still normal, mainly because the threshold for excretion of uric acid in the kidney was higher than that of normal people. The patient's blood uric acid value exceeded that of normal people by 1-2 mg/dl. Only began to have considerable uric acid excretion, which is especially evident in patients with normal uric acid. Renal excretion of uric acid depends on glomerular filtration, proximal tubular resorption (98% to 100%), secretion (50%) and Re-absorption after secretion (40% ~ 44%), Henle rise branch and collecting tube, can also absorb a small amount of uric acid, the final excretion accounted for 6% to 12% of the filtration (Figure 3), drug-induced hyperuricemia Such as diuretics, low-dose aspirin, anti-tuberculosis drugs or anti-rejection drugs after organ transplantation, cyclosporine A is related to the inhibition of secretion, patients drink more water, maintain urine volume and alkalinize urine pH, reduce uric acid Prevention of kidney stone formation and sodium urate nephropathy is of great significance.
Pathogenesis:
Pathogenesis
A uric acid (oxidase) enzyme that converts uric acid into a more soluble, more easily discharged allantoin, so serum uric acid levels are low without gout, human (Homo sapient) and several Hominoid species are mutational inactivation of the urate oxidase gene during evolution. From this point of view, human hyperuricemia is caused by congenital defects in uric acid catabolism, dissolved uric acid. As a scavenger of reactive oxygen species including peroxynitrite derived from oxygen and superoxide, it may be beneficial to humans. The concentration of uric acid in hyperuricemia serum depends on the relationship between uric acid production and excretion rate. Balance, there are two sources of uric acid in the human body. One is the decomposition of nucleotides from foods rich in nuclear protein. It is exogenous, accounting for about 20% of uric acid in the body. The second is from amino acids, phosphoribosose and others. Small molecule synthesis and nucleic acid catabolism are endogenous, accounting for about 80% of total uric acid in the body. For the occurrence of hyperuricemia, it is clear that endogenous metabolic disorders are more important than exogenous factors. In the tracer study, the average uric acid in the uric acid pool in normal people is 1200 mg, about 750 mg per day, 500-1000 mg is discharged, about 2/3 is excreted by the urine, and another 1/3 is excreted by the intestine, or is oxidized by bacterial uric acid in the intestine. Enzymatic decomposition, serum uric acid concentration in normal people fluctuates within a narrow range, the average domestic normal male is 339mol / L (5.7mg / dl), the female average is 256mol / L (4.3mg / dl), blood uric acid The level of the level is affected by many factors such as race, eating habits, age and body surface area. Generally speaking, uric acid increases with age, especially after women's menopause. Men are often higher than women, but Female postmenopausal blood uric acid levels can be close to males, clinically often more than the above average or higher than the normal gender of the same sex two standard deviations (SD) or more for hyperuricemia, because gout is caused by uric acid crystals In the non-dissolved state caused by uric acid, so "hyperuricemia" is determined by the statistical distribution of the solubility of uric acid in body fluids rather than uric acid levels. The amount of uric acid produced per unit time exceeds the treatment and remains dissolved. Force, there is uric acid monosodium crystal deposited outside the cell, the temperature of the peripheral joint (about 32 ° C knee joint, ankle joint about 29 ° C), also makes the uric acid solubility greatly reduced, such as triggering the inflammatory reaction, gout can occur .
(1) There may be molecular defects in the mechanism leading to excessive strontium biosynthesis; for example, the amount of sputum metabolizing enzyme is increased or the activity is too high; and the enzyme activity is decreased or absent.
1 The number of enzymes is increased or the activity is too high:
A. Increased number and activity of phosphoribosyl pyrophosphate amide transferase (PRPPT): This enzyme is a rate-limiting enzyme that catalyzes the formation of 1-amino-5-phosphate ribose (PRA) reaction, with increased PRPPAT and increased PRA production. When the synthesis of hypoxanthine nucleotides is increased, the production of uric acid is increased, and when adenylate or guanylic acid is decreased, the inhibition of the enzyme is reduced, and the production of uric acid is increased.
B. Increased activity of PRPP synthase: This enzyme promotes the synthesis of nucleic acids and purines and increases the production of uric acid.
C. Increased activity of xanthine oxidase (XO): This enzyme can accelerate the oxidation of hypoxanthine to xanthine, thereby accelerating the production of uric acid from jaundice, and the XO activity is increased. It is caused by secondary liver enzyme induction, not congenital. defect.
D. Excessive glutathione reductase: this enzyme can catalyze the reduced type of nicotinamide adenine dinucleotide (IVADPH) and oxidized glutathione (GSSG) to become nicotinamide adenosine Acid phosphate (NADP) and reduced glutathione (GSH), NADP is a coenzyme of the pentose phosphate loop. When it is too much, it promotes the pentose phosphate loop, which leads to an increase in 5-phosphate ribose synthesis, which leads to phosphoribosyl phosphate. Increased pyrophosphate (PRPP) and increased production of uric acid.
2 decreased or lack of enzyme activity:
A. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency: This enzyme can promote the conversion of hypoxanthine to hypoxanthine nucleotides, and guanine is converted to guanylate. When HGPRT is deficient, PRPP consumption is reduced. The accumulation of PRPP increases the production of uric acid.
B. Glucose-6-phosphatase deficiency: can cause type I glycogen accumulation, glucose 6-phosphate can not become glucose, metabolism shifts to phosphogluconic acid, and partially converts to 5-phosphate ribose.
C. Glutaminase deficiency: The enzyme is deficient, which reduces the decomposition of glutamine, stores glutamine, and increases the matrix of synthetic muscarine.
D. Low activity of glutamate dehydrogenase: the dehydrogenation of glutamic acid can reduce the production of -ketoglutaric acid, and the conversion to glutamine increases, and the synthesis of strontium and uric acid increases.
The main cause of hyperuricemia is excessive production of uric acid, accounting for 70% to 80%, and only 25% of patients with low uric acid excretion. In most patients with primary hyperuricemia, the 24-hour uric acid excretion is within the normal range. 20% to 25% of patients have increased discharge, and patients with increased uric acid excretion in urine have abnormally increased sputum synthesis; while in patients with normal uric acid excretion, 2/3 of patients have excessive sputum production, and kidney excretion of uric acid depends on Glomerular filtration, proximal renal tubular reabsorption (98% to 100%), secretion (50%) and reabsorption after secretion (40% to 44%), when glomerular filtration is reduced, or renal tubular pair Hyperuricemia can be caused by increased reabsorption of urate or decreased renal tubular urate.
(2) Mechanism of uric acid production and clearance: The systemic total uric acid pool that can communicate with sodium urate in plasma is determined by the rate of uric acid production and treatment, and is enlarged during gout (Table 3A B), xanthine oxidase (xanthine oxidase) It acts on the substrate hy hypoxanthine and xanthine to produce uric acid. The dietary sputum passes through the intestinal epithelial decomposing enzymes (including xanthine oxidase), mostly decomposed into uric acid, limiting sputum intake. The serum uric acid level can be slightly decreased (0.6 ~ 1.8 mg / dl), but the difference in absorption in the occurrence of hyperuricemia, no effect, most uric acid is hepatic xanthine oxidase on hypoxanthine And jaundice, they are derived from the aging of nucleic acids and cellular nucleotide metabolism, the latter's biosynthetic pathways are two, that is, "remediation" ("reuse") and "new synthesis."
Most uric acid is cleared by the kidneys, about 1/3 is degraded by bacteria in the intestines. When renal dysfunction occurs, the degradation of uric acid by bacteria is significantly increased, and uricouric agents that promote the increase of uric acid excretion in urine are blocking uric acid. The recovery, while other drugs and weak organic acids, inhibits the secretion of uric acid from the kidneys, and increases serum uric acid levels, fasting, alcohol metabolism, and hyperuricemia during ketoacidosis, which is due to this mechanism.
Intracellular sputum metabolism and "metabolic" hyperuricemia occur, the "new synthesis" pathway, the inosine (inosine) (IMP) anthracycline (hypoxanthine) is composed of phosphoribosyl pyrophosphate ( PPRP) Derived from the ribose-5-phosphate backbone precursor, this pathway is separated at the IMP to produce adenosine (Adenosine-phosphate) (AMP) and guanylate (guanosine-phosphate) (GMP) And its derivatives, the "remediation" pathway, pre-formed guanidine-based jaundice, guanine and adenine (from IMP, GMP and AMP) in hypoxanthine phosphoribosyltransferase (HPRT) and adenine to phosphoric acid Under the action of ribosylase (APRT), it directly condenses with PP-ribose-P, and then regenerates these ribonucleotides. The hypoxanthine formed by nucleotide turnover, some enter the liver, and xanthine oxidase (XO) Decomposed into uric acid, the rest are treated by HPRT.
The salvage pathway (more economical in terms of energy requirements) can reduce the regenerative synthesis activity because (1) HPRT and APRr have higher affinity for PP-ribose-P than amide ribosyltransferase (amide PRT).
The lack of HPRT inevitably causes all jaundice and guanine to be lost as uric acid, and the new synthetic pathway is modernized due to the decrease in inhibitory nucleotide formation and the increase in PP-ribose-P concentration that can be used in the amide PRT reaction. Increasingly, the hereditary PP-ribose-P synthase "promoting" variant individuals increased the formation of PP-ribose-P, stimulating the amide PRT, and greatly increased the new synthesis.
Increased nucleotide decomposition can increase blood uric acid levels due to increased production of XO substrate and inhibition of amide PRT release, and hyperuricemia and gout in the absence of glucose-6-phosphatase (type I glycogen). Related to this mechanism: Glucose-6-phosphate accumulates at the expense of hepatic glandular triphosphate (ATP), and AMP degrades into uric acid, which can decompose nucleotides such as hypoxia, metabolism of certain sugars. In normal people with strenuous exercise and moderate exercise in patients with metabolic myopathy, uric acid in the blood may increase rapidly. (5NT=5-nucleotidase; PNP= nucleotide phosphorylase; ADA=adenosine deaminase; AK=adenosine kinase)
(3) Mechanism of hyperuricemia: There is evidence that about 10% of patients with gout have excessive uric acid production, that is, urinary uric acid excretion exceeds the normal value +2SD (ie, 600mg when the meal is restricted, and >800mg during the normal meal) ), the most frequently generated is the genetic defect of two rare purine nucleotide synthesis regulation, namely the reductive hypoxanthine-guanine phosphoribosyltransferase deficiency and phosphoribosyl pyrophosphate synthesis The enzyme (phosphoribosyl pyrophosphate synthetase) is hyperactive.
Uric acid, or trioxane, is a product of the body's metabolism. Under normal circumstances, most of the uric acid is in the form of sodium urate in the blood. At 37 ° C, pH 7.4, the uric acid is in a deep state, free in the blood, the uric acid is mainly from the kidney. Excretion, the body maintains a certain range of blood uric acid by dynamic balance, male does not exceed 417mol / L (7mg / dl), female does not exceed 357mol / L (6mg / dl).
The majority of the causes of primary gout are unknown. The direct mechanism of about 90% of the incidence is related to the decrease of renal excretion. Very few gouts in children and adolescence are related to heredity. Those with clear pathogenic factors are called secondary gout. For Lesch-Nyhan syndrome and von Gieke disease, the interaction of genetic factors and environmental factors determines the formation of hyperuricemia, and hyperuricemia is present in first-degree relatives of 20% of gout patients.
Most patients with idiopathic gout have normal renal function, but because of the reduced uric acid excretion from filtration, the blood uric acid level is increased (hyperuricemia). Why is this, no specific kidney changes have been found to explain In renal dysfunction, uric acid excretion is reduced, but gout is rare in chronic renal failure. Several families have been reported, early onset hyperuricemia, gout and progressive renal failure (sometimes accompanied by high Blood pressure) is interrelated (Table 1), chronic lead-toxic nephropathy, alcoholism, diuretics and other drugs, which can cause hyperuricemia and gout due to renal mechanisms. Heart and kidney transplant patients can be treated with cyclosporine. Severe hyperuricemia occurs and gout occurs rapidly.
Hyperuricemia and idiopathic gout are associated with obesity and hypertriglyceridemia. Some gout patients can eliminate high triglyceride, hyperuricemia, excessive uric acid production and renal clearance disorders due to weight loss and alcohol withdrawal. .
1 Acute gout attack mechanism: Neutrophils are an indispensable medium for acute inflammation in gout. When neutrophils phagocytose monosodium urate crystals, they release leukotrienes, interleukin-1 and glycoproteins. Factor ("crystal chemotactic factor"), which intensifies the infiltration of neutrophils into the affected joints. Activated neutrophils can also produce superoxide, and lysosomal membrane rupture and cells Dissolves and releases lysosomal enzymes. Complement peptides and kinins are cleaved by the precursor, causing pain, vasodilation and permeability, and released lysosomes and cytoplasmic enzymes are produced by the mesenchymal cells. Collagenase, like prostaglandin, causes chronic joint destruction and tissue necrosis.
A. Asymptomatic arthritis in patients with gout: uric acid crystals are often found outside the cell. Attacks and terminations may be caused by plasma proteins. They selectively adsorb to crystals, which may affect their interaction with neutrophils. An IgG antibody produced by using monosodium urate crystal as an antigen can act as a nucleating agent, promote the crystallization of monosodium urate, and increase the phagocytosis of these crystals by neutrophils, thereby promoting the release of lysosomal enzymes. In the late episode, lipoproteins containing apoprotein B enter the inflamed joint from plasma and coat monosodium urate crystals; this effect on phagocytosis, neutrophil oxidative metabolism, superoxide production and cytolysis All have inhibitory effects, and the difference in protein regulating agent quality and quantity can explain the difference in inflammatory reaction of uric acid crystals during gout and non-gout.
B. Acute gouty arthritis: sodium urate salt forms microcrystalline precipitates in the joints and joints around the joints, causing non-specific joint inflammation is a complex process, which may be the result of a combination of various factors, the solubility of urate in normal physiology In the case of pH 7.0, the temperature is 37 ° C at 381 mol / L (6.4 mg / dl), beyond this concentration is super saturated state, due to articular cartilage, less blood vessels in the synovium and around the joints, the matrix contains sticky Polysaccharic acid and connective tissue are abundant. When the urate in the body fluid reaches supersaturation, under certain induced conditions, such as damage, local temperature decreases, local pH decreases, or whole body fatigue, alcoholism, or due to plasma 1, When 2 globulin is reduced and urate is reduced in combination, urate is easily crystallized, urate crystals can catalyze leukocytes, and leukocytes in the white blood cells and joint capsules can liberate white in a few minutes after phagocytizing urate. Triene B4 (LTB4) and glycoprotein chemotactic factors, the role of urate crystals and leukocytes or other phagocytic cells can be regulated by proteins adhering to the surface of crystals, and IgG on the surface of crystals can enhance white The phagocytosis of cells, and some specific proteins such as LDL can inhibit this effect. This phenomenon can explain the inconsistency of urinary crystallization caused by urate crystals in patients with gout. In vitro tests show that monocytes can be released after stimulation with urate crystals. Interleukin-1 (IL-1), IL-1 can cause gout and increase inflammation. It has been reported that other cytokines such as IL-8, TNF and complement system are also involved in the above inflammatory response, but not every factor mentioned above. All are essential factors. After urate crystals are phagocytosed by cells, leukocytes degranulate rapidly, decompose, destroy lysosomal membrane, release hydrolase, cause leukocyte necrosis, release inflammatory peptides and other inflammatory factors, leading to acute inflammation and Intensified, the phospholipid membrane of organelles, such as cholesterol and testosterone, is sensitive to cytosolic lysis caused by urate. For example, -estradiol inhibits the above reaction, so gout occurs in men and postmenopausal women. Especially the lower extremity joints: the toe joints are subjected to the greatest pressure, easy to damage, and the local temperature is low, so it is a good site for gout, and acute gouty arthritis is self-limiting. Can be related to the following factors: a. local temperature increase at the onset of inflammation, increased uric acid dissolution, decreased formation of new crystals, b. increased local blood flow, urate absorption into the blood circulation, c. phagocytized urate can be The destruction of medullary peroxidase of leukocytes reduces the amount of urate released when leukocytes rupture, d. stress of inflammation, excitement of adrenal cortex, increased secretion of hormones, inhibition of inflammatory process, rapid fluctuation of blood uric acid value can cause acute gout Sexual arthritis episodes, if the sudden decrease in blood uric acid can dissolve the tophi in the joint and release insoluble needle crystals, which may explain why acute gouty arthritis occurs in patients with gout when applying uric acid and inhibiting uric acid-producing drugs. .
2 tophi stone mechanism: tophus (tophus) is the deposition of succinic acid monosodium needle-shaped fine crystals, surrounded by chronic monocyte reaction and epithelial cells, giant cells of foreign body granuloma, may be multi-core, tophi is common in Joints and other cartilage, synovium, tendon sheath, mucous sac and other joint structures, osteophytes, subcutaneous tissue and renal interstitial.
Compared with acute gout attacks, the inflammatory response caused by tophi is negligible. It usually occurs in silence and no feeling. Some gouts of gout patients are found by radiographic examination on bone and articular cartilage. There may be no such thing, the tophi is gradually increasing in the joints, causing degeneration of cartilage and subchondral bone, proliferation of the synovial membrane and bone, sometimes fibrotic or ossified joints, and radiographic imaging of common bone piercing lesions ( Punched out lesions) are caused by bone marrow tophi, which can communicate with the surface of the joint through the cartilage defect. The urate deposit of the vertebral body can reach the medullary cavity near the intervertebral disc.
3 Gout of kidney disease: 90% of patients with gout have kidney damage, there are three main changes:
A. Gouty nephropathy: Its characteristic histology is the presence of urate crystals in the renal medulla or nipple, surrounded by round cells and macrophages, often accompanied by acute or chronic interstitial inflammatory changes. Fibrosis, tubular atrophy, glomerular sclerosis and renal arteriosclerosis, the earliest changes are partial inflammation and tubular damage in Henle, followed by mild and slow progressive lesions, often due to hypertension, renal arteriosclerosis , urinary tract stones and infections, lead poisoning and other factors, making the disease complicated.
B. uric acid kidney stones: gout patients with normal uric acid output, 20% can have uric acid stones, and patients with increased uric acid output can have up to 40% of uric acid stones, 89% of pure uric acid (non- urate) Stones, the rest still contain calcium oxalate, calcium phosphate and calcium carbonate stones, the incidence of stones with the increase of blood uric acid concentration, the increase of uric acid output increased, the pH value decreased the urate into free uric acid, leading to urine The solubility of the acid salt is reduced, making uric acid stones easy to form. At pH 5.0, 85% uric acid is non-ionic, only 15ml of uric acid is dissolved per 100ml of urine, and the solubility of uric acid can be increased by 10 times when the urine is alkalized to pH 7.0. When the pH is 8.0, it can be increased by 100 times.
C. Acute uric acid nephropathy: due to uric acid crystallization in the renal collecting duct, renal pelvis and ureteral deposition, urinary obstruction can cause oliguria and acute renal failure, which is common in myeloproliferative diseases during chemotherapy or radiotherapy. A large number of patients are produced.
The autopsy of gout patients often reveals that the renal medulla and cone have monosodium urate crystal deposition, surrounded by mononuclear and megakaryocyte reactions, ie "urate nephropathy", uric acid (not urate) crystals Deposition in the distal tubules and collecting ducts, resulting in proximal tubule dilatation and atrophy. Although nephropathy is common in gout, it is generally mild and slow to progress. Interstitial nephropathy may be due to urate deposition but no urine. Also seen in the acid salt, other may have high blood pressure, secondary renal calcium deposition, uric acid stone disease, infection, aging and lead poisoning.
4 uric acid nephrolithiasis: 10% to 25% of patients with gout suffer from kidney stones, which is about 200 times higher than the incidence in the general population. When the uric acid output is >700mg per day, the incidence of stones is >20%; When the blood level reaches 1100mg, the stone rate is about 50%. The incidence of stones is also related to hyperuricemia. When the serum uric acid level is >12mg/dL, the stone rate can reach 50%. More than 80% of the stones are uric acid (not sodium urate). Stones, the rest are mixed with uric acid and calcium oxalate or pure calcium oxalate.
5 phosphate stones: patients with gout and non-goutic uric acid stones, urine PH continues to decrease, which is conducive to the occurrence of uric acid stones; the original reason is still unknown, at pH 5 and 37 ° C, free uric acid solubility Only 15mg/dL, so in the case of normal urine volume, the uric acid that discharges the average load must also form supersaturated urine. The solubility can increase by more than 10 times at pH 7, and can increase by more than 100 times at pH 8.
(4) Etiology and pathogenesis of traditional Chinese medicine: Chinese medicine believes that the main cause of primary gout is congenital spleen and kidney dysfunction, spleen transport function is reduced, then turbidity endogenous; kidney division dysfunction, wet The turbid excretion is less slowly, resulting in turbid cohesion. At this time, feeling the cold, dampness and heat, excessive fatigue, injury to the seven emotions, or alcoholism, or joint trauma, etc., aggravate and promote turbidity to flow joints, muscles, Bone, blood and blood run poorly and form sputum pain, that is, gouty arthritis. Therefore, the cause of gout can be divided into three aspects: internal cause, external cause and inducement.
1 Internal cause: mainly due to lack of congenital endowment and deficiency of righteousness, lack of endowment, loss of liver and kidney, lack of blood and bones, dysfunction of kidney and muscle meridians, or dysfunction of kidney and urine, wet turbid cohesion, flow joints, muscles, obstruction The meridians can form sputum pain; lack of endowment, yin and yang imbalance affect other viscera, mainly involving the spleen, making it transport disorder, especially for thick taste, wine and food can not be transported, causing turbidity endogenous, stagnation in the joint, or Insufficient source, qi and blood can not support joint meridians, can also lead to rickets, righteous qi deficiency, can be weak, can also be caused by other diseases, postpartum qi and blood, or fatigue, diet, emotional injury, Or over-serving certain chemical drugs caused by internal injuries, righteous qi deficiency, one muscles and muscles are dying, and the second is unable to resist external evils. The above internal causes, and then the external factors and incentives add up, the meridians are blocked, the blood is not running. Smooth and disease-based.
2 external factors: mainly to feel the wind, cold, wet, hot evil, due to the dampness of the residence, the work environment is wet and cold, or work in the water, or rain wading, or rainy, summer wet weather lingering, or sweat out of the wind, sweat After entering the water and other reasons, when the righteousness is not enough, when the outside is not solid, the wind and cold dampness, or the evil of rheumatism, or the evil of cold and dampness, or the evil of rheumatism and heat, or the evil of damp heat, can invade the human meridians, leaving In the limbs, bones and muscles, between the joints, the obstruction is unreasonable, and it is caused by the disease. Because of the different feelings of evil, or the evil spirits are different, the corresponding syndromes are formed. In addition, the syndrome caused by the wind and cold dampness is long-lasting. Unhealed, stagnation of heat, can also be converted into rheumatic fever or damp heat syndrome.
3 incentives: mainly in the sinister evil, or evil stagnation meridians, add overwork, seven emotions hurt, internal consumption of righteousness; or diet, alcoholism, taste, damage to the spleen and stomach, endogenous turbidity; Or re-injury trauma, or surgery, or joint damage, etc., can increase the meridian stagnation, blood and blood flow is not smooth and induce the disease.
The pathogenesis of this disease is mainly congenital deficiency, righteous qi deficiency, meridian dystrophy; or wet turbid excretion slow, leaving the meridians; or spleen transported by the Secretary, phlegm and stagnation of joints; or feeling external evils, evil sputum meridians, qi and blood Poor operation, all joints, bones, muscle pain, swelling, red heat, numbness, heavy, flexion and extension are unfavorable to form the disease, long-term illness is not bloody, blood stasis, sputum, turbid blood stasis Joint swelling, deformity, stiffness, ecchymosis around the joints, nodules, and internal damage to the internal organs, can be complicated by the visceral disease syndrome, the condition is complex and serious.
The initial stage of the disease is in the limbs, joints and meridians, followed by erosion of the bones and bones, internal damage and viscera. In fact, before the symptoms appear, there are congenital liver and kidney deficiency and spleen loss, can not be ignored.
The nature of the disease is the virtual standard, with liver and kidney deficiency, spleen imbalance, and later he is dirty; with wind, cold, dampness, turbidity, blood stasis and obstruction meridians as the standard.
2. Pathology
The characteristic pathological change of gout is tophi, which is the deposition of urate needle crystals and produces a chronic foreign body reaction. The surrounding foreign body nodules formed by epithelial cells and macrophages, the urate crystals are water-soluble. When the tissue is fixed with a water-insoluble fixative such as ethanol, the crystal is needle-shaped under a polarizing microscope and has a double-fold phenomenon. The tophi is common in articular cartilage, synovial membrane, tendon sheath, periarticular tissue, subcutaneous tissue, osteophyte and Renal interstitial, articular cartilage is the most common deposition site of urate, sometimes the only deposit, articular cartilage degeneration, synovial hyperplasia, glenoid, subchondral bone destruction, bone margin hyperplasia, fibrous appearance Or osteoarthrosis, a small number of patients with Lesch-Nyhan syndrome, demyelinating changes in brain tissue at the time of autopsy, multiple small infarcts in the brain and cerebellar white matter, degranulation of Purkinje cells, necrosis of nerve cells, cortical thinning and Ganglion hyperplasia.
Prevention
Gout and hyperuricemia prevention
Disability analysis
(1) Acute arthritis and chronic arthritis of gout can cause multiple joints of body size, acute joint redness, swelling, heat, pain and limited mobility, with recurrent acute arthritis and intra-articular gout As the stone enlarges, the joint structure can be destroyed to cause joint deformity and movement disorders.
(2) The incidence of renal uric acid stones in gout patients is about 25%. Stones block the renal tubules, which can cause acute renal failure and endanger the lives of patients.
2. Population prevention
For middle-aged and elderly men with joint pain, the possibility of gouty arthritis should be considered. The serum uric acid content can be determined for screening.
3. Individual prevention
(1) Primary prevention: diet control: patients with gout should use low-calorie diet to maintain ideal body weight, while avoiding sorghum food, mainly including animal internal organs, sardines, clams, snakes, seafood and thick broth, followed by Fish and shrimp, meat, peas, etc., various cereal products, fruits, vegetables, milk, dairy products, eggs, tofu soy milk, with the least amount of alcohol, strictly stop drinking all kinds of alcohol, drink plenty of water to maintain urine output.
(2) Secondary prevention: avoid the cause of urate crystallization: avoid cold and damp, excessive fatigue, mental stress, wear shoes should be comfortable, prevent joint damage, use drugs that affect uric acid excretion, such as diuretics, low-dose aspirin Etc., in the case of typical arthritis episodes, with a family history, older men should consider this disease in order to achieve early diagnosis.
(3) Tertiary prevention: If there is a risk of perforation of huge gout stones, or if the joints affect the joint function in the vicinity of the joint, surgical resection should be considered. If the sinus has been worn out, the urate crystals can be scraped off. , after the formation of granulation tissue and then skin grafting, such as joints have been severely damaged, if necessary, can be used for joint fusion.
Prevention and treatment of concomitant diseases: simultaneous treatment of associated hypertension, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease.
Complication
Gout and complications of hyperuricemia Complications, hypertension, arteriosclerosis, coronary heart disease, type 2 diabetes
Patients with hyperuricemia are obese, often complicated with hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease, type II diabetes (NIDDM). Among the causes of death in elderly gout patients, cardiovascular factors exceed renal insufficiency.
Symptom
Symptoms of gout and hyperuricemia Common symptoms Urine is black gout nodules, body discomfort, white blood cells in joint fluid... Toe gout fatigue, fatigue, coma, slow growth, methionine malabsorption syndrome
Asymptomatic hyperuricemia
Serum urate concentration increased with age, more than 416mol / L (7mg / dl), can be described as hyperuricemia, this period only increased blood uric acid, no urate deposition and tissue inflammation, male patients from adolescence After the increase in blood uric acid, most women are seen in the menopause, most patients stay at this stage, and no clinical symptoms, only a small number of patients develop gout, but the higher the serum uric acid concentration, the longer the duration, the gout occurs The more opportunities there are.
2. Acute gouty arthritis
Is the most common first symptom of primary gout, occurs in the lower extremity joints, more than half of the first episodes in the big toe, about 90% of the patients in the whole course of the big toe is involved, the typical onset of acute onset, patients can It was very healthy when going to bed, but suddenly awakened by foot pain at night, the symptoms reached a peak within a few hours, and the joints and surrounding tissues appeared red, swollen, hot, painful, painful, and even unable to endure the cover of the bedding. The vibration of the indoor footsteps may cause joint exudation when the large joints are involved, which may be accompanied by systemic symptoms such as fever, headache, increased white blood cells, and increased erythrocyte sedimentation rate. Some patients have fatigue before the onset, body discomfort and local pain of the joints, sometimes Back to several years ago, except for the big toe is the most common site of the disease, the toe, ankle, knee, finger, wrist, elbow joint are also good sites, shoulders, hips, spine and other joints are less involved, the initial incidence of 75% ~90% begins in a single joint, repeated attacks will increase the number of joints, all seasons can be affected, but spring and autumn, frequent, mid-night disease, minor joint damage, surgery, fatigue, infection, spirit Stress, excessive fatigue, high sorghum diet, alcohol abuse, etc. are common causes.
The untreated gout attack process is also different. Most gout attacks can be relieved for several days to several weeks. The joint inflammation subsides and the activity can be completely restored. The local skin changes from redness to brownish red and gradually returns to normal. Sometimes it can appear off. Chips and itching, then enter the asymptomatic stage, which is intermittent, this period can last from several months to several years, most of them relapse within half a year to one year, and then can be attacked several times a year or several times a year, occasionally only for life One episode, recurrence can occur in the same joint, can cause chronic arthritis with joint deformity, can also occur in other joints, after the inflammation subsides can completely return to normal, individual patients with mild inflammation is not typical, to be deformed At the time, attention was paid to the fact that most patients became more and more frequent, and the condition became heavier and heavier. Eventually, the joint deformity was caused. Only a very small number of patients had no intermittent period after the initial attack, and the continuation of the development of chronic arthritis, before, during, and after the attack The concentration of uric acid does not necessarily change specifically. Sometimes uric acid can be in the normal range and it is difficult to diagnose. A larger series of statistics, 62% of the disease Relapse during the first year, 16% in 1 to 2 years relapse, recurrence of 11% and 2 to 5 years at 4% recurrence 5 to 10 years, 7% in long-term follow no recurrence.
3. Chronic gouty arthritis
As the disease progresses, the deposition of urate in the joints gradually increases, the seizures gradually become more frequent, the intermittent period gradually shortens, the affected joints gradually increase, and the inflammation gradually enters the chronic phase and cannot completely disappear.
(1) Joint deformity and stiffness: due to the continuous deposition of tophi, the irregular swelling of the joints, the destruction of joint tissues, the increase of fibers, and the defect of bone erosion often lead to joint hypertrophy, deformity, stiffness and limited mobility. Inflammation is not obvious, only chronic joint disease, spinal column, sterno-lock joint and costal cartilage are involved, sometimes the symptoms are not obvious, chest pain, low back pain, intercostal neuralgia and sciatica, sometimes resemble angina, from The first episode of gout to chronic arthritis forms an average of about 10 years.
(2) tophi: urate crystals are deposited in the tendon near the joint, tendon sheath and subcutaneous connective tissue, forming yellow-white, ridges of varying sizes are tophi, which can increase with urate deposition. Small as rice grains, as large as eggs, often occur in the ear wheel, toe, finger, palm and elbow joints, less common tophi can invade the tongue, epiglottis, vocal cords, sacral cartilage, cavernous body, penis foreskin And heart valve, tophi will not affect the liver, spleen, lung and central nervous system, the process of tophi deposition is occult development, no pain, toads gradually increase, the appearance is meager, can be broken to form fistula, may have The white powdered sodium urate is crystallized, and the urate has a bacteriostatic effect, so secondary infection is rare. If the tophi is not scraped, it is not easy to heal, the occurrence of tophi and the degree of hyperuricemia. The severity of the affected kidney is related to the course of the disease. There are reports of blood urate below 472mol/L (8mg/dl), 90% without gout nodules, and blood urate concentration greater than 531mol/L (9mg/dl). % has gout nodules, the longer the course of the disease, The more opportunities students nodules.
(3) Kidney disease: Kidney disease of gout is often asymptomatic in the early stage. When there is stone formation and kidney function damage is serious, various clinical manifestations can occur, which can be divided into three manifestations.
1 gouty nephropathy: mainly refers to the interstitial nephritis caused by urate crystal deposition in the renal medulla, which may involve the renal tubules and glomeruli, but different from the concept of uric acid nephropathy, the early manifestation of intermittent proteinuria, after Development is persistent, with hematuria, low urine weight, increased nocturia and other impaired renal function, often accompanied by hypertension, urinary tract infection, urinary tract stones and other factors, the progression of the disease can develop into azotemia and Uremia, uremia is the cause of death in 17% to 25% of patients with gout, and there is no characteristic difference between gouty nephropathy and other causes of renal failure.
2 urinary calculi: 20% to 25% of patients with primary gout complicated with urinary acid urinary calculi, the higher the degree of hyperuricemia, the greater the excretion of uric acid in 24h, the more easily complicated with urinary calculi, about 1/3 The patient's kidney stone symptoms occur earlier than gouty arthritis. Small sediment-like stones can be asymptomatic with urine excretion. The larger ones often cause renal colic, hematuria and urinary tract infection symptoms. Pure uric acid stones can be X-ray. Through the development without transmission, the mixed calcium salt can be found on the flat film of the urinary tract.
3 acute uric acid nephropathy: a large number of uric acid crystals block the renal tubular lumen, which can lead to obstruction of urine flow and acute renal failure.
Because blood uric acid is mostly increased, uric acid crystals are rapidly deposited in the renal collecting duct, renal pelvis, renal pelvis and ureter, and more often secondary to myeloproliferative diseases. When chemotherapy or radiotherapy is used, cell division proliferates too rapidly and rapidly, and nucleic acid decomposition suddenly increases. Produced by a large amount of uric acid, blood uric acid value can be as high as 40 ~ 60mg / dl, uric acid crystal deposition in the renal tubules severely block the urinary tract, manifested as oliguria, no urine and rapid development of azotemia, a large number of urine Uric acid crystals and red blood cells, if not treated in time, can die due to renal failure, effective treatment such as alkalized urine, large amounts of infusion and diuretics can often use kidney function to quickly return to normal, primary gout acute obstructive nephropathy Less common.
(4) Cardiovascular disease: patients with gout can be associated with hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease and type 2 diabetes. In the cause of death of elderly patients, cardiovascular factors far exceed the factors of renal insufficiency, limiting diet,
(5)
(6)1%2
(von Gierke)
A.6-
B.
C.
D.10
Lesch-Nyhan-(HGPRT)16881020%-
Examine
1. Blood routine and blood sedimentation
60mm/h
2. Urine routine
3.
416µmol/L(7mg/dl)357µmol/L(6mg/dl)
4.
24h3.54mmol(600mg/24h)
5.
10007000/mm350000/mm3
Diagnosis
Diagnostic criteria
1.()50005/mm3
2.24h3600mg/1.72m2/d800mg(HGPRT);
Differential diagnosis
1.
()()3624h24h210600mg0.340.4324h
2.
(1)(ASO>500U>80U>128U)C
(2)
(3)X
(4)
3.
(1)X
(2)()20%
(3)ASOC
(4)
