What is gout?

Gout is a crystal-related arthropathy caused by the deposition of monosodium urate (MSU), which is directly related to hyperuricemia caused by purine metabolism disorder and/or decreased uric acid excretion, especially acute characteristic arthritis and chronic tophi diseases, mainly including acute paroxysmal arthritis, tophi formation, tophi chronic arthritis, uric acid nephropathy and uric acid urinary calculi, and in severe cases, joint disability and renal insufficiency may occur. Gout is often accompanied by abdominal obesity, hyperlipidemia, hypertension, type 2 diabetes and cardiovascular diseases.

The cause of disease

The most important biochemical basis of gout is hyperuricemia. Normal adults produce about 750mg uric acid every day, of which 80% is endogenous and 20% is exogenous. These uric acids enter the uric acid metabolic pool (about 1200mg), and about 60% of uric acid in the metabolic pool is metabolized every day, of which 1/3 is metabolized by the intestine and 2/3 is excreted by the kidney, so it can be used.

1 primary gout

Most of them are hereditary, but only 10% ~ 20% have a family history of gout. Excessive uric acid production accounts for 10% of the etiology of primary hyperuricemia. The main reasons are the deficiency of purine metabolizing enzymes, hypoxanthine guanine phosphoribosyltransferase and the high activity of phosphoribosylpyrophosphate (PRPP) synthetase. Primary renal uric acid excretion reduction accounts for about 90% of primary hyperuricemia. The specific pathogenesis is unclear, and it may be a polygenic genetic disease, but organic nephropathy should be excluded.

2. Secondary gout

Refers to a clinical manifestation secondary to other diseases, and can also be caused by certain drugs. Myeloproliferative diseases such as leukemia, lymphoma, multiple myeloma, polycythemia, hemolytic anemia and cancer can lead to accelerated cell proliferation, increased nucleic acid transformation and increased uric acid production. After radiotherapy and chemotherapy, malignant tumors cause a lot of cell destruction, and nucleic acid conversion also increases, leading to an increase in uric acid production. Kidney diseases, including chronic glomerulonephritis, pyelonephritis, polycystic kidney disease, lead poisoning and advanced hypertension, can reduce uric acid excretion and lead to an increase in blood uric acid concentration. Drugs such as thiazide diuretics, furosemide, ethambutol, pyrazinamide, low-dose aspirin and nicotinic acid can competitively inhibit renal tubular excretion of uric acid and cause hyperuricemia. In addition, long-term use of immunosuppressants in renal transplant patients can also lead to hyperuricemia, which may be related to the inhibition of renal tubular excretion of uric acid by immunosuppressants.

classify

Gout can be divided into primary and secondary according to different causes. Primary gout refers to congenital purine metabolism disorder and/or uric acid excretion disorder on the basis of excluding other diseases; Secondary gout refers to the decrease of uric acid excretion caused by kidney diseases or some drugs, and the increase of uric acid production caused by myeloproliferative diseases and tumor chemotherapy.

clinical picture

Gout is more common in middle-aged men, only 5% in women, mainly in postmenopausal women. The occurrence of gout tends to be younger. The natural course of gout can be divided into four stages, namely asymptomatic hyperuricemia stage, acute stage, intermittent stage and chronic stage [3]. Clinical manifestations are as follows:

1. Acute gouty arthritis

Most patients have no obvious symptoms before onset, or only fatigue, general discomfort and joint tingling. Typical attacks are often awakened by joint pain in the middle of the night, and the pain gradually intensifies, reaching a peak in about 12 hours, showing tearing, cutting or biting, and the pain is unbearable. The affected joints and surrounding tissues are red, swollen, fever, pain and limited in function. Relieve itself in more than a few days or two weeks. The first attack mostly involved a single joint, and some occurred in the first metatarsophalangeal joint. In the later course of the disease, some patients are involved in this part. Followed by instep, heel, ankle joint, knee joint, wrist joint and elbow joint, shoulder, hip, spine and temporomandibular joint are less involved, and multiple joints can be involved at the same time, showing polyarthritis. Some patients may have fever, chills, headache, palpitation, nausea and other systemic symptoms, which may be accompanied by an increase in white blood cell count, erythrocyte sedimentation rate and C-reactive protein.

2. Intermittent attacks

Gout attacks can be relieved by themselves after several days to weeks. Generally, there is no obvious sequelae, or local skin pigmentation, desquamation and itching are left behind. After that, it enters an asymptomatic interval that lasts for months, years or more than ten years. Most patients relapsed within 65,438+0 years, with more and more times, more and more joints involved and longer symptoms. The affected joints generally develop from lower limbs to upper limbs, from distal small joints to large joints, and fingers, wrists, elbows and other joints are involved. A few patients may involve shoulder, hip, sacroiliac joint, sternoclavicular joint or spinal joint, or synovial sac, tendon and tendon sheath around the joint, and the symptoms tend to be atypical. A few patients have no intermission, and they show chronic arthritis after the first onset.

3. Chronic tophus lesion stage

Subcutaneous tophus and chronic tophus arthritis are the results of long-term hyperuricemia, and a large number of monosodium urate crystals are deposited under the skin, synovium, cartilage, bone and soft tissue around the joints. The typical part of subcutaneous tophi is auricle, and it is also common around recurrent joints and parts such as olecranon, achilles tendon and patellar bursa. The appearance is yellowish-white vegetation with different sizes under the skin, and the skin surface is thin. After rupture, white powder or paste is discharged, which will not heal for a long time. Subcutaneous tophi often coexists with chronic tophi arthritis. A large number of tophi deposited in joints can cause joint bone destruction, tissue fibrosis around joints and secondary degenerative changes. The clinical manifestations are persistent joint swelling and pain, tenderness, deformity and dysfunction. Chronic symptoms are relatively mild, but acute attacks may also occur.

4. Kidney disease

(1) Chronic urate nephropathy urate crystals are deposited in renal interstitium, leading to chronic tubulointerstitial nephritis. The clinical manifestations are decreased urine concentration function, increased nocturia, low specific gravity urine, small molecular proteinuria, leukocytosis, mild hematuria and tubular urine. In the late stage, glomerular filtration function may decrease and renal insufficiency may occur.

(2) Uric acid urinary calculi The uric acid concentration in urine is supersaturated and deposited in the urinary system to form stones. The incidence rate in gout patients is above 20%, which may appear before gouty arthritis. Those with smaller stones are gravel-like, which can be excreted with urine without symptoms; Larger cases can block the urinary tract, causing renal colic, hematuria, dysuria, urinary tract infection, renal pelvis dilatation and hydronephrosis.

(3) The levels of uric acid in blood and urine of acute uric acid nephropathy increased sharply, and a large number of uric acid crystals were deposited in renal tubules and collecting ducts, which led to acute urinary tract obstruction. The clinical manifestations were oliguria, anuria and acute renal failure. There are a lot of uric acid crystals in urine. It is mostly caused by malignant tumor and its secondary causes such as radiotherapy and chemotherapy (tumor lysis syndrome).