What is gout?
Gout: Pain that comes and goes like a gust of wind.
What is gout?
n It is a group of disorders in which purine metabolism is disturbed and/or uric acid excretion is impaired, resulting in an increase in uric acid in the blood
n Clinical features: hyperuricemia
Recurrent episodes of acute gouty arthritis
Gout stone deposits
Chronic arthritis with gouty nodular swelling
Uric acid nephropathy
History and current status of gout
n 5th century B.C. Greece Hippocrates
Imperial disease Wealthy disease Genetic disease/Spanish Empire, French Royals, English Tudors
Alexander the Great, King of Macedonia; Charles V, Emperor of the Roman Empire; Louis VII and Louis XIV, Kings of France; Anne, Queen of England; Kublai, Emperor of China; Franklin, President of the United States; Martin Luther and John Calvin, religious leaders; Newton, famous scientist
n Gout patronizes the wise
Spanish researchers found that a small finger of the Holy Roman Emperor Charles V had uric acid crystals 500 years ago, confirming that the ruler, who ruled across Europe, Asia and Africa, gave up his throne because he could not stand the pain of gout.
Despite his war record, gout produced “severe joint pains that severely limited his adult life and required him to travel in a special chair.
Historians speculate that the pain caused him to delay his military campaign against the French city of Metz, which he was unable to capture in 1552. This failure, combined with his illness, forced him to abdicate to his brother in 1556.
Charles V, who was particularly fond of meat and avid drinker of beer and wine, died at the age of 58.
The production and excretion of uric acid
Where does uric acid come from and where does it go?
Excretion of uric acid by the kidneys
Classification of hyperuricemia
and causes
Classification of hyperuricemia
I. Primary hyperuricemia
n Excessive production of uric acid – 10%
High purine diet;
Enzyme abnormalities: xanthine oxidase ↑
Phosphoribosyl pyrophosphate (PRPP) synthase ↑ (ATP → AMP)
n Decreased uric acid excretion – 90%
Unexplained molecular defects leading to renal excretion of UA ↓;
Classification of hyperuricemia
II. Secondary hyperuricemia
n Excessive production of uric acid
1. Massive breakdown of nucleic acids: malignant tumor radiotherapy, myelodysplasia, malignant lymphoma
2. Increased purine synthesis: glycogen accumulation disorder type I with G-6-P deficiency
n Decreased uric acid excretion
Chronic kidney disease, hypothyroidism, ketoacidosis, thiazide and tachyphylaxis, aspirin, ethambutol application.
Causes of hyperuricemia
n Genetic predisposition: Children of families with a history of gout and hyperuricemia are about 10 times more likely to develop the disease than the general population.
n Inappropriate diet: Often overeating, or eating too much protein-rich food and high-purine food.
n Obesity: The breakdown of subcutaneous fat produces a lot of ketone volume in the body, which prevents the kidneys from excreting uric acid.
n Gender: Men are about 20 times more likely than women to have uric acid, because female hormones facilitate the excretion of uric acid in the blood.
n Excessive exercise
: After excessive exercise, the body will produce a lot of lactic acid, which will also increase the burden on the kidneys and affect the excretion of uric acid. However, not exercising at all will slow down the blood flow and affect the kidney’s function of uric acid excretion, so you should exercise moderately every day.
n Medications: The formation of uric acid is accelerated when taking anti-cancer drugs, asthma medications, and antifungal drugs. When taking salicylic acid preparations (such as aspirin), diuretics, and anti-tuberculosis drugs, the excretion of uric acid is hindered.
n Alcohol : Drinking alcoholic beverages (especially beer) or using alcohol-containing drugs (such as nitroglycerin) increases uric acid concentration.
n Another 30% of patients with secondary hyperuricemia are due to diseases (e.g. leukemia, cardiac insufficiency, liver insufficiency, kidney disease)
Types of hyperuricemia
n Poor excretion: total uric acid excretion of less than 300 mg in 24hr
n Overproduction: Total uric acid excretion of more than 600mg in 24hr
Classification
Gout
High uric acid = painful L?
n Normally, the average uric acid value is about 2.4 to 6mg/dl in women and about 3.5 to 7.5mg/dl in men.
n About 7% of the average adult male has hyperuricemia, while only 17% have experienced gout symptoms.
n Uric acid values in children are generally only 3-4mg/dl
Male children have significantly higher uric acid after testosterone treatment.
n Gout attacks are almost never detected in women during childbearing years
Age and gender of gout prevalence
n Males Middle age and older account for 95% of prevalence
The peak age of prevalence is around 50 years
n Women account for about 5% of the prevalence
Occurs mostly after menopause
Pathogenesis of gout
Deposition of uric acid in the tissues
n Uric acid is present in all tissues except the central nervous system
n The solubility of uric acid in blood is 381µmol/l (6.4mg/dl)
(pH 7.4, 37°C), which is greater than this value and is saturated
n Deposition in the urine: pH dependent
PH 5.0, only 15% of free uric acid
PH 6.6, almost all uric acid is in the free state and is easily excreted
Clinical manifestations
n Acute gouty arthritis
n Gouty stones and chronic arthritis
n Gouty nephropathy
Pathogenesis of gouty arthritis
n Acute attacks are mainly due to rapid fluctuations in blood uric acid values
n It is an inflammatory response caused by uric acid sodium salt crystals
n Sudden ↑ of blood uric acid: uric acid crystals precipitate in the synovial fluid to form needle-shaped urates
n Sudden ↓ of blood uric acid: gout stone surface dissolves, releasing insoluble needle-like crystals
n Uric acid is phagocytosed by lysozyme w of neutrophilic white blood cells è lysozyme w out è PGèlitis
Clinical features of acute gouty arthritis
n rapid onset, usually appearing at night or early in the morning
n rapid development, with a peak in a few hours to 48h
n marked redness, swelling, heat and pain
n Severe pain
n 50%-70% (90%) of cases start in the first toe and metatarsal joint
n Single joint involvement
n No residual discomfort during remission
Gout-prone joints
Characteristics of acute gouty arthritis (II)
n Supersaturation of uric acid in the synovial fluid is a condition for acute gout attack.
n Role of temperature.
The solubility of sodium urate is 6.0 mg/dl at 37°C and
4.5mg/dl at 30°C
The temperature of the knee joint is 32 °C at rest and rises during exercise.
n Role of trauma.
The first metatarsophalangeal joint is most likely to be involved: maximum pressure per unit area
Connective tissue injury releases urate crystals into the joint cavity
Characteristics of acute gouty arthritis (III)
n is self-limiting
1. Local temperature rises and solubility increases
2.Local blood flow increases and urate enters the blood
3, phagocytosed urate can be destroyed by myeloperoxidase of leukocytes
4, Stress excites the adrenal cortex and inhibits inflammation.
Gout stone and chronic arthritis
- Gout stone (aggregates of sodium urate crystals)
Gout stones are yellowish-white flabby, irregular in shape, broken for a long time, with white material discharged and sodium urate crystals precipitated.
It can affect multiple sites, such as the heart, the ear, the first big toe, fingers, wrists, knees and elbows, and can affect joint movement.
Gouty nephropathy
- Chronic hyperuricemic nephropathy
Early proteinuria and microscopic hematuria Mostly interstitial lesions
Progressive increase in nocturia and decrease in specific gravity of urine
Eventually uremic syndrome
- Acute uric acid nephropathy
Rapid increase in blood uric acid concentration within a short period of time
Most often occurs in patients undergoing radiotherapy
Crystals in urine, hematuria, leukocyturia
Eventually, death occurs due to oliguria, anuria, and acute renal failure
- Uric acid kidney stones: 20% to 25%
Diagnosis of gout
n 1.According to medical history;
n 2.Blood uric acid examination: hyperuricemia can be determined for men >420μmol/L; for women >360μmol/L.
n 3.Bone and joint X-ray examination: non-specific soft tissue swelling is seen in the acute stage; in the chronic stage, cartilage rim destruction, joint surface irregularity, and gouty stone deposits are seen.
n 4, joint fluid: microscopic visible tonsure rod-shaped urate crystals.
n 5. Arthroscopy reveals urate crystals (white, small flocculent flakes) attached to various tissues within the joint.
Differential diagnosis
n 1, rheumatoid arthritis: slow onset, mostly female adolescents. The pain is mild and the rheumatoid factor is positive. Blood uric acid level is normal.
n 2, rheumatoid arthritis: mostly female, mostly wandering pain. Often accompanied by circumscribed erythema.
n 3. Pseudogout or cartilaginous calcium deposition. It is a synovitis caused by double hydrated calcium pyrophosphate crystals, similar to gout symptoms, but not due to urate crystals.
n 4, traumatic arthritis: because gout often attacks after trauma, it is easy to misdiagnose.
5.Septic arthritis: heavy symptoms of systemic toxicity and no uric acid crystals in joint fluid.
Prevention and treatment of gout
Treatment of asymptomatic hyperuricemia
Dietary principles for gout patients
n During acute illness, choose foods with low purine content as much as possible
n Do not consume too much protein: 1 g/kg/day
n Exercise moderately every day
n Drink plenty of water.
n Avoid alcohol (drinking on an empty stomach can cause acute attacks).
n Avoid overeating.
n Strict dietary control can only lower blood uric acid values by 1-2 mg/dl
Foods with high purine content
n Sprouted beans, soybeans.
n Animal offal
Fish
n Seafood, etc.
n Purple cabbage, shiitake mushrooms.
n Gravy, thick broth (juice), chicken essence, etc. .
n Yeast powder, yogurt.
-Three, vegetarian-based alkaline food
Watermelon and winter melon are not only alkaline foods, but also diuretic and have a therapeutic effect on gout.
Eat less lychee, cinnamon, tomatoes
Easy to cause acute attacks!
Beneficial health food
n Supplement Vit B12 folic acid to prevent the rise of uric acid value
n Celery seeds contain more than 20 anti-inflammatory ingredients and promote uric acid excretion
n Black cherry juice concentrate eliminates hyperpurine in the body
n Anthocyanins promote blood circulation, prevent enzymes from destroying collagen, and increase tissue anti-inflammatory capacity
Regular and moderate exercise
Do not suddenly do a lot of or strenuous exercise, it will accelerate the breakdown of muscle cells, so that the amount of uric acid suddenly increased
And strenuous exercise will produce a lot of sweat, which will reduce the amount of urine and affect the discharge of uric acid.
Therefore, you should exercise regularly and moderately every day to maintain your ideal weight on the one hand, and to promote blood circulation and prevent gout attacks on the other.
Treatment of acute arthritis
w Rest in bed and elevate the affected limbs
w Early treatment with anti-inflammatory and pain-relieving drugs
including colchicine, NSAID, hormones, analgesics
The early or late start of treatment is more important than the specific type of medication chosen
The earlier treatment is started, the faster and more complete the patient’s remission
w Do not change uric acid-lowering medication regimen
”Don’t add non-stop”
Colchicine (colchicine)
w Inhibits Fibrillar microtubule formation, reduces white blood cell activity
w Does not promote uric acid excretion, and cannot prevent gout from becoming chronic gouty arthritis, only relieves acute painful attacks
w 8-10mg for one day treatment
w 0.5-0.8mg/Kg Colchicine can cause bone marrow insufficiency and a 10% mortality rate
Timing of use
Within hours of onset 90% effective
12h-48h 75% effective
>72 hours Efficacy = NSAIDs
Colchicine
w Colchicine
1mg for the first time, 0.5mg every 1 hour thereafter
Until ① Pain relief
② Nausea, vomiting or diarrhea occur
③24h total amount up to 6mg
Later change to 0.5mg Tid maintenance for 7 to 10 days
Side effects: gastrointestinal reactions, bone marrow suppression, liver and kidney function damage, hair loss, depression
Contraindications: use with caution in cases of myelodysplasia, hepatic and renal insufficiency!
Non-steroidal anti-inflammatory drugs (NSAID)
w Oral: Traditional NSAID: anti-inflammatory pain 25-50mg,tid
Fenbid Rodin
Diclofenac Intacrine
COX-2 (cycloxgenase-2) inhibitor: Ciloxib
w Intramuscular injection: Coxsackie
w Side effects: peptic ulcer, bleeding
Steroids
w No response to colchicine, NSAIDs
w Exclusion of bacterial inflammation
w Prednisone 10mg, 3/day
w Combination with colchicine reduces rebound with colchicine alone
w 1/3 rebound after discontinuation
Sodium bicarbonate
w Oral 1~2g, 3/day
w Uric acid – urate (17 times more soluble)
Sodium bicarbonate
w Uric acid excretion-promoting drug
w Drugs that inhibit uric acid production
Benzbromarone
Benzbromarone
(Gout Rexin, Raglan Rexin)
w Inhibits uric acid reabsorption in the renal tubules
w Minor toxic effects
w No effect on liver or kidney function
w Low starting dose! 50mg qd after breakfast
w Gradually increase the dose to 100mg qd
w Normal uric acid after 6~8 days
w Contraindicated in moderate to severe renal insufficiency
Usage of Allopurinol
w 50-300mg/day, once daily in the morning or in divided doses
w Dose adjustment required in renal insufficiency
Ccr Allopurinol dose
≥90ml/min 300mg/d
≥60ml/min 200mg/d
≥30ml/min 100mg/d
<30ml/min 50~100mg/d
w Single or in combination with uric acid excretory agents
n Allergic dermatitis, exfoliative dermatitis in severe cases
n Hepatic impairment, acute hepatocellular necrosis
n Bone marrow suppression: granulocytopenia, reduced platelets
Crystal arthritis
w Gout: urate crystals (MSU)
w Pseudogout: calcium pyrophosphate (CPPD)
w Pseudopseudogout: calcium alkaline phosphate (hydroxyapatite, apatite)
w Steroids
w Cholesterol
w Charcot-Leyden crystals
w Other