Uric acid is produced in the body by the breakdown of purines. These purines in turn are sourced from the breakdown of genetic material when old or damaged cells are normally destroyed in the body. Other purines comes from the metabolism of purine-rich foods, primarily proteins, that are ingested. These are found in foods like anchovies, asparagus and red meats, particularly offals. Since the human body does not have enzymes like uricase which can metabolize the uric acid further, it has to be eliminated from the body. Most of this elimination occurs by way of the kidneys but it can also be eliminated through the bowels.
Uric acid may exist in the forms of salts and ions known as urates. This is then passed out of the body by excretion through the kidney. Urates are filtered at the the glomerulus of the nephron, reabsorbed, secreted back into the tubule and then reabsorbed again. In this way 90% of the uric acid in the body is reabsorbed back into the body. However, the activity of the kidneys are sufficient to regulate the levels of uric acid in the body. While the intestinal elimination can to some extent compensate in the event of kidney failure, the kidneys are necessary for continued maintenance of the uric acid levels within a normal range in the body.
What is hyperuricemia?
Hyperuricemia is the term for excessively high levels of uric acid in the blood. This may happen when there is an overproduction of uric acid and/or an underexcreation of uric acid in the body for various physiological and pathological causes. Hyperuricemia is largely asymptomatic but when it does produce symptoms in the body, this is mainly limited to the joints and kidneys in the form of gouty arthritis and kidney stones respectively.
Causes of Hyperuricemia
Most cases of hyperuricemia are a result of underexcretion rather than overproduction. Some of the causes of underexcretion of uric acid includes :
- Renal insufficiency (underfunctioning of the kidney)
- Hypertension (high blood pressure)
- Hypothyroidism (underactivity of the thyroid gland)
- Hyperparathyroidism (overactivity of the parathyroid gland)
- Lead poisoning
- Acidosis (ketoacidosis and lactic acidosis)
- Down syndrome
- Drugs (aspirin, cyclosporine, diuretics, ethambuol, levodopa, nicotinic acid, pyrazinamide)
- Idiopathic (unknown causes)
Uric acid overproduction may be caused by :
- Deficiency of enzymes that are responsible for uric acid excretion
- Diet high in purines
- Increased cell breakdown (purines are present in nucleic acid which is the genetic material of cells)
- Tumor lysis syndrome (complications from the destruction of cancer cells) is more frequently seen with lymphoma and leukemia.
- Idiopathic (unknown causes)
Sometimes a combination of both underexcretion and overproduction of uric acid may be responsible for hyperuricemia. This may be caused by :
- Excess alcohol consumption
- Strenuous exercise
- Disorders with carbohydrate metabolism
Signs and Symptoms
Hyperuricemia is largely asymptomatic. The saturation level for uric acid is approximately 6.4 to 6.8mg/dL. The maximum level is about 7.0 mg/dL and symptoms may only become apparent once this level is exceeded significantly. This means that the urates cannot remain dissolved and will begin to precipitate and form crystals.
The synovial fluid in joints are a poor solvent of urates compared to blood and precipitation will occur much sooner. Crystals can become very large and form sharp needle-like structures. This condition of the joint is known as gout and can lead to attacks of painful joint inflammation (gouty arthritis). Other symptoms include redness of the overlying skin with joint swelling and at times fever.
Precipitation can also occur within the kidneys where it leads to uric acid (not urate) stones. Furthermore hyperuricemia increases the chances of other kidney stones forming including the more common calcium oxalate and calcium phosphate stones. Kidney stones may be asymptomatic if it is small enough to pass out of the urinary tract or can cause intense symptoms like flank pain, blood in the urine (hematuria) and pain upon urination (dysuria).
Dietary modification is helpful but does not remove the need for other measures as most purine is derived from endogenous sources. It should involve limiting the intake or avoiding certain foods altogether and increasing water intake. The latter is especially of value in a person repeatedly passing uric acid and gravel stones.
Ideally the water intake should be between 2 to 3 liters per day in a person with hyperuricemia although about 1.8 liters of water daily is sufficient. Water consumption should be spread out over the waking hours and large amounts should not be drank at one sitting to make up for shortfalls. Alcohol should be avoided altogether, particularly beer. However, a small amount of alcohol can be consumed if a person is not experiencing an acute attack of gout. Caffeine intake should also be limited. Should there be alcohol or caffeine intake, it is essential to drink sufficient water as these substances dehydrate the body thereby increasing the chance of precipitation.
There are a number of foods that are high in purine and should be eaten in small quantities or avoided where possible. It is important to bear in mind that all meat, poultry and fish are high in purines and should be consumed in moderation – less than 7 ounces (200 grams) daily. Proteins from vegetables, grains and legumes may be a safer alternative. Certain foods that are very high in purines should be avoided altogether and this includes anchovies, herring, mackerel and offals (organ meats).
Asparagus and mushrooms should also be eaten sparingly. Dairy consumption should be consistent and low fat or fat free dairy products are a better option. Refined carbohydrates such as wheat/flour and sugar are best kept to a minimum in the diet. Maintaining the prescribed diet does not mean that medication and other treatment options should be stopped.
Asymptomatic hyperuricemia is usually not treated although prophylactic (preventative) treatment may be considered in patients at risk of symptomatic hyperuricemia like with tumor lysis syndrome in patients on chemotherapy. Medication for hyperuricemia involves the use of drugs that either reduce uric acid production (xanthine oxidase inhibitors like allopurinol or febuxostat) or increases uric acid excretion (probenicid). Symptomatic treatment in the event of gout or uric acid kidney stones includes the use of non-steroidal anti-inflammatory drugs (NSAIDs like indomethacin), corticosteroids and/or colchicine (less frequently used these days). Potassium citrate may help to reduce the acidity and decrease uric acid solubility in patients at risk of kidney stones.