Hyperuricemia: Description, Causes and Risk Factors:
Hyperuricemia is defined as a serum uric acid level greater than 7.0 mg/dL, as measured by the automated enzymatic (uricase) method. Causes of hyperuricemia can be primary (increased uric acid levels due to purine) and secondary (high uric acid levels due to another disease or condition). Sometimes, the body produces more uric acid than it is able to excrete.
Incidence of hyperuricemia among the women totaled 34%, among the men - 32%. The largest share of hyperuricemia in women (24.8%) and men (45.4%) was revealed in the age group of 60-69 years.
There are two circumstances in which an excessive intracellular level of phosphoribosyl pyrophosphate is probably responsible for overproduction of purines and hyperuricemia. The first of these is Type I glycogen storage disease, in which the absence of glucose-6-phosphatase activity results in augmented disposition of glucose-6-phosphate by way of the oxidative pathway of glucose catabolism. Children with this form of glycogen storage disease overproduce uric acid, quite possibly because of excessive biosynthesis of phosphoribosyl pyrophosphate. The second circumstance is found in patients with severely diminished activity of hypoxanthine guanine phosphoribosyltransferase. This is the enzyme that catalyzes the reaction of hypoxanthine or of guanine with phosphoribosyl pyrophosphate in a salvage pathway which returns these purine bases to the ribonucleotide pool.
Three different inherited enzyme defects result in early development of marked hyperuricemia and gout. In glucose-6-phosphatase deficiency (glycogen storage disease type I), hyperuricemia results from both excessive uric acid production and impaired uric acid excretion. In severe and partial deficiencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and in superactivity of 5-phosphoribosyl-1-pyrophosphate synthetase (PRS), the basis of hyperuricemia is purine nucleotide and uric acid overproduction. Accelerated purine synthesis in these two disorders is a consequence of increased intracellular availability of PP-ribose-P, a critical regulatory intermediate in the pathway of purine synthesis de novo. The precise biochemical bases of neurologic manifestations encountered in patients with severe HPRT deficiency or defects in the regulation of PP-ribose-P synthetase (PRS) activity remain unknown.
Certain cancers, or chemotherapy agents may cause an increased turnover rate of cell death. This is usually due to chemotherapy, but high uric acid levels can occur before chemotherapy is administered. After chemotherapy, there is often a rapid amount of cellular destruction, and tumor lysis syndrome may occur. You may be at risk for tumor lysis syndrome if you receive chemotherapy for certain types of leukemia, lymphoma, or multiple myeloma, if there is a large amount of disease present.
- Kidney disease - this may cause you to not be able to clear the uric acid out of your system, thus causing hyperuricemia.
- Medications - can cause increased levels of uric acid in the blood.
- Endocrine or metabolic conditions - certain forms of diabetes, or acidosis can cause hyperuricemia.
- Elevated uric acid levels may produce kidney problems, or none at all. People may live many years with elevated uric acid levels, and they do not develop gout or gouty arthritis (arthritis means "joint inflammation"). Only about 20% of people with elevated uric acid levels ever develop gout, and some people with gout do not have significantly elevated uric acid levels in their blood.
- Any metabolic aberration which reduces the rate of synthesis of AMP (adenosine monophosphate) or GNIP (glycogenin-interacting protein) from IMP (inosine monophosphate), or from purine bases by the salvage mechanism, or which accelerates the removal of nucleotides into macromolecules or through increased catabolism, may in theory result in reduced intracellular concentrations of regulatory nucleotides and release of the amidotransferase from inhibition. This would permit excessive synthesis of phosphoribosylamine and ultimately of uric acid.
Both genetic and environmental factors contribute to the high prevalence of hyperuricemia in many populations. Cumulative effects of multiple genes are more prominent when heterogeneous populations are studied. Single gene influences, some autosomal dominantly transmitted and some X-linked, are identifiable in studies of less genetically diverse groups. Glucose-6-phosphatase deficiency is an autosomal recessive trait. Both HPRT deficiency and PRS superactivity are X-linked traits.
A positive association between hyperuricemia and cardiovascular disease has been reported, but no study has evidenced yet the precise role of serum uric acid in the development of cardiovascular disease. In addition, no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia, even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage.
The present prospective cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population. The subjects were 49,413 Japanese male railroad workers, aged 25-60 years at enrollment. Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982. The vital status of the subjects was traced until the end of 1985 for those who remained alive. During an average 5.4-year study period, 984 deaths were recorded. Those with serum uric acid over 8.5 mg/dL showed elevated relative risks (RRs) of death in all causes (RR 1.62, p<0.01), coronary heart disease (RR 1.52), stroke (RR 2.33, p<0.01), hepatic disease (RR 3.58, p<0.01), and renal failure (RR 8.52, p<0.01), as compared with those with serum uric acid levels of 5.0-6.4mg/dL. The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol (2.00, p<0.01), age and alcohol intake (1.85, p<0.001), age and smoking (1.69, p<0.001), age and gout treatment (1.61, p<0.05), and also age and BMI (1.50, p< 0.05). On the other hand, the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose (1.62), age and systolic blood pressure (1.32), age and GOT (1.23), and also age and history of cardiovascular disease (1.17). These results showed that hyperuricemia has a strong association with the RRs of death in all causes, coronary heart disease, stroke, hepatic disease and renal failure, and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy.
Often times, you would not experience any symptoms. Hyperuricemia without symptoms is referred to asymptomatic hyperuricemia. However, if you have the following symptoms you may have hyperuricemia:
If you certain forms of cancer (leukemia
, lymphoma, or multiple myeloma), you may experience chills, fever and fatigue.
- Kidney problems associated with the formation of kidney stones.
- Problems with urination.
- Inflammation of joints caused by gout (a disease often associated with hyperuricemia).
During the physical, the doctor will examine the painful joints and ask you questions about the pain and swelling to determine if the hyperuricemia is from gout.
Have a blood test to determine the amount of uric acid in your blood. A simple blood test will show increased levels of uric acid. For those who have kidney disease, the level of uric acid in the blood can indicate a worsening condition. A blood test will help the doctor diagnose hyperuricemia and determine the treatment you need.
Test for crystals of hyperuricemia with a joint fluid draw. In this test, the doctor withdraws fluid from the affected joint and examines it under a microscope. If you have swollen and painful joints, it may be caused by crystals that form when the body does not get rid of the uric acid. The uric acid that remains will form crystals that can be seen under the microscope. The crystals are pointy and cause a great deal of pain when surrounding the joint. The crystals, named urate crystals, are also responsible for certain types of kidney stones. For recurring bouts of hyperuricemia or gout, you should have a blood test and joint fluid test to determine if the medication you take is effective.
Treatment of metabolic disorders, including hyperuricemia, always starts from an assessment that goes beyond the finding of analysis outside normal limits. The finding of hyperuricemia can be not followed by any specific measure, if it predicts that the uric acid will return to normal values (unbalanced diabetes), or require a long term treatment (gout). Of course, if there are clinical manifestations (joints, kidneys), the doctor will recommend specific measures for each problem.
In all cases, if is necessary to set a long-term treatment to lower the uric acid, this treatment refers to two measures: diet and medication.
Reducing fat can directly contribute to a better elimination of uric acid. At the same time is recommended a good hydration and consumption of food with beneficial proprieties: low-fat dairy products, foods rich in vitamin C. Also, if there is a recommendation for medication (allopurinol), treatment should be followed and reviewed regularly (depending not only on uric acid, but others parameters like creatinine, age, weight).
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.