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Questions and Answers
What is the primary function of the enzyme uricase in other mammals?
What is the primary function of the enzyme uricase in other mammals?
What percentage of uric acid is reabsorbed in the Proximal Convoluted Tubule (PCT)?
What percentage of uric acid is reabsorbed in the Proximal Convoluted Tubule (PCT)?
What is the molecular formula of uric acid?
What is the molecular formula of uric acid?
What is the net amount of uric acid excreted by the kidney?
What is the net amount of uric acid excreted by the kidney?
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What is the primary source of purine in the body?
What is the primary source of purine in the body?
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What is the primary function of measuring uric acid levels?
What is the primary function of measuring uric acid levels?
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What is the form of uric acid present in plasma?
What is the form of uric acid present in plasma?
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What is the significance of uric acid levels above 6.8 mg/dl?
What is the significance of uric acid levels above 6.8 mg/dl?
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What is the primary cause of pain and inflammation in joints in patients with hyperurecemia?
What is the primary cause of pain and inflammation in joints in patients with hyperurecemia?
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What percentage of patients with hyperuricemia have the condition due to overproduction of uric acid?
What percentage of patients with hyperuricemia have the condition due to overproduction of uric acid?
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What is the primary method used to measure uric acid levels in the blood?
What is the primary method used to measure uric acid levels in the blood?
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What is the reference range for uric acid levels in males?
What is the reference range for uric acid levels in males?
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What is the age range for patients typically affected by gout?
What is the age range for patients typically affected by gout?
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What is the cause of hyperuricemia in patients with chronic renal disease?
What is the cause of hyperuricemia in patients with chronic renal disease?
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What is the effect of allopurinol on uric acid synthesis?
What is the effect of allopurinol on uric acid synthesis?
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What is the classification of gout based on the underlying cause?
What is the classification of gout based on the underlying cause?
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Study Notes
Uric Acid Metabolism
- Uric acid is the final breakdown product of purine metabolism (adenosine/guanine) in the liver.
- 70% of uric acid is transported to the kidney and filtered, with 98% reabsorbed in the proximal convoluted tubule (PCT).
- 6-12% of the filtered amount is secreted by the distal convoluted tubule (DCT).
- The remaining 30% is eliminated through the gastrointestinal tract (GIT).
Biochemistry
- Uric acid has a molecular formula of C5H4N4O3 and a molecular weight of 168.
- Humans lack the enzyme uricase, which converts uric acid into the more soluble compound allantoin, unlike most other mammals.
- Purine bases, including adenine and guanine, are present in DNA and RNA and are derived from:
- Breakdown of ingested meat containing nucleic acid.
- Synthesis from small molecules.
Renal Excretion
- Uric acid is transported through the plasma to the kidney, where it is filtered by the glomerulus.
- Most uric acid in plasma is present as monosodium urate, which is insoluble in water.
- Renal excretion of uric acid involves four pathways: filtration, reabsorption, secretion, and post-secretary reabsorption.
Clinical Applications
- Uric acid measurement is used to:
- Assess inherited disorders of purine metabolism.
- Confirm diagnosis and monitor treatment of gout.
- Assist in the diagnosis of renal calculi.
- Prevent uric acid nephropathy during chemotherapeutic treatment.
Abnormalities of Uric Acid
Hyperuricemia
- Defined as a high level of serum uric acid (> upper normal range).
- Mainly affects men.
- Causes:
- Overproduction of uric acid in 25-30% of cases.
- Increased catabolism of nucleic acids.
- Chronic renal disease, which impairs filtration and secretion.
- Effects:
- Pain and inflammation of joints due to sodium urate precipitation in tissues.
- Increased risk of renal calculi.
Hypouricemia
- Defined as a low level of serum uric acid (< lower normal range).
- Less common than hyperuricemia.
- Causes:
- Severe liver disease.
- Defective renal tubular reabsorption.
- Chemotherapy with 6-mercaptopurine, which inhibits purine synthesis.
- Over-treatment with allopurinol.
Analytical Methods
- Primary method uses enzyme uricase (urate oxidase) to convert uric acid to allantoin.
- Differential absorption at 293 nm, where uric acid has a UV absorbance peak.
- Newer methods couple uricase with catalase or peroxidase action on hydrogen peroxide product from allantoin production.
Gout
- A disease primarily affecting men between 30 and 50 years of age.
- Characterized by pain and inflammation of joints due to sodium urate precipitation.
- Classified into two categories:
- Primary gout: defect in urate metabolism (lack of enzyme).
- Secondary gout: due to other factors.
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Description
Learn about the breakdown of purine metabolism, transportation, and filtration of uric acid in the liver and kidneys. Understand its reabsorption, secretion, and plasma concentration.
