Uric Acid PDF

Uric Acid  Uric acid is a final breakdown product of purine metabolism (adenosine/guanine) in liver.  Uric acid is transported to kidney and filtered (70%)  98% reabsorbed in PCT  Some secreted by DCT Net amount 6-12% of filtered amount  Remaining 30% by GIT...

Uric Acid  Uric acid is a final breakdown product of purine metabolism (adenosine/guanine) in liver.  Uric acid is transported to kidney and filtered (70%)  98% reabsorbed in PCT  Some secreted by DCT Net amount 6-12% of filtered amount  Remaining 30% by GIT  Present in plasma as monosodium urate  At plasma pH → relatively insoluble  Conc. > 6.8 mg/dl → plasma saturated → urate crystals may form & precipitate in tissue  Biochemistry  Molecular formula C5H4N4O3 ,and M.W=168.  It is problematic because humans do not possess the enzyme uricase, which converts uric acid into the more soluble compound allantoin.  Most other mammels can convert it to allantoin  Biochemistry  Purine bases include adenine and guanine which are present in the nucleus of the cells specifically in DNA and RNA.  Purine is used by the body to synthesis the nucleic acid and purine is derived from :- 1.Break down of ingested meat contains nucleic acid. 2.Synthesis from small molecules.  After uric acid formation ,it transported through the plasma to the kidney to be filtered by the glomeruolous.some of uric acid reabsorbed by proximal tubules and the remaining excreted by distal convoluted tubules.  Most of uric acid present in plasma in form of mono Na+ urates which are not soluble in water.  Renal excretion of uric acid involves 4 pathways: filtration, reabsorption, secretion, and post secretary reabsorption.  Urate is freely filtered at the glomerulus.  An active anion-exchange process in the early proximal convoluted tubule reabsorbs most of it.  Clinical application  Uric acid is measured 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 1- Hyperurecaemia :- High level of serum uric acid more than upper N.R.  Mainly in men  Pain & inflammation of joints by precipitation of sodium urates in tissues  ◦ Increased risk of renal calculi  hyperuricemia due to overproduction of uric acid in 25- 30%  Increased catabolism nucleic acids ◦ occurs in patients on chemotherapy for diseases such as leukemia & multiple myeloma.  ◦ Allopurinol inhibits xanthine oxidase, an enzyme in the uric acid synthesis pathway, is used to treat these patients.  Chronic renal disease ◦ causes elevated levels of uric acid because filtration and secretion are impaired.  However, uric acid is not useful as an indicator of renal function, because many other factors affect its plasma concentration.  Hypouricemia  less common than hyperuricemia  Secondary to severe liver disease  Defective renal tubular reabsorption  Chemotherapy with 6-mercaptopurine inhibit 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  uric acid has a UV absorbance peak at 293 nm.  Whereas allantoin does not  Newer methods couple uricase with catalase or peroxidase action on hydrogen peroxide product from allantoin production  Some interferences from reducing agents  Rferance range:  Males: 3.5-7.2 mg/dl  Females: 2.6-6.0 mg/dl  Gout  Gout is a disease found in men  between 30 and 50 years of age.  Affected individuals have pain and inflammation of the joints caused by precipitation of sodium urates. In 25% to 30% of these patients, hyperuricemia is a result of overproduction of uric acid,  It classify into two classes 1. Primary gout:- defect in urate metabolism (lack of enzyme). 2. when there is a complete absence of enzyme (HGPRT)”hypoxanthine guanine phosphoriposyl transferase” this case known as Lesch-Nyhan syndrome “very rare congenital condition found only in males. 2.Secondary gout:- In this case uric acid increases either from high production ( secondary) or impaired excretions like (polythythaemia –leukemia – chronic hemolytic anemia). Patient of gout suspected to renal stones. B- Increase nuclear breakdown :-like in:- Patient on chemotherapy (multiplemyloma ,lymphoma) C- Renal disease:- such as:- CRF( decrease GFR). Any question