Document on Kidney Function Tests-Uric Acid .pdf

Document on Kidney Function Tests-Uric Acid .pdf

• 1.
  by M.Sc. Ahmed Kareem Clinicalchemistry College of Pharmacy 5.st Estimation of Serum uric acid Kidney Function Tests
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  -The breakdown productof purines in man is uric acid . -The catabolism of purine nucleotides is accomplished as given below. Adenosine is first deaminated to form inosine. this reaction is catalyzed by adenosine deaminase which is found in liver and other tissues inosine is converted to hypoxanthine by the action of nucleoside phosphorylase -Guanosine is converted to guanine which is then deaminated to form xanthine . this conversion is catalyzed by guanase which is found in liver , spleen , pancreas and kidneys. -Hypoxanthine is oxidized to form xanthine by xanthine oxidase which also catalyzes the formation of uric acid from xanthine -In man ,purine metabolism ends as uric acid which is excreted in urine-- In mammals other than primates , however , uric acid is further metabolized to form allantoin by the enezyme uricase Introduction
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  -Abnormalities of purinemetabolism are often found in clinical practice, notably hyperuricemia and gout. -Urate is the end product of purine metabolism in humans. -The purines adenine and guanine are constituents of nucleic acid from deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). -The purines used by the body for nucleic acid synthesis may be derived from the breakdown of ingested nucleic acid, mostly from cell-rich meat, or they may be synthesized de novo from small molecules. About two-thirds of the body's urate (3-4 mmol/day) is produced endogenously, with one-third coming from exogenous dietary purines (1-2 mmol/day). Because of the poor solubility of urate humans are prone to the clinical effects of hyperuricemia, such as gout and renal damage.
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  Purines is oxidizedto urate. -Some adenine is oxidized to hypoxanthine, which is further oxidized to xanthine. -Guanine can also form xanthine. Xanthine, in turn, is oxidized to form urate. -The oxidation of both hypoxanthine and xanthine is catalyzed by xanthine oxidase in the liver. -Thus the formation of urate from purines depends on xanthine oxidase activity: gout may be treated using an inhibitor of this enzyme (allopurinol). -Purines can be reused for nucleic acid synthesis. -Some xanthine, and hypoxanthine can be resynthesized to purine nucleotides.
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  Purines Metabolism
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  -The serious consequencesof abnormal uric acid metabolism depend in part upon the insolubility of uric acid and its sodium monurate salt. -The former crystallizes in the kidney and urinary tract while the latter in cartilage and other tissues around the joints in gout -Plasma uric acid is filtered by the glomerulus's and is subsequently reabsorbed to about 90% by the tubules . -Uric acid concentration in serum are greatly affected by extra renal as well as renal factors. Clinically of Hyperuricemia -crystallization on joint -Precipitate of urate in the tissue -Precipitate of urate in kidney Excretion of urate Urate is filtered through the glomeruli and most is reabsorbed in the proximal tubules. Renal tubules can further excrete urate as well. Urinary excretion is slightly lower in males than in females, which may contribute to the higher incidence of hyperuricemia in men.
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  The factors thatmay contribute to hyperuricemia are: 1- increased synthesis of purines. 2- increased intake of purines>>>> High purine diets (meat and sea food) 3- increased turnover of nucleic acids. 4- increased rate of urate formation. Tim an 5- reduced rate of excretion>>> depends on GFR
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  Medications
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  Renal secretion maybe enhanced by uricosuric drugs (e.g. probenecid), which block tubular urate reabsorption. Tubular secretion of urates is inhibited by organic acids, such as lactic acid, and by ketones and thiazide diuretics. Salicylates and many other uricosuric agents have paradoxical and dose-dependent effects on the renal tubular handling of urate. Low doses of salicylates mainly reduce distal tubular secretion, tending to cause hyperuricemia. The dominant effect of high doses is increased urate excretion through inhibition of urate reabsorption.
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  -In acute caseof gout plasma urate level increase to a maximum of 15 mg /dl liver disorders such as cirrhosis lead to hypouricimia wherein the blood uric acid level of <2 mg/dl has been recorded ,as liver is the major site for uric acid synthesis Consequences of hyperuricemia 1- Crystallization in joints, especially those of the feet, produces the classic picture of gout. 2- Precipitation may occur in subcutaneous tissues, especially of the ears, and in the olecranon and patellar bursae and tendons. Such deposits are called gouty tophi. 3- Precipitation of urate in the kidneys and formation of renal calculi, causing progressive renal damage. For this reason it has been recommended that even asymptomatic cases should probably be treated if the plasma urate concentration is consistently higher than 10 mg/dl.
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  Hyperuricemia -Acute and chronicNephritis -Urinary obstruction -Gout -Diabetic ketoacidosis -High purine diet -Glycogen Storage Disease – Type1 -Leukemia -Malignant tumors especially with extensive necrosis -Acute infections -Alcohol ingestion and certain toxins and some diuretics -Elevate uric acid levels In clinical conditions wherein , the uric acid concentration exceed 8 mg/dl is normally referred to as hyperuriciemia . Various diseased states such as Renal (acute or cronic ) - nephrolithiasis - polycythemia - -chronic nephritic
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  - Decreased serum uricacid levels are associated with : - Hyporuricemia  Pernicious anemia  Acute yellow atrophy of the liver  -Salicylate(high doses is increased urate excretion through inhibition of urate  reabsorption. and cinchophen therapy  -Alcohol ( incease lactate and keoacid formaion ). Interfering factors that increase the level of uric acid -Hypertension -Diabetes -Hypercholesterolemia -Atherosclerosis -Thiazide drugs -Asprine (Low doses of salicylates mainly reduce distal tubular secretion) Hyperuricemia Increase synthesis of purine Increase intake of purine Increase excessive catabolism
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  primary gout -No obvioussecondary cause. -High serum urate (not always evident in an acute attack). -Presents usually with an acute monoarthritis. -Asymptomatic periods with recurrent acute arthritis leading to chronic joint damage if untreated. -Topni, renai siones, renal dysfunction may develop in chronic gout. Secondary causes of hyperuricemia and gout. Increased production • Myeloproliferative disorders • Malignancy • Tumor lysis syndrome • Psoriasis • Alcohol (nucleotide breakdown)
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  For the definitivediagnosis of gout, it is necessary to aspirate joint fluid during an acute attack. This is then examined microscopically, and the finding of needle-shaped urate crystals establishes the diagnosis. Further investigations should be directed toward the presence of a secondary cause of gout as well as the presence of the possible complications of hyperuricemia such as renal dysfunction. Because acute changes in serum (urate) (increases or decreases) can precipitate attacks of gout, the uricosuric drugs and allopurinol should be avoided within several weeks of an acute attack. To prevent acute flare-up of arthritis, NSAID should be continued whilst these drugs are introduced
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  Microscopically needle-shaped urate crystals
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  Estimation of Serumuric acid Principle: Uricase acts on uric acid to produce allantoin ,carbon dioxide and hydrogen peroxide .hydrogen peroxide in presence of peroxidase reacts with a chromogen ( amino- antipyrine and dichloro-hydroxybenxen sulfonate ) to yeld quinoneimine a red coloured complex.the absorbance measured at 520 nm Reagents
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  : Procedure Calculation:
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  Normal value Homework 1-case A 50-yearold man His biochemical results post –chemotherapy - Serum.Uric acid 16 mg/dl Interpretations