uric acid Non electrolytes of the plasma

Transcription

1 73 uric acid Non electrolytes of the plasma 1

2 Purines and uric acid Fig 2 JFI Uric acid is the major product of catabolism of the purine nucleosides adenosine and guanosine, Uric acid is sparingly soluble but, it is excreted through the kidneys because it can ionise to Na salt 2

3 Catabolism of common purine neucleotides JFI AMP IMP XMP GMP inosine hypoxanthine xanthine Uric acid 3

4 Purine catabolism and excretion Free purine bases from diet or obtained from other nucleotide metabolism can be reused ( salvaged) Diet 30% De novo synthesis (liver) Salvage pathways Purine nucleotides (IMP, AMP, GMP) ~98% of uric acid is filtered by the glomeruli is reabsorbed by th distal tubules and despite this ~3/4 of uric acid is eliminated by the kidneys. The remaining uric acid is secreted to the gastrointestinal tract (GIT), uric acid in GIT is metabolised by gut bacteria in a process called uricolysis : Uric acid +4H₂O 4NH₄++ + 3CO₂+ glyoxylic acid Purine catabolism 3/4 Fig 5: Degradation of purines to uric acid and its excretion 4

5 Gout : mainly caused by Super activity of PRPPS enzyme, which leads to Increase production of PRPP hence increased IMP,inosine, and uric acid Fig4 outline of de novo synthetic pathway for purines AMP IMP GMP Uric acid 5

6 Gout is an inflammatory disease, diagnosed by presence of crystals of mono sodium urate in synovial fluid Hyperuicaemia is excess uric acid in serum, and may result either from overproduction of or decreased excretion of uric acid Most cases of hyperuricemia are due to: 1-disturbed uric acid excretion via the kidneys 2-increased nucleic acid turnover (leukaemia, myeloma, radiotherapy, chemotherapy, trauma) 3-A high-purine diet (e. g., meat) 4- A rare hereditary disease. 5-Pb poisoning 6

7 Serum Uric acid test: 1-uric acid In blood it is used to diagnose gout. 2-The test is also used to monitor uric acid levels in people undergoing chemotherapy or radiation treatment for cancer. Rapid cell turnover from such treatment can result in an increased uric acid level. 3-The uric acid urine test is used to help diagnose the cause of recurrent kidney stones and to monitor people with gout for stone formation. Ammonium urate is most common kidney stone in patients who have prolonged increased levels of uric acid. 7

8 -Not all patients with gout will have increased uric acid levels, therefore, synovial fluid analysis is performed, the fluid is aspirated from the joint and examined under the microscope for Naurate crystals ( needle shape). This method is the most accurate reliable way for gout diagnosis -urineanalysis and radiology (only at early stages) may also be performed for confirmation Na urate crystals viewed by Polar microscope Na urate viewed by conventional microscopes 8

9 Treatment and management of gout -usually with non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen (90% of patients the attack is resolved within 5-8 days from the start of treatment) -corticosteroids (Adernocortictrophic hormone) useful for those intolerant to NSAID. - tricyclic plant alkaloid (Colchicine )that inhibits cell division, can be given orally to treat gout (effective and pain and swelling usually abates within 12 hours) -Diuretic can exacerbate hyperuricemia -Weight control, reduce alcohol, limiting purine rich foods advised 9

10 -Following recurrent attacks, uric acid-lowering drugs (uricosurics) may be prescribed (sulin pyrazole). Their action prevents the kidney from reabsorbing uric acid -Uric acid lowering drugs may be beneficial when given in conjunction with the xanthine oxidase inhibitor, allopurinol, which inhibits the synthesis of uric acid from xanthine. Xanthine, being more water soluble than uric acid, is excreted in urine and plasma uric acid concentrations are decreased xanthine oxidase inhibitor, allopurinol AMP IMP XMP GMP inosine hypoxanthine xanthine Uric acid 10 10

11 Hypouricemia Is a condition where the conc of uric acid is less than 2mg/dL It is much less common than hyperuricemia And it is mainly caused by: 1-severe hepatocellular disease with reduced purine synthesis or xanthine oxidase activity, the result is increased excretion of xanthine and hypoxanthine, and formation of xanthine stones (xanthinuria). 2-defective renal reabsorbtion of uric acid 3-over treatment with chemotherapy Q) What is pseudogout? 11