uric acid

Pathology

1. URIC ACID Uric acid  is a waste product created during the normal breakdown of purines , naturally occurring substances found in foods such as liver, mushrooms, and dried beans etc.   Uric acid  is normally cleaned out of the blood by the kidneys, and passes out of the body along with urine

2. Chemically Uric acid is a nitrogenous compound ( 2,6,8 Tri hydr oxy purine ). Principal nitrogenous component of excrement of reptiles and birds. Small amount in mammalian Urine and its salts occours in the joints in gout.

3. Uric acid Uric acid is a heterocyclic compound of Carbon Hydrogen Nitrogen and Oxygen Formula : C 5 H 4 N 4 O 3 .

4. Bichemistry In humans, uric acid is the major product of the catabolism of the purine nucleosides adenosine and guanosine Purines from catabolism of dietary nucleic acid are converted to uric acid directly . The bulk of purines excreted as uric acid arise from degradation of endogenous nucleic acids . The daily synthesis rate of uric acid is approximately 400 mg. Dietary sources contribute another 300mg. In men consuming a purine-free diet, the total body pool of exchangeable urate is estimated at 1200 mg.

5. Gouty arthritis By contrast, patients with gouty arthritis and tissue deposition of urate may have urate pools as large as 18,000 to 30,000 mg . Overproduction of uric acid may result from increased synthesis of purine precursors.

6. URIC ACID produced through catabolism of purines nuclic acids(adenosine and guanine) in the liver, transported to kidney, filtered through glomerulus, most of which Is reabsorbed in the proximal tubules. Reabsorptin : 98-100% in proximal tubules. Excretion : through urinary system = 70% Through GIT = 30% Daily synthesis rate of uric Acid is 400 mg Dietary source 300mg

7. Cont…. Uric acid is insoluble in plasma and at high concentrations can be deposited in the joints and tissue, causing painful inflammation.

8. Renal Handling Renal handling of uric acid is complex and involves four sequential steps 1.glomerular filtration of virtually all the uric acid in capillary plasma entering the glomerulus; 2.reabsorption in the proximal convoluted tubule of about 98% to 100 % of filtered uric acid ; 3.subsequent secretion of uric acid into the lumen in the distal portion of the proximal tubule ; 4.further reabsorption in the distal tubule . The net urinary excretion of uric acid is 6% to 12% of the amount filtered. .

9. Cont ….. Approximately 8 to 12 % of the filtered urate is excreted in the urine as uric acid . Uric acid in urine exists as mono and disodium, potassium, ammonium and calcium urates . An average adult on a low protein diet excretes approximately 275 to 600 mg of uric acid in a 24 hours period.

10. Clinical applications Uric acid is measured to assess : Diagnosis and monitor treatment of gout. Diagnosis of renal calculi To detect kidney function. Inherited disorders of purine metabolism

11. Specimen required Heparinized plasma Serum Urine: must be alkaline

12. URIC ACID Measurement Two methods for uric acid measurement are commonly used in the clinical laboratory : Uricase Phosphotungstic acid.

13. Uricase Method: it is highly specific The hydrogen peroxide produced is reacted with chromogen in the presence of peroxidase enzyme, produces red Colour, the intensity of which is proportional to the amount of uric acid present in the sample.

14. Phosphotungstate Method: it is non specific The phosphotungstic acid reagent reacts with uric acid in alkaline solution. This oxidise uric acid to allantoin and is itself reduced to tungsten which is blue in colour . The intensity of the blue colour is proportional to the amount of uric acid

15. Normal values Adult male = 3.5 - 7.5 mg/dl Adult female= 2.6 - 6.0 mg/dl Urine = 250 - 750mg/dl Conversion Factor…… 59 umol /L

16. Factors affecting uric acid level Sex: higher in males due to increase body mass Body mass: level is increased in obesity. Diet: increased in meet intake, decreased fluid intake leads to increased retention of uric acid by the kidney. Exercise Pregnancy

17. HYPERURICEMIA A term used to describe individuals who have increased uric acid in the blood. Such individuals may be asymptomatic, but are at increased risk for associated renal problems . Hyperuricemia is defined as a serum urate concentration greater than 7mg/dl (416 umol /L) and may result from a number of disorders and conditions associated with increased urate production and/ or decreased renal excretion. Hyperuricemia Hyperuricemia is most commonly defined by plasma uric acid concentrations greater than 7.0 mg/ dL (0.42 mmollL ) in men or greater than 6.0 mgldL (0.36 mmol /L) in women. The major causes of hyperuricemia are summarized

18. HYPERURICEMIA Gout Sepsis Inherited disorders Anaemia ( hemolytic or megaloblastic anaemia) Leukaemias Lymphomas Polycythemia, chronic renal disorders Serum uric acid can be elevated due to reduced excretion by the kidneys. Ingestion of certain drugs (ethanol, cytotoxic drugs) Excessive consumption of purine rich foods (meats, viscera, leguminous vegetables) Obesity

19. DECREASED EXCRETION CAUSES: Hypertension Chronic renal failure Ketoacidosis Lactic acidosis Toxemia of pregnancy Diuretics (thiazides, furosemide)

20. Gout comprises a heterogeneous group of disorders characterized by: Hyperuricemia Attack of acute inflammatory arthritis Deposition of monosodium urate crystals through out the body ( tophi ). Nephrolithiasis GOUT

21. The four phases of gout progression include : Asymptomatic hyperuricemia Acute gouty arthritis Intercritical gout (intervals b/w acute attacks) Chronic tophaceous gout

22. Cont …. Gout is much more common in men than women. Gout in women occurs exclusively after menopause. Acute gout most commonly affects the first metatarsal joint of foot. Recent studies have shown that as many as 98% individuals with gout have a defect in the renal handling of uric acid. The acute inflammation in gout is a result of the interaction between monosodium urate deposits in the tissues and polymorph nuclear Leukocytes with a subsequent release of lysosomal enzymes, leukotrienes , prostaglandins and protease.

23. Abnormal serum uric acid level in endocrine disorders Among the factors, which may influence on the uric acid metabolism, the excess or deficiency of some hormones apparently induces the abnormal serum uric acid level. We described hyperuricemia and hypouricemia associated with endocrine disorders. Hyperuricemia due to ).

24. Cont ……. The increased production of uric acid is observed in myopathy associated with hypothyroidism, hyperthyroidism or hypoparathyroidism . Hyperuricemia due to the decreased renal uric acid clearance is associated with hypopituitarism, hypothyroidism, hyperparathyroidism, central diabetes insipidus , nephrogenic diabetes insipidus , Bartter syndrome, and diabetic ketoacidosis. Hypouricemia due to the increased renal uric acid clearance is associated with hypoparathyroidism , primary aldosteronism and inappropriate secretion of antidiuretic hormone (SIADH

25. Uric acid stone formation Saturation levels of uric acid in blood may result in one form of kidney stones when the urate crystallizes in the kidney. These uric acid stones are radiolucent and so do not appear on an abdominal plain X-ray, and thus their presence must be diagnosed by ultrasound for this reason or stone protocol CT. Very large stones may be detected on X-ray by their displacement of the surrounding kidney tissues