URIC ACID

Question 1

product of catabolism of the purine nucleic acids. Although it is filtered by the glomerulus and secreted by the distal tubules into the urine, most uric acid is reabsorbed in the proximal tubules and reused

Answer 1

Uric acid

Question 2

Uric acid is relatively insoluble in plasma and, at high concentrations, can be deposited in the

Answer 2

joints and tissue, causing painful inflammation

Question 3

Purines, such as

Answer 3

adenine and guanine

Question 4

such as adenine and guanine from the breakdown of ingested nucleic acids or from tissue destruction, are converted into uric acid, primarily in the liver.

Answer 4

Purines

Question 5

Uric acid is transported in the plasma from the liver to the kidney, where it is filtered by the

Answer 5

glomerulus

Question 6

98% to 100% of the uric acid from the glomerular filtrate occurs in the proximal tubules

Answer 6

Reabsorption

Question 7

Renal excretion accounts for about 70% of uric acid elimination; the remainder passes into the

Answer 7

GI tract and is degraded by bacterial enzymes

Question 8

Nearly all of the uric acid in plasma is present as

Answer 8

monosodium urate

Question 9

At the pH of plasma (pH ~ __), urate is relatively insoluble; at concentrations greater than 6.8 mg/dL, the plasma is saturated

Answer 9

7

Question 10

may form and precipitate in the tissues

Answer 10

urate crystals

Question 11

In acidic urine (pH < ____), uric acid is the predominant species and uric acid crystals may form.

Answer 11

5.75

Question 12

Uric acid is measured to confirm diagnosis and monitor treatment of _____, to prevent uric acid nephropathy during chemotherapeutic treatment, to assess inherited disorders of purine metabolism, to detect kidney dysfunction, and to assist in the diagnosis of renal calculi.

Answer 12

gout

Question 13

based on the oxidation of uric acid in a protein-free filtrate, with subsequent reduction of phosphotungstic acid in alkaline solution to tungsten blue

Answer 13

Caraway method

Question 14

Caraway method method lacks

Answer 14

specificity

Question 15

the enzyme that catalyzes the oxidation of uric acid to allantoin, are more specific and are used almost
exclusively in clinical laboratories. The simplest of these methods measures the differential absorption of uric acid and allantoin at 293 nm.21 The difference in absorbance before and after incubation with uricase is proportional to the uric acid concentration

Answer 15

Methods using uricase (urate oxidase, EC 1.7.3.3)

Question 16

can cause high background absorbance, reducing sensitivity

Answer 16

Proteins

Question 17

can cause negative interference

Answer 17

hemoglobin and xanthine

Question 18

measure the hydrogen peroxide produced as uric acid is converted to allantoin

Answer 18

Coupled enzyme methods

Question 19

used to catalyze a chemical indicator reaction. The color produced is proportional to the quantity of uric acid in the specimen

Answer 19

Peroxidase or catalase (EC 1.11.1.6)

Question 20

this kind have been adapted for use on traditional wet chemistry analyzers and for dry chemistry slide analyzers

Answer 20

Enzymatic methods

Question 21

which destroy peroxide, if present in sufficient quantity, can interfere

Answer 21

Bilirubin and ascorbic acid

Question 22

Commercial reagent preparations often include
___________________________________ to minimize these interferences

Answer 22

potassium ferricyanide and ascorbate oxidase

Question 23

typically using UV detection, have been developed

Answer 23

HPLC (high-performance liquid chromatography)

Question 24

Uric acid may be measured in

Answer 24

heparinized plasma, serum, or urine

Question 25

should be removed from cells as quickly as possible to prevent dilution by intracellular contents

Answer 25

Serum

Question 26

may affect uric acid concentration overall, but a recent meal has no significant effect and a fasting specimen is unnecessary

Answer 26

Diet

Question 27

should be avoided

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Gross lipemia

Question 28

may falsely decrease results obtained by peroxidase methods

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High bilirubin concentration

Question 29

with concomitant glutathione release, may result in low values

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Significant hemolysis

Question 30

shown to increase values for uric acid

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Drugs such as salicylates and thiazides

Question 31

after red blood cells have been removed

Answer 31

Uric acid is stable in plasma or serum

Question 32

Serum samples may be stored refrigerated for _____days

Answer 32

3 to 5

Question 33

should not be used for specimens that will be tested by a uricase method

Answer 33

Ethylenediaminetetraacetic acid (EDTA) or fluoride additives

Question 34

Urine collections must be

Answer 34

alkaline (pH 8)

Question 35

expressed in conventional units of milligrams per deciliter can be converted to SI units using the molecular mass of uric acid (168 g/mol)

Answer 35

Results

Question 36

Abnormally increased plasma uric acid concentration is found in

Answer 36

gout, increased catabolism of nucleic acids, and renal disease

Question 37

disease found primarily in men and is usually first diagnosed between 30 and 50 years of age. Affected individuals have pain and inflammation of the joints caused by precipitation of sodium urates.

Answer 37

Gout

Question 38

result of overproduction of uric acid, although may be exacerbated by a purine-rich diet, drugs, and alcohol.

Answer 38

hyperuricemia

Question 39

In women, urate concentration rises after

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menopause

Question 40

may develop hyperuricemia and gout. In severe cases, deposits of crystalline uric acid and urates called tophi form in tissue, causing deformities

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Postmenopausal women

Question 41

Another common cause of elevated plasma uric acid concentration is increased metabolism of cell nuclei, as occurs in patients on chemotherapy for such proliferative diseases as

Answer 41

leukemia, lymphoma, multiple myeloma, and polycythemia

Question 42

which inhibits xanthine oxidase (EC 1.1.3.22), an enzyme in the uric acid synthesis pathway, is used for treatment

Answer 42

Allopurinol

Question 43

may exhibit elevated uric acid concentration

Answer 43

Patients with hemolytic or megaloblastic anemia

Question 44

Increased urate concentrations may be found following ingestion of a _____________________________________ or as a result of increased tissue catabolism due to inadequate dietary intake (starvation)

Answer 44

diet rich in purines (e.g., liver, kidney, sweetbreads, and shellfish)

Question 45

associated with significant increases in physiological uric acid concentrations

Answer 45

Inherited disorders of purine metabolism

Question 46

X-linked genetic disorder (seen only in males) caused by the complete deficiency of hypoxanthine–guanine phosphoribosyltransferase (EC 2.4.2.8), an important enzyme in the biosynthesis of purines

Answer 46

Lesch-Nyhan syndrome

Question 47

Mutations in the first enzyme in the purine synthesis pathway, phosphoribosylpyrophosphate synthetase (EC 2.7.6.1), also cause

Answer 47

elevated uric acid concentration

Question 48

produced in excess and compete with urate for renal excretion in these diseases

Answer 48

Metabolites such as lactate and triglycerides

Question 49

Hyperuricemia as a result of decreased uric acid excretion is a common feature of

Answer 49

toxemia of pregnancy (preeclampsia) and lactic acidosis

Question 50

causes elevated uric acid concentration because filtration and secretion are impaired

Answer 50

Chronic renal disease

Question 51

formation of kidney stones (renal calculi), may occur due to a variety of predisposing factors and conditions

Answer 51

Uric acid nephrolithiasis

Question 52

In acidic urine, the relatively insoluble uric acid precipitates to form calculi, which can cause

Answer 52

intense flank pain

Question 53

may be dissolved by alkalinization of the urine or treated by increased fluid intake and administration of xanthine oxidase inhibitors to reduce uric acid production

Answer 53

stones

Question 54

less common than hyperuricemia and is usually secondary to severe liver disease or defective tubular reabsorption, as in Fanconi syndrome (a disorder of reabsorption in the proximal convoluted tubules of the kidney)

Answer 54

Hypouricemia

Question 55

Decreased plasma uric acid can be caused by chemotherapy with 6- mercaptopurine or azathioprine, inhibitors of de novo purine synthesis, and as a result of overtreatment with allopurinol. Some studies have shown an association between low uric acid concentrations and neurodegenerative conditions such as

Answer 55

Alzheimer's and Parkinson's diseases

Question 56

Decreased uric acid Concentration

Answer 56

Liver disease Defective tubular reabsorption (Fanconi syndrome) Chemotherapy with azathioprine or 6-mercaptopurine Overtreatment with allopurinol

Question 57

increased uric acid Concentration

Answer 57

Gout Treatment of myeloproliferative disease with cytotoxic drugs Hemolytic and proliferative processes Purine-rich diet Increased tissue catabolism or starvation Enzyme deficiencies Lesch-Nyhan syndrome (hypoxanthine guanine phosphoribosyltransferase deficiency) Phosphoribosylpyrophosphate synthetase deficiency Glycogen storage disease type I (glucose-6-phos- phatase deficiency) Fructose intolerance (fructose-1-phosphate aldolase deficiency) Toxemia of pregnancy Lactic acidosis Chronic renal disease Drugs and poisons

Answer 58

Lesch-Nyhan syndrome (hypoxanthine guanine phosphoribosyltransferase deficiency) Phosphoribosylpyrophosphate synthetase deficiency Glycogen storage disease type I (glucose-6-phosphatase deficiency)