SERUM URIC ACID TEST Flashcards
In humans,_____ is the maior product of the catabolism of the purine nucleosides adenosine and guanosine.
uric acid (2,6,8-trihydroxypurine)
In humans, uric acid (2,6,8-trihydroxypurine) is the major product of the catabolism of the purine nucleosides____ and _____
adenosine and guanosine
Purines from catabolism of dietary nucleic acid are converted to ____directly.
uric acid
The bulk of purines excreted as uric acid prise from degradation of endogenous nucleic acids.
The daily synthesis rate of uric acid is approximately_____; dietary sources contribute another_____.
400 mg
300mg
Overproduction of uric acid may result from increased synthesis of
purine precursors
The metabolic pathways leading to endogenous uric acid synthesis are mediated by several enzymes in a complex fashion.
There is ______ from ribose-1-phosphate to inosine as well as a secondary “_____” pathway which leads to the production of uric acid by converting guanine and adenine bases into______, which is in the main pathway of xanthine production.
de novo synthesis
salvage
inosine
_______ is the main pathway of xanthine production
Xanthine is oxidized by_____ to uric acid.
inosine
xanthine oxidase
Renal handling of uric acid is complex and involves four sequential steps:
(1) ______ of virtually all the uric acid in capillary plasma entering the glomerulus;
(2)______ in the proximal convoluted tubule of about 98% to 100% of filtered acid;
(3) subsequent______ of uric acid into the lumen in the distal portion of the proximal tubule; and
(4) further______ in the distal tubule.
glomerular filtration
reabsorption
secretion
reabsorption
The net urinary excretion of uric acid is_______ of the amount filtered.
6% to 12%
The_____ properties of uric acid are important in considering uric acid concentrations in the circulation, in tissue, and in the kidneys.
Physicochemical
The first pKa of uric acid is
_____; above this pH, uric acid exists chiefty as rate ion, which is more soluble than uric acid.
At a urine pH below____, uric acid is the predominant form.
5.57
5.75
______ is measured
to confirm diagnosis and monitor treatment of gout,
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.
Uric acid
_______ occurs when monosodium urate precipitates from supersaturated body fluids;
the deposits of____ are responsible for the clinical signs and symptoms.
Gout
urate
_______ may be associated with rate crystals in joint fluid and with deposits of crystals (tophi) in tissue surrounding the joint.
Gouty arthritis
The deposits may occur in other soft tissue as well, and wherever they occur they elicit an interise inflammatory response consisting of polymorphonuclear leukocytes and macrophages.
The____ toe (first metatarsophalanges) joint is the classic site for gout.
big toe
_____ is a condition characterized by occasional attacks and long periods of remission: it is important to appreciate that the plasma uric acid concentration is often normal during an acute attack.
Gout
Kidney disease associated with______ may take one or more of several forrns:
1) gouty nephropathy with urate deposition in renal parenchyma,
2) acute intratubular deposition of urate crystals, and
3) urate nephrolithiasis
hyperuricemia
is associated with “essential” hyperuricemia, which has a polygenic basis.
In greater than 99% of cases, the cause is uncertain but is probably due to a combination of:
— metabolic overproduction of purines (25% of patients have increased PRPP-amidotransferase activity)
— decreased renal excretion (30% of patients show decreased renal tubular secretion of uric acid), and
— increased dietary intake.
Primary gout
Very rarely, primary gout is attributable to inherited defects of enzymes in the pathways of purine metabolism.
The______ is characterized by complete deficiency of_____ (EC 2.4.2.8), the major enzyme of the purine salvage pathways.
Lesch-Nyhan syndrome
HGPRT
This X-linked genetic disorder is manifested clinically by mental retardation, abnormal muscle movements, and behavioral problems (self-mutilation and pathological aggressiveness.
Lesch Nyhan Syndrome
is a result of hyperuricemia attributable to several identifiable causes.
Renal retention of uric acid may occur in acute or chronic kidney disease of any type or as a consequence of administration of drugs; diuretics, in particular, are implicated in the latter instance.
Secondary gout
_____ caused by increased acetoacetic acid in diabetic ketoacidosis or by lactic acidosis may interfere with tubular secretion of urate.
Increased nucleic acid turnover and a consequent increase in catabolism of purines may be encountered rapid proliferation of tumor cells and in massive destruction of tumor cells on therapy with certain chemotherapeutic agents.
Organic acidemia
About _____ patients with clinical gout also has______ .
one in five
urinary tract uric acid stones
T or F
Although plasma and urinary uric acid should be measured in stone formers, many uric acid stone formers do not demonstrate either hyperuricosuria or hyperuricemia.
True
The etiology of uric acid stone formation also involves the passage of persistently acid urine with loss of the postprandial alkaline tide.
Undissociated uric acid (9K, 5.57) is____, whereas urate at pH 7.0 is greater than 10 times more_____. Thus, in patients with urinary pH persistently less than 6.0, normal urinary concentrations of acid will produce supersaturation.
insoluble——soluble
This condition is associated with increasing plasma uric acid concentration, probably caused by uteroplacental tissue breakdown and decreased kidney perfusion.
Preeclamptic Toxemia
Often defined as plasma urate concentrations less than 2.0 mg/dL (0.12 mmol/L.), is much less common than hyperuricemia.
It may be secondary to any one of a number of underlying conditions.
Hypouricemia
Severe hepatocellular disease with reduced purine synthesis or xanthine oxidase activity is one possibility.
Hypouricemia
Defective reabsorption may be congenital, as in generalized______ , or acquired.
_______ in combination with xanthinuria is rarely encountered and suggests a deficiency of xanthine oxidase, either in isolation or as part of combined molybdenum cofactor deficiency (sulfite: oxidase/xanthine oxidase deficiency).
Fanconi’s syndrome
Hypouricemia
These methods are based on the development of a blue reaction (tungsten blue) as it is reduced by urate in an alkaline medium (Caraway Method);
the color is read by spectrophotometry at wavelengths of 650 to 700nm.
Phosphotungstic Acid Method
Phosphotungstic Acid Method color
Tungsten blue
_____ methods are subject to rany interferences, and efforts to modify them have had little success in improving their specificity.
Phosphotungstic Acid Method
______ are more specific than PTA approaches.
Uricase methods
is used either as a single step or as the initial step to oxidize uric acid.
Uricase
became feasible and popular as a result of the availability of high-quality, low-cost preparations of the bacterial enzyme.
Preliminary precipitation of protein is not required.
Generally, only guanine, xanthine, and a few other structural analogues of uric acid act as alternative substrates, and then only at concentrations improbable in biological fluids.
Uricase methods
have replaced PTA methods in most current instrumentation.
Uricase methods
acts on uric acid to produce allantoin, hydrogen peroxide, and carbon dioxide.
Uricase
measure the hydrogen peroxide produced as uric acid is converted to allantoin.
____ or _____ (EC 1.11.1.6) is used to catalyze a chemical indicator reaction.
The color produced is proportional to the quantity of uric acid in the specimen.
Coupled enzyme methods
Peroxidase or catalase
In Enzymatic methods
_____ and _____, which destroy peroxide, if present in sufficient quantity, can interfere.
Commercial reagent preparations often include ______ and _____ to minimize these interferences.
Bilirubin and ascorbic acid
potassium ferricyanide and ascorbate oxidase
Uric acid may be measured in
heparinized plasma, serum, or urine
Specimen requirements
______ should be removed from cells as quickly as possible to prevent dilution by intracellular contents.
Serum
Specimen requirements
_____may affect uric acid concentration overall, but a recent meal has no significant effect and a fasting specimen is unnecessary- Gross lipemia should be avoided.
Diet
______ concentration may falsely decrease results obtained by peroxidase methods.
_____ , with concomitant glutathione release, may result in low values.
High bilirubin
Significant hemolysis
Drugs such as _____ and ____ have been shown to increase values for uric acid.
salicylates and thiazides
Uric acid is stable in plasma or serum after______ have been removed.
Serum samples may be stored refrigerated for______
red blood cells
3 to 5 days
_____ or _____ additives should not be used for specimens that will be tested by an uricase method. Urine collections must be alkaline (pH 8).
Ethylenediaminetetraacetic acid (EDTA) or fluoride
