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Clinical Chemistry (nonprotein nitrogen compounds, bilirubin)
Terms in this set (39)
Name 3 substances that are elevated in the blood with renal disease.
BUN (blood urea nitrogen), creatinine, and uric acid.
What is urea?
The end product of protein metabolism. It is synthesized in the liver from ammonia and carbon dioxide.
What does azotemia mean?
An elevated level of urea in the blood.
What is the most common method for measuring BUN?
Enzymatic, using the enzyme urease to hydrolyze urea. The resulting ammonium ion is measured.
Why should tubes containing fluoride or citrate not be used when collecting blood for urea if analysis will be
by the urease method?
Fluoride and citrate inhibit urease.
Where is 98% of the body's creatine located?
What is creatinine?
The anhydride of creatine. Creatinine is formed from creatine by splitting out of water.
What reaction is used to measure creatinine?
The Jaffe reaction using alkaline picrate. It is a nonspecific but still clinically useful method.
What is the significance of the BUN:creatinine (BUN:CR) ratio?
It can be used to differentiate between the three types of azoternia: prerenal, renal, and postrenal.
What is the least variable nitrogenous constituent of blood?
Creatinine, because it is related to muscle mass and is not affected by diet.
What is uric acid?
The end product of purine metabolism. The purines are adenosine and guanine, components of nucleic acids. Uric
acid is increased with gout, renal disease, and conditions where there is high cellular turnover, such as leukemia.
What reagent is commonly used to measure uric acid?
The preservative sodium fluoride must not be used to collect the blood sample because it destroys uricase.
Why must the pH of urine for a uric acid determination be adjusted to 7.5-8?
To prevent precipitation of uric acid. Uric acid precipitates at acid pH.
Where is ammonia formed?
Mainly in the intestines from deamination of amino acids. It is converted to urea by the liver.
When is ammonia elevated?
With hepatic failure and Reye's syndrome. High levels are neurotoxic.
What is Reye's syndrome?
An acute, often fatal encephalopathy and fatty degeneration of the liver, seen primarily in children. It is associated with the use of aspirin in children with viral infections
Which amino acid is increased in the blood of patients with phenylketonuria (PKU)?
Phenylalanine. PKU is due to a deficiency of the enzyme phenylalanine hydroxy lase which catalyzes the
conversion of phenylalanine to tyrosine. If untreated, PKU leads to mental retardation. The traditional method to
test for PKU, the Guthrie bacterial inhibition assay, is being replaced by tandem mass spectrometry (MS/MS),
which can detect more than 25 genetic disorders in a single blood specimen. All states screen newborns for PKU.
What may result if blood for PKU is drawn before 24 hours of age?
Which amino acids are increased in maple syrup urine disease (MSUD)?
Leucine, isoleucine, and valine. The urine bas a burnt sugar odor. MSUD leads to mental retardation and
sometimes death. A modified Guthrie test or MS/MS are used for diagnosis. MSUD can be treated by dietary
modification if diagnosed early. Some states include MSUD in their newborn screening panel.
What is bilirubin?
The degradation product of heme. It is produced in the reticuloendothelial cells following breakdown ofRBCs.
Which protein transports bilirubin in the blood?
Name the 3 types of bilirubin
Unconjugated, congugated, and delta.
Together these fractions make total bilirubin. Unconjugated (indirect) bilirubin is bilirubin en route to the liver. Once it goes through the liver it is known as conjugated (direct) bilirubin or bilirubin diglucuronide.
Delta bilirubin is covalently bound to albumin and is only present with hepatic obstruction. It reacts as conjugated bilirubin in most methods.
What happens to bilirubin in the liver?
It is conjugated with glucuronic acid by the enzyme uridyldiphosphate glucuronyl transferase (UDPG-T).
Following conjugation, it is excreted into the intestine via the bile duct and is reduced by bacteria to urobilinogen.
Urobilinogen is oxidized to urobilin, which gives stools their normal color.
What is the significance of clay-colored or light stools?
It is a sign of obstruction of the bile duct. Urobilin is not being produced because bilirubin is not reaching the
Which substances related to bilirubin metabolism are normally found in the urine?
Only urobilinogen. Bilirubin should not be present in urine.
What urine chemistry abnormality is seen with complete obstruction of the biliary tract?
Which bilirubin fractions are analyzed in the laboratory?
Total and conjugated (direct). The unconjugated (indirect) level is calculated by subtracting conjugated from total.
Compare the solubility of conjugated and unconjugted bilirubin.
Conjugated bilirubin is soluble in water; uncongugated bilirubin is not. Both are soluble in alcohol.
Which form of bilirubin can be excreted in the urine?
Only conjugated bilirubin. It is not bound to protein, whereas uncongugated bilirubin is bound to albumin and is too large to be filtered through the glomeruli.
What methods are used for determination of billrubin levels?
Malloy-Evelyn and Jendrassik-Grof. Both use a diazo reagent to react with bilirubin and produce colored
azobilirubin. The Malloy-Evelyn procedure is carried out at at an acid pH; Jendrassik-Grof at an alkaline pH.
Conjugated bilirubin reacts without an accelerator (therefore called direct bilirubin); unconjugated bilirubin
requires the addition of an accelerator (therefore called indirect bilirubin). The Jendrassik-Grof method has some
advantages over the Malloy-Evelyn method. Both have been automated.
Name the accelerators for the Malloy-Evelyn and Jendrassik-Grof methods.
How do normal values for billrubin in a newborn compare to those in an adult?
Levels are higher in the newborn. The total bilirubin in a 3- 5 day old full-term infant is 4-6 mg/dL; for a premature
infant, 10-12 mg/dL.
What would cause an increase in total bilirubin with a normal concentration of conjugated bilirubio?
Prehepatic jaundice, for example, hemolytic transfusion reaction, hemolytic anemia, or hemolytic disease of the fetus and newborn.
What causes physiologic j auodice of the newborn?
Bilirubin metabolism is impaired because the newbom's immature liver does not produce the enzyme required for
bilirubin conjugation. Bilirubin may remain elevated for up to 2 weeks. Phototherapy is used to reduce the level of
bilirubin when necessary.
lo hemolytic disease of the newborn, which bilirubio fraction is elevated and why?
Uncongugated, due to excessive breakdown ofRBCs by maternal antibody.
What is the risk to the newborn from a high level of uncongugated bilirubin?
Unconjugated bilirubin (indirect) has a high affinity for brain tissue and causes necrosis (kemicterus). Without
appropriate treatment, mental retardation, hearing deficits, or cerebral palsy may result.
Name 2 conditions in which congugated bilirubin is elevated.
Hepatic and posthepatic jaundice.
What are the typical lab findings in posthepatic jaundice?
Increased total bilirubin, increased congugated bilirubin, decreased urine urobilinogen, and clay-colored stools.
Which disorder results in the highest levels of conjugated bilirubin?
Obstructive liver disease.
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