Which of the two is more liver specific and increases more during liver disease: Aspartate aminotransferase (AST) or

Alanine aminotransferase (ALT)

ALT for both, however they are present in other tissues as well so increased levels may indicate other tissue damage.
Hepatitis A is transmitted mainly via which route and is vaccine available?
Fecal-Oral
Yes
What are the three antigens for Hepatitis B and what time of infection are they present in:
Core (Present in acute infection)
Surface (Not infectious, but may indicate HBV. anti-HBs can also develop which makes patient immune to HBV)
E antigen (Acute and Chronic, only present when HBsAg is present and is an extracellular form of HBcAg)
Hepatitis C is transmitted mainly via which route and is vaccine available?
Blood transfusion/needles
No vaccine available
Hepatitis D is transmitted mainly via which route and is vaccine available?
Requires HBsAg from HBV for replication so it can only infect HBV positive patients
Vaccine available
Hepatitis E is transmitted mainly via which route and is vaccine available?
Fecal-Oral
No
Hyperbilirubinemia in newborns usually
produces no serious consequences
All of the following statements concerning urobilinogen are correct EXCEPT:
urinary levels increased in biliary obstruction
Ehrlich reagent is used in the measurement of:
urobilinogen
In the liver, bilirubin is converted to
bilirubin glucuronide
A breakdown product of bilirubin metabolism that is produced in the colon from the oxidation of urobilinogen by
microorganism is:
urobilin
All of the following methods have been used for the quantitation of serum bilirubin concentrations EXCEPT:
picric acid
Which of the following is characteristic of hemolytic jaundice?
unconjugated serum bilirubin level greater than normal
The product formed from the reduction of bilirubin in the small intestine is:
urobilinogen
The term delta bilirubin refers to
bilirubin tightly bound to albumin
Which reagent is used in the Jendrassik-Grof method to solubilize unconjugated bilirubin?
caffeine
The reference range for total bilirubin in adults is
0.2-1.0 mg/dL
Which of the following statements regarding infection with hepatitis D virus is true?
occurs in patients with hepatitis B
Caffeine is used in bilirubin assays to:
accelerate indirect bilirubin reaction
Functions of the liver
Carbohydrate metabolism
Protein metabolism
Lipid metabolism
Conjugation, detoxification and excretion
Vitamin storage
Digestion and formation of bile
Enzymes
Bilirubin metabolism
Hemoglobin is broken down into bilirubin by what?
Reticuloendothelial cells of the spleen, bone marrow, or thymus
Hemoglobin breakdown
1. Hemoglobin
2. Verdohemoglobin
3. Biliverdin + Fe + Globulin
(Biliverdinreductase)
4. Bilirubin + Albumin
5. Bilirubin - Albumin Complex
Hemoglobin conjugation
1. Bilirubin - Albumin Complex
2. Bilirubin
3. Bilirubin + UDP-glucuronic acid
(Glucuronyltransferase)
4. Bilirubin diglucuronide
Where does bilirubin conjugation occur?
Parenchymal cells (Hepatocytes)
What is delta bilirubin?
Bilirubin that is covalently bound to albumin
Conjugated bilirubin is bilirubin that is bound to?
Diglucuronic acid
*Describe bilirubin levels in serum and urine during normal liver function.
Normal in serum
Negative in urine
*Describe urobilinogen levels during normal liver function
Trace amounts
Cause of prehepatic jaundice
Increased hemoglobin breakdown
Describe bilirubin levels in serum during prehepatic jaundice
Increased unconjugated / indirect bilirubin
Describe urobilinogen levels in stool and and urine during prehepatic jaundice
Stool is increased
Urine is increased
Only __________ bilirubin can be excreted into the urine
Conjugated
Target cells are usually found in this condition
Hemolytic anemia
Causes of Hepatic Jaundice
Conjugation failure
Transport failure
Cell damage
Describe bilirubin levels in serum during hepatic jaundice
Increased unconjugated
OR
Increased conjugated
Describe urobilinogen levels of stool & urine during hepatic jaundice
Stool is variable
Urine is increased
Urine bilirubin is found in _________ jaundice
Hepatic
Post hepatic
Causes of Post Hepatic Jaundice
Obstruction of the bile duct
Describe bilirubin levels in serum during post hepatic jaundice
Increased conjugated
Normal - increased unconjugated
Urobilinogen is decreased in both urine and feces during _____________
Post hepatic jaundice
LD is increased during?
Prehepatic jaundice
AST is increased during?
Hepatic jaundice
ALT is increased during?
Hepatic jaundice
GGT is increased during?
Post hepatic jaundice
ALP is increased during?
Post hepatic jaundice
These enzymes are increased during hepatic jaundice
AST
ALT
These enzymes are increased during post hepatic jaundice
GGT
ALP
Why is it that unconjugated bilirubin cannot be excreted in urine?
It is not water soluble
Alpha bilirubin
Unconjugated / indirect
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Beta bilirubin
Conjugated / direct
Which type of bilirubin has a high affinity for brain tissue?
Unconjugated
Conjugated bilirubin is soluble in?
Water
Alcohol
Unconjugated bilirubin is soluble in?
Alcohol
Specimen requirements for bilirubin testing
Serum / heparinized plasma
No hemolysis
Protect from the light
In bilirubin assays, hemolysis interferes with what?
Diazo reaction
Diazo reagent
Sulfanilic acid + HCl + Sodium nitrite (NaNO3)
In an Evelyn Malloy reaction, ______________ bilirubin gives an immediate reaction
Conjugated
This type of bilirubin assay can only be used for newborns
Bilirubinometer
Reference range for total bilirubin
0.1 - 1.1 mg/dL
Reference range for direct bilirubin
0.0 - 0.3 mg/dL
Reference range for indirect bilirubin
0.1 - 1.1 mg/dL
Bilirubin diglucuronide + diazonium salt
Azobilirubin
Erhlich's reagent
P - dimethylaminobenzaldehyde
Potential interference for measurement of urobilinogen
Porphobilinogen
Specimen for ammonia assay method
Heparinized plasma on ice
Reference range for ammonia
9 - 33 umols/L
Reyes Syndrome is associated with?
Viral infections
Aspirin use
ALP
Alkaline phosphatase
Increased in post hepatic jaundice
GGT
Gamma GT
Greatly increased in cirrhosis
Wilson's disease
Decreased ceruloplasmin
Increased copper
Kayser - Fleischer rings
Dubin - Johnson syndrome
Defect in the ability of hepatocytes to transport conjugated bilirubin into the bile
Factor VIII deficiency
Most common hereditary cause of increased bilirubin
Gilbert's syndrome
Gilbert's Syndrome
Reduced activity of the enzyme UDP - glucuronyltransferase
Hepatic Jaundice
Biliary Atresia
Rare condition in newborn infants in which the common bile duct between the liver and the small intesting is blocked or
absent
Post hepatic
Crigler - Najjar syndrome
Severely defective UDP - glucuronyltransferase
Hepatic jaundice
Reference range for AST
0 - 30
Reference range for ALT
0 - 37
Reference range for ALP
30 - 90
Liver and Congestive Heart Failure
Failure of the heart to pump blood at the rate required by the metabolizing tissues
Hypoxia is caused by?
Perfusion of blood through the liver is compromised congestive heart failure
Pernicious anemia is a type of which jaundice?
Prehepatic jaundice
Diagnose Kernicterus
Bilirubin > 15mg/dL
OR
>10 mg/dL for more than 2 weeks
Cirrhosis
Architecture of the liver is permanently damaged
Hepatitis
Necrosis & inflammation of hepatocytes
Decreased liver function
_________ is the most liver specific enzyme
ALT
Enzyme levels if the bile duct is obstructed or if the bile canals are inflamed
Increased AST
Increased ALT
Increased LD
Enzyme levels during true hepatic disease
Highly increased ALT
Significantly increased AST
Significantly increased LD
Enzyme levels during obstruction or inflammation of bile ducts
Increased ALP
Increased GGT
Which enzyme would best aid in identifying hepatobiliary disease?
ALP
Which type of cell does the conjugation of bilirubin take place?
Hepatocyte
Which enzyme is responsible for the conjugation of bilirubin?
UDP - glucuronyltransferase
Which form of bilirubin is water soluble and reacts with a diazo reagent without the addition of an accelerator?
Conjugated bilirubin
Which form of hepatitis is caused by a DNA virus?
Hepatitis B
Which enzyme is most useful in establishing the hepatic origin of an elevated ALP?
5'-Nucleotidase
Hepatitis E is likely to cause serious consequences in which portion of the population?
Pregnant women
Worldwide, most primary malignant tumors of the liver are related to?
Alcoholism
The reagent p-dimethylaminobenzaldehyde is used to measure what?
Urobilinogen
Which condition would result in primarily conjugated bilirubin?
Dubin - Johnson syndrome
A urinalysis dipstick test was indicated that urobilinogen was absent. What condition does this support?
Biliary obstruction
Target cells are usually found in this condition
Hemolytic anemia
What is bilirubin?
The degradation product of heme. It is produced in the reticuloendothelial cells following breakdown of RBCs.
Which protein transports bilirubin in the blood?
Albumin.
Name the two types of bilirubin.
Direct and indirect. Indirect or unconjugated bilirubin is bilirubin en route to the liver. Once it goes through the liver it is
known as direct bilirubin, conjugated bilirubin or bilirubin diglucuronide.
Explain what happens to bilirubin in the liver.
It is unconjugated with glucoronic acid by the enzyme uridyldiphosphate glucoronyl transferase (UDPG-T). Following
conjugation, direct bilirubin is excreted into the intestine via the bile duct and is reduced by bacteria to urobilinogen.
Urobilinogen is oxidized to urobilinand gives the normal color to stools.
What is the significance of clay colores or light stools?
It is a sign of obstruction of the bile duct. Urobilin is not being produced because bilirubin is not reaching the intestines.
Which substances related to bilirubin metabolism are normally found in the urine?
Only urobilinogen. Bilirubin should not be present in urine.
What urine abnormality is seen with complete obstruction of the biliary tract?
Decreased urobilinogen
Which bilirubin fractions are analyzed in the laboratory?
Total and indirect. The indirect level is calculated by subtracting direct from total.
Compare the solubility of direct and indirect bilirubin.
Direct bilirubin is soluble in water; indirect bilirubin is not. Bot are soluble in alcohol.
Which form of bilirubin can be excreted in the urine?
Only direct bilirubin.
What is a common method for determination of bilirubin levels?
Diazotization with sulfanilic acid. Bilirubin reacts with diazotized sulfanillic acid to produce azobilirubin.
Name several accelerators that are used in the total bilirubin reaction.
Alcohol or caffeine benzoate-acetate can be used to make the indirect bilirubin soluble.
Name a source of error that can decrease the level of bilirubin in a specimen.
Exposure to light. Hemolysis will also cause a decreased level by the Jendrassik-Grof method.
What is the normal range for total bilirubin in an adult?
0.2-1.0 mg/dL. Conjugated (direct) bilirubin is <0.2 mg/dL.
How do normal values for bilirubin 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 direct bilirubin?
Prehepatic jaundice for example, hemolytic transfusion reaction, hemolytic anemia, or hemolytic disease of the newborn.
What causes physiologic jaundice of the newborn?
Bilirubin metabolism is impaired because the newborn's immature liver doesn't produce the enzyme required for bilirubin
conjugation. Phototherapy is used to reduce the level of bilirubin.
In hemolytic disease of the newborn, which bilirubin fraction is elevated and why?
Indirect due to excessive breakdown of RBCs by maternal antibody.
What is the risk to the newborn from a high level of indirect bilirubin?
Unconjugated bilirubin (indirect) has a high affinity for brain tissue and causes necrosis (kernicterus). WIthout appropriate
treatment, mental retardation, hearing deficits, or cerbral palsy may result.
At what level of bilirubin would an exchange transfusion be indicated in a neonate?
Each institution establishes its own criteria, but an exchange transfusion is usually performed when the unconjugated
bilirubin reaches 20mg/dL.
What method is used to determine neonatal bilirubin?
Direct spectrophotometry at 454nm. This method can't be used for patients over one month of age because of interfering
lipochromes, such as carotenes.
Name two conditions in which direct bilirubin is elevated.
Hepatic and posthepatic jaundice.
What are the typical lab findings in posthepatic jaundice?
Increased total bilirubin, increased direct bilirubin, decreased urine urobilinogen, and clay colored stools.
T
T/F: Bilirubin is produced from the destruction of RBCs
Albumin
Bilirubin is transported from reticuloendothelial cells to the liver by:
Glucuronyl groups
In the liver, bilirubin is conjugated by addition of:
UDP-glucuronyl transferase
Which enzyme is responsible for the conjugation of bilirubin?
Bilirubin tightly bound to albumin
The term δ-bilirubin refers to:
Methene bridges of bilirubin are reduced by intestinal bacteria to form urobilinogens
Part of the normal metabolism of bilirubin
Water soluble
Characteristic of conjugated bilirubin
T
T/F: Urobilinogen is formed in the intestines by bacterial reduction of bilirubin
T
T/F: Bilirubin undergoes rapid photo-oxidation when exposed to daylight
Dubin-Johnson syndrome
Which condition is caused by deficient secretion of bilirubin into the bile canaliculi?
Failure of the enterohepatic circulation
In hepatitis, the rise in serum conjugated bilirubin can be caused by:
Ratio of direct to total bilirubin is greater than 1:2
Characteristic of obstructive jaundice
Hemolytic anemia
This would cause an increase in only the unconjugated bilirubin
Crigler-Najjar syndrome
Which form of hyperbilirubinemia is caused by an inherited absence of UDP-glucuronyl transferase?
T
T/F: Total bilirubin level is a less sensitive and specific marker of liver disease than the direct level
Jaundice is usually first seen 48—72 hours postpartum in neonatal hyperbilirubinemia
Serum bilirubin levels in the first week following delivery
Lucey-Driscoll syndrome
Which form of jaundice occurs within days of delivery and usually lasts 1-3 weeks, but is not due to normal neonatal
hyperbilirubinemia or hemolytic disease of the newborn?
Falsely low due to inhibition of the diazo reagent by hemoglobin
A lab measures total bilirubin by the Jendrassik-Grof bilirubin method with sample blanking. What would be the effect of
moderate hemolysis on the test result?
Caffeine
Which reagent is used in the Jendrassik-Grof method to solubilize unconjugated bilirubin?
T
T/F: Most colorimetric bilirubin methods are based upon reaction with diazotized sulfanilic acid
T
T/F: Fehling's reagent is added after the diazo reaction to reduce optical interference by hemoglobin
Hgb interference in the second assay
A neonatal bilirubin assay performed at the nursery by bichromatic direct spectrophotometry is 4.0 mg/dL. Four hours
later, a second sample assayed for total bilirubin by the Jendrassik-Grof method gives a result of 3.0 mg/dL. Both samples
are reported to be hemolyzed. What is the most likely explanation of these results?
Using different pH for total and direct assays
In the enzymatic assay of bilirubin, how is measurement of both total and direct bilirubin accomplished?
Multiwavelength reflectance photometry
What is the principle of the transcutaneous bilirubin assay?