(25) Liver Function Flashcards
The liver receives its blood supply from what two major sources?
The hepatic artery and the portal vein.
Describe the significance of lobules.
Lobules are the functional unit, responsible for metabolic and excretory functions performed by the liver.
What are the two cell types within the liver?
Hepatocytes and Kupffer cells.
Describe the function of hepatocytes.
Major function associated with the liver and the regenerative properties of the liver.
Describe the function of Kupffer cells.
Macrophages that line the sinusoids that act as active phagocytes capable of engulfing bacteria, debris, and toxins.
Excretion of endogenous and exogenous substances are deposited into:
bile or urine.
A substance that are excreted by the liver is:
Major heme waste product, bilirubin.
How long do red blood cells exist before they are phagocytized by the liver?
126 days.
What are the three components produced when hemoglobin is broken down?
Heme, globin, and iron.
When hemoglobin is broken down iron is transported by what transfer protein?
Transferrin.
Where is iron returned after being broken down from hemoglobin?
Iron stores in the liver or bone marrow for reuse.
The heme portion of hemoglobin is converted to:
bilirubin.
Bilirubin is bound by ________ and transported to the ________.
albumin; liver
When bound bilirubin arrives at the liver, what form is it in?
Unconjugated/Indirect bilirubin.
Unconjugated bilirubin is ________ in water and cannot be removed from the body until it has been ________ by the liver.
insoluble; conjugated
What is used to transport unconjugated bilirubin?
Ligandin
Once ligandin is bound to unconjugated bilirubin, what component of the liver conjugates bilirubin?
Endoplasmic reticulum.
The conjugation (esterification) of bilirubin occurs in the presence of the enzyme:
uridine diphosphate glucuronosyltransferase (UDPGT)
Describe the function of UDPGT.
Transfers glucuronic acid to each of the two propionic acid side chains of bilirubin to form bilirubin diglucuronide (conjugated bilirubin).
Conjugated bilirubin is water ________ and is able to be secreted from the ________ into the ________.
soluble; hepatocytes; bile canaliculi
Intestinal bacteria converts conjugated bilirubin to produce what two intermediates and what end product?
(1) Mesobilirubin (int)
(2) Mesobilirubinogen (int)
(3) Urobilinogen (EP)
Urobilinogen is oxidized to product called:
Urobilin.
Urobilin is excreted:
In the feces
What gives stool its brown color?
Urobilin or stercobilin.
What happens to the remaining urobilinogen that doesn’t get excreted from the stools?
(1) Absorbed by extrahepatic circulation to be recycled (majority)
(2) Enter systemic circulation and filtered by the kidney and into the urine (small amount).
When carbohydrates are ingested and absorbed, the liver can do three things:
(1) use the glucose for its own cellular energy requirements
(2) circulate the glucose to peripheral tissues
(3) store glucose as glycogen
Almost all proteins are synthesized by the liver except:
the immunoglobulins and adult hemoglobin
Describe first pass.
Substance that is absorbed in the GI tract must first pass through the liver.
Describe the two mechanism for detoxification of foreign materials and metabolic products.
Either it may bind the material reversibly to inactivate the compound, or chemically modify the compound and can be excreted.
Define jaundice.
It is used to describe the yellow discoloration of the skin, eyes, and mucous membranes resulting from the retention of bilirubin.
Define icterus.
To refer to a serum or plasma sample with a yellow discoloration due to elevated bilirubin level.
Prehepatic jaundice occurs:
when the problem causing the jaundice occurs prior to liver metabolism.
Give an example of a disease state that is consistent with prehepatic jaundice.
Chronic hemolytic anemias.
Describe what occurs during hemolytic anemia.
An increased amount of RBC destruction and the subsequent release of increased amounts of bilirubin presented to the liver for processing.
Define unconjugated hyperbilirubinemia.
Another name for prehepatic jaundice; indicative of an overabundance of unconjugated bilirubin traveling to the liver.
In prehepatic jaundice, would bilirubin be seen in the urine?
No, since its not water soluble the kidneys have no way of disposing of the unconjugated bilirubin.
Hepatic jaundice is due to:
diseases resulting in hepatocellular injury or destruction.
What are examples of hepatic jaundice?
Gilbert’s disease, Crigler-Najjar syndrome, and physiologic jaundice of the newborn.
Gilbert’s disease, Crigler-Najjar syndrome, and physiologic jaundice of the newborn are indicative to what laboratory testing?
Elevations of unconjugated bilirubin.
Dubin-Johnson and Rotor’s syndrome are indicative to what laboratory testing?
Elevations of conjugated bilirubin (hepatic jaundice).
Define Gilbert’s syndrome.
Hereditary disorder resulting from a mutation in the UGT1A1 gene that produces uridine diphosphate glucuronosyltransferase, an enzyme important in bilirubin metabolism.
Define Type 1 Crigler-Najjar syndrome.
Complete absence of enzymatic bilirubin conjugation.
Define Type 2 Crigler-Najjar syndrome.
A mutation causing a severe deficiency of the enzyme responsible for bilirubin conjugation.
Gilbert’s disease and Crigler-Najjar syndrome are characterized as primarily ________ hyperbilirubinemias; Dubin-Johnson syndrome and Rotor’s syndrome are characterized as ________ hyperbilirubinemias.
unconjugated; conjugated
Define delta bilirubin.
Conjugated bilirubin bound to albumin.
Physiologic jaundice of the newborn is the result of a deficiency in the enzyme:
UDPGT.
Define kernicterus.
A buildup of unconjugated bilirubin in neonates. Often deposited in the nuclei of brain.
Describe how phototherapy works with neonates with jaundice.
Using halogen or fluorescent lights to transform bilirubin into water-soluble isomers without conjugation in the liver.
Posthepatic jaundice results from:
biliary obstructive disease; physical obstructions (gallstones or tumors) that prevent the flow of conjugated bilirubin into the bile canaliculi.
Describe the significance of clay-colored stools.
During obstructive jaundice, since bile is not being brought to the intestines, stool loses its source of normal pigmentation.
Define cirrhosis.
A clinical condition in which scar tissue replaces normal, healthy liver tissue.
In cirrhosis, as scar tissue replaces the normal liver tissue:
it blocks the flow of blood through the organ and prevents the liver from working properly.
What is the most common cause of cirrhosis?
Chronic alcoholism.
In addition to chronic alcoholism, other causes of cirrhosis include:
Chronic hepatitis C (HBV), C (HCV), and D (HDV).
90% to 95% of all hepatic malignancies are classified as ________.
metastatic.
The common benign tumors of the liver include what?
Hepatocellular adenoma & hemangiomas
The malignant tumors of the liver include what?
Hepatocellular carcinoma & bile duct carcinoma.
How does Reye’s syndrome affect the hepatic system?
Characterized by a mild hyperbilirubinemia, and threefold increase in ammonia and ALT and AST.
When ethanol enters the liver, what enzymes are required for the elimination?
Alcohol dehydrogenase and acetaldehyde dehydrogenase.
Alcoholic fatty liver is characterized by changes in what analytes?
Slight elevations in AST, ALT, and GGT.
Alcoholic hepatitis is characterized by changes in what analytes?
Moderately elevated AST (2x upper limit), ALT, GGT, and ALP. Total bilirubin >5 mg/dL.
In alcoholic hepatitis, AST/ALT ratio is what?
Greater than 2.
Alcoholic cirrhosis characterized by changes in what analytes?
Increased AST, ALT, GGT, ALP, Total Bilirubin
Decreased albumin
Describe the diazo reaction.
Bilirubin with diazotized sulfanilic acid solution to form a colored product.
What is the calculation for unconjugated bilirubin?
Unconjugated bilirubin (indirect) = total bilirubin (measured) - conjugated bilirubin (measured)
In the diazo reaction, which type of bilirubin requires a accelerator?
Unconjugated bilirubin.
What accelerator is used for the diazo unconjugated bilirubin reaction?
diazotized sulfanilic acid solution
What condition would cause an increase in delta bilirubin?
Significant hepatic obstruction.
What three fractions are included in total bilirubin?
Conjugated, unconjugated, and delta.
How does lipemia affect bilirubin measurements?
Will increase measured bilirubin concentrations.
How does hemolysis affect bilirubin measurements?
May decrease the reaction of bilirubin with the diazo reagent.
If left unprotected from light, bilirubin values may reduce by:
30% to 50% per hour.
What is the reference method for total bilirubin?
Jendrassik-Grof; uses caffeine-benzoate as a solubilize.
Describe the Malloy-Evelyn Procedure for bilirubin measurement.
Bilirubin is reacted with diazotized sulfanilic acid splitting the molecule into two molecules of azobilirubin. pH = 1.2 which causes the product to be red-purple. Absorption is read at 560 nm.
Increased levels of urinary urobilinogen are found in what condition(s)?
Hemolytic disease and defective liver cell function (seen in hepatitis).
Describe the testing method of urobilinogen.
Urobilinogen is reacted with Ehrlich’s reagent (p-dimethylaminobenzaldehyde) to form a red color.
What enzymes are the most useful in determining liver function?
ALT, AST, ALP, 5’-nucleotidase, GGT, and LD.
ALT is the most abundant:
in the liver.
________ is a more specific liver marker than ________.
ALT; AST
The highest levels of AST and ALT are found in what conditions?
Viral hepatitis, drug- and toxin-induced liver necrosis, and hepatic ischemia.
The clinical utility of ALP lies in its ability to differentiate:
hepatobiliary disease from osteogenic bone disease.
Very high ALP values can be seen in:
Extrahepatic obstruction.
Moderately elevated ALP values can be seen in:
Hepatocellular disorders such as hepatitis and cirrhosis.
5’NT is significantly elevated in what hepatic condition?
Hepatobiliary disease.
Highest levels of GGT are seen in:
biliary obstruction.
Measurement of GGT is useful if ________ is absent for the confirmation of ________.
jaundice; hepatic neoplasms
Moderate elevations of LD are seen in:
acute viral hepatitis and in cirrhosis.
High serum LD levels may be seen in:
metastatic carcinoma of the liver.
What anticoagulants are best for ammonia collection?
EDTA, lithium heparin, potassium oxalate.
Why should ammonia samples be placed on ice?
To prevent metabolism of other nitrogenous compounds to ammonia; leads to false elevations.
Hemolyzed samples for ammonia testing should be avoided because:
RBCs have a concentration of ammonia 2-3X higher than that of plasma.
How would an elevated GGT value affect ammonia?
GGT is a major contributor to the endogenous production of ammonia; therefore, concentrations may be artificially increased.
________ infections account for the majority of hepatitis cases observed in the clinical setting.
Viral
What subtype viral hepatitis is the most common?
Hepatitis A Virus
What is the primary means of HAV transmission?
Fecal-oral route.
For hepatitis A, ________ are detectable at or prior to the onset of clinical illness and decline in 3 to 6 months.
IgM antibodies to HAV (IgM anti-HAV)
In hepatitis A, ________ appear soon after IgM, persist for years after infection, and confer lifelong immunity.
IgG antibodies to HAV (IgG anti-HAV)
For hepatitis A, the presence of elevated titers of ________ in the absence of ________ indicates past infection.
IgG anti-HAV; IgM
________ detection techniques are more sensitive than ________ for viral antigen to detect HAV in samples.
Nucleic acid (RT-PCR); immunoassays
What antigen is routinely tested on all donated units of blood?
Hepatitis B Surface Antigen (HBsAg)
________ is the only serologic marker detected during the first 3 to 5 weeks after infection in newly infected patients of hepatitis B.
HBsAg
