Liver Function

What are the major functions of the liver?

• process dietary and endogenous carbs

• produce lipoproteins and most plasma proteins

• synthesize cholesterol for cell membranes

• detoxify the body of bilirubin, alcohol, and drugs

• produce bile

What major molecules does the liver store?

• glycogen

• iron

• fat-soluble vitamins

• copper

What is bilirubin?

• compound formed by the breakdown of hemoglobin from RBCs

• heme oxygenase reduces heme into biliverdin, which is then converted to unconjugated/indirect bilirubin by bilirubin reductase

indirect/unconjugated bilirubin

• form of bilirubin that is bound to albumin in the blood

• NOT water soluble! (cannot be filtered by the kidneys)

• converted into direct/conjugated bilirubin in the kidneys

direct/conjugated bilirubin

• form of bilirubin conjugated to glucuronic acids from the liver

• IS water soluble!

  • can be filtered by the kidneys and found in urine

• stored in bile in the gallbladder until bile is excreted into the small intestine

urobilinogen

• product formed in the intestine by the action of bacteria on bilirubin

• some is reabsorbed into circulation, reentering the liver, and is reexcreted in bile OR is excreted by the kidneys in urine

• the rest is excreted in stool

pre-hepatic jaundice

• increased bilirubin production not caused by liver dysfunction

• causes: hemolytic anemia, HDFN, CHF, transfusion reactions

• results in mostly increased unconjugated bilirubin levels

  • the liver is working at maximum capacity trying to conjugate the bilirubin, but the excess production leads to a backlog of unconjugated bilirubin in the bloodstream

• urine urobilinogen can also be increased

hepatic jaundice

• jaundice due to liver dysfunction

• causes: inherited disorders, cirrhosis, viral hepatitis, alcoholism, carcinoma, toxic liver injury

• results in increased unconjugated and conjugated bilirubin

• increased urine urobilinogen

post-hepatic jaundice

• aka obstructive jaundice

• bile is blocked from leaving the liver

• causes: gallstones, cancer, bile duct stricture

• results in increased conjugated bilirubin

  • the liver can still conjugate, but cannot excrete it

• stool has decreased urobilin and urine has decreased urobilinogen

neonatal physiologic jaundice

• clinical complication caused by a deficiency in UDPGT, an enzyme needed for bilirubin conjugation

• can present in premature infants because they are not using their mother’s liver to conjugate bilirubin, leading to a buildup of unconjugated bilirubin

• can lead to kernicterus

liver function panels consist of:

• liver enzymes

• bilirubin

• total protein

• albumin

What is the classic method of bilirubin measurement?

• Ehrlich’s Reaction/Diazo Reaction

  • bilirubin reacts with diazotized sulfanilic acid to produce a pigment that is measured

describe the Evelyn-Malloy procedure for bilirubin measurement

• utilizes the classic Diazo reaction and a methanol solution as an accelerator

  • serum/plasma bilirubin reacts with the diazo reagent

  • two molecules of azobilirubin are produced

  • azobilirubin absorbance is measured

describe the Jendrassic-Grof method of bilirubin measurement

• modifies the classic Diazo reaction using caffeine as an accelerator

  • one aliquot of the sample is taken to react with the diazo reagent and another aliquot is taken to react with diazo and caffeine

  • diazo and caffeine yields the total bilirubin result, only diazo yields conjugated bilirubin only

  • alkaline tartrate shifts the absorbance spectrum of the azobilirubin products to an intense blue color that is less prone to interference during measurement

  • azobilirubin product is measured at 600 nm

Why must bilirubin specimens be protected from light?

bilirubin degrades in light, leading to falsely decreased results

prothrombin time is often ___ in liver disease

prolonged (increased)

What is ammonia?

• a waste product of amino acid and protein metabolism

• converted to urea as it passes through the liver

  • therefore, liver dysfunction can lead to increased ammonia

• neurotoxic, can lead to encephalopathy

When is ammonia increased?

• in advanced liver disease and renal failure

  • hepatic coma, viral hepatitis, chronic hepatitis, Reyes Syndrome

ammonia test method and specimen requirements

• test method

  • glutamate dehydrogenase

• specimens

  • serum or plasma

  • must be on ice

  • centrifuged ASAP (ammonia can increase rapidly upon standing)

Which liver enzymes can be used to evaluate liver status?

• AST

• ALT

• alkaline phosphatase

• GGT

• LD