liver function

what are the main functions of the liver?

• excretion/secretion of waste products (heme and bile)

• metabolism, synthesis, and storgae of carbs, fats, and proteins

• detoxification/drug metabolism (everything intestinally absorbed passes through the liver)
  -can modify, activate, or deactivate chemicals

bilirubin metabolism pathway

1. breakdown of hemoglobin (globin into amino acids, iron returns to liver/bone marrow)

2. bilirubin binds to albumin to become unconjugated in blood vessels

3. unconjugated travels to the liver

4. unconjugated becomes conjugated (is now water soluble)

5. secreted into bile and into the intestines

6. intestines turn into urobilinogen

7. majority excreted in stool

8. some excreted in urine by kidneys

9. some recirculated into liver

Bu

unconjugated bilirubin

water insoluble

majority of bilirubin in plasma

also known as indirect bilirubin

Bc

conjugated bilirubin

made in the liver

excreted into the bile duct and intestines

also known as direct

delta bilirubin

part of conjugated bilirubin

• created when there is excess Bc and it binds to albumin

• long half life

• associated with hepatic obstructions

hyperbilirubinemia clinical presentation

jaundice

• yellowing of skin, eyes, and mucous membranes

• appears when bilirubin levels are 3.0-5.0 mg/dL

• neurological symptoms appear when greater than 25 mg/dL

prehepatice jaundice

• the problem occurs before the liver

• “unconjugated hyperbilirubinemia”

• associated with hemolytic anemia or HDFN

• increased levels of bilriubin in liver

• increased urobilinogen in feces and urine

• there is no unconjuagted bilirubin in urine

hepatic jaundice

• intrinsic liver defect/disease

• associated with physiological jaundice of newborns

• results in increased levels of unconjugated bilirubin

• hepatocellular injury

posthepatic jaundice

• cholestasis

• biliary obstruction

• gallstones or cancer

• bilirubin is conjugated but cant get out

• no fecal/urine urobilinogen

• increased conjugated and unconjugated bilirubin in circulation

methodology of bilirubin assessment

• diazosulfanilic acid is the reagent for all

• two types of assays: direct and total

Bc assay methodology

measured conjugated and delta bilirubin

• reacts directly with diazo

• all soluble

• checks for post hepatic conditions

• no accelerator needed

• bilirubin + diazo = azobilirubin

Bu assay methodology

technically it measures the total bilirubin

• requires an accelerator (caffeine, sodium benzoates, salicylates)

• the accelerator alters the solubility

• checks for prehepatic conditions

• bilirubin + diazo + accelerator = azobilirubin (total)

• then subtract conjugated from total to get unconjugated

specimen considerations for bilirubin

• no hemolysis (causes a false decrease with the diazo reagent)

• oxyhemoglobin also destroys bilirubin

• no sunlight (decreases bilirubin)

what enzyme assays measure hepatic function?

• albumin (production)

• total bilirubin

• Direct bilirubin (won’t increase till 50% of liver function is lost)

• INR/PT (producing enough)

enzyme assays for measuring hepatic damage?

• assesses the cell membrane of liver cells and sees if theyre leaking

• ALT (higher than AST except with alcoholic liver disease)

• AST

• ALP

• GGT