Liver function Flashcards
what are the majr liver functions
lipid metabolism
protein metabolism
hormone metabolism
carb regulation and metabolism
plasma protein synth
drugs, toxic
storage
bilirubin metabolism and excretion
do normal LFTs indicate a healthy liver
not always
which analytes tell us how well the liver is functioning
albumin, bilirubin, prothrombin time
what are the common markers of hepatocellular injury
aspartate aminotransferase (AST), alanine aminotransaminase(ALT)
ALT- cytosolic
AST - cytosolic and mitochondrial
hepatocyte necrosis in hepatitis, toxic injury or ischemic injury causes these enzymes to leak into circulation
what is the relation between serum ALT and chronic liver diseases
serum ALT correlates only moderately well with liver inflammation meaning it lacks some sensitivity in detecting chronic liver disease
why do AST and ALT lack some specificity
because they are found in skeletal muscle - can rise several times the normal level after severe muscular exertion i.e gym
describe the distribution shape of AST and ALT
skewed distribution- long tail at the high end of the scale
why are AST and ALT increased in obese patients
because these people commonly have fatty livers
what are the values of ALT and AST seen in typical viral or toxic liver injury vs alcoholic hepatitis
serum ALT rises more than the AST value in viral/toxic injury
alcoholic hep sees ratio of AST to ALT greater than 1 i 90% of cases and is typically greater than 2
*higher the AST to ALT ratio, the greater the likelihood that alcohol is contributing to te abnormal LFTs
write out ALT assay principle
look at slide for this
what is cholestasis and associated markers
is a lack of bile flow resulting from a blockage in bile ducts, or from disease that affects bile formation in liver
alkaline phosphatase (ALP) and gamma-glytamyltransferase (GGT) rise several times after some time of bile duct obstruction or intrahepatic cholestasis
what makes up bile
bile salts, phospholipids, cholesterol, conjugated bilirubin, electrolytes and water
what can elevation of ONLY GGT be indicative of
enzyme induction by alcohol or aromatic medications in the absense of liver disease - makes GGT useful for immoderate alcohol intake
where does serum ALP originate from
liver and bone- produces slightly diff versions of the enzyme (isoenzymes)
write out the ALP assay
look at slides
write the GGT assay
look at slides
how is bilirubin formed
old RBCs are phagocytosed by macrophages of spleen and hepatic sinusoids. heme is broke into green biliverdin by heme oxygenase, which is then broken into orange bilirubin by biliverdin reductase
how is unconjugated bilirubin conjugated
with glucuronic acid in hepatocytes to increase water solubility and is then transported into bile.
why are levels of conjugated bilirubin low in healthy people
because secretion of conjugated bilirubin into bile is really rapid in comparison with the conjugation step
how does liver disease affect bile secretion
impairs secretion of conjugated bilirubin into bile, so conjugated bilirubin is filtered into the urine where it can be tested via dipstick test -> indictive of increased serum conjugated biliubin
*haemolysis in spherocytosis/autoimmune haemolytic anaemia can also result in inc unconjugated bilirubin values- check blood FBC
write a note on gilberts syndrome
caused by genetic variant of UGT1A1 resulting in decreased bilirubin metabolism. causes fluctuating unconjugated hyperbilirubinemia that increased with fasting. person has a normal life span
write a note on Crigler Najjar syndrome
severe deficiency of UGT = Type 1
partial deficiency = Type 2
Autosomal recessive, Type 1 results in non-haemolytic jaundice and increased unconjugated bilirubin. can cause kernicterus - death
write a note on Rotor syndrome
mutations in SLCO1B1 and SCLO1B3 cause short, non functional OATP1B1 and OATP1B3 proteins which are responsible for bilirubin transport.
is autosomal recessive. causes a mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia.
patient has a normal life span
write a note on Dubin Johnson syndrome
mutations in MRP2 and reduced biliary excretion of bilirubin glucuronides. autosomal recessive.
causes mild fluctuating conjugated hyperbilirubinemia and polymerised adrenaline metabolites -> pigmented liver
patient has normal life span, is jaundiced and has icterus during pregnancy and if on hormonal contraceptives
