LIVER FUNCTION TESTS
Assist Prof Dr. Nadya Ghassan AbdulKareem
Objectives of studying liver function test
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The student can be able to:
Assess normal hepatic functions
Explain bilirubin metabolism
Employ serum enzymes in diagnosis of liver
diseases.
Use plasma protein in assessing liver diseases
• Lobules of the liver divided into 3 zones, zone one
which is nearest to the portal tract, has the highest
oxygen and nutrient contents so it is more active in
gluconeogenesis and has a greater content of
alkaline phosphatase and transaminases than the
other area.
• Zone 3 has the highest concentrations of drug
metabolizing enzymes and it is the area most
susceptible to viral, toxic and anoxic liver damage.
Daily assessment of liver
functions in clinical practice
• Total serum Bilirubin
• Measuring serum levels of hepatic enzymes
• Total serum proteins
• Prothrombin time (the activity of Vit. K-dependent
clotting factors).
Bilirubin metabolism
• Synthesis of Bilirubin:
Bilirubin is an end product of heme metabolism
(formed by breakdown of heme present in
hemoglobin, myoglobin [protein found in the muscle
tissue], cytochromes, catalase, peroxidase and
tryptophan pyrrolase).
Heme oxidized by heme oxidase to biliverdin (green
pigment), then reduced by biliverdin reductase
generating bilirubin.
•Measurement of bilirubin is a test for excretory
function of the liver.
Unconjugated Bilirubin
• Bilirubin function as cellular antioxidant.
• Unconjugated bilirubin in plasma bound to albumin,
because bilirubin is lipophilic and to prevents taken
up by the tissues.
• It is not filtered by the glomerulus so does not
appear in the urine.
• Normal serum level: 0.2-0.6 mg/dl
Conjugated Bilirubin
• The intracellular protein ligandin shuttles bilirubin
to the rough endoplasmic reticulum where most is
conjugated with glucuronic acid by Uridyl
diphosphate (UDP)-glucuronyl transferase forming
bilirubin diglucuronide and excretion of the
conjugated compound into bile canaliculi is energy
dependent process and rate limiting step.
• Normal serum level: less than 0.2 mg/dl.
• Unconjugated Bilirubin is normally not secreted.
Formation of urobilins in the
intestine
• Bilirubin diglucuronide is hydrolyzed and reduced
by bacteria in the gut to yield urobilinogen
(colorless compound) which is reduced to
stercobilinogen then oxidized by intestinal
bacteria to stercobilin (gives the brown color to
the feces). Some of urobilinogen is reabsorbed
from the gut and enters the portal circulation, the
remainder is transported by blood to the kidneys
where it converted to yellow urobilin and
excreted in the urine (gives urine its characteristic
color).
Serum enzymes in liver disease
• Cellular dysfunction causes leakage of
enzymes from their intracellular location into
serum.
• Measuring activities of enzymes help in the
investigation of the diseases.
Aminotransferases
• They are normally intracellular enzymes with low
levels found in the plasma (due to normal cell
turnover). So presence of elevated plasma levels of
aminotransferases indicate damage to the cells rich
in this enzymes.
• Those enzymes are involve in amino acid
metabolism, and all aminotransferases require the
coenzyme pyridoxal phosphate (vit B6).
Aspartate aminotransferase (AST)
Serum Glutamic Oxaloacetic Transaminase
(SGOT)
• Found in both cytosol and mitochondria of cells. It
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is more sensitive than ALT because liver contains
larger amounts, associated with cell necrosis.
Two isoenzymes of AST:
GOT1/cAST, the cytosolic isoenzyme derives mainly
from RBC and heart.
GOT2/mAST, the mitochondrial isoenzyme is
present predominantly in the liver.
Normal serum AST level is 5-30 IU/L.
Alanine aminotransferase (ALT)
Serum Glutamic Pyruvic Transaminase(SGPT)
• It is cytosolic enzyme, more specific for liver
disease diagnosis than AST, associated with cell
inflammation.
• Normal serum ALT level is 5-30 IU/L.
• Serum ALT level between 50-100 IU/L mean there is
chronic liver disease (cirrhosis), hepatitis or nonalcoholic steatohepatitis.
Lactate Dehydrogenase
• LDH is raised in hepatocellular dysfunction. It
is not specific due to widely distributed in
the body.
Alkaline Phosphatase (ALP)
• ALP level increase in cholestasis (any condition of
retained substances excretion into the bile) because
of increase synthesis of the enzyme.
• To establish if the enzyme of hepatic origin or from
another organ (such as bone) so estimating ALPisoenzyme or the activity of another biliary enzyme
usually γ-glutamyl transferase (GGT).
• Normal serum ALP level 50-100 IU/L.
ALP
• Optimum pH for ALP reaction between 9-10.
• Its location in the cell membrane of biliary canaliculi
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epithelia.
Its level increase in children due to osteoclast
activity.
Its level increase 10-12 times in extra or
intrahepatic obstruction that cause cholestasis.
Its level increase 2-3 times in an infective hepatitis
or alcoholic hepatitis.
Its level increase up to 25 times in bone diseases
like Pagets disease (the disease can cause affected
bones to become fragile and misshapen).
Paget’s disease
γ-Glutamyl Transferase (GGT)
• Increased serum activities are found in both hepatic
and cholestatic disease, associated with alcoholism
or biliary stasis.
• Higher activities are found in cholestasis when
levels greater than 50 times the upper limit of
normal.
• Normal serum GGT level is 6-50 IU/L.
Plasma proteins in liver disease
• Albumin has a half life in serum of 20 days and levels
fall slowly if no synthesis occurs, so normal serum
albumin level found in acute hepatic failure while low
serum albumin level is found in chronic liver diseases
such as cirrhosis.
• α1-Antitrypsin deficiency causes neonatal jaundice
and cirrhosis in children and young adults.
• α- Fetoprotein is produced by the fetus but
disappears from the circulation after a few weeks of
birth. Modest levels when hepatic regeneration occur
(during acute viral hepatitis), while very high values
occur in hepatocellular carcinoma.
• Caeruloplasmin is low in Wilson’s disease (too much
copper accumulate in the liver, brain and other vital
organs and symptoms typically begin between the
ages of 12 and 23).
Investigation of liver disease
Biochemical liver function tests done for:
• Diagnosis.
• Prognosis.
• Monitoring of treatment.
• Monitoring of treatment’s side effect and
toxicity.
• Establish patterns of liver disease.
When to perform liver blood tests
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Non-specific symptoms that may indicate liver
disease, such as anorexia, fatigue, or nausea.
Evidence of chronic liver disease in patients who
have symptoms or signs of cirrhosis, portal
hypertension, or liver failure. Signs and symptoms
include ascites, peripheral oedema, spider naevi,
and hepatosplenomegaly.
Conditions associated with a risk of developing liver
disease like patients with other autoimmune
diseases if patients with autoimmune diseases
develop symptoms that suggest liver disease, such
as pruritus in primary biliary cholangitis.
When to perform liver blood tests
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Use of hepatotoxic drugs, such as carbamazepine,
methyldopa,
macrolide
antibiotics,
statins,
sulphonamides and methotrexate.
Family history of liver diseases, including
haemochromatosis or Wilson’s disease.
Alcohol misuse, at harmful levels (in excess of 50
units per week and 35 units per week for men and
women, respectively) for several months.
Viral hepatitis
Risk factors for non-alcoholic fatty liver disease,
such as obesity and metabolic syndrome.