Jaundice and liver function
tests
KVB
Normal Liver:
• The liver is the largest internal
organ,measuring on an average 1500 g.
• The liver has a dual blood supply: 2/3rd by
the portal circulation & 1/3rd of blood
arriving from the hepatic artery.
• This dual blood supply accounts for the
red colour of hepatic infarcts.
The hepatic acinus:
The three zones of the acinus:
• Zone 1: Bordering on the portal tract & first to
receive blood from the branches of the portal
vein & hepatic artery. Susceptible to toxinmediated damage.
• Zone 3: Comprises hepatocytes around the
THV,consequently the last to receive blood
entering the acinus.This area is susceptible to
ischemic injury during hypoperfusion of the liver.
• Zone 2 :Located between Zones 1 & 3.
FUNCTION OF THE LIVER
• The liver regulates most chemical levels in the blood and
excretes bile, which helps carry away waste products
from the liver.
• All the blood leaving the stomach and intestines passes
through the liver.
• The liver processes this blood and breaks down the
nutrients and drugs into forms that are easier to use for
the rest of the body.
• More than 500 vital functions have been identified with
the liver. Some of the more well-known functions include
the following:
Glucose metabolism
Ammonia conversion
Protein metabolism
Fat metabolism
Vitamin and iron storage
Drug metabolism
Bile formation
Main functions of the liver:
Metabolic functions:
 Processing nutrients.
 Removal of impurities and neutralizing various
toxins.
Storage functions:
 Storage of energy & metabolites,predominantly
in the form of lipids & carbohydrates.
 Vitamins A & B12,folate.
 Oligo-minerals like iron and copper.
Secretory functions:
Most of the plasma proteins,
Lipids in the form of lipoproteins
Carbohydrates that are being transported
to other organs for metabolic conversion
into energy.
Excretory function:
Excretes bile into the intestine.
Proteins secreted by the liver:
•
•
•
•
Albumin.
Clotting factors.
Acute-phase reactants: C-RP,SAA protein.
Binding & carrier proteins, eg, transferrin,
ceruloplasmin, thyroid-binding protein.
• Alpha-fetoprotein (AFP) is produced by fetal
liver cells. Levels rise in patients with
hepatocellular carcinoma.
jaundice
The main forms of jaundice:
1)
•
•
•
•
•
•
•
Prehepatic hemolytic jaundice:
Bilirubin is predominantly in an unconjugated form.
Seen in:
Autoimmune hemolytic anemia.
Transfusion reaction.
Malaria.
Erythroblastosis fetalis.
Resorption of bilirubin from internal hemorrhages
( massive hematoma, intestinal hemorrhage).
Inefficient hematopoiesis (pernicious anemia,
thalassemia).
2) Hepatic jaundice:
• Bilirubin is partially conjugated & partially
in an unconjugated form.
• Results from liver cell injury.
The Hereditary Hyperbilirubinemias
• Inborn errors of bilirubin metabolism
resulting in excessive amounts of
bilirubin in the circulating blood, either
because of increased bilirubin
production or because of delayed
clearance of bilirubin from the blood.
• Hereditary hyperbilirubinemias can be
divided into conjugated forms and
unconjugated forms.
Congenital hyperbilirubinemias
Unconjugated
1. Gilbert’s syndrome
2. Crigler-Najjar
syndrome
Conjugated
1. Rotor syndrome
2. Dubin-Johnson
syndrome
• Both types of conjugated
hyperbilirubinemias have a relatively
benign course, but establishing the
diagnosis is important to spare patients
from undergoing multiple unnecessary
procedures and to exclude other more
serious causes of hyperbilirubinemia.
Rotor syndrome
• Rotor syndrome is a rare, relatively benign
autosomal recessive bilirubin disorder of
unknown origin.
• It has many things in common with DubinJohnson syndrome except that in Rotor
Syndrome, the liver cells are not pigmented. The
main symptom is a non-itching jaundice.
• There is a rise in bilirubin in the patient's serum,
mainly of the conjugated type.
3) Post-hepatic obstructive
jaundice:
• Bilirubin is mostly in conjugated form.
• Results from the obstruction of major
extrahepatic biliary ducts.
Bilirubinuria:
• Unconjugated bilirubin, typically found in
hemolytic jaundice, circulates bound to
albumin.
• Conjugated bilirubin typically found in the
blood of patients suffering from
hepatocellular or obstructive jaundice is
water soluble & will readily pass into the
urine.
Kernicterus:
• The deposition of bilirubin in basal ganglia
of the brain.
• Occurs typically in infants affected by the
massive hemolysis of eryhthroblastosis
fetalis.
• High levels of unconjugated bilirubin
enable it to cross blood-brain barrier.
• Deposition of bilirubin causes brain injury.
Causes of neo-natal jaundice:
•
•
•
•
•
•
•
sepsis
hypoxia
hypoglycemia
hypothyroidism
hypertrophic pyloric stenosis
galactosemia
fructosemia
Evaluation of liver function:The liver
function tests(LFTs)
These tests monitor:
1) Liver cell integrity (known as
necroinflammatory indices):
 AST,ALT,which can rise 50 times over
normal values in massive liver
necrosis.In viral hepatitis, levels of AST &
ALT are 4-6 times above the normal
values.
2) Hepatic secretory function:
 Albumin:Normal values are 3.5-5
g/dL.Reduced to < 3g/dL in chronic liver
injury.
 Coagulation proteins: Measure
prothrombin time(PT).Prolonged PT is a
very sensitive index of liver function loss.
Serum protein electrophoresis:
• This is an evaluation of the types of proteins that are
present with in a patient's serum.
• By using an electrophoretic gel, major proteins can be
separated out.
• This results in four major types of proteins. These are:
1) Albumin,
2) Alpha globulins
3) Beta globulins
4) Gamma globulins
Serum Electrophoresis
• Serum protein electrophoresis is useful for
evaluation of patients who have abnormal
liver function tests since it allows a direct
quantification of multiple different serum
proteins.
• If the gamma globulin fraction is elevated,
autoimmune hepatitis may be present.
• In addition a deficiency in the alpha globulin
fraction can result in the diagnosis, or a
clinical clue, to alpha-1 antitrypsin
deficiency. This is a simple blood test that is
commonly performed by hepatologists.
Coagulation tests (e.g. INR)
• The liver is responsible for the production of
coagulation factors.
• The international normalized ratio (INR)
measures the speed of a particular pathway of
coagulation, comparing it to normal.
• If the INR is increased, it means it is taking
longer than usual for blood to clot.
• The INR will only be increased if the liver is so
damaged that synthesis of vitamin K-dependent
coagulation factors has been impaired: it is not a
sensitive measure of liver function.
Serum glucose
• The liver's ability to produce glucose
(gluconeogenesis) is usually the last
function to be lost in the setting of
fulminant liver failure.
3) Biliary excretory function:
 Bilirubin:Conjugated bilirubin that cannot be
excreted into the intestine can be readily
measured as direct bilirubin.
 Alkaline phosphatase: Elevated levels are
typical of obstructive jaundice.
 Gamma-glutamyl transferase(GGT): Primarily
a hepatic enzyme and its rise is a reliable sign of
biliary obstruction.Is also induced in liver cells in
alcohol or phenobarbital injury to the p450
system.GGT is thus a marker of liver-cell
injury,especially alcohol-induced injury.
4) Hepatic catabolic function: include the
detoxification of many metabolites.
 In practice,only the capacity of the liver
to remove ammonia is measured.
 Elevation of blood ammonia is a good
marker of severe liver injury.
Other tests commonly requested
alongside LFTs:
• 5' nucleotidase (5'NTD) :
• 5' nucleotidase is another test specific for
cholestasis or damage to the intra or
extrahepatic biliary system, and in some
laboratories, is used as a substitute for
GGT for ascertaining whether an elevated
ALP is of biliary or extra-biliary origin.
Lactate dehydrogenase (LDH)
• Lactate dehydrogenase is an enzyme
found in many body tissues, including the
liver.
• Elevated levels of LDH may indicate liver
damage
Why is it important to fractionate
bilirubin in the serum?
• Fractionation of bilirubin is important for elucidating the
causes & pathogenesis of jaundice.
• Normally,blood contains <1.2 mg/dL of bilirubin,most of it
being in an unconjugated (indirect) form-95%.
• According to laboratory analysis, hyperbilirubinemia can
be classified as the following:
 Predominantly unconjugated(<20%).
 Mixed (CB 20-50%).
 Predominantly conjugated (>50%).
Thank you