CLINICAL CASE
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CASE 1
24 y/o male with Malaria was put on Primaquine. He developed
malaise, fatigue and yellow discoloration of skin and sclera.
Investigation results:
HGB – 6 g/dl, bilirubin – 6mg/dl (mainly unconjugated bilirubinemia)
Q: What is the probable diagnosis? What type of jaundice does the
patient have: Pre-hepatic? Intra-hepatic? Post-hepatic?
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Classification of Jaundice
Pre-hepatic: pathology occuring prior to the liver
Any cause of increased haemolysis (e.g. Spherocytosis, thalassaemia, sickle cell disease,
transfusion reaction, auto-immune, malaria etc.) and some drugs
Causes unconjugated hyperbilirubinaemia
Intra-Hepatic: pathology occuring within the liver
All the causes of hepatitis/cirrhosis (e.g. Alcohol, viral, auto-immune, primray biliary cirrhosis, haemochromatosis, wilsons,
alpha-1 antitrypsin deficiency etc.), inherited condition on previous slide and some drugs
Can result in hepatocyte destruction and therefore unconjugated hyperbilirubinaemia or in bile cannaliculi destruction and
therefore conjugated hyperbilirubinaemia or both
Note/ neonatal jaundice: occurs in most newborns as hepatic machinary for conjugation and excretion of bilirubin not fully
matured until 2 weeks of age
Post-hepatic: pathology occuring after conjugation of bilirubin within the liver (aka obstructive
jaundice)
Any cause of biliary obstruction (e.g. Gallstones)
Causes conjugated hyperbilirubinaemia
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CASE 2
50 y/o woman had 8 day history of loss of appetite, nausea and flu-like
symptoms. She had noticed that her urine had been dark in color over the
past two days. On examination she had tenderness in the right upper
quadrant.
Laboratory investigations showed: Total bilirubin – 4.5 mg/dl, Direct
bilirubin – 2.5 mg/dl, ALT – 115 U/L, AST – 44 U/L, ALP – slightly
elevated.
Q: What is the probable diagnosis?
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Determining etiology of Jaundice
Total bilirubin and its conjugated and unconjugated levels
help to determine nature of jaundice
Test Pre-hepatic Hepatic Post-hepatic
Total bilirubin + ++ +++
Conjugated bilirubin Normal Increased Increased
Unconjugated bilirubin Increased Increased Normal
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Determining etiology of jaundice
Liver Enzymes
ALT/AST
ALT/AST mainly
mainly present
present in
in hepatocytes
hepatocytes
ALP/GGT
ALP/GGT mainly
mainly present
present in
in bile
bile cannaliculi
cannaliculi biliary
biliary tree
tree
Derrangement of particular liver enzymes in association with
jaundice can determine nature of the jaundice
Test Pre-hepatic Hepatic Post-hepatic
ALT/AST Normal +++ +
ALP/GGT Normal + +++
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Symptoms are indicative of viral hepatitis.
The conjugated bilirubin is not efficiently secreted in to the bile, but
instead diffuses in to the blood. Damage to liver cells can cause
unconjugated bilirubin to increase in the blood as a result of decreased
conjugation. ALT and AST are elevated.
This is the case of hepatic jaundice.
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CASE 3
Based on the following laboratory data, give the most probable diagnosis:
Serum bilirubin – 4 mg/dl
Direct bilirubin – 0.2 mg/dl
ALT, AST, ALP – within the norm
Urine bilirubin – negative
Urine urobilinogen - positive
hepa
Determining etiology of Jaundice
Total bilirubin and its conjugated and unconjugated levels
help to determine nature of jaundice
Test Pre-hepatic Hepatic Post-hepatic
Total bilirubin + ++ +++
Conjugated bilirubin Normal Increased Increased
Unconjugated bilirubin Increased Increased Normal
hepa
Determining etiology of jaundice
Liver Enzymes
ALT/AST
ALT/AST mainly
mainly present
present in
in hepatocytes
hepatocytes
ALP/GGT
ALP/GGT mainly
mainly present
present in
in bile
bile cannaliculi
cannaliculi biliary
biliary tree
tree
Derrangement of particular liver enzymes in association with
jaundice can determine nature of the jaundice
Test Pre-hepatic Hepatic Post-hepatic
ALT/AST Normal +++ +
ALP/GGT Normal + +++
hepa
Determining etiology of Jaundice
Urine bilirubin
Normally, tiny amount bilirubin (conjugated) excreted in urine
Pre-hepatic jaundice: Haemolysis causes rise in unconjugated bilirubin (water insoluble) and this is not excreted by the kidney therefore there is no rise in
urine bilirubin
Some causes of Hepatic jaundice: result in damage to biliary cannaliculi and therefore result in poor biliary drainage and therefore elevated conjugated
bilirubin levels in blood, excreted into urine (giving dark urine)
Post-Hepatic juandice: Obstruction to biliary drainage and so conjugated bilirubin (water soluble) levels in the blood increase and appear in the urine (giving
dark urine)
Urine urobilinogen
Pre-hepatic jaundice: Haemolysis results in increased bilirubin production and subsequent increase bilirubin metabolism and urobilinogen in stool and
therefore in the urine.
Some causes of Hepatic jaundice : result in hepatocellular destruction and therefore reduced re-excretion of re-absorbed urobilinogen (i.e. Reduction in
entero-hepatic circulation of urobilinogen) resulting in elevated levels in urine
Post-Hepatic jaundice: Less bilirubin reaching intestine therefore reduction in urobilinogen therefore reduction in urine urobilinogen
Test Pre-hepatic Hepatic Post-hepatic
Urine Bilirubin negative Negative (but maybe increased depending on cause) Increased
Urine Increased Normal (but maybe increased depending on cause) Decreased/negative
urobilinogen
Urine colour Normal Normal (but maybe dark depending on cause) Dark
Stool colour Normal Normal Pale
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Normal enzyme profile, hyperbilirubinemia, absence of urinary
bilirubin, and positive urobilinogen are indicative of hemolytic (pre-
hepatic) jaundice.
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CASE 4
A 40 y/o fat female presents with intolerance to fatty foods, pain in the
right side of abdomen, yellowing of eyes and passage of clay colored
stools.
Laboratory investigations revealed:
Serum: Total bilirubin – 20 mg/dl, Direct bilirubin – 18 mg/dl, ALT –
90 U/L, ALP – 800 U/L
Urine: Color – deep yellow, Bilirubin ++, Urobilinogen – absent
Stools: Clay colored, stercobilinogen – absent.
WHAT IS THE LIKELY DIAGNOSIS?
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Determining etiology of Jaundice
Total bilirubin and its conjugated and unconjugated levels
help to determine nature of jaundice
Test Pre-hepatic Hepatic Post-hepatic
Total bilirubin + ++ +++
Conjugated bilirubin Normal Increased Increased
Unconjugated bilirubin Increased Increased Normal
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Determining etiology of jaundice
Liver Enzymes
ALT/AST
ALT/AST mainly
mainly present
present in
in hepatocytes
hepatocytes
ALP/GGT
ALP/GGT mainly
mainly present
present in
in bile
bile cannaliculi
cannaliculi biliary
biliary tree
tree
Derrangement of particular liver enzymes in association with
jaundice can determine nature of the jaundice
Test Pre-hepatic Hepatic Post-hepatic
ALT/AST Normal +++ +
ALP/GGT Normal + +++
hepa
Determining etiology of Jaundice
Urine bilirubin
Normally, tiny amount bilirubin (conjugated) excreted in urine
Pre-hepatic jaundice: Haemolysis causes rise in unconjugated bilirubin (water insoluble) and this is not excreted by the kidney therefore there is no rise in
urine bilirubin
Some causes of Hepatic jaundice: result in damage to biliary cannaliculi and therefore result in poor biliary drainage and therefore elevated conjugated
bilirubin levels in blood, excreted into urine (giving dark urine)
Post-Hepatic juandice: Obstruction to biliary drainage and so conjugated bilirubin (water soluble) levels in the blood increase and appear in the urine (giving
dark urine)
Urine urobilinogen
Pre-hepatic jaundice: Haemolysis results in increased bilirubin production and subsequent increase bilirubin metabolism and urobilinogen in stool and
therefore in the urine.
Some causes of Hepatic jaundice : result in hepatocellular destruction and therefore reduced re-excretion of re-absorbed urobilinogen (i.e. Reduction in
entero-hepatic circulation of urobilinogen) resulting in elevated levels in urine
Post-Hepatic jaundice: Less bilirubin reaching intestine therefore reduction in urobilinogen therefore reduction in urine urobilinogen
Test Pre-hepatic Hepatic Post-hepatic
Urine Bilirubin negative Negative (but maybe increased depending on cause) Increased
Urine Increased Normal (but maybe increased depending on cause) Decreased/negative
urobilinogen
Urine colour Normal Normal (but maybe dark depending on cause) Dark
Stool colour Normal Normal Pale
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This is a case of obstructive jaundice due to gall stones. The patient fits the classic criteria
for gallbladder disease: female, middle-aged, overweight.
Gallstones are collection of solid material (predominantly crystals of cholesterol) in the
gallbladder. Gallstones may cause pain. Pain develops when the stones pass from the
gallbladder into the cystic duct, common bile duct or ampulla of Vater and block the duct.
Then the gallbladder dilates causing pain, called the biliary colic. The pain is felt in the
upper abdomen, usually on the right side.
High direct bilirubin, high ALP (marker of cholestasis), slightly increased ALT level
are suggestive of post-hepatic or obstructive jaundice.
Furthermore the diagnosis is supported by the presence of bilirubin and absence of
urobilinogen (since there is obstruction to the out flow of bile) in urine. Due to the same
reason of obstruction stool is clay colored as stercobilnogen is absent.
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