This document discusses jaundice in multiple patients and the underlying causes. It begins by summarizing different causes of jaundice, including unconjugated hyperbilirubinemia from excessive production or failure of conjugation, and conjugated hyperbilirubinemia from hepatocellular damage or obstruction of bile flow. It then analyzes several case studies: three with unconjugated hyperbilirubinemia from megaloblastic anemia, hereditary spherocytosis, and an unknown cause; two with conjugated hyperbilirubinemia, one from hepatocellular damage and one from obstruction; and one with malaria-induced cholestasis. The document emphasizes different

1. Jaundice
Dr Manoj K Ghoda MD, MRCP
Consultant Gastroenterologist
Visiting Faculty at GCS Hospital

2. 18 yrs old female
Consulted as family noticed her to be yellow.
Fitness fanatic
Cautious about food
Had no symptoms whatsoever
On examination:
She appeared yellow
Physical examination : Normal
S. Bil: 0.8 ( 0.4+0.4)
ALT/SGPT: 21 i.u.
ALP: 121 i.u.

3. Why does this young lady have yellow discolouration
when her bilirubin level is normal?
This young girl was fitness fanatic and diet conscious.
Drank lots of carrot juice
Developed hypercarotinemia and hence appeared yellow
So.. “All that glitters is not Gold”
All yellowness is not jaundice.
Do you know any other compound causing yellow
discoloration?
At about 2-3 mg one can appreciate jaundice; in
sclera, conjunctiva and mucus membrane

4. Examination of sclera
Sun light is always preferable

5. 18 yrs old male
Tiredness
Pallor
Recurrent mouth ulcers
On examination:
Pallor ++
Abdomen was unremarkable, no liver and no spleen
Hb: 5.4
MCV: 125
MCH: 35.2
P.S.: Megalo-ovaloblastic anemia
S. Bil: 3.1 (Conjugated 0.8, unconjugated 2.5)
ALT/SGPT: 26 I.U.
ALP: 123 I.U.
PT: 13/13 sec
Why this young man with megaloblastic anemia is having jaundice?

6. 18 yrs old male
Persistent jaundice from birth
Pallor
Tiredness
On Examination:
Spleen ++
CBC:
Hb7.0
MCV :75
P.S. Uniformly small RBCs without central pallor
Retics: 6%
LFT:
S. Bil: 3.2 (70% unconjugated)
ALT: 18
ALP: 100
Why this young man with (hereditary) spherocytosis is having jaundice?

7. 18 yrs F
Intermittent jaundice when catches routine illnesses
No complaints
On Examination:
Mild icterus
Liver and spleen not palpable
CBC: Normal , retics 1.5%
LFTs:
S.Bil: 3.5 ( Conjugated 0.2; unconjugated 3.3)
ALT: 21 I.U.
ALP: 135 I.U.
Why this young lady having jaundice and no anemia?

8. Analysis of all three patients:
•All three have unconjugated hyperbilirubinemia
•One has megaloblastic anemia
•One has hemolysis ; and
•The third has neither of these
So, now we know that unconjugated hyperbilirubinemia is one cause of
jaundice.
But what is common between spherocytosis and megaloblastic anemia?
The third patient doesn’t have even anemia, but he still has same pattern of
jaundice; why?
What could have caused rise in unconjugated bilirubin levels in these three
apparently unrelated patients ?
What exactly is the underlying mechanism?
To understand this we have to look at bilirubin metabolism

9. Bilirubin Metabolism
Bilirubin Metabolism
Excess
production
X
+ Albumin
1
2
1= Heme oxygenase
2= Biliverdine reductase
UDP-GT
Failure of
conversion

10. This is the only
reaction in
entire body that
produces CO
It is easy to break things
which are not tightly
organized.
Let us look at breakdown
of hemoglobin bit more
closely
Remember!
Biliverdin is
GREEN

11. Green jaundice: an unusual case revisited
(Gåfvels M, Holmström P,
Somell A et al. A novel mutation in the
biliverdin reductase-A gene combined
with liver cirrhosis results in
hyperbiliverdinaemia [green jaundice].
Liver Int 2009; 29:1116–24)
Deficiency of Heme oxygenase would result in
hemolysis without unconjugated
hyperbilirubinemia
Let me see ..if you brain is working
X
X

12. How to differentiate excessive production from failure of conversion
Excess production
•Clinical context
•Low Hb
•High retics
•High LDH
•Hemoglobunuria
•Splenomegaly
•Other clinical features of
anemia
Failure of conversion
•Clinical context
•Hb Normal
•Retics normal
•LDH normal
•No hemoglobinuria
•No splenomegaly
•No other features of
anemia
•May be other
features of
hyperbilirubinemia
Features of hemolysis

13. Summary:
One reason of jaundice is unconjugated hyperbilirubinemia.
This could be because of
excessive production; or
Failure of conjugation
Therefore when you see unconjugated hyperbilirubinemia it is
mandatory that you differentiate between the two.
Hemolytic anemias, Gilbert’s syndrome, Criggler Najjar syndrome,
low albumin

14. 18 yrs old female
H/o
fever 3 days
Nausea
Vomiting
Aversion to food
Yellowish discoloration
Epigastric pain
Yellow urine
O/E: Tenderness in RUQ, mild hepatomegaly
CBC: Normal
LFTs:
S. Bil: 5.5 (Direct 70%, indirect 30%)
ALT: 1500 i.u.
ALP: 135 i.u.
Why this young lady feeling so unwell and has jaundice?

15. 48 yrs old female
H/O sudden onset of right upper quadrant pain radiating to the tip of scapula
Fever with severe chills
Yellowish discoloration
O/E:
Tenderness in RUQ
CBC: High WCC, 35,000
LFTs:
S. Bil: 5.5 (70% direct, 30% indirect)
ALT: 135 i.u.
ALP: 1500 i.u.
USG: Dilated CBD with an acoustic shadowing
at the lower end.
Why this patient has so much pain and fever with chills with jaundice?

16. Analysis of these two cases:
•Both have conjugated hyperbilirubinemia
•The first pt has no pain but is very symptomatic with
anorexia, nausea, vomiting and her ALT is elevated
•The second pt had severe pain and fever with dramatic
chills with discomfort on touching RUQ
So now we know that Second cause of jaundice is Rise in
conjugate bilirubin levels
This could be because of
Hepatocellular damage, or
Obstruction to bile flow

17. Let us see how conjugated bilirubin is formed
and disposed off

18. Bilirubin Metabolism
Bilirubin Metabolism
x
x
Hepatocellular
jaundice
Obstructive jaundice
Conjugated hyperbilirubinemia

19. Conjugated hyperbilirubinemia:
Differentiating hepatocellular from
obstruction
Hepatocellular damage is detected by high ALT/AST/GGT. USG
may show altered echo pattern of liver parenchyma
Obstruction to outflow is detected b high ALP/GGT. USG may
show dilatation of Biliary tree
Note:
GGT sits on the fence.
With High ALT/AST it suggests hepatocellular damage;
And with high ALP it suggests obstructive jaundice

20. Summary
Any case of jaundice will qualify for label of conjugated
hyperbilirubinemia if conjugated bilirubin is above 2 mg.
Usually it constitutes 70% of total bilirubin
Hepatocellular
•Clinical context
•High ALT/AST/GGT
•Altered PT which may not be
corrected by vitamin K
•USG may show altered
parenchymal echo pattern
Obstructive
•Clinical context
•High GGT/ALP
•Altered PT easily corrected by
vitamin K
•USG may show dilated biliary
tree and many times the cause
also

21. This was easy. Wasn’t it ?
Let us try some more cases.....

22. 18 yrs old female
H/o
fever 3 days
Yellowish discoloration
Epigastric pain
Yellow urine
O/E: Hepatomegaly ++
CBC:
Hb: 5.4
MCV: 82 fl
MCH: 28.2
P.S.: suggestive of hemolysis
Retics: 5% ( up to 2)
LFTs:
S. Bil: 5.5 (Direct 550%, indirect 45%)
ALT: 500 i.u.
ALP: 135 i.u.
Practically only two conditions are
able to produce combined
hyperbilirubinemia;
Wilson’s disease
Autoimmune hepatitis

23. 18 yrs old female
H/o
fever with rigors for 3 days
Headache
Yellowish discoloration
O/E: mild splenomegaly
CBC: Normal, P.S showed falciparum malaria, retics: normal
LFTs:
S. Bil: 5.5 (Direct 70%, indirect 30%)
ALT: 15 i.u.
ALP: 135 i.u.
Why this young lady is having jaundice when
everything else we have discussed so far is normal?

24. TNF-alpha, IL-1,6
X
Transport of conjugated bilirubin from hepatocytes to
bile canaliculi
This is cholestasis of inflammation
This is seen in any condition where cytokines
are released

25. Jaundice
Viral Hepatitis
Drug induced
Alcoholic
Autoimmune
Wilson’s
Stone
Tumor
Stricture
Hemoglobinopathies
Malaria, Drug induced
Autoimmune
Wilson’s
Megaloblastic
anemia
Prematurity
Gilbert’s
Criggler
Najjar

26. Any questions?
Dr Manoj K Ghoda M.D., M.R.C.P.
Consultant Gastroenterologist
Visiting faculty at GCS Hospital