Jaundice
Dr Manoj K Ghoda MD, MRCP
Consultant GastroenterologistVisiting Faculty at GCS Hospital
18 yrs old femaleConsulted as family noticed her to be yellow.
Fitness fanaticCautious 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.
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 juiceDeveloped 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
Examination of sclera
Sun light is always preferable
18 yrs old male
TirednessPallorRecurrent mouth ulcers
On examination:Pallor ++Abdomen was unremarkable, no liver and no spleen
Hb: 5.4MCV: 125MCH: 35.2P.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?
18 yrs old male
Persistent jaundice from birthPallorTiredness
On Examination:Spleen ++
CBC:Hb7.0MCV :75P.S. Uniformly small RBCs without central pallorRetics: 6%
LFT:S. Bil: 3.2 (70% unconjugated)ALT: 18ALP: 100
Why this young man with (hereditary) spherocytosis is having jaundice?
18 yrs F
Intermittent jaundice when catches routine illnesses
No complaints
On Examination:Mild icterusLiver 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?
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
Bilirubin Metabolism
Bilirubin Metabolism
Excess production
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+ Albumin
1
2
1= Heme oxygenase2= Biliverdine reductase
UDP-GTFailure of conversion
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
Green jaundice: an unusual case revisited(Gåfvels M, Holmström P, Somell A et al. A novel mutation in thebiliverdin reductase-A gene combined with liver cirrhosis results inhyperbiliverdinaemia [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
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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
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
18 yrs old female
H/o fever 3 daysNauseaVomitingAversion to foodYellowish discolorationEpigastric painYellow urine
O/E: Tenderness in RUQ, mild hepatomegaly
CBC: NormalLFTs:
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?
48 yrs old female
H/O sudden onset of right upper quadrant pain radiating to the tip of scapulaFever with severe chillsYellowish 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?
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
Let us see how conjugated bilirubin is formed and disposed off
Bilirubin Metabolism
Bilirubin Metabolism
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Hepatocellular jaundice
Obstructive jaundice
Conjugated hyperbilirubinemia
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
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
This was easy. Wasn’t it ?
Let us try some more cases.....
18 yrs old female
H/o fever 3 daysYellowish discolorationEpigastric painYellow urine
O/E: Hepatomegaly ++
CBC:
Hb: 5.4MCV: 82 flMCH: 28.2P.S.: suggestive of hemolysisRetics: 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 diseaseAutoimmune hepatitis
18 yrs old female
H/o fever with rigors for 3 daysHeadacheYellowish discoloration
O/E: mild splenomegaly
CBC: Normal, P.S showed falciparum malaria, retics: normalLFTs:
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?
TNF-alpha, IL-1,6
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Transport of conjugated bilirubin from hepatocytes to bile canaliculi
This is cholestasis of inflammationThis is seen in any condition where cytokines are released
Jaundice
Viral HepatitisDrug inducedAlcoholicAutoimmuneWilson’s
StoneTumorStricture
HemoglobinopathiesMalaria, Drug inducedAutoimmuneWilson’s
Megaloblastic anemia
PrematurityGilbert’sCriggler Najjar
Any questions?
Dr Manoj K Ghoda M.D., M.R.C.P.
Consultant GastroenterologistVisiting faculty at GCS Hospital