Jaundice

Question 1

Metabolism of BilliRubin

Answer 1

~ Major: BiliRubin is derived from break down of senescent RBCs- catabolism of haemoglobin
~ Minor: cytochromes, red-cell precursors in bone marrow, immature RBCs

~ Heme —> Biliverdin ( heme oxygenase)
~ Biliverdin —> Bilirubin ( biliverdin reductase)
~ Blood: Bilirubin + albumin - unconjugated bilirubin
~ complex associated after entering hepatocytes
~ bilirubin + glutathione S transferase ( ligandin)
~ conjugation of BiliRubin in liver: Bilirubin glucoronides - water soluble
~ excreted in bile
~ converted to urobilinogen in intestine by beta glucoronidases - 80% excreted - stercobilinogen - stercobilin ( stool)
~ 20% urobilinogen formed in intestine is reabsorbed- re excreted in bile - ~urobilinogen in urine

~ conjugated appears in urine
~ unconjugated is tightly bound to albumin, not excreted in urine

Question 2

Definition and mechanism of jaundice

Answer 2

~ Yellowish pigmentation of skin, mucous membranes and sclera due to increased BiliRubin in blood
~sclera is involved because of rich elastic tissue + affinity for BiliRubin
~ normal serum bilirubin: 0.3-1.2 mg/dl
~ jaundice: clinically detected > 2-2.5 mg/dl
~ severe disease: 30-40 mg/dl

Mechanism of jaundice
1. Unconjugated hyperbilirubinaemia - water insoluble, hemolytic Disease of newborn - crosses BBB - reach brain - Kernicterus
~ excessive extrahepatic production of BiliRubin- haemolytic anaemia, GI bleeding
~ reduced hepatocyte uptake - drugs, diffuse liver disease
~ impaired conjugation- Gilbert syndrome, physiologic jaundice of the newborn,Criggler Nazar syndrome

2. Conjugated hyperbilirubinaemia - water soluble, non toxic
   ~ decrease hepato-cellular excretion: Dubin Johnson syndrome, rotor syndrome
   ~ impaired bile flow - gall stones, cholangitis , pancreatic carcinoma

Question 3

Classification of Jaundice

Answer 3

1. Based on underlying cause
   ~ unconjugated
   ~ conjugated
2. Pathological mechanism
   ~ hemolytic jaundice - prehepatic
   ~hepatocellular jaundice - hepatic
   ~obstructive jaundice - surgical/ post hepatic / cholestatic

Question 4

Haemolytic jaundice

Answer 4

~ increased haemolyses or ineffective erythropoiesis
~ Increase production of unconjugated bilirubin
~ mild jaundice

Laboratory findings
~ unconjugated hyperbilirubinaemia
~ liver function test normal
~ LDH raised
~ no BiliRubin in urine : alcoluric jaundice
~ urinary urobilinogen increased

Question 5

Hepatic jaundice

Answer 5

~ consequence of Parenchymal liver disease- Inability to transport BiliRubin

Laboratory findings
~ transaminase raises - infections, drugs, ischaemia
~ unconjugated and conjugated bilirubin raised
~ BiliRubin present in urine
~urobilinogen present

Question 6

Obstructive jaundice

Answer 6

~ surgical jaundice- due to cholestasis- failure of bile flow
~ Retention of bile acids and BiliRubin
~ deficiency of bile acids in intestine

Laboratory findings
~ serum BiliRubin raised
~ serum ALP markedly increased
~ increase in gamma glutamyl transpeptidase
~ anti mitochondrial Ab
~ Bilirubinuria - yellow - conjugated
~urobilinogen absent - conjugated bilirubin in bile does not enter bowel

Question 7

Laboratory investigations in jaundice

Answer 7

Van def bergh reaction
~calorimetric test, estimation of serum BiliRubin
~ serum + diazo Regent (diazotised sulfanilic acid) - purple coloured AzoBiliRubin

~ direct positive: conjugated- red colour immediately
~ indirect positive: Sitam is first mixed with alcohol- red colour- unconjugated
~ biphasic reaction: both unconjugated and conjugated

Question 8

Congenital hyperbilirubinaemia

Answer 8

1. Crigler Najjar syndrome. Type 1
   ~ AR - complete absence of UGT1A1 enzyme
   ~ chronic severe unconjugated hyperbilirubinaemia- jaundice, icterus, kernicterus
   ~bile contains conjugated - colourless
   ~ Treatment phenobarbital - no effect
   ~ Liver is normal morphologically
2. Crigler Najjar Type 2
   ~ less severe non-fatal
   ~ partial deficiency of above enzyme
   ~AD
   ~ Phenobarbital treatment can improve condition
3. Gilbert syndrome
   ~ common harmless
   ~ mutations in UFT1 gene
   ~AR
   ~ asymptomatic
   ~ Mild chronic unconjugated, fluctuating hyperbilirubinaemia
4. Dubin Johnson syndrome
   ~ benign, AR
   ~ complete absence of multidrug resistance protein 2 -defective excretion of glucuronides
   ~ Darkly Pigmented ( polymers of epinephrine) liver, melanin granules
   ~ Chronic conjugated, Billy Rubin India
5. Rotor syndrome.
   ~ Asymptomatic conjugated hyperbilirubinaemia
   ~ defect in hepatoCellular uptake and excretion of BiliRubin
   ~AR
   ~ morphologically normal liver