It is characterized by a yellow appearance of the (1) Skin (2) Mucous membranes and (3) Sclera caused by bilirubin deposition. It is the most specific clinical manifestation of Hepatic dysfunction. Jaundice is usually present clinically when the plasma bilirubin concentration reaches 2 to 3 mg/dl. When bilirubin clearance from the Liver to the Intestinal tract is impaired (as in acute hepatitis and bile duct obstruction) it may be accompanied by alcoholic (Gray coloured) stools.Solubility increases in water , soluble conjugated bilirubin leads to Tea coloured urine.

1. METABOLISM OF
BILIRUBIN
Tapeshwar Yadav
(Lecturer)
BMLT, DNHE,
M.Sc. Medical Biochemistry

2. JAUNDICEJAUNDICE
 It is characterized by a yellow appearance of the (1) Skin
(2) Mucous membranes and (3) Sclera caused by bilirubin
deposition. It is the most specific clinical manifestation of
Hepatic dysfunction.
 Jaundice is usually present clinically when the plasma
bilirubin concentration reaches 2 to 3 mg/dl.
 When bilirubin clearance from the Liver to the Intestinal
tract is impaired (as in acute hepatitis and bile duct
obstruction) it may be accompanied by alcoholic (Gray
coloured) stools.Solubility increases in water , soluble
conjugated bilirubin leads to Tea coloured urine.

3. JAUNDICEJAUNDICE
 It is characterized by a yellow appearance of the (1) Skin
(2) Mucous membranes and (3) Sclera caused by bilirubin
deposition. It is the most specific clinical manifestation of
Hepatic dysfunction.
 Jaundice is usually present clinically when the plasma
bilirubin concentration reaches 2 to 3 mg/dl.
 When bilirubin clearance from the Liver to the Intestinal
tract is impaired (as in acute hepatitis and bile duct
obstruction) it may be accompanied by Alcoholic (Gray
coloured) stools.Solubility increases in water , soluble
conjugated bilirubin leads to Tea coloured urine.

4.  Bilirubin is the orange – yellow pigment derived from
RBC, following formation in the Reticuloendothelial cells.
Bilirubin is transported to and bio – transformed mainly in
the liver and excreted in bile and urine.
 Bilirubin is a Linear Tetra pyrrole molecule. It is insoluble
in water and readily soluble in variety of non polar
solvents.
 It has both Trans and Cis Isomers. When exposed to
light, bilirubin in the Trans Configuration is converted to Cis
Configuration, which is more water soluble.
BILIRUBIN & CHEMISTRYBILIRUBIN & CHEMISTRY

5. SYNTHESIS OF BILIRUBINSYNTHESIS OF BILIRUBIN
HEMOGLOBIN
- Globin → AminoAcid pool
HEME
(Ring opens)
Heme - oxygenaze System
(NADPH, cytochrome C &
O2) -‘CO’ released
- Iron liberated – Iron re-
utilized
Biliverdin (Green)
Biliverdin Reductase NADPH + H +
NADP +
Bilirubin (RED YELLOW)

6. Generation and excretion ofGeneration and excretion of
BilirubinBilirubin

7. GENERATION OF BILIRUBINGENERATION OF BILIRUBIN
 Bilirubin has no function in the body and excreted
through bile the senescent RBC’s break down liberating
the Hemoglobin.
 From hemoglobin, the globin chains are separated, they
are hydrolysed and aminoacids are channeled in to the
body -aminoacid pool.
 The Iron liberated from Heme is re – utilzed. (The Fe+2
liberated is oxidized to Fe+3 and taken up by transferrin.

8.  The porphyrin Ring is broken down in
Reticuloendothelial (RE) cells of liver, spleen and bone
marrow to bile pigments, mainly bilirubin.
 6 grams of HB is broken down per day from which
about 250 mg of bilirubin is formed.
 From myoglobin and other heme containing proteins
another 50mg of bilirubin is formed.
 Approximately 35 mg of bilirubin is formed from 1gm of
HB.
 A total of 300 mg of bilirubin is formed every day of
which 80% is from distruction of old RBC’s, 10% from
ineffective erythropoisis and rest 10% from degradation
of Myoglobin and HEME containing proteins.

9. TRANSPORT TO LIVER
 The liver plays the central role in the further disposal of the
bilirubin. The bilirubin formed in the RE cells is insoluble in
water. the lipophilic bilirubin is there fore transported in plasma,
bound to Albumin.
 One molecule of Albumin can bind 2 molecules of biliru-
-bin.100ml of plasma can transport up to 25mg of
bilirubin.
Albumin binds bilirubin forms Albumin-Bilirubin complex,
It reaches at the sinusoidal surface of the liver,The
bilirubin is taken up , The uptake is a Carrier
mediated Active process.

10. CONJUGATION IN LIVERCONJUGATION IN LIVER
INSIDE THE LIVER CELL
UDP - glucuronyl transferase
Blilirubin Bilirubin
Monoglucuronide
UDP Glucuronic Acid UDP
UDP-glucuronyl transferase
Birubin monoglucuronide Bilirubin
Di-glucuronide
UDP Glucuronic Acid UDP

11. IN SIDE CELLIN SIDE CELL
 The bilirubin is conjugated with glucuronic acid, to make it
water soluble.
 The first carbon of glucuronic acid is combined with the
carboxyl group of the propionic acid of bilirubin molecule.
80% of bilirubin in Di-glucuronide form, 20% are in
Monoglucuronide form.

12. EXCRETION OF BILIRUBIN TO BILEEXCRETION OF BILIRUBIN TO BILE
The water soluble conjugated bilirubin is excreted
in to the bile by an active process and this occurs
against a concentration gradient.
It is rate limiting step in catabolism of HEME

13. FATE OF CONJUGATED BILIRUBIN IN INTESTINEFATE OF CONJUGATED BILIRUBIN IN INTESTINE
 The conjugated bilirubin reaches the Intestine through
the bile. Intestinal bacteria Deconjugate the conjugated
bilirubin to free Bilirubin.[beata glucuronidase]
 This free bilirubin (36 Hydrogen Atoms) is further
reduced to a colourless tetrapyrrole Uroblinogen (UBG).
 Further reduction of the Vinyl substituent groups of UBG
leads to formations of Mesobilinogen and stercobilinogen
(SBG).
 The stercobilinogen [SBG] is mostly excreted
through feces (250– 300mg/day)

14. ENTEROHEPATIC CIRCULATION
 20% of the Urobilinogen [UBG] is reabsorbed from
the INTESTINE and returned to the liver by portal
blood.
 The Urobilinogen [UBG] is again re-excreted
(Entero hepatic circulation), since Urobilinogen[UBG]
is passed though blood a small fraction is excreted in
urine (Less than 4mg/day) .

15. FINAL EXCRETION
 Urobilinogen [UBG] and Stercobilinogen[SBG] are
both colourless compounds but are oxidized to
coloured products, Urobilin (42 Hydrogens) or
Stercobilin (46 hydrogens) respectively by atmospheric
oxidation.
 Both Urobilin and Stercobilin are present in urine as
well as in feces. The Normal colour of Feces is due to
these compounds. Normal plasma bilirubin levels
ranges from 0.2 – 1 mg/dl. Conjugated bilirubin 0 - 0.2
mg/dl.

18. BIOCHEMICAL
ASSESSMENT OF
SURGICAL JAUNDICE
By
Dr. G.SRINIVASA REDDY

19. OBSTRUCTIVE / POST HEPATICOBSTRUCTIVE / POST HEPATIC
JAUNDICEJAUNDICE
Obstruction is caused by extra/intra hepatic cholestatis
Extra hepatic obstruction [surgical jaundice] is caused,
Eg : Gall stones
Hepatic Tumors
Hepato cellular carcinoma
Carcinoma head of the pancreas
Enlarged lymph glands pressing
on bile duct.

20. CHOLESTASIS (Stoppage of the flow of Bile) :
 Prolonged cholestasis may lead to Bile deficiency
causing Malabsorption of fat and fat soluble Vitamins
A,D,E and K. Accumulation of normal bile contents
lead to jaundice,and development of an abnormal
lipoprotein X, Containing phospholipid, cholesterol,
albumin, fragments of cell membranes[along with
ATP].
Increased bilirubin generally occurs only with
complete obstruction by Extra/ Intra hepatic cholestasis .

21. EVALUATION OF BIOCHEMICAL VARIABLES IN
SURGICAL JAUNDICE:
SPECIFIC ENZYMES.
1. Alkaline phosphatase (ALP)
Normal range:23-100IU/lt
Very high levels of ALP (10 - 12) times
Seen in obstructive Jaundice
Higher than 300IU/lt is Strongly diagnosis of
Obstructive Jaundice
2. . Gamma Glutamyl Transferase (γ GT)
Normal range 10 to 47 IU/L.
Markedly Increased in obstructive Jaundice

22. OTHER CANALICULAROTHER CANALICULAR
ENZYMESENZYMES
3.Serum Sorbitol Dehydrogenase (SDH)3.Serum Sorbitol Dehydrogenase (SDH)
 Serum levels of SDH is elevated inSerum levels of SDH is elevated in
obstructiveobstructive jaundice.jaundice.

23. 4. Serum 5’nucleotidase4. Serum 5’nucleotidase ::
 Normal range 2 to 17 IU/LNormal range 2 to 17 IU/L
It may reach up to 100 IU in obstructiveIt may reach up to 100 IU in obstructive
jaundice .jaundice .
NO elevation in bone diseases.NO elevation in bone diseases.

24. 5.Serum Leucine Amino Peptidase (LAP)
Normal range is 15 to 56 m IU
Increase is more in malignant obstruction than
Benign obstruction
In Benign obstruction showed 75 to 184 m IU
Average (101.25 m.IU)
In malignant obstruction showed 67 to 340 m.IU
Average (105 m.lU)

25. OTHER ANALYTES.OTHER ANALYTES.
6.Serum Bilirubin6.Serum Bilirubin
 Normal Range 0.2 to 1mg/dl.Normal Range 0.2 to 1mg/dl.
 Increased up to 50mg %.Increased up to 50mg %.
 Conjugated & unconjugated bilirubin isConjugated & unconjugated bilirubin is
raisedraised
 Urobilinogen decreased or absent inUrobilinogen decreased or absent in
urineurine
 Stercobilinogen is decreased orStercobilinogen is decreased or
absent inabsent in feces (clay coloured stools)feces (clay coloured stools)

26. 7. ALT (SGPT)
(Alanine Amino transferase)
This Enzyme needs pyridoxal phosphate as co-
enzyme.
Normal serum level of ALT
For male 13 – 35 U/L For female 10 – 30 U/L
Increased 100 to 300 U/L is in obstructive
Jaundice.
8.AST(SGOT)
[Aspartate amino transferase] Normal levels same
as in ALT.
Increased 100 to 300U/L is in obstructive jaudice.

27. 9. Prothrombin Time.
Increased in obstructive jaundice.
10.Cancer Antigen (CA 19 - 9) is seen in bile duct
obstruction.
It is diagnostic test for carcinoma of bile duct.
11.Steatorrhorea
Fat present above 6grams in stools

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