BY

DR ENAS M. FODA
Amal shawky bakir
professor of internal
medicine,
gastroentrology
&hepatology
Ain Shams university
What is bilirubin?
 When red blood cells have completed their life span,
or when they are damaged, hemoglobin, are
subsequently released into the blood.
 The hemoglobin split into its heme and globin .
 The globin , a protein, is degraded into amino
acids .

 The heme oxidation in biliverdin (green color
pigment).
 Reduction bilirubin (yellow color l
pigment)
("unconjugated,“ or "indirect"
bilirubin).
 The unconjugated bilirubin then
travels to the liver bound
to serum albumin.
 at the liver, it is conjugated (to
form "conjugated bilirubin“)
 This conjugated bilirubin is
excreted from liver as part
of bile.
 Intestinal bacteria convert the
bilirubin into urobilinogen. Which
can take two pathways.
 It can either be further
converted into stercobilin and
passed out in the feces, or
 it can be reabsorbed by the
intestinal cells, transported
in the blood to the kidneys,
and passed out in
the urine as urobilin.
 Stercobilin and urobilin
are the products
responsible for the
coloration of feces and
urine, respectively.
What is jaundice?
 Jaundice results from excess bilirubin in
the blood.
 Jaundice is classified into three
categories, depending on which part of
the physiological mechanism the
pathology affects.
 The three categories are:
 Pre-hepatic-/hemolytic
The pathology is
occurring prior to
the liver.
 Hepatic/ hepatocellular
The pathology is located
within the liver
 Post-Hepatic/
cholestatic
The pathology is located
after the conjugation of
bilirubin in the liver.
Prehepatic (haemolytic )Jaundice
 is caused by increased destruction of erythrocytes
either:

- mature cells ( haemolysis ),

or
- precursors (ineffective erythropoiesis).
 as:

thalassaemia, where the structure

of haemoglobin is abnormal.

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Prehepatic (haemolytic )Jaundice
 Hyperbilirubinaemia in prehepatic jaundice results from
the accumulation of unconjugated bilirubin;

 Jaundice occurs because the conjugating capacity of the liver

is saturated,

- the capacity of the liver for conjugation is

greater than the normal rate of bilirubin production.

 Increased fluxes of bilirubin through the liver into the gut

 Greater amounts of urobilinogen are produced, with

- increased urobilinogen excretion in urine.

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* Increased bil. production (e.g. haemolysis), or
resorption of haematoma, pulmonary infarction .
KEY POINTS
Prehepatic jaundice is most commonly
Caused by haemolytic disease

jaundice caused by unconjugated

hyperbilrubinaemia

Urinary urobilinogen concentration is increased

Normal colour of urine & feces

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Cholestatic (obstructive) Jaundice
 Intra- and extra-hepatic cholestasis

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Cholestatic (obstructive)
Jaundice
 extrahepatic
cholestasis
 Choledocholithiasis
(CBD or CHD stone)
 Cancer
(cholangioCA)
 Pancreatic cancer.
Cholestatic (obstructive) Jaundice
 Jaundice is due to impaired excretion and
accumulation of conjugated bilirubin.

 bilirubin does not reach the gut, therefore

urobilinogen is not produced
 no stercobilin,so the stools are pale.,
 and no urobilin in urine.

 conjugated bilirubin which can be filtered by

the kidney and appear in urine.(dark urine)

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KEY POINTS
Cholestasis may be caused by lesions
within or outside the liver

Jaundice is due to conjugated bilirubin

conjugated Bilirubin is found in urine\

no urobilinogen in urine

dark urine& pale stools

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Hepatocelluler Jaundice
 The pathogenesis of jaundice in these
conditions is complex,
- reduced hepatic uptake,
- decreased conjugation (Impaired
bilirubin conjugation)
- impaired intracellular transport
of bilirubin,
all contributing.
Serum bilirubin may be unconjugated or
conjugated,

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Hepatocelluler Jaundice
 When hyperbilirubinaemia is caused by
impaired conjugation of bilirubin

- unconjugated bilirubin ,

- urinary urobilinogen is not increased.

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Hepatocelluler Jaundice
If the defect is in the intracellular transport
of bilirubin,

- conjugated hyperbilirubinaemia will occur

and bilirubin excreted,in urine, (dark urine).

Hence in hepatocellular jaundice,

concentration of both
unconjugated and conjugated
bilirubin rises in the blood.

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KEY POINTS
Jaundice due to hepatocyte dysfunction may be
caused by selective transport defects
Or generalized cell dysfunction

Both conjugated and unconjugated hyperbilrubinaemia

may occur in hepatocellular jaundice

Bilirubin may be found in urine (dark urine)

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 clinically- Jaundice(icterus)
 Excess bilirubin accumulation in the ,
mucous membrane ., sclera.,and skin.
 When level of bilirubin is more than
2.5mg/dl.
 Scleral elastin has a high affinity for
bilirubin, and with a white
background, it is a sensitive indicator
of jaundice.
 – Hemolysis(unconjugated) gives a lemon-
yellow tint.
 - obstruction (conjugated) gives a olive-
greenish tint

 – hepatocellular disease (unconjugated &

conjugated) gives an orange-yellow color.

 Dark urine confirms a conjugated

hyperbilirubinemia and excludes hemolysis.
Laboratory, Evaluation:
*Serum Biochemical Tests:
Bilirubin:
-The normal serum bilirubin is <1.5mg/dl of which
<0.5% is conjugated.
-In haemolysis there is unconjugated (indirect)
hyperbilirubinaemia.

-In obstructive j., the circulating bilirubin is mainly

conjugated (direct) hyperbilirubinaemia.

-In hepatocellular j. bilirubin is mixed conjugated.and

unconjugated
International normalized ratio (INR) &
Prothrombin time (PT):
INR/PT is a valuable index of the ability of liver to
synthesize vit. K-dependent clotting factors.
An increasing INR/PT implies relatively severe
hepatocellular dysfunction.
The INR/PT may be increased in cholestatic
jaundice as well, but this is due to the
malabsorption of vit. K & is rapidly corrected by
parenteral administration of vit K.
 Post-hepatic Hepatic Pre-hepatic
Function test
Jaundice Jaundice Jaundice
Increased Increased
Increased Total bilirubin

Unconjugated
Normal Increased Increased
bilirubin

Conjugated
Increased Increased Normal
bilirubin

Urobilinogen
Negative Decreased Increased
in urine

N-Dark
Dark (conjugated
( conjugated Normal Urine Color
bilirubin)
bilirubin)

Pale Normal/Pale Normal Stool Color

Normal -Increased
Normal Increased
ALT & AST
 In Cholestatic (obstructive)
Jaundice which is true :
A)increase Unconjugated bilirubin .
B)increase Urobilinogen in urine.
C)normal coloured urine.
D) pale stool.
 In thalassemea ,all are true execpt
 A) urine is dark.
 B)unconjugated bilirubin increased.
 C)there is anemea .
 D) Urinary urobilinogen concentration
is increased
 In case of jaundice due to cancer
pancreas, which is true:
 A)prothrombin time can be corrected by
oral vit k.
 B)it is lemon yellow jaundice.
 C)there is increase urobilinogen in urine.
 D) there is dark urine.
 In case of jaundiced cirrhotic
patient,all true except
 A) there is increased urobilinogen in
urine.
 B)there is increased conjugated
bilirubin.
 C)there is increased unconjugated
bilirubin.
 D)there is increased prothrombin time.
 Enumerate types of jaundice and
compare between the types as regard :
Types of bilirubin ,colour of urine , colour
of stool.
Thank You