Part A

Chapter 1.12

Jaundice
Si Xi-jian

Jaundice
yellow, medical use reserves the term for
bilirubin staining .

1 Clinical Definition
Jaundice means visible color (most yellow) of skin,
mucosa, or sclerae because of increase in the
concentration of bilirubin in serum (usually exceeding
34.2 mol/L 20mg/L).

Normal value:
Normal serum concentration range from
Bilirubin: 1.7-17.1 mol/L
Conjugated bilirubin(CB): 0-3.42 mol/L
Unconjugated bilirubin(UCB): 1.7-13.68 mol/L

Bilirubin stains all tissues, but jaundice is most

intense in the face , trunk, and sclerae.
Yellow skin is also caused by carotene or rare
chemical toxins, but carotene doesnt stain the sclerae,
it accumulates in the skin of the forehead, around the
alae nasi, and in the palms and soles.

Jaundice pictrues

Jaundice is less visible in artificial light than

daylight. When the jaundice is of long
standing, the deep yellow may acquire a green
hue.

2 Normal Bile Pigment Cycle

When senescent erythrocytes are destroyed in the spleen and
other reticuloendothelial tissues, hemoglobin is metabolized
to unconjugated bilirubin, iron, and globin.

Unconjugated bilirubin is insoluble in water and circulates

bound to albumin, hence it cannot be filtered by the kidneys.
The liver takes up the unconjugated bilirubin, combines it
with glucuronic acid to form watersoluble conjugated
bilirubin, excretes it into the gut with the bile, where
bacterial enzymes convert it to urobilinogen.

 UDPGT:

Uridine Diphosphate Glucuronyl

Transferase, an important enzyme to catalize
the conjugation.

UCB:

because of its tight albumin binding and

lipid solubility, it is not excreted in urine.

CB:

is less tightly bound to albumin and is

water soluble, so it is filtered at the glomerulus

and appears in the urine.

 Most

urobilinogen is lost in the feces,

but small amounts are reabsorbed by

the intestine and reexcreted, some in
the bile (entero-hepatic
and some in the urine.

circulation)

Entero-hepatic circulation
CB
mostly
20%

be degraded
Bacterial Enzymes

Urobilinogens (colorless)

Excreted in the feces (feceal urobilinogens)

liver reexcreted
plasma

90%

Reabsorbed
From the intestine
And colon and enters
The portal circulation

Bile excreted feces

Remainder bypasses the liver

circulation

kidneys

urine urobilinogen

3 Jaundice classification
Unconjugated

hyperbilirubinemia

Pathophysiologic classification as
Haemolytic jaundice
Conjugated

hyperbilirubinemia

Pathophysiologic classification as
Cholestasis / obstructive jaundice
Mixed

hyperbilirubinemia

Pathophysiologic classification as
Hepatocellular jaundice

Pathogenesis
Jaundice occurs when there is a marked
increase in production of unconjugated
bilirubin, with impairment of hepatocellular
uptake, conjugation or excretion of bilirubin, or
obstruction of the intrahepatic or extrahepatic
bile ducts.

3.1 Unconjugated Hyperbilirubinemia

Haemolytic jaundice
Usually caused by hemolysis producing
unconjugated bilirubin at a rate exceeding the
maximal rate of liver conjugation and excretion.

 The stools are normal in color. The increase in bilirubin

excretion into the gut leads to an increase in urinary
urobilinogen.
The urine contains no bilirubin because only watersoluble conjugated bilirubin is excreted in the urine. The
urine contains hemoglobin.
Skin is light lemon-yellow, Anemia.
Tests for intrinsic liver disorders are negative.

Hemolytic Jaundice
Pathogenesis
Overproduction
Hemolysis (intra and extra vascular)

inherited or genetic disorders

acquired immune hemolytic anemia

(Autoimmune hemolytic anemia)

nonimmune hemolytic anemia

(Paroxysmal Nocturnal Hemoglobinuria,PNH)

Ineffective

erythropoiesis

Overproduction may overload the liver with UB

Hemolytic Jaundice
Symptoms
Weakness, Dark urine, Anemia,
Icterus, Splenomegaly

Lab

UB without bilirubinuria

fecal and urine urobilinogen

hemolytic anemia

hemoglobinuria (in acute intravascular hemolysis)

Reticulocyte counts

Hemolytic Jaundice
(pre-hepatic)
Serum / blood:

bilirubin (mol/l) 50-150; normal 3-17

AST(Aspartate transaminase ) I.U.< 35; nor <35

ALP(alkaline phosphatase) I.U. <250; nor

<250

gamma GT(glutamyl transpeptidase) I.U.15-40;

nor 15-40

albumin (g/l ) 40-50; nor 40-50

reticulocytes(%) 10-30; nor <1

prothrombin time (seconds) 13-15; nor 13-15

Hemolytic Jaundice
(pre-hepatic)

urinary changes:
bilirubin:

absent

urobilinogen:

increased or normal

fecal changes:
stercobilinogen: normal

Haemolytic Jaundice Mechanic Figure

reticulo-endothelial tissues

HB

Cycle blood

RBC HB
kidneys

UCB
UCB

TB

CB
normal
CB/TB
Urobilirubin Urobilinogen

HB urine

CB

Urobilinogen

Urobilin

Urobilinogen
feceal urobilinogens

3.2 Conjugated hyperbilirubinemia

Cholestasis / obstructive jaundice
This results from impaired excretion of
conjugated bilirubin from the hepatocyte into
the bile canaliculi or obstruction of the biliary
flow through the canaliculi, intrahepatic, and
extrahepatic bile ducts to the duodenum.

 The feces may be acholic.

The urine lacks urobilinogen but contains bilirubin.
The serum alkaline phosphatase is elevated out of
proportion to the transaminases.
Pigmentation may be deep with evidence of pruritus-cutaneous excoriation (irritation by skin deposition of bile
salts) and bradycardia.

pruritus:an intense itching sensation that can have various

causes (as by allergies or infection or lymphoma or jaundice
etc.)

Etiology of Obstructive Jaundice

Intrahepatic-Liver cell Damage
Blockage of Bile Canaliculi
Drugs

or chemical toxins

Dubin-Johnson

syndrome :Dubin-Johnson syndrome

is an autosomal recessive disorder which causes an

increase of conjugated bilirubin without elevation of liver
enzymes
Estrogens

or Pregnancy

 Hepatitis-viral,chemical
Infiltrative

tumors

Intrahepatic

biliary hypoplasia or

atresia
Primary

biliary cirrhosis

Etiology of Obstructive
Jaundice
Extrahepatic-Obstructive of bile Ducts
Compression
Congenital

obstruction from tumors

choledochal cyst

Extrahepatic
Intraluminal

biliary atresia

gallstones

Stenosis-postoperative

or inflammary

Cholestasis
clinical features
pain, due to gallbladder disease, malignancy, or

stretching of the liver capsule

fever, due to ascending cholangitis
palpable and / or tender gallbladder
enlarged liver, usually smooth

General signs of Cholestasis

xanthomas: palmar creases, below the breast, on the

neck. They indicate raised serum cholesterol of several

months. Xanthomas on the tendon sheaths are
uncommonly associated with cholestasis.
xanthelasma on the eyelids
scratch marks: excoriation
finger clubbing
stools: loose, pale, bulky, offensive
Urine: dark orange

Obstructive Jaundice
Lab Findings

Serum

Bilirubin

Feceal

urobilinogen (incomplete obstruction)

Feceal

urobilinogen absence(complete obstruction)

urobilinogenuria

jaundice

bilirubinuria

ALP

cholesterol

is absent in complete obstructive

Obstructive Jaundice
extrahepatic
serum / blood

bilirubin (micromoles/l) 100-500; normal 3-17

AST I.U. 35-400; normal <35

ALP I.U. >500; normal <250

gamma GT I.U. 30-50; normal 15-40

albumin g/l 30-50; normal 40-50

reticulocytes(%) <1; normal <1

prothrombin time (secs) 15-45; normal 13-15

Obstructive Jaundice
extrahepatic

urinary changes
bilirubin:

increased

urobilinogen:

reduced or absent

faecal changes
stercobilinogen: reduced or absent

Cholestasis / Obstructive Jaundice Mechanic Figure

reticulo-endothelial tissues

HB

Cycle blood

RBC

kidneys

UCB
CB

TB

CB/TB

Urobilirubin +++
Urobilinogen -

CB

urobilirubin

3.3 Mixed hyperbilirubinemia

Hepatocellular jaundice
This results from a combination of hepatocellular and
biliary tract injury.
The plasma will contain both conjugated and
unconjugated bilirubin;
The serum transaminase level will depend upon the
degree of active liver injury and the remaining
hepatocyte mass;
The alkaline phosphatase is variably elevated.
The stools may be acholic.
Urine contains urobilirubin and urobilinogen.

Hepatic Jaundice
Pathogenesis
Familiar or hereditary disorders
Impaired or absent hepatic conjugation of bilirubin
decreased GT activity (Gilberts syndrome)
hereditary absence or deficiency of UDPGT (GriglerNajjar Syndrome)

Problem in conjugated bilirubin transfer and excretion

Dubin-Johnson Syndrome
Rotor syndrome both
Acquired disorders
hepatocellular necrosis
intrahepatic cholestasis (Hepatitis, Cirrhosis, Drugrelated)

Hepatic Jaundice
Symptoms
weakness, loss appetite, hepatomegaly,
palmar erythema, spider angioma
Lab Findings

liver function tests are abnormal

both CB and UCB

Bilirubinuria

Hepatic Jaundice
serum / blood

bilirubin (micromoles/l) 50-250; normal 3-17

AST I.U. 300-3000; normal <35

ALP I.U. <250-700; normal <250

gamma GT I.U. 15-200; normal 15-40

albumin g/l 20-50; normal 40-50

reticulocytes(%) <1; normal <1

prothrombin time (secs) 15-45; normal 13-15

Hepatic Jaundice
urinary changes
bilirubin: normal or increased
urobilinogen: normal or reduced

faecal changes
stercobilinogen: normal or reduced

Hepatocellular Jaundice Mechanic Figure

reticulo-endothelial tissues

HB

Cycle blood

RBC

kidneys

UCB
CB
UCB
TB

CB/TB >30%-40%
Urobilirubin +
Urobilinogen

CB

CB
Urobilinogen
Urobilin

urobilinogen
feceal urobilinogens

4 Clinical occurrence

4.1 Pruritus
Itching leading to cutaneous excoriation often
accompanies obstructive jaundice and biliary
cirrhosis; it may become excruciating. The
intensity of the itching is usually proportional
to the bilirubin concentration and the
duration of jaundice.

4.2 Urine color

conjugated, but not unconjugated, bilirubin is
excreted in the urine. High concentrations of
conjugated bilirubin in the urine impart a darkyellow to brown color. Shaking a specimen in a
test tube produces yellow foam because of the
ability of the bile salts to lower the surface
tension of water. Jaundice without darkening of
the urine suggests unconjugated bilirubinemia.

4.3 Acholic feces

In

complete biliary obstruction or

severe hepatocellular degeneration,

the stools are malodorous and appear
white or gray, that is ,clay colored.

5 Jaundice Diagnosis

History and examination

familial occurrence of jaundice

Urine, stools

Serum biochemistry

bilirubin
transaminases - AST, ALT
albumin
alkaline phosphatase

5 Jaundice Diagnosis
Haematology
haemoglobin
WBC
platelets
prothrombin time +
abdominal ultrasound and chest X-ray

5 Jaundice Diagnosis

Further investigations - determined by the basis of

the jaundice, e.g. pre-hepatic, hepatic, extrahepatic

duodenal biliary drainage

imagine techniques: Ultrasonography, CT,

Pandaendoscopy ERCP, PTC, X_ray (GI series,

Angiography) etc.

6 Biochemical abnormalities in different types of

jaundices
specimen

test

haemolysis hepatocellular cholestasis

urine

Urobilinogen
CB

N/
+

Faeces

stercobilinogen

serum

Bilirubin
Liver enzymes

UCB
N

UCB and CB
AST / ALT

CB
ALP /
GGT

6 Biochemical abnormalities in different types of

jaundices
Hemolytic
TB

CB
N
CB/TB
<0.15-0.2
Urobilinogen
Bilirubiriuria ALT AST
N
ALP
N
GGT
N
PT
N

hepatic

>0.3-0.4

increase

obstructive

>0.5-0.6

++

increase

7 Jaundice exercise
1. Which one is not the cause of hemolytic jaundice?
A. inherited or genetic disorders
B. acquired immune hemolytic anemia
C. Ineffective erythropoiesis
D. Extra Hepatic Biliary Obstruction
2. Which of the following lab finding could hemolytic
jaundice have?
A increased CB B. decreased CB C. decreased UCB
D. increased UCB

3. Which kind of jaundice does Dubin-Johson Syndrome

have?
A. hemolytic B. hepatic C. obstructive D. mixed
4. Jaundice coupled with skin itch can be found in ( ).
A. autohemolysis B. common bile duct stones C.
acute hepatitis D. liver abscess
5. Which kind of jaundice may be due to common bile
duct stone?
A. hemolytic B. hepatic C. obstructive D. mixed
KEY: D D B B C

Review questions
1. What is jaundice? How to physically
examine? What is bilirubin's normal value in
serum?
2. Where does bilirubin come from? What is
bilirubin's entero-hepatic circulation?
3. How jaundice is classified? What are the
pathogenesis symptom and lab findings
of the 3 kinds of jaundice?
4. How to differentiate the 3 kind of jaundice?