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?
