Chapter 15
Bilirubin
and Urobilinogen
Zhang Lixia
Content
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BILIRUBIN AND UROBILINOGEN
* DISORDERS OF BILIRUBINMETABOLISM
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SUGGESTED READINGS
*
important
BILIRUBIN
AND UROBILINOGEN
Bilirubin -1
■
■
Roughly 1% of a person's red blood cells
normally turn over on any given day.
This results in the production of 175 to 250 mg
of bilirubin daily. Another 75 to 100 mg
of bilirubin is derived from ineffective
erythropoiesis and the turnover of other
hemoproteins
Bilirubin -2
■
■
Heme is degraded to biliverdin, and biliverdin is
rapidly converted to bilirubin through a series of
enzymes
Bilirubin readily binds to albumin, and this
complex is transported through the circulation to
the liver. Bilirubin is transferred to ligandins
within the hepatocyte.
Bilirubin - 3
■
■
■
Conjugated bilirubin is secreted into the bile.
Unconjugated bilirubin is protein-bound and
does not pass into the urine.
Urine bilirubin reflects the conjugated form
and may be elevated in conjugated
Hyperbilirubinemia.
Bilirubin Metabolism (normal)
Urobilinogen -1
■
Some bilirubin is deconjugated by bacterial
β- glucuronidases in the terminal ileum and
colon, and the unconjugated bilirubin is
reabsorbed into the blood stream via the
enterohepatic circulation.
Urobilinogen -2
■
The remainder of unconjugated bilirubin
is reduced to form d-urobilinogen,
mesobilirubinogen, and stercobilinogen
(collectively known as urobilinogen).
Urobilinogen -3
■
Urine urobilinogen may be elevated
in conditions associated with increased
bilirubin production such as hemolytic
jaundice.
Laboratory Assays
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■
■
Typical reference ranges for total and direct
bilirubin are 0.3 to 1.2 mg/dL (5 to 20μmol/L)
and <0.3 mg/dL (<5μmol/L), respectively.
Normal levels of urobilinogen, up to 1
mg/dL(17μmol/L) of urine .
Urobilinogen is not measured routinely in serum.
DISORDERS
OF BILIRUBIN METABOLISM
DISORDERS OF BILIRUBIN
MRTABOLISM
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■
Disorders of heme catabolism are, for all
practical purposes, disorders of bilirubin
metabolism.
When serum bilirubin levels exceed about
2 mg/dL (34μmol/L), a yellow discoloration
of the skin (jaundice) or sclera (icterus)
becomes evident.
DIFFEERENTIAL DIANNOSIS
OF JAUNDICE
Unconjugated hyperbilirubinemia
Conjugated hyperbilirubinemia
Increased heme catabolism
Impaired hepatic excretion
Hemolytic anemia
Hepatocellular disease
Hematoma
Dubin-Johnson syndrome
Impaired hepatic conjugation
Rotor syndrome
Neonatal jaudice
Posthepatic obstruction
Gilbert syndrome
Crigler-najjar syndrome, types 1 and 2
Unconjugated Hyperbilirubinemia
Unconjugated Hyperbilirubinemia -1
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■
Unconjugated hyperbilirubinemia is
diagnosed when total bilirubin is
elevated and <20% is direct.
The amount of unconjugated bilirubin
is especially large , the conjugation
capacity of liver is relatively low, or
both.
Unconjugated Hyperbilirubinemia -2
■
The diagnosis of hemolysis may be aided by
evaluation of the patient’s history, complete
blood count, and measurement of the serum
haptoglobin among other tests.
■
The most common form of unconjugated
hyperbilirubinemia is neonatal jaundice
Hemolytic jaundice
NEONATAL HYPERBILIRUBINEMIA
Epidemiology:
Most, if not all infants
Clinical presentation:
Jaundice, usually more pronounced in upper body
Laboratory findings:
Increased total bilirubin, with undetectable direct bilirubin.
Transaminase, ALP, albumin, PT and PTT normal
Differential diagnoses:
Hemolytic disease of the newborn
Conjugated Hyperbilirubinemia
Conjugated Hyperbilirubinemia -1
■
■
Whenever there are defects with hepatic
excretion or post-hepatic obstruction,
conjugated bilirubin levels generally will
rise before unconjugated levels.
If more than 50% of the total bilirubin is
direct, the condition is termed conjugated
hyperbilirubinemia.
Conjugated Hyperbilirubinemia -2
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■
Conjugated bilirubin is elevated, the urinary
bilirubin also may be increased.
Hepatocellular diseases and cholestasis also
may be accompanied by elevations of
alanine and aspartate transaminases and
alkaline phosphatase.
Hepatic jaundice
Obstructive jaundice
Pattern of Jaundice
in Conjugated Hyperbilirubinemia
Jaundice pattern
elevated enzymes
disease
（1）hepatocellular pattern
ALT, AST↑>ALP, 5’NT
hepatitis
（2）obstructive pattern
ALP, 5’NT ↑ >ALT, AST
cholelithiasis
tumors
（3） mixed pattern
ALP, 5’NT with (2)
ALT, AST with (1)
Intrahepatic
cholestasis
CRIGLER-NAJJAR SYNDROME TYPE І
Epidemiology:
Rare
Clinical presentation:
Severe jaundice, typically resulting in kernicterus
Laboratory findings:
Increased total bilirubin above 20mg/dl (340μmol/L ), with
undetectable direct bilirubin.
Total bilirubin unchanged after phenobarbital ingestion
Transaminase, alkaline phosphatase, albumin, PT and PTT normal
Differential diagnoses:
Crigler-Najjar syndrome type 2
CRIGLER-NAJJAR SYNDROME TYPE Ⅱ
Epidemiology:
Rare
Clinical presentation:
Mid-moderate jaundice, exacerbated under stress
Laboratory findings:
Increased total bilirubin between 6 and 20mg/dl, with low to
undetectable direct bilirubin.
Total bilirubin diminishes after phenobarbital ingestion
Transaminase, alkaline phosphatase, albumin, PT and PTT normal
Differential diagnoses:
Crigler-Najjar syndrome type 1, Gilbert’s syndrome complicated by
hemolytic anemia
DUBIN- JOHNSON SYNDROME
Epidemiology:
Rare, except among Sephardic Jews
Clinical presentation:
Mid-moderate jaundice, red to brown urine
Laboratory findings:
Increased direct bilirubin ranging from 3-15mg/dl
Total bilirubin unchanged after phenobarbital ingestion
Urinary coproporphyrin 1 levels can distinguish heterozygotes from
homozygotes
Transaminase, alkaline phosphatase, albumin, PT and PTT normal
Differential diagnoses:
Rotor syndrome
Diagnosis and differential diagnosis
of jaundice
Jaundice pattern
Bilirubin of blood
STB
CB
UCB
Bilirubin in urine
Urobilinogen
Enzymes pattern
hemolytic
cholestatic
<75mmol/L
hepatocellular
later
-
-
negative
LDH
or negative
or normal
ALP>3 times ALP later
upper limit of
reference range;
AST, ALT, LDH,
moderately