Post on 25-Dec-2015
Chapter 15
Bilirubin and Urobilinogen
Zhang Lixia
Content Content
● BILIRUBIN AND UROBILINOGEN
* DISORDERS OF BILIRUBINMETABOLISM
● SUGGESTED READINGS
* important
BILIRUBIN
AND UROBILINOGEN
Bilirubin -1 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 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 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) Bilirubin Metabolism (normal)
Urobilinogen -1 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 Urobilinogen -2
■ The remainder of unconjugated bilirubin
is reduced to form d-urobilinogen,
mesobilirubinogen, and stercobilinogen
(collectively known as urobilinogen).
Urobilinogen -3Urobilinogen -3
■ Urine urobilinogen may be elevated
in conditions associated with increased
bilirubin production such as hemolytic
jaundice.
Laboratory AssaysLaboratory Assays
■ 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 DISORDERS OF BILIRUBIN MRTABOLISM
■ 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
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 -1Unconjugated Hyperbilirubinemia -1
■ 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 -2Unconjugated 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 jaundiceHemolytic jaundiceHemolytic jaundiceHemolytic 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 -1Conjugated 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 -2Conjugated Hyperbilirubinemia -2
■ 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 jaundiceHepatic jaundiceHepatic jaundiceHepatic jaundice
Obstructive jaundiceObstructive jaundiceObstructive jaundiceObstructive jaundice
Pattern of Jaundice in Conjugated Hyperbilirubinemia 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) Intrahepatic ALT, AST with (1) cholestasis
CRIGLER-NAJJAR SYNDROME TYPE І
Epidemiology: RareClinical presentation: Severe jaundice, typically resulting in kernicterusLaboratory 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 normalDifferential diagnoses: Crigler-Najjar syndrome type 2
CRIGLER-NAJJAR SYNDROME TYPE Ⅱ
Epidemiology: RareClinical presentation: Mid-moderate jaundice, exacerbated under stressLaboratory 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 normalDifferential 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
Diagnosis and differential diagnosis of jaundice
Jaundice pattern hemolytic cholestatic hepatocellular
Bilirubin of blood <75mmol/L later
STB - - CB
UCB
Bilirubin in urine negative
Urobilinogen or negative or normal
Enzymes pattern LDH ALP>3 times ALP later
upper limit of
reference range;
AST, ALT, LDH,
moderately