1. Chapter 15 Bilirubin and Urobilinogen
Zhang Lixia

2. Content * DISORDERS OF BILIRUBINMETABOLISM ● SUGGESTED READINGS
● BILIRUBIN AND UROBILINOGEN
* DISORDERS OF BILIRUBINMETABOLISM
● SUGGESTED READINGS
* important

3. BILIRUBIN AND UROBILINOGEN

4. Bilirubin -1 normally turn over on any given day.
■ 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

5. 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.

6. Bilirubin - 3 does not pass into the urine.
■ 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.

7. Bilirubin Metabolism (normal)

8. Urobilinogen -1 β- glucuronidases in the terminal ileum and
■ 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.

9. Urobilinogen -2 is reduced to form d-urobilinogen,
■ The remainder of unconjugated bilirubin
is reduced to form d-urobilinogen,
mesobilirubinogen, and stercobilinogen
(collectively known as urobilinogen).

10. ■ Urine urobilinogen may be elevated
in conditions associated with increased
bilirubin production such as hemolytic
jaundice.

11. Laboratory Assays bilirubin are 0.3 to 1.2 mg/dL (5 to 20μmol/L)
■ 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.

12. DISORDERS OF BILIRUBIN METABOLISM

13. 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.

14. 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

15. Unconjugated Hyperbilirubinemia

16. Unconjugated 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.

17. 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

18. Hemolytic jaundice

19. 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

20. Conjugated Hyperbilirubinemia

21. 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.

22. Conjugated 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.

23. Hepatic jaundice

24. Obstructive jaundice

25. 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

26. 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

27. 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

28. 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

29. 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

30. Thanks!