4 Bilirubin -1 normally turn over on any given day. ■ Roughly 1% of a person's red blood cellsnormally turn over on any given day.■ This results in the production of 175 to 250 mgof bilirubin daily. Another 75 to 100 mgof 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 anddoes not pass into the urine.■ Urine bilirubin reflects the conjugated formand may be elevated in conjugated Hyperbilirubinemia.
8 Urobilinogen -1 β- glucuronidases in the terminal ileum and ■ Some bilirubin is deconjugated by bacterialβ- glucuronidases in the terminal ileum andcolon, and the unconjugated bilirubin isreabsorbed into the blood stream via theenterohepatic circulation.
9 Urobilinogen -2 is reduced to form d-urobilinogen, ■ The remainder of unconjugated bilirubinis reduced to form d-urobilinogen,mesobilirubinogen, and stercobilinogen(collectively known as urobilinogen).
10 ■ Urine urobilinogen may be elevated in conditions associated with increasedbilirubin production such as hemolyticjaundice.
11 Laboratory Assays bilirubin are 0.3 to 1.2 mg/dL (5 to 20μmol/L) ■ Typical reference ranges for total and directbilirubin 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.
13 DISORDERS OF BILIRUBIN MRTABOLISM ■ Disorders of heme catabolism are, for all practical purposes, disorders of bilirubin metabolism.■ When serum bilirubin levels exceed about2 mg/dL (34μmol/L), a yellow discolorationof the skin (jaundice) or sclera (icterus) becomes evident.
16 Unconjugated Hyperbilirubinemia -1 ■ Unconjugated hyperbilirubinemia isdiagnosed when total bilirubin iselevated and <20% is direct.■ The amount of unconjugated bilirubinis especially large , the conjugationcapacity of liver is relatively low, orboth.
17 Unconjugated Hyperbilirubinemia -2 ■ The diagnosis of hemolysis may be aided by evaluation of the patient’s history, completeblood count, and measurement of the serum haptoglobin among other tests.■ The most common form of unconjugated hyperbilirubinemia is neonatal jaundice
19 NEONATAL HYPERBILIRUBINEMIA Epidemiology:Most, if not all infantsClinical presentation:Jaundice, usually more pronounced in upper bodyLaboratory findings:Increased total bilirubin, with undetectable direct bilirubin.Transaminase, ALP, albumin, PT and PTT normalDifferential diagnoses:Hemolytic disease of the newborn
21 Conjugated Hyperbilirubinemia -1 ■ Whenever there are defects with hepatic excretion or post-hepatic obstruction, conjugated bilirubin levels generally willrise 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.
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 cholelithiasistumors（3） mixed pattern ALP, 5’NT with (2) IntrahepaticALT, AST with (1) cholestasis
26 CRIGLER-NAJJAR SYNDROME TYPE І Epidemiology:RareClinical presentation:Severe jaundice, typically resulting in kernicterusLaboratory findings:Increased total bilirubin above 20mg/dl (340μmol/L ), withundetectable direct bilirubin.Total bilirubin unchanged after phenobarbital ingestionTransaminase, alkaline phosphatase, albumin, PT and PTT normalDifferential diagnoses:Crigler-Najjar syndrome type 2
27 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 toundetectable direct bilirubin.Total bilirubin diminishes after phenobarbital ingestionTransaminase, alkaline phosphatase, albumin, PT and PTT normalDifferential diagnoses:Crigler-Najjar syndrome type 1, Gilbert’s syndrome complicated byhemolytic anemia
28 DUBIN- JOHNSON SYNDROME Epidemiology:Rare, except among Sephardic JewsClinical presentation:Mid-moderate jaundice, red to brown urineLaboratory findings:Increased direct bilirubin ranging from 3-15mg/dlTotal bilirubin unchanged after phenobarbital ingestionUrinary coproporphyrin 1 levels can distinguish heterozygotes fromhomozygotesTransaminase, alkaline phosphatase, albumin, PT and PTT normalDifferential diagnoses:Rotor syndrome
29 Diagnosis and differential diagnosis of jaundice Jaundice pattern hemolytic cholestatic hepatocellularBilirubin of blood <75mmol/L laterSTBCBUCBBilirubin in urine negativeUrobilinogen or negative or normalEnzymes pattern LDH ALP>3 times ALP laterupper limit ofreference range;AST, ALT, LDH,moderately