[BIOCHEMISTRY: DR.

KUA PORPHYRINS AND BILE

PIGMENTS 2]
Secretion Step:
MRP 2 (multidrug resistance-like
protein 2)
MOAT (multispecific organic anion
transporter)
Conjugated bilirubin is secreted into
the bile
Excretion step
Via urine and feces
conjugated bilirubin: reduced to
urobilinogen by intestinal bacteria
Beta glucoronidase (distal ileum
and colon)
Stercobilinogen: oxidized to
stercobilin feces
Renal: Urobilinogen: oxidized to
urobilin urine: normal yellow
Entero hepatic circulation and renal filtration:
Small amounts of urobilinogen: reabsorbed
back to circulation and reexcreted by the
liver
Normal Individual:
yellow plasma
predominantly higher unconjugated
bilirubin
small amount of conjugated form
normal urobilinogen content
yellow brown stool
+ urobilinogen
yellow urine
+ urobilinogen
+ conjugated bilirubin (trace)
Unconjugated
Conjugated
Water insoluble
Water soluble
Lipid-soluble
Aka Bilirubin
Pred. form in the
diglucoronide
plasma/serum
Small fraction in the
High affinity for lipid
plasma/serum
membrane (eg brain,
Direct Bilirubin (van
KERNICTERUS)
Den Bergh rxn)
Bound to albumin
Filterable by the
(nonfilterable in the
kidneys
kidneys)
Indirect bilirubin (van
Den Bergh rxn)
NB:

B1:
1 in Spanish is UNo hence B1 is also the
Unconjugated form
1 looks like I, hence it is the Indirect bilirubin
Biochemical and clinical abnormalities of
Bilirubin:
***Hyperbilirubinemia
Increased bilirubin level: brown
plasma (Normal: yellow serum)
Bilirubin > 2 mg %
Passage of tea colored urine: dark
color
a. Jaundice
Yellowish skin and mucous
membranes
b. Icteresia
Yellowish conjunctiva and sclerae
Classification of elevation of bilirubin
Unconjugated vs conjugated
Prehepatic vs hepatic vs post hepatic
Hemolytic (increased RBC production) vs non
hemolytic
Medical vs surgical
Benign vs malignant
Infectious vs non infectious
Acquired (more common) vs hereditary
Pathophysiology of jaundice:
1. Hemolytic jaundice/Pre-hepatic Jaundice
Increased bilirubin production (pred.
unconjugated)
Hemolysis of RBC
Hereditary (RBC disease)
Thalassemia
Spherocytosis (pediatrics)
G6PD enzyme deficiency
RBC disorders
Acquired
Drug induced
Autoimmune
Malaria (infectious cases)
Characteristics of pts w/ hemolytic jaundice:
o Elevated bilirubin (B1 predom)
o Classical triad
Pallor/anemia + jaundice + splenomegaly at
Left upper quadrant (+ fever)
o Elevated CO gas level
o Increased urobilinogen (urine and feces)

Medisina 2017

[BIOCHEMISTRY: DR. KUA PORPHYRINS AND BILE

PIGMENTS 2]
2. Impaired conjugation/Hepatic Jaundice
(increased unconjugated)
a. Diseases of the Liver parenchyma
b. Conjugating enzyme (Glucuronosyl
transferase) deficiency
c. Decreased bilirubin uptake by the
liver cell
Hereditary: GT deficiency
Gilberts Syndrome: mild
Crigler Najjar I: moderate
Crigler Najjar II: severe
Acquired:
Viral Hepatitis
TB of the liver
Drug-induced/alcoholinduced
Autoimmune
Congenital
Biliary atresia
Obstructions to the biliary
system which can damage
liver cells
Choledochal cyst
Characteristics of Hepatic Jaundice
o Usually no anemia
o Hyperbilirubinemia: unconjugated >
conjugated
o Elevation of liver enzymes: AST, ALT
o Low/Normal Albumin
o Prolonged PT and aPTT
3. Impaired secretion/Post Hepatic
Jaundice
a. Obstructive

Along the biliary duct system: B2

regurgitates back to cell
No anemia
Elevated B2 (conjugated)
Low urobilinogen (fecal and urinary)
o Acholic stool= pale (milky white);
no fecal urobilinogen
Associated mass (liver, biliary
duct, pancreas), stone,
enlarged nodes
Associated with abdominal
pain
b. Deficiency of transport enzyme
functional obstructive jaundice
o Dubin Johnsons Syndrome:
def. in main transporter protein;
char by liver pigmentations;
represent trapped B2
o Rotors syndrome: similar to
Dubin Johnsons but w/o liver
pigmentations

Alice: Mamamatay ako ate pag kinuha mo sa

akin si Alex.
Lorna: Ipalilibing kita.
Alice: Ate, please!
Lorna: Nung inagaw mo sakin si TOOT
muntik na rin akong mamatay. Puwes ikaw
naman ngayon ang mamamatay.
-Nagbabagang Luha, 1988

Medisina 2017