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AND JAUNDICE
Rizka Adi
hemoglobin is destroyed in
the body, globin is degraded to its
constituent amino acids, which are
reused, and the iron of heme enters iron + Bile pigments
the iron pool, also for reuse.
most heme from RBCs (85%) - rest
from turnover of cytochromes, p450s,
immature erythrocytes
Amino acids
Heme
globin
iron
Bile pigments
Bile pigments
Any of several coloured compounds
derived from porphyrin that are found in
bile; principally bilirubin and biliverdin.
Bilirubin Metabolism
Bilirubin formation
Hepatic uptake
Conjugation
Biliary excretion
Bilirubin formation
microsomal
cytosol
Heme oxygenase
Heme oxygenase (HO) is an enzyme that
catalyzes the degradation of heme. This
produces biliverdin, iron, and carbon
monoxide.
Heme oxygenase
There are three known isoforms of heme oxygenase.
HOOC
CH2
CH2
M
CH
O
N
H
N
H
M -CH2
V -CH=CH2
M V
COOH
CH2
CH2 M
CH2
N
H
CH
N
H
The building of
intermolecular
hydrogen bonds by the
NH and COOH groups
is spatially hided.
Bilirubin is lipophilic
and therefore insoluble
in aqueous solution.the
solubility in water is
less.
Significance:
Increase
Prevent
Molar
Ratio
>2:1
Bilirubin
L affinity binding sites
Plasma protein
Albumin
Bilirubin
can be replaced by
UB
blood
membrance
[bilirubin-albumin]
Other
antibiotics
cytosol
[bilirubin-lipids]
[albumin]
[bilirubin]
[bilirubin]
Hepatic phase
On coming in contact with the hepatocyte surface,
unconjugated bilirubin is preferentially
metabolized which involved 3 steps:
Hepatic uptake
Conjuation
Secretion in bile
Bilirubin
carrier protein
(be) bound to
transfer
ER
Conjugation of bilirubin
UDPGT Bilirubin
Bilirubin +UDP-gluconic acid
monoglucuronides + UDP
UDPGT
UDP-gluconic acid
HOOC
M V
COOH
CH2
CH2
CH
N
H
CH2
CH2 M
CH
N
H
N
H
OH
N
H
HO
M V
N
H
OH
CH
O
C
CH
O2
CH2
N
H
CO
CH2
CH M
CH2
CH
COOH
O
MV
N
H
OH
OHHOOC
O
OH
conjugated bilirubin
M V
CH
N
H
bilirubin diglucuronides
Unconjugated bilirubin:
Bilirubin that are not conjugated with
gluconic acid , also called hemobilirubin,
indirected bilirubin.
conjugated bilirubin:
Bilirubin that are conjugated with gluconic
acid, also called hepatic bilirubin, directed
bilirubin.
Unconjugated
bilirubin
CONJUGATED
BILIRUBIN
More
Water solubility
Absent
Present
Present
Absent
High
Low
Direct
Reanal excretion
Absent
Present
Present (kernicterus)
Absent
Bilirubin diglucuronide
urobilinogen
bilin
stercobilin
Conjugated
bilirubin
blood
0.5 4mg/day
urobilin
bilinogen
prototype
Portal
vein
Sterobilin
excrection
reabsorbed
10
20%
80% 90%
bilinogen
bilinogen enterohepatic
circulation
BLOOD
CELLS
Stercobilin
excreted in feces
Urobilin
excreted in urine
Hemoglobin
Globin
Heme
O2
Heme oxygenase
Urobilinogen
formed by bacteria
INTESTINE
KIDNEY
reabsorbed
into blood
CO
Biliverdin IX
NADPH
Bilirubin diglucuronide
(water-soluble)
Biliverdin
reductase
NADP+
Bilirubin
(water-insoluble)
unconjugated
Catabolism of hemoglobin
2 UDP-glucuronic acid
via blood
to the liver
Bilirubin
(water-insoluble)
LIVER
Bile is secreted into intestine where glucuronic acid is removed and the
resulting bilirubin is converted to urobilinogen.
A portion of urobilinogen is reabsorbed into blood, where it is converted to the
yellow urobilin and excreted by kidneys.
Urobilinogen is oxidized by intestinal bacteria to the brown stercobilin.
normal
occult
Hyperbilirubinemia
jaundice
Hemolytic jaundice
massive lysis of red blood cells (for example, in patients
with sickel cell anemia or malaria) may produce bilirubin
faster than the liver can conjuagte it.
More bilirubin is excreted into the bile, the amount of the
urobilinogen entering the enterohepatic circulation is
increased, and urinary urobilinogen is increased.
Unconjugated bilirubin is elevated in blood.
Malaria
Side effects of certain drugs :antibiotic and anti-tuberculosis medicines,
levodopa,
Certain drugs in combination with a hereditary enzyme deficiency known as
glucose-6-phosphate dehydrogenase (G6PD)
Poisons Snake and spider venom, certain bacterial toxins, copper, and
some organic industrial chemicals directly attack the membranes of red
blood cells
Artificial heart valves
Hereditary RBC disorders sickle cell disease
Enlargement of the spleen
Diseases of the small blood vessels
Immune reactions to RBCs cancer
Transfusions
Kidney failure and other serious diseases
Erythroblastosis fetalis
Hepatocellular jaundice
Damage to liver cells( for example in patient with
cirrhosis or hepatitis) causes a decrease in both
bilirubin uptake and production of conjuagted bilirubin.
Unconjugated bilirubin occur in the blood and
increased urobilinogen in the urine.
The urine is dark in color and stool are pale, clay
color.
Plasma level of AST and ALT are elevated and the
patient experience nausea and anorexia.
Obstructive jaundice
In this instance jaundice is results from obstruction of
the bile duct.
For example, the presence of a hepatic tumor or bile
stone may block the bile ducts, preventing passage of
bilirubin into the intestine, patients with obstructive
jaundice experience GI pain, nausea and produce
stools that are a pale, clay color.
Biliary stones
Sample
Indices
Normal
Serum
Total Bil
1mg/dl
1mg/dl
Direct Bil
0
0.8mg/dl
Indirect Bil
1mg/dl
Color
normal
deep
deeper
deep
Bilirubin
Urobilinogen
a little
uncertain
Urobilin
a little
uncertain
Color
normal
Argilous
(complete
obstruction)
deeper
lighter or
normal
Urine
Stool
Obstructive Hemolytic
Jaundice
Jaundice
1mg/dl
Hepatic
Jaundice
1mg/dl
Diagnoses of Jaundice