Jaundice: Know As
Jaundice: Know As
Jaundice: Know As
Complications
Hyperbilirubinemia, more precisely
hyperbilirubinemia due to the unconjugated
fraction, may cause bilirubin to accumulate in
the gray matter of the central nervous system,
potentially causing irreversible neurological
damage leading to a contion known as
kernicterus. Depending on the level of
exposure,the effects range from clinically
unnoticeable to severe brain damage and even
death.Newborns are especially vulnerable to
hyperbilirunemia-induced neurological damage
and therefore must be carefully monitored for
alterations in their serum bilirubin levels
Differential diagnosis
When a pathological process interferes with the
normal functioning of the metabolism and excretion
of bilirubin just described, jaundice may be the result.
Jaundice is classified into three categories, depending
on which part of the physiological mechanism the
pathology affects. The three categories are:
Category Definition
Pre-hepatic/ The pathology is occurring prior to the liver due to either:
Haemolytic A. Intrinsic defects in RB cells B. Extrinsic causes external to RB
cells
Hepatic/ The pathology is located within the liver caused due to
Hepatocellular disease of parenchymal cells of liver.
Post-Hepatic/ The pathology is located after the conjugation of bilirubin
Cholestatic in the liver caused due to obstruction of biliary passage.
Pre-hepatic
Pre-hepaticular jaundice is caused by anything which
causes an increased rate of hemolysis (breakdown of
red blood cells).Unconjugated bilirubin comes from
the breakdown of the heme pigment found in red
blood cells’ hemoglobin.
The increased breakdown of red blood cells lead to
an increase in the amount of unconjugated bilirubin
present in the blood and deposition of this
unconjugated bilirubin into various tissues can lead to
a jaundiced appearance.
In tropical countries, severe malaria can jaundice in
this manner.
Certain genetic disease such as sickle cell anemia,
spherocytosis, thalassemia, pyruvate kinase
deficiency, and glucose 6-phosphate dehydrogenase
deficiency can lead to increased red cell lysis and
therefore haemolytic jaundice.
Commonly, diseases of the kindly, such as haemolytic
uremic syndrome, can also lead to coloration.
In jaundice secondary to hemolysis, the increased
production of bilirubin leads to the increased
production of urine-urobilinogen. Bilirubin is not
usually found in the urine because unconjugated
bilirubin is not water-soluble,so the combination of
increased urine-urobilinogen with no bilirubin(since,
unconjugated)in urine is suggestive of haemolytic
jaundice.
Laboratory findings include:
Urine : no bilirubin present, urobilinogen > 2 units
(i.e., hemolythic anemia causes increased heme
metabolism; exception: infants where gut flora has
not developed).
Serum: increased unconjugated bilirubin.
Kernicterus is associated with increased
unconjugated bilirubin; neonates are especially
vulnerable to this due to increased permeability of
the blood brain barrier.
Hepatocellular
Hepatocellular (hepatic) jaundice can be caused by acute or
chronic hepatitis, hepatotocity, cirrhosis, drug-induced and
alcoholic liver disease. Cell necrosis, reduces the liver’s
ability to metabolize and excrete bilirubin leading to a
buildup of unconjugated bilirubin in the blood. Other causes
included primary biliary cirrhosis leading to an increase in
plasma conjugated bilirubin because there is impairment of
excretion of conjugated bilirubin into the bile. The blood
contains an abnormally raised amount of conjugated
bilirubin and bile salts which are excreted in the urine
.Jaundice seen in the newborn, known as neonatal jaundice,
is common in newborns as hepatic machinery for the
conjugation and excretion of bilirubin does not fully mature
until approximately two weeks of age. Rat fever
(leptospirosis) can also cause hepatic jaundice. In hepatic
jaundice, there is invariably cholestasis. Defects in bilirubin
metabolism also leads to jaundice, as in Gilbert’s syndrome
(a genetic disorder of bilirubin metabolism which can result
in mind jaundice, which is found in about 5% of the
population) and Crigler-Najjar syndrome. Type I and II
Laboratory findings depend on the cause of jaundice.
Urine : Conjugated bilirubin present, urobilirubin >2 units
but variable (expect in children ).Kernicterus is a condition
not associated with increased conjugated bilirubin.
Plasma protein show characteristic changes .
Plasma albumin level is low but plasma globulins are raised
due to an increased formation of antibodies.
Bilirubin transport across the hepatocyte may be impaired
at any point between the uptake of unconjugated bilirubin
into the cell and transport of conjugated bilirubin into
biliary canaliculi. In addition, swelling of cells and oedema
due to inflammation cause mechanical obstruction of
intrahepatic biliary tree. Hence in hepatocellular jaundice,
concentration of both unconjugated and conjugated
bilirubin rises in the blood. in hepatocellular dieseas, there
is usually interference in all major steps of bilirubins
metabolism-uptake, conjugation and excretion. However,
excretion is the rate-limiting step,and impaired to the
greatest extent. As a result, conjugated hyperbilirubinaemia
predominates.
The unconjugated bilirubins still enters the liver cells and
becomes conjugated in the usual way. This conjugated
bilirubin is them returned to the probably by rupture of the
congested bile canaliculi and direct emptying of the bile into
the lymph leaving the liver. Thus, most of the bilirubin in
the plasma becomes the conjugated type rather than the
conjugated type, and this conjugated bilirubin which did not
go to intestine to become urobilinogen gives the urine the
Dark color.
Post-hepatic
Post-hepatic jaundice also, called obstructive
jaundice, is caused by an interruption to the drainage
of bile containing conjugated bilirubin in the biliary
system. The most common causes are gallstone in the
common bile duct, and pancreatic cancer in the head
of the pancreas. Also, a group of parasites known as
“liver flukes” can live in the common bile duct,
causing obstructive jaundice. Other causes include
strictures of the common bile duct, biliary artesia,
cholaniocarcinoma, pancreatitis, cholestasis of
pregnancy, and pancreatic pseudocysts. A rare cause
of obstructive jaundice is Mirizzi’s yndrome (gallstone
impaction in the cystic duct or gallbladder neck, with
the enlarged gallbladder squeezing on the common
hepatic duct).
In complete obstruction of the bile duct, no
urobilinogen is found in the urine, since bilirubin has
no access to the intestine and it is in the intestine that
bilirubin gets converted to urobilinogen by
microorganisms, with the urobilinogen later being
partially reabsorbed from the intestine into the
general circulation, and then excreted into the urine.
In this case, presence of bilirubin(conjugated)in the
urine without urine-urobilinogen suggests an
obstructive jaundice, either intra-hepatic or post-
hepatic.
The presence of pale stools and dark urine suggests
an obstructive or post-hepatic cause as normal feces
get their color from bile pigments. However, although
pale stools and dark urine are a feature of biliary
obstruction, they can occur in many intra-hepatic
illnesses and are therefore not a reliable clinical
feature to distinguish obstruction from hepatic causes
of jaundice.
Patients also can present with elevated serum
cholesterol, and often complain of severe itching or
“pruritus” because of the direct and indirect effects of
pruritogens in bile such as bile salts.
No single test can differentiate between various
classification of jaundice. A combination of liver
function test is essential to arrive at a diagnosis.
Diagnostic Tests
Function test Pre-hepatic Hepatic jaundice Post-hepatic
jaundice Jaundice
Total bilirubin Normal/Increased Increased
Conjugated Normal Increased
bilirubin
Unconjugated Normal/increased Increased Normal
bilirubin
Unrobillinogen Normal/increased Decreased/
Decreased/Negative
Urine color Normal Dark Dark
(urobilinogen+conjugated (conjugated
bilirubin) bilirubin)
Stool color Normal Slightly Pale Pale
Alkaline Increased
phosphatase
levels
Alanine Normal Increased
transferase
and aspartate
transferase
levels
Conjugated Not present Present
bilirubin in
urine
Large spleen Present Present Absent
NEONATAL JAUNDIC
NEONATAL JAUNDIC is usually harmless:
This condition is often seen in infant around the
second day after birth, lasting until day 8 in normal
birth, or to around day 14 in premature births. Typical
causes for neonatal jaundice include normal
physiologic jaundice, jaundice due to formula
supplementation & haemolytic disorder that include
hereditary Spherocytosis, Glucose-6-phosphate
dehydrogenase deficiency, pyruvate kinase
deficiency, ABO/Rh blood type autoantibodies, or
infantile pyknocytosis.
SERUM BILIRUBIN normally drops to a low level
without any intervention required in cases where
bilirubin rises higher, a brain damaging condition
know as kernicterus can occur, leading to significant
disability.
This condition has been rising in recent year due
to less time spent outdoors.
A BILI light is often the tool used for early
treatmen , which often consists of exposing the baby
to intensive phototherapy. Sunbathing is effective
treatment & has the advantage of ultra-violet-b,
which promotes vitamin D production.
BILIRUBIN count is lowered through bowel movement
& urination, so frequent & effective feedings are
especially important.
PATHOPHYSIOLOGY
JAUNDICE itself is not a disease, but rather a sign of
many possible processes that occur at some point
along the normal physiological pathway of the
metabolism of bilirubin in blood.
When red blood cells have completed their life span
of approximately 120 days, or when they are damage,
their membranes become fragile and prone to
rupture. as each red blood cell traverses through the
reticuloendothelial system, its cell membrane
ruptures when its membrane is fragile enough to
allow this cellular contents, including haemoglobin
,are subsequently released into the blood. The
haemoglobin is phagocytosed by macrophages, and
split into its heme and globin portions, The globin
portion, a protein,is degraded into amino acid and
plays no role jaundice.
Two reaction then take place with the heme
molecule. the first oxidation reaction is catalyzed by
the microsomal enzyme heme oxygenase and result in
biliverdin ,iron & carbon monoxide.
The next step is the reduction of biliverdin to a yellow
color tetrapyrol pigment called bilirubin by cytosolic
enzyme biliverdin reductase.
This bilirubin is “unconjugated” “free” or “indirect”
bilirubin. approximately 4mg of bilirubin per kg of
blood is produced each day.
The majority of this bilirubin come from the
breakdown of heme from expired red blood cells in
the process just described. However approximately
20 percent come from other heme sources, including
ineffective erythropoiesis &the breakdown of other
heme-containing proteins, such as muscle myoglobin
& cytochromes.
Hepatic events
The unconjugated bilirubin then travels to the liver
through the bloodstream. Because this bilirubin is not
soluble, however, it is transported through the blood
bound to serum albumin. Once it arrives at the liver it
is conjugated with glucuronic acid to become more
water-soluble.
The reaction is catalyzed by the enzyme UDP-
glucuronly transferase.
This conjugated bilirubin is excreted from the liver
into the biliary & cystic ducts as part of bile. Intestinal
bacteria convert the bilirubin into urobilinogen. from
here urobilinogen can take two pathways. it can
either be further converted into stercobilinogen,
which is then oxidized to stercobilin &passed out in
the feces or it can be reabsorbed by the intestinal
cells transported in the blood to the kidneys, and
passed out in the urine as the oxidised product
urobilin.
Stercobilin & urobilin are the products responsible for
the coloration of feces and urine respectively.