Jaundice, a chronic liver disease

Jaundice, also known as icterus (attributive adjective: "icteric"), is
yellowish discoloration of the skin, sclerae (whites of the eyes) and mucous
membranes caused by hyperbilirubinemia (increased levels of bilirubin in the
blood). This hyperbilirubinemia subsequently causes increased levels of
bilirubin in the extracellular fluids. Typically, the concentration of bilirubin
in the plasma must exceed 1.5 mg/dL[1], three times the usual value of
approximately 0.5mg/dL[1], for the coloration to be easily visible. Jaundice
comes from the French word jaune, meaning yellow.



Contents [hide]

1 Normal Physiology

1.1 Pre-Hepatic events

1.2 Hepatic events

1.3 Post Hepatic events

2 Causes

2.1 Pre-hepatic

2.2 Hepatic

2.3 Post-hepatic

3 Laboratory Results

3.1 Laboratory Tests

4 Neonatal jaundice

5 Jaundiced eye

6 External links

7 See also

8 Footnotes







[edit] Normal Physiology

In order to understand how jaundice results, it is important to understand where
the pathological processes that cause jaundice take their effect. It is also
important to further recognize that jaundice itself is not a disease, but rather
a symptom of an underlying pathological process that occurs at some point along
the normal physiological pathway of the metabolism of bilirubin.





[edit] Pre-Hepatic events

When red blood cells have completed their life span of approximately 120 days,
their membranes become fragile and prone to rupture. As the cell traverses
through the reticuloendothelial system, their cell membranes rupture and the
contents of the red blood cell is released into the blood. The component of the
red blood cell that is involved in jaundice is hemoglobin. The hemoglobin
released into the blood is phagocytosed by macrophages, and split into its heme
and globin portions. The globin portion, being protein, is degraded into amino
acids and plays no further role in jaundice. Two reactions then take place to
the heme molecule. The first reaction is the oxidation of heme to form
biliverdin.This reaction is catalyzed by microsomal enzyme heme oxygenase and it
results in biliverdin (green color pigment), iron and carbon monoxide. Next step
is reduction of biliverdin to yellow color tetrapyrol pigment bilirubin by
cytosolic enzyme biliverdin reductase. This bilirubin is known as "unconjugated",
"free" or "indirect" bilirubin. Approximately 4 mg per kg of bilirubin is
produced each day.[2] The majority of this bilirubin comes from the breakdown of
heme from expired red blood cells in the process just described. However
approximately 20 per cent comes from other heme sources, including ineffective
erythropoiesis, breakdown of other heme protrins such as muscle myoglobin and
cytochrome enzymes.[2]





[edit] 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 form bilirubin diglucuronide, or just "conjugated
bilirubin") to become more water soluble. The reaction is catalyzed by the
enzyme UDP-glucuronide transferase.





[edit] Post Hepatic events

This conjugated bilirubin is excreted from the liver into the biliary and cystic
ducts as part of bile. Intestinal bacteria convert the bilirubin into
urobilinogen. From here the urobilinogen can take two pathways. It can either be
further converted into stercobilinogen, which is then oxidized to stercobilin
and passed out in the faeces, 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 and urobilin are the products responsible
for the coloration of faeces and urine, respectively.





[edit] Causes

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:



Pre-hepatic: The pathology is occurring prior the liver

Hepatic: The pathology is located within the liver

Post-Hepatic: The pathology is located after the conjugation of bilirubin in the
liver



[edit] Pre-hepatic

Pre-hepatic jaundice is caused by anything which causes an increased rate of
hemolysis (breakdown of red blood cells). In tropical countries, malaria can
cause jaundice in this manner. Certain genetic diseases, such as sickle cell
anemia, spherocytosis and glucose 6-phosphate dehydrogenase deficiency can lead
to increased red cell lysis and therefore hemolytic jaundice. Commonly, diseases
of the kidney, such as hemolytic uremic syndrome, can also lead to coloration.
Defects in bilirubin metabolism also present as jaundice. Jaundice usually comes
with high fevers.



Laboratory findings include:



Urine: no bilirubin present, urobilirubin > 2 units (except in infants where gut
flora has not developed).

Serum: increased unconjugated bilirubin.



[edit] Hepatic

Hepatic jaundice causes include acute hepatitis, hepatotoxicity and alcoholic
liver disease, whereby cell necrosis reduces the liver's ability to metabolise
and excrete bilirubin leading to a buildup in the blood. Less common causes
include primary biliary cirrhosis, Gilbert's syndrome (a genetic disorder of
bilirubin metabolism which can result in mild jaundice, which is found in about
5% of the population), Crigler-Najjar syndrome and metastatic carcinoma.
Jaundice seen in the newborn, known as neonatal jaundice, is common, occurring
in almost every newborn as hepatic machinery for the conjugation and excretion
of bilirubin does not fully mature until approximately two weeks of age.



Laboratory Findings include:



Urine: Conjugated bilirubin present, Urobilirubin > 2 units but variable (Except
in children)



[edit] Post-hepatic

Post-hepatic jaundice, also called obstructive jaundice, is caused by an
interruption to the drainage of bile in the biliary system. The most common
causes are gallstones in the common bile duct, and pancreatic cancer in the head
of the pancreas. Also, a group of parasites known as "liver flukes" live in the
common bile duct, causing obstructive jaundice. Other causes include strictures
of the common bile duct, biliary atresia, ductal carcinoma, pancreatitis and
pancreatic pseudocysts. A rare cause of obstructive jaundice is Mirizzi's
syndrome.



The presence of pale stools and dark urine suggests an obstructive or
post-hepatic cause as normal feces get their color from bile pigments.



Patients also can present with elevated serum cholesterol, and often complain of
severe itching or "pruritus".





[edit] Laboratory Results



[edit] Laboratory Tests

Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice

Total bilirubin Normal / Increased Increased Increased

Conjugated bilirubin Normal Normal / Increased Increased

Unconjugated bilirubin Increased Normal / Increased Normal

Urobilinogen Increased Normal / Increased Decreased / Negative

Urine Colour Normal Dark Dark

Stool colour Normal Normal Pale





[edit] Neonatal jaundice

Main article: Neonatal jaundice

Neonatal jaundice is usually harmless: this condition is often seen in infants
around the second day after birth, lasting until day 8 in normal births, or to
around day 14 in premature births. Serum bilirubin normally drops to a low level
without any intervention required: the jaundice is presumably a consequence of
metabolic and physiological adjustments after birth. In extreme cases, a
brain-damaging condition known as kernicterus can occur; there are concerns that
this condition has been rising in recent years due to inadequate detection and
treatment of neonatal hyperbilirubinemia. Neonatal jaundice is a risk factor for
hearing loss.[3]





[edit] Jaundiced eye

It was once believed persons suffering from the medical condition jaundice saw
everything as yellow. By extension, the jaundiced eye came to mean a prejudiced
view, usually rather negative or critical. Alexander Pope, in 'An Essay on
Criticism' (1711), wrote: "All seems infected that the infected spy, As all
looks yellow to the jaundiced eye."[4] Similarly in the mid 19th century the
English poet Lord Alfred Tennyson wrote in the poem 'Locksley Hall': "So I
triumphe'd ere my passion sweeping thro' me left me dry, left me with the
palsied heart, and left me with a jaundiced eye."