what is jaundice?

jaundice means the yellow appearance of the skin and whites of the eyes that
occurs when the blood contains an excess of the pigment called bilirubin.

bilirubin is a natural product arising from the normal breakdown of red blood
cells in the body and is excreted in the bile, through the actions of the liver.

although jaundice is most often the result of a disorder affecting the liver it
can be caused by a variety of other conditions affecting for example the blood or
spleen. it should be thoroughly investigated so that the underlying cause can be
identified and treated.

how does a person get jaundice?

the red blood cells in our circulation carry oxygen to all parts of the body and
have a life span of about 120 days. at the end of their life they are broken down
and removed from the circulation by special cells called phagocytes, which are
found within the bone marrow, spleen and liver.

new red cells are of course continually manufactured and this also takes place
within the bone marrow.

following breakdown of the red cells some of their component parts such as amino
acids and iron can be re-used by the body. other components such as bilirubin need
to be removed.

knowing how this removal pathway works is the key to understanding how jaundice
occurs.

most waste products of the body are excreted in the urine via the kidneys but the
liver and bile system is the other main physical route out of the body for these
substances.

by 'waste products' we mean the many compounds that arise in the course of the
body's metabolism but almost all forms of drugs must also be eliminated either via
the urine or bile routes.

in the case of bilirubin released from old red cells, it passes through the
bloodstream to the liver, where the liver cells process it.

these cells carry out many complex chemical functions and also produce the liquid
bile, which is the 'vehicle' by which the cells discharge their output to the bile
duct system. this is a branching network of tiny tubes throughout the liver, which
merge in the same way as the branches of a tree.

ultimately a single main bile duct comes out of the liver and joins the first part
of the small intestine (duodenum). bile (and therefore bilirubin) then passes out
through the small and large intestines and is excreted in the stool (faeces).

bile is green in colour, but bacteria in the large bowel act to change the
bilirubin to substances that are brown, which gives stool its characteristic
colour.

some of the bilirubin is reabsorbed back into the body through the bowel wall,
eventually appearing in the urine as a substance called urobilinogen (although the
typical yellow/orange colour of urine is in fact due a different pigment called
urochrome).
therefore, any failure of the bilirubin removal pathway will lead to a build-up of
bilirubin in the blood. when this happens the individual's skin turns yellow,
causing jaundice.

what is jaundice?

jaundice is not a disease but rather a sign that can occur in many different
diseases. jaundice is the yellowish staining of the skin and sclerae (the whites
of the eyes) that is caused by high levels in blood of the chemical bilirubin. the
color of the skin and sclerae vary depending on the level of bilirubin. when the
bilirubin level is mildly elevated, they are yellowish. when the bilirubin level
is high, they tend to be brown.

what causes jaundice?

bilirubin comes from red blood cells. when red blood cells get old, they are
destroyed. hemoglobin, the iron-containing chemical in red blood cells that
carries oxygen, is released from the destroyed red blood cells after the iron it
contains is removed. the chemical that remains in the blood after the iron is
removed becomes bilirubin.

the liver has many functions. one of the liver�s functions is to produce and
secrete bile into the intestines to help digest dietary fat. another is to remove
toxic chemicals or waste products from the blood, and bilirubin is a waste
product. the liver removes bilirubin from the blood. after the bilirubin has
entered the liver cells, the cells conjugate (attaching other chemicals, primarily
glucuronic acid) to the bilirubin, and then secrete the bilirubin/glucuronic acid
complex into bile. the complex that is secreted in bile is called conjugated
bilirubin. the conjugated bilirubin is eliminated in the feces. (bilirubin is what
gives feces its brown color.) conjugated bilirubin is distinguished from the
bilirubin that is released from the red blood cells and not yet removed from the
blood which is termed unconjugated bilirubin.

jaundice occurs when there is 1) too much bilirubin being produced for the liver
to remove from the blood. (for example, patients with hemolytic anemia have an
abnormally rapid rate of destruction of their red blood cells that releases large
amounts of bilirubin into the blood), 2) a defect in the liver that prevents
bilirubin from being removed from the blood, converted to bilirubin/glucuronic
acid (conjugated) or secreted in bile, or 3) blockage of the bile ducts that
decreases the flow of bile and bilirubin from the liver into the intestines. (for
example, the bile ducts can be blocked by cancers, gallstones, or inflammation of
the bile ducts). the decreased conjugation, secretion, or flow of bile that can
result in jaundice is referred to as cholestasis: however, cholestasis does not
always result in jaundice.

what problems does jaundice cause?

jaundice or cholestasis, by themselves, causes few problems (except in the

newborn, and jaundice in the newborn is different than most other types of
jaundice, as discussed later.) jaundice can turn the skin and sclerae yellow. in
addition, stool can become light in color, even clay-colored because of the
absence of bilirubin that normally gives stool its brown color. the urine may turn
dark or brownish in color. this occurs when the bilirubin that is building up in
the blood begins to be excreted from the body in the urine. just as in feces, the
bilirubin turns the urine brown.
besides the cosmetic issues of looking yellow and having dark urine and light
stools, the symptom that is associated most frequently associated with jaundice or
cholestasis is itching, medically known as pruritus. the itching associated with
jaundice and cholestasis can sometimes be so severe that it causes patients to
scratch their skin �raw,� have trouble sleeping, and, rarely, even to commit
suicide.

it is the disease causing the jaundice that causes most problems associated with
jaundice. specifically, if the jaundice is due to liver disease, the patient may
have symptoms or signs of liver disease or cirrhosis. (cirrhosis represents
advanced liver disease.) the symptoms and signs of liver disease and cirrhosis
include fatigue, swelling of the ankles, muscle wasting, ascites (fluid
accumulation in the abdominal cavity), mental confusion or coma, and bleeding into
the intestines.

if the jaundice is caused by blockage of the bile ducts, no bile enters the
intestine. bile is necessary for digesting fat in the intestine and releasing
vitamins from within it so that the vitamins can be absorbed into the body.
therefore, blockage of the flow of bile can lead to deficiencies of certain
vitamins. for example, there may be a deficiency of vitamin k that prevents
proteins that are needed for normal clotting of blood to be made by the liver,
and, as a result, uncontrolled bleeding may occur.

what diseases cause jaundice?

increased production of bilirubin

there are several uncommon conditions that give rise to over-production of

bilirubin. the bilirubin in the blood in these conditions usually is only mildly
elevated, and the resultant jaundice usually is mild and difficult to detect.
these conditions include: 1) rapid destruction of red blood cells (referred to as
hemolysis), 2) a defect in the formation of red blood cells that leads to the
over-production of hemoglobin in the bone marrow (called ineffective
erythropoiesis), or 3) absorption of large amounts of hemoglobin when there has
been much bleeding into tissues (e.g., from hematomas, collections of blood in the
tissues).

acute inflammation of the liver

any condition in which the liver becomes inflamed can reduce the ability of the
liver to conjugate (attach glucuronic acid to) and secrete bilirubin. common
examples include acute viral hepatitis, alcoholic hepatitis, and tylenol-induced
liver toxicity.

chronic liver diseases

chronic inflammation of the liver can lead to scarring and cirrhosis, and can
ultimately result in jaundice. common examples include chronic hepatitis b and c,
alcoholic liver disease with cirrhosis, and autoimmune hepatitis.

infiltrative diseases of the liver

infiltrative diseases of the liver refer to diseases in which the liver is filled
with cells or substances that don�t belong there. the most common example would be
metastatic cancer to the liver, usually from cancers within the abdomen. uncommon
causes include a few diseases in which substances accumulate within the liver
cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one
antitrypsin deficiency), and copper (wilson�s disease).

inflammation of the bile ducts

diseases causing inflammation of the bile ducts, for example, primary biliary
cirrhosis or sclerosing cholangitis and some drugs, can stop the flow of bile and
elimination of bilirubin and lead to jaundice.

blockage of the bile ducts

the most common causes of blockage of the bile ducts are gallstones and pancreatic
cancer. less common causes include cancers of the liver and bile ducts.

drugs

many drugs can cause jaundice and/or cholestasis. some drugs can cause liver
inflammation (hepatitis) similar to viral hepatitis. other drugs can cause
inflammation of the bile ducts, resulting in cholestasis and/or jaundice. drugs
also may interfere directly with the chemical processes within the cells of the
liver and bile ducts that are responsible for the formation and secretion of bile
to the intestine. as a result, the constituents of bile, including bilirubin, are
retained in the body. the best example of a drug that causes this latter type of
cholestasis and jaundice is estrogen. the primary treatment for jaundice caused by
drugs is discontinuation of the drug. almost always the bilirubin levels will
return to normal within a few weeks, though in a few cases it may take several
months.

genetic disorders

there are several rare genetic disorders present from birth that give rise to
jaundice. crigler-najjar syndrome is caused by a defect in the conjugation of
bilirubin in the liver due to a reduction or absence of the enzyme responsible for
conjugating the glucuronic acid to bilirubin. dubin-johnson and rotor�s syndromes
are caused by abnormal secretion of bilirubin into bile.

the only common genetic disorder that may cause jaundice is gilbert�s syndrome
which affects approximately 7% of the population. gilbert�s syndrome is caused by
a mild reduction in the activity of the enzyme responsible for conjugating the
glucuronic acid to bilirubin. the increase in bilirubin in the blood usually is
mild and infrequently reaches levels that cause jaundice. gilbert�s syndrome is a
benign condition that does not cause health problems.

developmental abnormalities of bile ducts

there are rare instances in which the bile ducts do not develop normally and the
flow of bile is interrupted. jaundice frequently occurs. these diseases usually
are present from birth though some of them may first be recognized in childhood or
even adulthood. cysts of the bile duct (choledochal cysts) are an example of such
a developmental abnormality. another example is caroli�s disease.

jaundice of pregnancy

most of the diseases discussed previously can affect women during pregnancy, but
there are some additional causes of jaundice that are unique to pregnancy.

cholestasis of pregnancy. cholestasis of pregnancy is an uncommon condition that

occurs in pregnant women during the third trimester. the cholestasis is often
accompanied by itching but infrequently causes jaundice. the itching can be
severe, but there is treatment (ursodeoxycholic acid or ursodiol). pregnant women
with cholestasis usually do well although they may be at greater risk for
developing gallstones. more importantly, there appears to be an increased risk to
the fetus for developmental abnormalities. cholestasis of pregnancy is more common
in certain groups, particularly in scandinavia and chile, and tends to occur with
each additional pregnancy. there also is an association between cholestasis of
pregnancy and cholestasis caused by oral estrogens, and it has been hypothesized
that it is the increased estrogens during pregnancy that are responsible for the
cholestasis of pregnancy.

pre-eclampsia. pre-eclampsia, previously called toxemia of pregnancy, is a disease

that occurs during the second half of pregnancy and involves several systems
within the body, including the liver. it may result in high blood pressure, fluid
retention, and damage to the kidneys as well as anemia and reduced numbers of
platelets due to destruction of red blood cells and platelets. it often causes
problems for the fetus. although the bilirubin level in the blood is elevated in
pre-eclampsia, it usually is mildly elevated, and jaundice is uncommon. treatment
of pre-eclampsia usually involves delivery of the fetus as soon as possible if the
fetus is mature.

acute fatty liver of pregnancy. acute fatty liver of pregnancy (aflp) is a very
serious complication of pregnancy of unclear cause that often is associated with
pre-eclampsia. it occurs late in pregnancy and results in failure of the liver. it
can almost always be reversed by immediate delivery of the fetus. there is an
increased risk of infant death. jaundice is common, but not always present in
aflp. treatment usually involves delivery of the fetus as soon as possible.

what is neonatal jaundice (jaundice in newborn infants)?

neonatal jaundice is jaundice that begins within the first few days after birth.
(jaundice that is present at the time of birth suggests a more serious cause of
the jaundice.) in fact, bilirubin levels in the blood become elevated in almost
all infants during the first few days following birth, and jaundice occurs in more
than half. for all but a few infants, the elevation and jaundice represents a
normal physiological phenomenon and does not cause problems.

the cause of normal, physiological jaundice is well understood. during life in the
uterus, the red blood cells of the fetus contain a type of hemoglobin that is
different than the hemoglobin that is present after birth. when an infant is born,
the infant�s body begins to rapidly destroy the red blood cells containing the
fetal-type hemoglobin and replaces them with red blood cells containing the adult-
type hemoglobin. this floods the liver with bilirubin derived from the fetal
hemoglobin from the destroyed red blood cells. the liver in a newborn infant is
not mature, and its ability to process and eliminate bilirubin is limited. as a
result of both the influx of large amounts of bilirubin and the immaturity of the
liver, bilirubin accumulates in the blood. within two or three weeks, the
destruction of red blood cells ends, the liver matures, and the bilirubin levels
return to normal.

there is another uncommon syndrome associated with neonatal jaundice, referred to

as breast-milk or breast feeding jaundice. in this syndrome, jaundice appears to
be caused by or at least accentuated by breast feeding. although the cause of this
type of jaundice is unknown, it has been hypothesized that there is something in
breast milk that reduces the ability of the liver to process and eliminate
bilirubin. with breast-milk jaundice, the bilirubin levels rise and reach peak
levels in approximately two weeks, remain elevated for a week or so, and then
decline to normal over several weeks or months. this timing of the elevation in
bilirubin and jaundice is different than normal physiological jaundice described
previously and allows the two causes of jaundice to be differentiated. the real
importance of the more prolonged jaundice associate with breast-milk jaundice is
that it raises the possibility that there is a more serious cause for the jaundice
that needs to be sought, for example, biliary atresia (destruction of the bile
ducts). breast-milk jaundice alone usually does not cause problems for the infant.

physiologic jaundice and breast-milk jaundice usually do not cause problems for
the infant; however, there is a concern that high or prolonged elevations in
levels of unconjugated bilirubin (the type of bilirubin that is not attached to
glucuronic acid and the main type of bilirubin that is present in physiologic and
breast-milk jaundice) will cause neurologic damage to the infant. therefore, when
unconjugated bilirubin levels are high or prolonged, treatment usually is started
to lower the levels of bilirubin. treatment may be started earlier in infants who
are born prematurely since their livers take longer to mature, and the risk of
higher and more prolonged elevations of bilirubin is greater. treatment involves
phototherapy with artificial or natural sunlight and, if phototherapy is not
successful, exchange transfusion in which the infant�s blood is exchanged for
normal blood from blood donors.

the benign nature of physiologic and breast-milk allergy need to be distinguished

from hemolytic disease of the newborn, a much more serious, even life-threatening
cause of jaundice in newborns that is due to blood group incompatibilities between
mother and fetus, for example rh incompatibility. the incompatibility results in
an attack by the mother�s antibodies on the babies red blood cells leading to
hemolysis. fortunately, because of modern management of pregnancy, this cause of
jaundice is rare.

how is the cause of jaundice diagnosed?

many tests are available for determining the cause of jaundice, but the history
and physical examination are important as well.

history

the history can suggest possible reasons for the jaundice. for example, heavy use
of alcohol suggests alcoholic liver disease, whereas use of illegal, injectable
drugs suggests viral hepatitis. recent initiation of a new drug suggests drug-
induced jaundice. episodes of abdominal pain associated with jaundice suggests
blockage of the bile ducts usually by gallstones.

physical examination

the most important part of the physical examination in a patient who is jaundiced
is examination of the abdomen. masses (tumors) in the abdomen suggest cancer
infiltrating the liver (metastatic cancer) as the cause of the jaundice. an
enlarged, firm liver suggests cirrhosis. a rock-hard, nodular liver suggests
cancer within the liver.

blood tests

measurement of bilirubin can be helpful in determining the causes of jaundice.

markedly greater elevations of unconjugated bilirubin relative to elevations of
conjugated bilirubin in the blood suggest hemolysis (destruction of red blood
cells). marked elevations of liver tests (aspartate amino transferase or ast and
alanine amino transferase or alt) suggest inflammation of the liver (such as viral
hepatitis). elevations of other liver tests, e.g., alkaline phosphatase, suggest
diseases or obstruction of the bile ducts.

ultrasonography

ultrasonography is a simple, safe, and readily-available test that uses sound

waves to examine the organs within the abdomen. ultrasound examination of the
abdomen may disclose gallstones, tumors in the liver or the pancreas, and dilated
bile ducts due to obstruction (by gallstones or tumor).

computerized tomography (ct or cat scans)

computerized tomography or ct scans are scans that use x-rays to examine the soft
tissues of the abdomen. they are particularly good for identifying tumors in the
liver and the pancreas and dilated bile ducts, though they are not as good as
ultrasonography for identifying gallstones.

magnetic resonance imaging (mri)

magnetic resonance imaging scans are scans that utilize magnetization of the body
to examine the soft tissues of the abdomen. like ct scans, they are good for
identifying tumors and studying bile ducts. mri scans can be modified to visualize
the bile ducts better than ct scans (a procedure referred to as mr
cholangiography), and, therefore, are better than ct for identifying the cause and
location of bile duct obstruction.

endoscopic retrograde cholangiopancreatography (ercp) and endoscopic ultrasound

endoscopic retrograde cholangiopancreatography (ercp) provides the best means for

examining the bile duct. for ercp an endoscope is swallowed by the patient after
he or she has been sedated. the endoscope is a flexible, fiberoptic tube
approximately four feet in length with a light and camera on its tip. the tip of
the endoscope is passed down the esophagus, through the stomach, and into the
duodenum where the main bile duct enters the intestine. a thin tube then is passed
through the endoscope and into the bile duct, and the duct is filled with x-ray
contrast solution. an x-ray is taken that clearly demonstrates the contrast-filled
bile ducts. ercp is particularly good at demonstrating the cause and location of
obstruction within the bile ducts. a major advantage of ercp is that diagnostic
and therapeutic procedures can be done at the same time as the x-rays. for
example, if gallstones are found in the bile ducts, they can be removed. stents
can be placed in the bile ducts to relieve the obstruction caused by scarring or
tumors. biopsies of tumors can be obtained.

ultrasonography can be combined with ercp by using a specialized endoscope capable

of doing ultrasound scanning. endoscopic ultrasound is excellent for diagnosing
small gallstones in the gallbladder and bile ducts that can be missed by other
diagnostic methods such as ultrasound, ct, and mri. it also is the best means of
examining the pancreas for tumors and can facilitate biopsy through the endoscope
of tumors within the pancreas.

liver biopsy

biopsy of the liver provides a small piece of tissue from the liver for
examination under the microscope. the biopsy most commonly is done with a long
needle after local injection of the skin of the abdomen overlying the liver with
anesthetic. the needle passes through the skin and into the liver, cutting off a
small piece of liver tissue. when the needle is withdrawn, the piece of liver
comes with it. liver biopsy is particularly good for diagnosing inflammation of
the liver and bile ducts, cirrhosis, cancer, and fatty liver.

how is jaundice treated?

with the exception of the treatments for specific causes of jaundice mentioned
previously, the treatment of jaundice usually requires a diagnosis of the specific
cause of the jaundice and treatment directed at the specific cause, e.g., removal
of a gallstone blocking the bile duct.

what conditions can be associated with jaundice?

an excessive breakdown of red blood cells

the balance between manufacture and breakdown of red cells is normally precisely
balanced and equal but there are several conditions in which the rate of breakdown
increases. if the amount of bilirubin thus released exceeds the liver's capacity
to remove it, then jaundice will develop.

the medical term for excessive red cell breakdown is 'haemolysis', and within the
developed world it is a fairly rare condition. malaria is however a major cause in
tropical climates as the malaria parasites live within the red cells and shorten
their life.

similarly the condition in which a foetus develops haemolysis due to

incompatibility of its rhesus blood group with that of its mother is now rarely
seen in the uk where we routinely check for 'rhesus antibodies' in the mother's
blood. in parts of the world where antenatal care is not as good haemolytic
disease of the newborn is much more common.

a temporary jaundice of newborn babies is however quite common, due to the

relative immaturity of the baby's liver cells and the higher than normal rate of
cell breakdown that occurs in the first few weeks of life. it improves rapidly
without treatment although when too high it can be speeded up by exposing the baby
to ultraviolet light. jaundice of the newborn is commoner in premature babies as
their liver is even more immature than a baby born at term.

autoimmune haemolytic anaemia is a rare disease in which the body's immune system
seems to attack the red cells. it usually affects adults. haemolysis can also be a
side effect of some drugs, eg dapsone.

impairment of liver cell function

the commonest cause is a viral infection of the liver cells (hepatitis). many
different types of infection including glandular fever (mononucleosis) can also be
responsible for this.

alcohol abuse and subsequent scarring of the liver (cirrhosis) can cause
significant cell damage leading to jaundice. other less common conditions causing
liver cell damage include haemochromatosis, alpha-1 antitrypsin deficiency and
primary biliary cirrhosis. tumours of the liver - either primary liver cancers
(arising from the liver tissue itself) or more commonly, the secondary spread of a
tumour from elsewhere in the body into the liver can lead to cell failure and
jaundice.

blockage of the bile ducts

this can occur as a result of abnormality inside or outside the ducts. the
commonest example of an internal blockage is a gallstone. tumours of the bile duct
are rare but if large enough, or situated just where the bile duct meets the
duodenum, then they can block the flow of bile. at this junction point, known as
the ampulla of vater, the tube from the pancreas gland also joins to the duodenum.
cancer of the pancreas tends to arise in the part of the pancreas nearest to the
ampulla of vater, so is another potential cause of 'obstructive' jaundice.

any external organ or mass lying nearby that becomes large enough to press on the
bile duct could be responsible. examples include swollen internal lymph glands, a
cyst (perhaps of the pancreas) or scar tissue following a previous infection or
surgery.

what are the symptoms?

the symptoms, other than that of the jaundice itself, will relate to the
underlying cause. for example someone with haemolysis might also be anaemic and
tired. if a gallstone were responsible there would probably have been a preceding
history of pain in the abdomen. a cancer might be accompanied by weight loss, and
so on.

when jaundice is due to obstruction of the bile duct the person will often notice
that their urine becomes dark and stools become pale, as the excess bilirubin
'spills over' into the urine and no longer colours the stool. obstructive jaundice
is also often accompanied by intense itching.

how is jaundice diagnosed?

the diagnosis is made by recognition of the patient's appearance and accompanying

symptoms. a blood test will confirm the raised bilirubin level and other tests
such as those for hepatitis and haemolysis are also done on the blood. ultrasound
is a good way to inspect the liver and bile ducts for signs of obstruction, and
often can give useful information on the pancreas gland. ct scanning also helps
diagnose obstructive jaundice accurately.

what can your doctor do?

if you or one of your friends or relatives suspect that you may have jaundice, it
is essential that you arrange to see your doctor in order that the underlying
cause is identified and any possible treatment initiated as soon as possible.

treatment will depend upon the diagnosis behind the symptom of jaundice. for
example, if the problem is one of gallstones, then removal of the gallbladder may
be required.