Yellowish discoloration of tissue resulting from
the deposition of bilirubin.
Slight increases in serum bilirubin are best
detected by examining the sclerae, which have
a particular affinity for bilirubin due to their
high elastin content.
The presence of scleral icterus indicates
a serum bilirubin of at least 3 mg/dL.
• A second place to examine is underneath the
• Another sensitive indicator of increased serum
bilirubin is darkening of the urine.
• Patients often describe their urine as tea- or colacolored.
• Bilirubinuria indicates an elevation of the direct
serum bilirubin fraction and, therefore, the
presence of liver disease
• The duration of jaundice;
• Presence of any accompanying symptoms
such as arthralgias, myalgias, rash, anorexia,
weight loss, abdominal pain, fever,
• changes in the urine and stool.
• Alcohol consumption.
• Jaundice associated with the sudden onset of severe right
upper quadrant pain and shaking chills suggests
choledocholithiasis and ascending cholangitis.
• parenteral exposures, including transfusions, intravenous
and intranasal drug use, tattoos, and sexual activity
• exposure to any medication, either physician-prescribed,
over-the-counter, complementary or alternative medicines
such as herbal and vitamin preparations, or other drugs
such as anabolic steroids.
recent travel history;
exposure to people with jaundice;
exposure to possibly contaminated foods;
occupational exposure to hepatotoxins
• Assessment of the patient's nutritional status.
• Stigmata of chronic liver disease, including spider
nevi, palmar erythema, gynecomastia, caput
medusae, Dupuytren's contractures, parotid
gland enlargement, and testicular atrophy.
• An enlarged left supraclavicular node (Virchow's
node) or periumbilical nodule (Sister Mary
Joseph's nodule) suggests an abdominal
• Jugular venous distention, a sign of right-sided
heart failure, suggests hepatic congestion.
• Right pleural effusion, in the absence of
clinically apparent ascites, may be seen in
• KF rings may be present in cornea in wilsons
• Patients with cirrhosis may have an enlarged left
lobe of the liver, which is felt below the xiphoid,
and an enlarged spleen.
• A grossly enlarged nodular liver or an obvious
abdominal mass suggests malignancy.
• An enlarged tender liver:
1. viral or alcoholic hepatitis; an
2. infiltrative process such as amyloid;
3. acutely congested liver secondary to right-sided
• Severe right upper quadrant tenderness with
respiratory arrest on inspiration (Murphy's
sign) suggests cholecystitis or, occasionally,
• Ascites in the presence of jaundice suggests
either cirrhosis or malignancy with peritoneal
Measurement of Serum Bilirubin
• Based on the van den Bergh reaction.
• Bilirubin is exposed to diazotized sulfanilic acid
• The direct fraction is that which reacts with
diazotized sulfanilic acid in the absence of an
accelerator substance such as
• The total serum bilirubin is the amount that
reacts after the addition of alcohol.
• The indirect fraction is the difference between
the total and the direct bilirubin and provides an
estimate of the unconjugated bilirubin in serum
• With the van den Bergh method, the normal
serum bilirubin concentration usually is (<1
• Up to 30%, (0.3 mg/dL), of the total may be
direct-reacting (conjugated) bilirubin.
• Direct-reacting bilirubin fraction includes conjugated
bilirubin that is covalently linked to albumin.
• By virtue of its tight binding to albumin, the clearance rate
of albumin-bound bilirubin from serum approximates the
half-life of albumin, 12–14 days, rather than the short halflife of bilirubin, about 4 hours. Resulting in:
1. Some patients with conjugated hyperbilirubinemia do not
exhibit bilirubinuria .
2. The elevated serum bilirubin level declines more slowly
than expected in some patients who otherwise appear to
be recovering satisfactorily.
• Unconjugated bilirubin is always bound to
albumin in the serum, and is not found in the
• Any bilirubin found in the urine is conjugated
• The presence of bilirubinuria implies the
presence of liver disease
• (1) overproduction of bilirubin;
• (2) impaired uptake, conjugation, or excretion
• (3) regurgitation of unconjugated or
conjugated bilirubin from damaged
hepatocytes or bile ducts
1. whether the hyperbilirubinemia is
predominantly conjugated or unconjugated
2. whether other biochemical liver tests are
Isolated Elevation of Serum Bilirubin
• The critical determination is whether:
1. the patient is suffering from a hemolytic
process resulting in an overproduction of
bilirubin (hemolytic disorders and ineffective
2. from impaired hepatic uptake/conjugation of
bilirubin (drug effect or genetic disorders).
• In these conditions, the serum bilirubin rarely
exceeds (5 mg/dL).
• Higher levels may occur when there is
coexistent renal or hepatocellular dysfunction.
• in acute hemolysis such as a sickle cell crisis.
• cause unconjugated hyperbilirubinemia by
diminishing hepatic uptake of bilirubin
Bilirubin UDPGT deficiency
• Crigler-Najjar type I (complete absence)is an
exceptionally rare condition found in neonates
and characterized by severe
jaundice,kernicterus, frequently leading to
death in infancy or childhood.
• Crigler-Najjar type II (Deficiency)is somewhat
more common than type I. Patients live into
adulthood with serum bilirubin levels that
range from (6–25 mg/dL).
• Gilbert's syndrome is also marked by the
impaired conjugation of bilirubin due to
reduced bilirubin UDPGT activity to
approximately 1/3 of normal.
• very common, with a reported incidence of 3–
• unconjugated hyperbilirubinemia with serum
levels almost always < (6 mg/dL).
• Dubin-Johnson syndrome and
• Rotor's syndrome.
• Present with asymptomatic jaundice, typically in
the second generation of life.
• Dublin Johnson: altered excretion of bilirubin into
the bile ducts.
• Rotor's syndrome : problem with the hepatic
storage of bilirubin.
Elevation of Serum Bilirubin with
Other Liver Test Abnormalities
• In a patient with unexplained jaundice,certain tests are
useful in initial evaluation. These include:
Total and direct serum bilirubin with fractionation,
prothrombin time tests.
• Patients with a hepatocellular process generally have a
disproportionate rise in the aminotransferases compared to the
• Patients with a cholestatic process have a disproportionate rise in
the ALP compared to the aminotransferases.
• A low albumin level suggests a chronic process such as cirrhosis or
• An elevated prothrombin time indicates
1. vitamin K deficiency due to prolonged jaundice and malabsorption
of vitamin K or
2. significant hepatocellular dysfunction.
• The failure of the prothrombin time to correct with parenteral
administration of vitamin K indicates severe hepatocellular injury.
• Patients with alcoholic hepatitis typically have an
AST:ALT ratio of at least 2:1. The AST rarely exceeds 300
• Patients with acute viral hepatitis and toxin-related
injury typically have aminotransferases > 500 U/L,
with the ALT greater than or equal to the AST.
• While ALT and AST values less than 8 times normal may
be seen in either hepatocellular or cholestatic liver
disease, values 25 times normal or higher are seen
primarily in acute hepatocellular diseases.
• Patients with jaundice from cirrhosis can have normal
or only slight elevations of the aminotransferases.
• Distinguish intrahepatic from extrahepatic cholestasis.
History, physical examination, and laboratory tests are often not
• The next appropriate test is an ultrasound.
• The absence of biliary dilatation suggests intrahepatic cholestasis,
while the presence of biliary dilatation indicates extrahepatic
• False-negative results
1. Partial obstruction of the common bile duct
2. Cirrhosis or primary sclerosing cholangitis (PSC) where scarring
prevents the intrahepatic ducts from dilating.
• The distal common bile duct is a particularly
difficult area to visualize by ultrasound
because of overlying bowel gas.
• CT, magnetic resonance cholangiography
(MRCP), and endoscopic retrograde
• ERCP is the "gold standard" for identifying
choledocholithiasis. ERCP allows for
therapeutic interventions, including the
removal of common bile duct stones and the
placement of stents.
• Both Hepatitis B and C can cause a cholestatic
hepatitis .Hepatitis A, alcoholic hepatitis, EBV,
and CMV may also present as cholestatic liver
Pure cholestasis—anabolic and contraceptive steroids
Cholestatic hepatitis—chlorpromazine, imipramine
erythromycin, Penicillins, cotrimoxazole…
Chronic cholestasis—chlorpromazine and prochlorperazine
• Primary sclerosing cholangitis is characterized by the
destruction and fibrosis of larger bile ducts.
• 95% of patients with PSC, both intra- and extrahepatic
ducts are involved. But may present as intrahepatic
• Approximately 75% of patients with PSC have
inflammatory bowel disease.
• Primary biliary cirrhosis is an autoimmune disease.
• there is a progressive destruction of interlobular bile
• Diagnosis is made by the presence of the
antimitochondrial antibody that is found in 95% of
• Cholestasis of pregnancy occurs in the second
and third trimesters and resolves after delivery.
Its cause is unknown, but the condition is
probably inherited. Cholestasis can be triggered
by estrogen administration.
Infiltrative disease:(TB, Lymphomas, Amyloiosis)
Infections: (Malaria, Leptospirosis)
Paraneoplastic (stauffers syndrome), GVHD
Total Parenteral Nutrition.
Inherited familial forms.
Veno occlusive Diseases.
Ampullary carcinoma.(Has the highest surgical cure rate)
Cholangiocarcinoma (associated with PSC,
appears similar to it and thus difficult to diagnose)
• Malignant involvement of the porta hepatis lymph