2. INTRODUCTION
Jaundice, or icterus, is a yellowish discoloration of tissue resulting from the
deposition of bilirubin.
Tissue deposition of bilirubin occurs only in the presence of serum
hyperbilirubinemia and is a sign of either liver disease or, less often, a hemolytic
disorder.
Slight increases in serum bilirubin level 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 level of at least 3 mg/dL.
Jaundice must be distinguished from yellow or green skin color resulting from
carotenemia or quinacrine ingestion.
3. FORMATION & METABOLISM
Most bilirubin is produced when Hb is broken down into unconjugated bilirubin
(and other substances).
Unconjugated bilirubin binds to albumin in the blood for transport to the liver,
where it is taken up by hepatocytes and conjugated with glucuronic acid to make
it water soluble.
Conjugated bilirubin is excreted in bile into the duodenum. In the intestine,
bacteria metabolize bilirubin to form urobilinogen.
Some urobilinogen is eliminated in the feces, and some is reabsorbed, extracted
by hepatocytes, reprocessed, and re-excreted in bile
4. HYPERBILIRUBINEMIA
Unconjugated hyperbilirubinemia is most
often caused by ≥ 1 of the following:
Increased production
Decreased hepatic uptake
Decreased conjugation
Conjugated hyperbilirubinemia is most often
caused by ≥ 1 of the following:
Dysfunction of hepatocytes
(hepatocellular dysfunction)
Slowing of bile egress from the liver
(intrahepatic cholestasis)
Obstruction of extrahepatic bile flow
(extrahepatic cholestasis)
► Hyperbilirubinemia may involve predominantly unconjugated or conjugated
bilirubin.
► Outcome is determined primarily by the cause of jaundice and the presence and
severity of hepatic dysfunction.
9. CLASSIFICATION OF JAUNDICE
Congenital Hyperbilirubinemia :
A. Unconjugated :
1. Disturbance of bilirubin transport : Gilbert syndrome
2. Disturbance of bilirubin conjugation: Crigler Najjar Syndrome.
B. Conjugated :
1. Distrubance in excretion of Bilirubin : Dubin Johnson syndrome, Rotor’s
Syndrome.
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15. CRIGLER – NAJJAR SYNDROME
Crigler - Najjar type I is an exceptionally rare
condition found in neonates and characterized
by severe jaundice (bilirubin >20 mg/dL) and
neurologic impairment due to kernicterus,
frequently leading to death in infancy or
childhood.
These patients have a complete absence of
bilirubin UDPGT activity, usually due to
mutations in the UDPGT gene and are totally
unable to conjugate bilirubin, and hence
cannot excrete it.
16. CRIGLER – NAJJAR SYNDROME
Crigler-Najjar type II is somewhat more common than type I.
Patients live into adulthood with serum bilirubin levels of 6-25 mg/dL.
In these patients, mutations in the bilirubin UDPGT gene cause the
reduction, but not the complete eradication of the enzyme’s activity.
Bilirubin UDPGT activity can be induced by the administration of
phenobarbital, which can reduce serum bilirubin levels in these patients.
Despite marked jaundice, these patients usually survive into adulthood,
although they may be susceptible to kernicterus under the stress of
intercurrent illness or surgery.
17. GILBERT’S SYNDROME
Gilbert's syndrome is also marked by the impaired conjugation of bilirubin
due to reduced bilirubin UDPGT activity.
Patients with Gilbert's syndrome have mild unconjugated
hyperbilirubinemia, with serum levels almost always < 6 mg/dL.
The serum levels may fluctuate, and jaundice is often identified only during
periods of fasting.
Unlike both Crigler- Najjar syndromes, Gilbert's syndrome is very common.
The incidence is 3-7% of the population with males predominating over
females by a ratio of 2-7: 1 .
18. DUBIN - JOHNSON SYNDROME &
ROTOR SYNDROME
Patients with either condition present with asymptomatic jaundice.
The defect in Dubin-Johnson syndrome is the presence of mutations in the
gene for MRP2.
These patients have altered excretion of bilirubin into the bile ducts.
Rotor syndrome may represent a deficiency of the major hepatic drug
uptake transporters OATP1B1 and OATP1B3.
In Rotor syndrome, serum bilirubin is usually less than 10 mg/dL and
equally split between conjugated and unconjugated fractions.
Differentiating between these syndromes is possible but is clinically
unnecessary due to their benign nature.
20. APPROACH TO PATIENT WITH
JAUNDICE
HISTORY
History of present illness should include onset and duration of jaundice.
Hyperbilirubinemia can cause urine to darken before jaundice is visible. Therefore,
the onset of dark urine indicates onset of hyperbilirubinemia more accurately than
onset of jaundice.
Important associated symptoms include fever, prodromal symptoms before
jaundice, changes in stool color, pruritus, steatorrhea, and abdominal pain
(including location, severity, duration, and radiation).
Important symptoms suggesting severe disease include nausea and vomiting,
weight loss, and possible symptoms of coagulopathy.
Family history should include questions about recurrent, mild jaundice in family
members and diagnosed hereditary liver disorders.
21. HISTORY
Review of systems should seek symptoms of possible causes, including weight loss
and abdominal pain, joint pain and swelling and missed menses.
Past medical history should identify known causative disorders, such as hepatobiliary
disease, disorders that can cause hemolysis, and disorders associated with liver or
biliary disease, including inflammatory bowel disease and infiltrative disorders.
Drug history should include questions about use of drugs or exposure to toxins
known to affect the and about vaccination against hepatitis.
Surgical history should include questions about previous surgery on the biliary tract.
Social history should include questions about risk factors for hepatitis, amount and
duration of alcohol use, injection drug use, and sexual history.
22. PHYSICAL EXAMINATION
Vital signs are reviewed for fever and signs of systemic toxicity
General appearance is noted, particularly for cachexia and lethargy.
Head and neck examination includes inspection of the sclerae and tongue
for icterus and the eyes for Kayser-Fleischer rings
Mild jaundice is best seen by examining the sclerae in natural light; it is
usually detectable when serum bilirubin reaches 2 to 2.5 mg/dL
The abdomen is inspected for collateral vasculature, ascites, and surgical
scars.
The liver is palpated for hepatomegaly, masses, nodularity, and tenderness.
23. PHYSICAL EXAMINATION
The spleen is palpated for splenomegaly.
The abdomen is examined for umbilical hernia, shifting
dullness, fluid wave, masses, and tenderness.
The rectum is examined for gross or occult blood.
Men are checked for testicular atrophy and gynecomastia.
The upper extremities are examined for Dupuytren
contractures
The skin is examined for jaundice, palmar erythema, needle
tracks, vascular spiders, excoriations, xanthomas, paucity of
axillary and pubic hair, hyperpigmentation, ecchymoses,
petechiae, and purpura.
27. INVESTIGATIONS
Blood tests (bilirubin, aminotransferase, alkaline phosphatase)
Usually imaging (Ultrasound, MRCP, EUS, ERCP)
Sometimes biopsy or laparoscopy.
28. MESSAGE TO TAKE HOME
Suspect acute viral hepatitis in patients, particularly young and healthy patients, who have
acute jaundice, particularly with a viral prodrome.
Suspect biliary obstruction due to cancer in elderly patients with painless jaundice, weight
loss, an abdominal mass, and minimal pruritus.
Suspect hepatocellular dysfunction if aminotransferase levels are > 500 U/L and alkaline
phosphatase elevation is < 3 times normal.
Suspect cholestasis if aminotransferase levels are < 200 U/L and alkaline phosphatase
elevation is > 3 times normal.
Hepatic dysfunction is significant if mental status is altered and coagulopathy is present.