By:

PALAK KHANNA
(group 2)
SADHANA SHUKLA
(group 2)
MADIHA REHAMANI
(group 2)
ISHWIN TANDON
(group 1)
Introduction
Jaundice is a clinical problem that can be caused by a variety
of disorders. Jaundice (also known as icterus) is a yellowish
pigmentation of the skin, the conjunctival membranes over
the sclerae and other mucous membranes caused by
hyperbilirubinemia. A concentration of total bilirubin higher
than 30 µmol/L leads to jaundice. Jaundice is classified into
three categories, depending on which part of the
physiological mechanism the pathology affects. The three
categories are: pre-hepatic, hepatic and post-hepatic.

Objective
After discussing this case, students will have knowledge of
different causes of jaundice. They will be able to specify types
of jaundice and learn to differentiate between the various
disorders based on history, physical examination and
diagnostic test results. Students will also learn about the main
treatment options of jaundice.
Stage I - Presentation of the patient’s problem

Case

A 16-year boy visits the office of the General Practitioner with complaints
of recurrent jaundice. The first episode began three months ago and he
recovered within two weeks. The second episode started one week ago.
Both episodes have been accompanied by reduced appetite.

Question 1. What is your first presumption about the main problem

of the patient? Which organ systems are possibly involved in this
problem?
Jaundice has to be differentiated from carotenemia - a harmless
condition when yellowish pigmentation is present only on the skin
(especially on the palms and the soles) and not on the sclera and
mucous membranes.
• Organ system involved – liver , common bile duct , gall-
bladder , pancreatic duct rarely
The recurrent course of disease could be typical for a pre-hepatic cause of
jaundice, but it does not rule out hepatic and post-hepatic jaundice.
Question 2 What is the most likely cause of
jaundice at this moment? List all possible causes
of the problem and classify them in three groups:
Likely, Less Likely, Not very likely but not
excluded.
 Likely Less Likely Not very likely
Impaired bilirubin
conjugation
Pancreatic cell
deficiency
alcohol misuse
Wilsons disease
liver cancer

Thalassemia
cholecystitis

peritonitis
cirrhosis    
gallstones     
A-1 antitrypsin
deficiency
hepatitis A    
Hepatitis B
Hepatitis C
 Glomerular nephritis    
biliary tract disease      
hemolysis
 Likely Less Likely Not very likely
Impaired bilirubin +
conjugation
Pancreatic cell +
deficiency
alcohol misuse +
Wilsons disease +
liver cancer +

Thalassemia +
cholecystitis +

peritonitis +
cirrhosis +    
gallstones  +    
A-1 antitrypsin +
deficiency
hepatitis A +    
Hepatitis B
Hepatitis C
 Glomerular nephritis   + 
biliary tract disease   +    
hemolysis
Question 3 Agree upon all relevant hypotheses and
discuss their cause or pathology on organ level or on
a more detailed level. Is there a problem in
anatomical, cellular, or biochemical respect?
• Most bilirubin is produced when hemoglobin
(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.
• For clinical purposes, the predominant type of
bile pigments in the plasma can be used to
classify hyperbilirubinemia into two major
categories:
• Plasma elevation of predominantly
unconjugated bilirubin due to the
overproduction of bilirubin (such as with
hemolysis), impaired bilirubin uptake by the
liver, or abnormalities of bilirubin conjugation
• Plasma elevation of both unconjugated and
conjugated (also called direct) bilirubin due to
hepatocellular disease , impaired canalicular
excretion
Question 4. Which questions must be asked to discriminate
between the most relevant hypotheses?
Questions that must be asked to confirm or reject
a hypothetical diagnosis can be following :

•Duration of jaundice
•Associated pain
•Previous episode of jaundice
•Pale-colored stools, dark -colored urine
•Skin itching
•Nausea, vomiting ,Diarrhea and Abdominal pain
•Rectal bleeding
•Fever and chills
•Weakness
• Weight loss
• Confusion
•Headache
•Swelling of the legs ( peritibial edema ), Swelling and distension of the
abdomen due to the accumulation of fluid (ascites)
•History of injections and blood transfusions
•Contact with jaundice patient
•Occupation
Stage II - Results of history taking
Hand-out 1 (shown on the screen and read out loud)

During the history taking, the patient tells that there is no history of fasting, sexual intercourse,
use of intravenous drugs, medications, alcohol or exposure to toxic substances. The patient has
no complaints of nausea, vomiting, abdominal pain and itching. He did not notice that he was
more dizzy or tired since the complaints of jaundice started. Dark colored urine or light colored
stool hadn’t been noticed either. The patient hasn’t undergone any abdominal operations,
including gallbladder surgery, and blood transfusion. There is no family history of inherited
disorders including liver diseases and hemolytic disorders. The patient visited youth camp 6
months ago.

Question 5. How does the history of the patient

influence your differential diagnosis?
History Hepatitis Hemolysis Impaired Biliary tract
information bilirubin disease
conjugation (obstruction)

Use of - -/+
medications
Toxic + +
substance
Alcohol abuse

Infection
Dark color
urine and
pale stool
Weakness
and fatigue
Genetics
History Hepatitis Hemolysis Impaired Biliary tract
information bilirubin disease
conjugation (obstruction)

Use of + -/+ + -
medications
Toxic + -/+ +/- -
substance
Alcohol abuse + - +/- +

Infection + + - -
Dark color + +/- +/- +
urine and
pale stool
Weakness + + -/+ +
and fatigue
Genetics - + + -
Question 6. Which parts of the physical examination are
required in order to exclude some unlikely, but important
hypotheses?
Vital signs :
1. Fever
2. Tachycardia
3. Hypotension
4. Tachypnea
Inspection :
1. Color of the skin and sclera- Pallor, Muscle atrophy, Edema, Skin excoriation from scratching
(pruritis) Petechia, Echomosis, Spider angiomas.
2. Edema , cyanosis
3. Nail changes
4. Clubbing

we can perform abdominal

examination
1. Ascultation :- Bowel sownd , peristalisis
movement, Abdominal dullness
1. Palpitation :- Swelling , tenderness , pain,
Ascites , Size (Firm, sharp ridge with a
smooth surface). Cirrhosis of the liver:
smooth, hard, shrunken, fibrotic Acute
Hepatitis: Soft edges and easily moves
2. Percussion : Liver /spleen dullness
Stage III - Results of physical examination
Hand-out 2 (shown on the screen and read out loud)

On examination, the general condition of the patient was not ill. His temperature was 36.7 °C.
He had a blood pressure of 119/75 mmHg with a heart rate of 70 bpm. The color of the skin and
sclerae was icteric. Further examination of the skin did not show spider naevi, erythema
palmare or collateral veins. On abdominal examination, there were no abnormal signs. On
auscultation there were normal peristaltic sounds; palpation did not show any abnormal masses
and painful areas. There was no enlargement of lever or spleen. The Courvoisier sign was
negative. Ascites was not present and palpable lymph nodes were not enlarged.

Question 7 Which hypotheses now remain in the

differential diagnosis to be investigated further?
Physical hepatitis Hemolysis Impaired Biliary tract
examination bilirubin disease
findings conjugation (obstruction)

Dark urine
Loss of appetite
Light colour stool
Palmar erythema
Skin colour
fatigue
Spider naevi
ascites
Lymph edema
Mass enlargement

Bowel sounds
Physical hepatitis Hemolysis Impaired Biliary tract
examination bilirubin disease
findings conjugation (obstruction)

Dark urine + +/- - +

Loss of appetite + + + +/-
Light colour stool +/- _ _ +
Palmar erythema + - - -
Skin colour + + + +
fatigue + + + +
Spider naevi + - - -
ascites +(alcoholic) +/- +/- +
Lymph edema + - + +
Mass enlargement + +/- (splenomegaly) - +

Bowel sounds - + + +
Question 8. Which diagnostic investigations
need to be done to confirm or exclude
remaining diagnoses?
• Lab Testing:
• Urine Test (bilirubin test): measures amount of bilirubin
in the blood.
• Liver Panel Test: also refered as “Liver Function Test”, are
groups of blood test that provides the state of patients
liver. It comprises of : ALT, ALP, AST, Albumin, GGT,
Prothrombin Time, Bilirubin test
• CBC (Complete Blood Count): It is used to evaluate the
level of erythrocytes and hemoglobin.
NON – LABORATORY TESTING
Imaging test and liver biopsy may be used to help in evaluating the
status and structure of liver, gall bladder and pancreas.

Ultra Sound
CT Scan (Computed Tomography)
MRI (Magnetic Resonance Imaging): often including MRCP(magnetic
resonance cholangiopancreatogram) to visualise pancreas and bile duct.
ERCP (Endoscopic Retrograde Cholangiopancreatography): direct
imaging of pancreas and bile duct.
Liver Biopsy
Question 9. Try to estimate what the
investigations cost in terms of burden for the
patient and cost for the hospital.
Ultrasound (100$)
Computerized tomography (CT ) Scan {300- 550 $}
Percutaneous transhepatic cholangiography (PTC) {200-300$}
Endoscopic retrograde cholangiopancreatography (ERCP),(3000-5000$)
Abdominal sonography is a valuable screening test in the jaundiced patient [100-
300$]

(The cost of the tests at hospitals varies from country to country and based on the
sectors as for private or government .)
Stage IV - Results of diagnostic tests
Hand-out 3 (shown on the screen and read out loud)
Full blood count:
• Hb - 10.1 (normal range in adult men: 8.5-11.1 mmol/L)
• Ht - 0.43% (normal range in adult men: 40.7 - 50.3%)
• MCV - 91 fL (85-98 fL).
Liver biochemistry:
• Total Bilirubin (TB) - 47 µmol/L (micromole/L) (normal range - 5.0-17.0);
• Direct (conjugated) Bilirubin (DB) - 4 µmol/L (normal range - 0.0-3.4).
• ALT - 24 (normal range - 7 to 55 U/L (units per liter))
• AST – 32 (normal range - 8 to 48 U/L)
• ALP (Alkaline Phosphatase) - 49 (normal range - 45 to 115 U/L)
• Albumin – 4.0 (normal range - 3.5 to 5.0 g/dL (grams per deciliter))
• PT – 11 (normal range - 9.5 to 13.8 seconds)
•Viral markers:
• IgM- anti-HAV (hepatitis A), HbsAg (hepatitis B), anti HCV (hepatitis C) – All
Negative
•Urine biochemistry:
• Bilirubin – 0 (normal range - 0)
• Urobilinogen – 2 (normal range <17 umol/l)

Question 10 Interpret the findings from the diagnostic tests. How much
certainty do they give about the hypotheses? What does normal serum
alkalinephosphatase indicate?
•Hyperbilirubinemia is noted and unconjugated bilirubin is extremely
high
•A normal haemoglobin level but low hematocrit level shows the
possibility of a haemolytic disorder, bleeding, or anemia.
•Normal serum alkalinephosphatase indicate more probability of pre-
hepatic jaundice like- hemolytic or gilbert syndrome.
•Viral markers are negative so possibility of hepatitis can be excluded.
•Prothrombin time is in normal range which is mostly seen in pre-
hepatic jaundice
Question 11. Which diagnosis prevails now?
There are several chronic hyperbilirubinemic conditions
Crigler–Najjar syndrome types I and II,
Gilbert's syndrome,
Dubin–Johnson syndrome

Noting the increase in unconjugated bilirubin without urobilinogen or darker stools and all
the other above mentioned signs and symptoms indicate more towards gilbert’s syndrome
than any other possibility of jaundice
Question 12 Given this diagnosis and patient
circumstances, which therapy or policy for care is now
indicated? What is the prognosis if the patient is
treated? What if the patient would not be treated?
 Gilberts syndrome
• Gilberts syndrome is an inherited (genetic) liver
disorder that affects the body's ability to process
bilirubin. People with Gilberts syndrome don't
produce enough liver enzymes to keep bilirubin at a
normal level.
• Gilbert’s syndrome doesn’t always cause noticeable
symptoms. In fact, 30 percent of people with Gilbert’s
syndrome may never have any symptoms. Some
people with Gilbert’s syndrome never even know they
have it. Often, it’s not diagnosed until early
adulthood.
What causes it ?
It’s caused by a mutation in the UGT1A1 gene. The gene normally controls an enzyme
that helps break down bilirubin in your liver. When you have an ineffective gene, your
blood contains excess amounts of bilirubin because your body doesn't produce enough
of the enzyme.

How is it diagnosed ?
Gilberts syndrome can be diagnosed:
by using a blood test to measure the levels of bilirubin in your blood.
Liver function test, when the liver is damaged, it releases enzymes into the blood.
The patient with gilberts syndrome might have jaundice with no other signs or
symptoms of a liver problem .

How is it treated ?
Gilberts syndrome doesn't require treatment. The bilirubin levels in your blood may
fluctuate over time, and you may occasionally have jaundice, which usually resolves on
its own with no ill effects.
However if you have symptoms of jaundice like fatigue or nausea the doctor might
prescribe phenobarbital to help the reduce the total amount of bilirubin in blood .
•Jaundice is a yellowing of the skin and the sclera of eyes that
happens when the body does not process bilirubin properly. It is also known as
icterus.
•Bilirubin is a yellow-colored waste material that remains in the bloodstream
after iron is removed from the blood.
•When bilirubin reaches the liver, conjugation occurs. A substance called
conjugated bilirubin is produced.
•The liver produces bile, a digestive juice. Conjugated bilirubin enters the bile,
then it leaves the body. It is this bilirubin that gives feces its brown color.
•If there is too much bilirubin, it can leak into the surrounding tissues. This is
known as hyperbilirubinemia, and it causes the yellow color in the skin and
eyes.
HEPATITIS
•Viruses that primarily attack the liver are called hepatitis viruses which includes types
A, B, C, D, E, and possibly G. Types A, B, and C are the most common.
•All hepatitis viruses can cause acute hepatitis.
•Viral hepatitis types B and C can cause chronic hepatitis.
•Symptoms of acute viral hepatitis include fatigue, flu-like symptoms, dark urine, light-
colored stools, fever, and jaundice.
Gilbert’s syndrome is a fairly common, mild liver disorder
that is caused by an inherited deficiency of an glucuronyltranferase enzyme
involved in the metabolism of bilirubin.
•The reduced activity of the enzyme glucuronyltransferase which conjugate
bilirubin results in increased unconjugated bilirubin.
•Usually occurs after puberty

The diagnosis can usually be made by clinical history, physical examination,

and blood tests.
•Hemolytic anemia is a
disorder in which red blood
cells are destroyed faster than
they can be made.
•The destruction of red blood
cells is called hemolysis.
•Red blood cells carry oxygen
to all parts of your body.

• inherited conditions, such

as sickle cell
• anemia and thalassemia.
• Stressors such as
infections, drugs,
snake or spider
venom, certain
foods. Toxins
from advanced
liver or kidney
disease.
Diagnosis
TREATMENT
No specific treatment, it depends on the cause of jaundice