Differential Diagnosis of

Increased Bilirubin
Dr. Ruchita Sanghani
1st Year Resident,
Under guidance of:
Dr. Mandakini M. Patel
Head & Professor of Department
Objectives
Definition
Classification
Pathophysiology
Clinical features
Investigations
Approach to diagnosis
Treatment
Case scenarios

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What is Bilirubin?

 A toxic end product of heme degradation

Processed by the liver and excreted in the bile

 A tetrapyrrole pigment

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 Bile Formation and Secretion
 Bile plays a critical role in elimination of
Bilirubin

Excess cholesterol

Xenobiotics

Trace metals such as copper, arsenic, selenium and zinc

 Its detergent action emulsifies dietary fat in the intestinal lumen,

enabling its absorption by the gut.
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 Bilirubin

Major
Phospho
-lipid Components Bile salts
of Bile

Cholesterol

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Bilirubin Production
Total Daily Bilirubin Production (0.3-1.2 mg/dL)

Majority (0.2-0.3 g, 85%) Remaining

Breakdown of senescent  Prematurely destroyed

RBCs by macrophages in erythroid cells in bone
spleen, liver and bone marrow
marrow  Turnover of hepatic
proteins containing
heme groups (e.g.
myoglobin, P-450
cytochromes)
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 Bilirubin Metabolism – Pre-hepatic

(1) Normal bilirubin production from heme (0.2 to 0.3 g/day) is derived primarily from the breakdown of senescent circulating erythrocytes. (2) Extrahepatic bilirubin is
bound to serum albumin and delivered to the liver.

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 Bilirubin Metabolism – Hepatic
Hepatic handling of bilirubin
involves:
• Uptake from the circulation
• Intracellular storage
• Conjugation with glucuronic acid
• Excretion into bile.

(3) Hepatocellular uptake and (4) glucuronidation in the endoplasmic reticulum generates bilirubin monoglucuronides and diglucuronides, which are water soluble and
readily excreted into bile.

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 Bilirubin Metabolism – Post-hepatic

(5) Gut bacteria deconjugate the bilirubin and degrade it to colorless urobilinogens. The urobilinogens and the residue of intact pigments are excreted in the feces, with some
reabsorption and excretion into urine.
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 Classification

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 According to type of Bilirubin:-
Hyperbilirubinemia

Unconjugated Conjugated
Hyperbilirubinemia Hyperbilirubinemia

Excess production of Reduced hepatic Impaired Bilirubin

Bilirubin uptake of UCB Conjugation Liver Cholestasis
damage

Hemolytic Resorption of Ineffective Drug Physiologic Breast milk Genetic

anemias interference jaundice of jaundice deficiency
blood from erythropoiesis with the new of UGT IAI
internal membrane born activity Deficiency of Hepatocellular Impaired bile
haemorrhage carrier β-
e.g. Glucuronidases canalicular Disease flow from duct
system
pernicious Decreased in milk Crigler- membrane obstruction or
e.g. anemia, UGT IAI Najjar transporters autoimmune
alimentary thalassemia Some activity, e.g. viral cholangiopathies
syndrome
tract cases of decreased or drug
types I Dubin-
bleeding, Gilbert excretion induced
and II, Johnson
hematoma syndrome hepatitis,
some syndrome,
cirrhosis
cases of Rotor
Gilbert syndrome
syndrome

UGT IAI, Uridine diphosphate-glucuronyltransferase family, peptide AI.

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According to site of disease
a) Pre-hepatic (Isolated hyperbilirubinemia)

b) Hepatic (Hepatocellular conditions)

c) Post-hepatic (Cholestatic conditions)

a) Pre-hepatic (Isolated hyperbilirubinemia)

I. Indirect hyperbilirubinemia

II. Direct hyperbilirubinemia (inherited conditions)

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Indirect hyperbilirubinemia
A. Hemolytic disease
1. Intraerythrocytic 2. Extraerythrocytic
• Autoimmune
I. Hereditary • Isoimmune
• RBC membrane • Alloimmune
disorders(spherocytosis) • Physical trauma
• Disorders of glycolysis • Prosthetic valve
(enzyme deficiencies) • Burns
• Chemical trauma (dapsone)
• Haemoglobinopathies.
• Infections (malaria)
II. Acquired • Toxic factors
• Dyserythropoietic states (B12 • Inflammations
and folate deficiency) • Neoplasms.

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I. Indirect hyperbilirubinemia
B. Ineffective erythropoiesis
C. Increased bilirubin production
1. Massive blood transfusion
2. Resorption of hematoma
D. Drugs
1. Rifampicin
2. Probenecid
3. Ribavirin
4. Protease inhibitors (Atazanavir, Indinavir)
E. Inherited conditions
1. Crigler-Najjar types I and II
2. Gilbert’s syndrome

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II. Direct hyperbilirubinemia (inherited
conditions)
A. Dubin-Johnson syndrome

B. Rotor syndrome

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b) Hepatic (Hepatocellular conditions)
A. Viral hepatitis E. Environmental toxins
1. Hepatitis A, B, C, D, and E 1. Vinyl chloride
2. Epstein-Barr virus 2. Jamaica bush tea—pyrrolizidine
3. Cytomegalovirus alkaloids
4. Herpes simplex virus 3. Kava Kava
B. Alcoholic hepatitis 4. Wild mushrooms—Amanita
C. Chronic liver disease and cirrhosis phalloides, A. verna
D. Drug toxicity
1. Predictable, dose-dependent (e.g., F. Wilson’s disease
acetaminophen)
2. Unpredictable, idiosyncratic (e.g.,
isoniazid) G. Autoimmune hepatitis
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c) Post-hepatic (Cholestatic conditions)
I. Intrahepatic

II. Extrahepatic

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 I. Intrahepatic
A. Viral hepatitis
1. Fibrosing cholestatic hepatitis—hepatitis B and C
2. Hepatitis A, Epstein-Barr virus infection, cytomegalovirus infection
B. Alcoholic hepatitis
C. Drug toxicity
3. Pure cholestasis—anabolic and contraceptive steroids
4. Cholestatic hepatitis—chlorpromazine, erythromycin estolate
5. Chronic cholestasis—chlorpromazine and prochlorperazine
D. Primary biliary cholangitis
E. Primary sclerosing cholangitis
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I. Intrahepatic
F. Vanishing bile duct syndrome L. Benign postoperative cholestasis
1. Chronic rejection of liver transplants
2. Sarcoidosis
M. Paraneoplastic syndrome
3. Drugs N. Veno-occlusive disease
G. Congestive hepatopathy and ischemic O. Graft-versus-host disease
hepatitis P. Infiltrative disease
H. Inherited conditions 1. Tuberculosis
4. Progressive familial intrahepatic cholestasis 2. Lymphoma
5. Benign recurrent intrahepatic cholestasis 3. Amyloidosis
I. Cholestasis of pregnancy
Q. Infections
J. Total parenteral nutrition 4. Malaria
K. Nonhepatobiliary sepsis 5. Leptospirosis

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II. Extrahepatic
A. Malignant B. Benign

1. Cholangiocarcinoma 1. Choledocholithiasis
2. Pancreatic cancer 2. Postoperative biliary strictures
3. Gallbladder cancer 3. Primary sclerosing cholangitis
4. Ampullary cancer 4. Chronic pancreatitis
5. Malignant involvement of the 5. AIDS cholangiopathy
porta hepatis lymph nodes 6. Mirizzi’s syndrome
7. Parasitic disease (ascariasis)

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 Patho - physiology
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Pathophysiology of Hyperbilirubinemia
 S. Bilirubin levels in normal adult vary between 0.3-1.2 mg/dL
 Rate of bilirubin production = Rate of hepatic uptake, conjugation
and biliary excretion
 Jaundice become evident when the S. Bilirubin levels rise above 2-
2.5 mg/dL.
 Depending on the underlying etiology, the elevation can
predominantly involve unconjugated (indirect) or conjugated (direct)
bilirubin.

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Pathophysiology of Hyperbilirubinemia
 Excess bilirubin production (e.g., due to hemolytic anemia or ineffective
erythropoiesis) or defective conjugation (due to immaturity or hereditary causes) leads
to the accumulation of unconjugated bilirubin.
This form is largely insoluble and cannot be excreted in the urine.
Although most unconjugated bilirubin is tightly bound to albumin in the blood, at
excessive levels the unbound fraction rises and may diffuse into tissues, particularly the
brain in infants, and produce neurologic damage (kernicterus).
Conjugated hyperbilirubinemia most often results from hepatocellular disease, bile duct
injury, and biliary obstruction.
Since this form is water-soluble and loosely bound to serum albumin, it can be excreted
in the urine.

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Difference between Conjugated and
unconjugated bilirubin
Features Unconjugated bilirubin Conjugated bilirubin

Normal Serum level More Less

Water solubility Absent Present

Affinity to lipids Present Absent

Serum albumin binding High Low

Van den bergh reaction Indirect Direct

Renal excretion Absent Present

Affinity to brain tissue Present Absent

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 New born
Jaundice
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Neonatal Jaundice
• Neonatal jaundice is a yellowish discoloration of the white parts of eyes
and skin in a newborn baby due to high bilirubin levels
• Neonatal jaundice is the most common condition requiring medical
evaluation in a newborn.
• Symptoms of neonatal jaundice are yellowish discoloration of skin, sclera,
poor feeding etc.
• 50-60% of all newborns are jaundiced in the first week of life
• Two types of neonatal jaundice:
1. Physiological jaundice
2. Pathological jaundice
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 1. Physiological Jaundice
• It is seen during first week of life.
• Physiologic jaundice is caused by the inability of the newborn's immature
liver to metabolize (conjugate) and thus excrete bilirubin, which accumulates
due to the breakdown of red blood cells which have a shorter life-span (70 to
90 days) than adult red blood cells (120 days). This increase in red blood cell
breakdown and decreased ability to metabolize bilirubin overwhelms the
newborns ability to properly process and excrete bilirubin. As the newborn's
liver matures, however, the jaundice eventually disappears after 1 to 2 weeks.
• Total serum bilirubin peaks at age of 3-5 days.
• Mean peak total bilirubin is 6 mg/dL
• It is normal physiology and requires no treatment.

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2. Pathological jaundice
• When jaundice is
- seen in first 24 hours or persists more than 1 week
- Direct bilirubin more than 2 mg/dL
- Bilirubin rising faster than 5 mg/dL in 24 hours
- yellowish discoloration of hands and feets
It is known as Pathological Jaundice.

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Causes of pathological jaundice are :

1. ABO Incompatibility(most common)

2. Breast Feeding Jaundice
3. Breast milk Jaundice
4. Sepsis
5. Cephalhematoma
6. Hereditary Syndromes (e.g. Gilbert syndrome, Crigler-Najjar syndrome
7. Hereditary Anemias (e.g. G6PD defi., Sickle cell anemia, thalassemia
8. Total Parenteral Nutrition
9. Biliary track atresia
10. Metabolic disease like Galactosaemia, Alpha 1 anti-trypsin deficiency
11. Reye’s syndrome
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• Breastfeeding jaundice :
- Also known as “Lack of breast milk jaundice”.
- This form of jaundice occurs when the breastfed newborn does NOT receive adequate breast milk
intake. This may occur because of delayed or insufficient milk production by the mother or
because of poor feeding by the newborn. This inadequate intake results in dehydration and fewer
bowel movements for the newborn, which results in decreased bilirubin excretion from the body.
- Treated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk
production.

• Breast milk jaundice :

- This form of jaundice occurs in breastfed newborns and often appears at the end of the first
week of life. Certain chemicals in breast milk are thought to be responsible (e.g. 3 alpha 20 beta
pregnanediol, epidermal growth factor etc) It is usually a harmless condition that resolves
spontaneously. Mothers typically do not have to discontinue breastfeeding.

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Hereditary Syndromes associated with
Jaundice:
1. Gibert’s Syndrome
2. Crigler-Najjar Syndrome 1 & 2
3. Dubin Johnson Syndrome
4. Rotor syndrome

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 Glucoronyl
transferase

Defect in this enzyme

leads to “Gilbert’s
Syndrome & Crigler-
Najjar Syndrome 1&2”
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 When defect is in
Bilirubin Glucoronide
Excretion, it leads to
“Dubin - Jhonson
Syndrome”

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Treatment for neonatal jaundice

• It includes:
1. Phototherapy
2. Exchange transfusion

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 Diagnosis

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 Signs & symptoms

Physical examination

 Investigations

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Signs & symptoms
 Icterus
• Yellowish pigmentation of Sclera, Skin
and Mucous membranes.
• This condition is also termed as
JAUNDICE.
• French word jaune meaning yellow.
• Yellow discoloration will be because of
accumulation of Bile Pigments in the
Sclera, Mucous membranes, Skin, Nails.
• Bile pigments have affinity to tissues
containing ELASTIN .
• More appropriate to be considered as a
symptom rather than a disease.

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Signs & symptoms
Fatigue Clay coloured stool
Weakness Fever
Pruritus Flu-like symptoms:
Abdominal pain • Nasal congestion
• Sorethroat
Nausea and vomiting • Cough
Arthropathy • Headache
Diarrhoea/constipation • Chills
• Myalgia

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Physical examination
• Yellowish discolouration:
• Skin
• Mucous membranes
• Scleral tissue(rich in elastin and has high affinity for bilirubin)
• Nail
• Urine
• Rashes
• Over extensor surface of arm and forearm
• Over abdomen(centripetal)
• Stool
• Clay coloured

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Investigations
1. Laboratory investigations
2. Radiological investigation
3. Serological tests
4. Liver Biopsy

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1. Laboratory investigations
a) Complete Blood Count:
It will be helpful in diagnosing various anemias associated with
jaundice.
Low hemoglobin value and poikilocytosis associated with various
hemolytic anemias like:
• Sickle Cells - sickle cell anemia
• Tear drop cells also known as dacryocytes - Thalassemia
• Spherocytes - Herediatary spherocytosis, ABO incompatibility of new born,
autoimmune hemolytic disease
• Schistocytes (fragmented RBCS) – Intravascular hemolysis

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 • Target Cells (Mexican hat cells) – Various Hemoglobinopathies, Obstructive
jaundice
• Acanthocytes ( cells with irregularly placed sharp projection) – in liver disease
• Blister cells (Hemi ghost cells) – G6PD deficiency
• Elliptocytes – Herediatry Eliptocytosis, thalassemia
• Stomatocytes ( Mouth cells) – alcoholic liver disease
• Leptocytes (Thin cell, wafer cell – thin, flat cells with hemoglobin at periphery) –
thalassemina, obstrutive liver disease
• Various Red Cell inclusions can be seen:
 Basophilic stippling – Thalassemia, Liver disease
 Howel Jolly body – Thalassemia, hemoglobinopathies
 Cabot’s ring – Ineffective erythropoiesis (e.g. Pernicious anemia)
 Nucleated RBCs – Hemolytic disease like Sickle cell disease
• In case of inflammation of biliary tree or liver WBC counts will be raised.

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 b) Urine Bilirubin:
- Simple test to determine whether hyperbilirubinemia is conjugated or unconjugated type
is to determine if bilirubinuria is present or not since its absence suggests unconjugated
hyperbilirubinemia as unconjugated bilirubin is not filtered by glomerulus.
There are many tests which are helpful in diagnosing bilirubinuria :
- Foam test
- Gmelin test
- Lugol iodine test
- Fouchet’s test:
This is simple and sensitive test.
Method: Take 5 ml of urine in test tube, add 2.5 ml of 10% of barium chloride, and mix well. Precipitate of Barium sulfate-bilirubin
complex will appear. Now filter to obtain precipitates. Now add 1 drop of Fouchet’s reagent (Consist of 25 g of trichloroacetic acid,
10 ml of ferric chloride, and distilled water 100 ml). Immediate development of blue-green color indicated presence of bilirubin.

- Reagent strip:
This tests are commonly done nowadays. These tests are based on reaction of bilirubin with diazo-reagent and
color change which is proportional to concentration of bilirubin.

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c) Urobilinogen:
There are 2 tests which are helpful for detection of
urobilinogen
a.) Ehrlich’s aldehyde test: This test is based on principle
that ehrlich’s reagent (p-dimethylaminobenaldehyde) reacts
with urobilinogen in urine to produce pink color.

b.) Reagent strip method

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d) LFT

Tests based on EXCRETORY Functions

• Bile salts
• Bilirubin – Total, Direct & Indirect
Tests based on serum ENZYMES of Liver
• ALT • ALP
• AST • GGT
Tests based on SYNTHETIC activity
• Prothrombin Time
• Albumin

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 Bile Salts
 Formed by conjugation of bile acids with taurine or glycine.

Predominant – Cholic acid & Chenodeoxycholic acid

Detected by Hay’s sulphur test

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 Serum Bilirubin
There is 2 methods for estimation of serum bilirubin:
a.) Diazo method: By this method direct and total bilirubin can be
measured & indirect bilirubin is obtained by subtracting direct from
total bilirubin.
- This method measures bilirubin by Van den Bergh reaction.

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 Van den Bergh reaction is a chemical reaction used to
measure bilirubin levels in blood. More specifically, it determines
the amount of conjugated bilirubin in the blood. The reaction
produces azobilirubin.
- Principle of this method is - bilirubin reacts with
diazotised sulphanilic acid to produce purple coloured azo bilirubin
and than spectrophotometrically this azobilirubin is measured.

Van den Bergh reaction??

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 b.) Direct Spectroscopic estimation:
- This method is used for measurment of total serum bilirubin in
newborns and infants.
Principle: Concentration of serum bilirubin is directly proportional to
its absorbance in spectrophotometer at 454 nm.
- This method can not be used in older children and adults as their
sera may also contain carotene and other pigments, which absorb
light at the same wavelength.

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 ALT=ALAT=SGPT
 Alanine Transaminase = Alanine Aminotransaminase = Serum
Glutamic Pyruvic Transaminase

 ALT – Viral Hepatitis, Liver damage, Bile duct pathology, Diabetes,

CCF, IM, Myopathies, NSAIDs, Antibiotics, Anti-convulsant,
Antipsychotics

 ALT+ ALP – Bile duct pathology

 ALT + CK Enzyme - Myopathies
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 AST=ASAT=SGOT
 Aspartate Transaminase = Aspartate Aminotransaminase = Serum
Glutamic Oxaloacetic Transaminase
 Found in Liver, Heart, Skeletal muscle, Kidneys, Brain, Pancreas,
Lungs, WBCs and RBCs.
 AST – MI, Hepatitis, Ac. Pancreatitis, Ac. Hemolytic Anaemia, ARF,
Trauma, Musculoskeletal diseases, Burns.

ALT is more specific indicator of Liver inflammation than AST

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 ALP – ALKALINE PHOSPHATASE
 Present in most tissues, richest being in Bone osteoblasts, Bile
canaliculi, S I Epithelium, PCT of Kidneys, Placenta, Lactating breasts.
 Adults – mainly derived from Liver.
 In Infancy, Childhood, Rickets, Paget’s disease, Fractures, Bone
cancers – mainly derived from Bones.
 ALP – Post Menopausal women on HRT, Pernicious Anaemia,
Aplastic Anaemia, CML, Cretinism, Wilson’s disease.

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 ALP – ALKALINE PHOSPHATASE
 ALP – Primary Hypothyroidism, Hyperthyroidism, Hodgkin’s
Lymphoma, Polycythemia Vera, IM, DM, CCF, Amyloidosis.
Ca – Liver, Breast, Colon, Lung, Pancreas.
Almost all Liver disorders – such as – Hepatitis, Cholecystitis,
Cholangitis, Cholestasis, Tumours, Cirrhosis, etc.

 LOOK FOR GGT & 5’-NUCLEOTIDASE

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 gGT
 γ-glutamyl transferase
 Present in cell membranes of many tissues – Liver, Bile duct, Gall
bladder, Kidneys, Pancreas, Spleen, Heart, Brain, Seminal vesicles.
 Isolated or disappropriate elevation – ALD
 GGT – Diseases of Liver, Biliary tract, Pancreas and also in MI.

 GGT has better sensitivity than ALP in biliary tract diseases.

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SERUM ALBUMIN
 Produced in Liver
 Half of the serum proteins
 Oncotic pressure, Carrier protein
 in – Chronic Liver diseases – Cirrhosis, Renal disorders, Burns,
Pregnancy.
 in – Severe or chronic Dehydration, high protein diet.

 IMP. IN CHRONIC CONDITIONS…

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PROTHROMBIN TIME
 Except factor VIII all others are synthesized in the Liver by
hepatocytes
 Factors II, VII, IX, X are Vit-K dependant
 Vit-K – Fat soluble vitamin
Prognostic tool
An elevated prothrombin time indicates either vitamin K deficiency due to
prolonged jaundice and malabsorption of vitamin K or significant hepatocellular
dysfunction.
This also helps in differentiation of both these disease – if after vitamin k
administration, PT is corrected than it is due to cholestatic liver disease rather than
hepatocellular dysfunction.
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2. Radiological investigations:
a.) Ultrasound:
USG is indicated in following situations:
1. Cholestasis of various etiologies to see dilated
intra and extrahepatic canalicular tree
2. Space occupying lesions within live to determine
they are neoplasms or non-neoplastic cysts.
3. To provide USG guidance for biopsy
b.) CT Scan:
CT scan is also very useful method in diagnosing
carcinoma, biliary cirrhosis, bile duct tumours etc

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c.) Endoscopic retrograde cholangiopancreatography (ERCP):
• In this method dye is injected in through endoscope in common bile duct and then
imaging is done.
• It is performed to diagnose conditions of the pancreas or bile ducts(e.g. cancer of
head of pancreas, bile duct atresia etc) and also to treat those conditions.
d.) Percutaneous transhepatic cholangiogram (PTCA):
• It is an x-ray of the bile ducts after injecting dye through skin in to liver.
• This test can help to diagnose the cause of bile duct blockage.

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3. Serological tests
• If no concern for obstructive jaundice:
• Viral (Hep B&C) serologies for viral hepatitis
• Anti-mitochondrial Ab (PBC)
• Anti-smooth muscle Ab (Auto-immune)
• Iron studies (Hemochromatosis)
• Ceruloplasmin (Wilson’s)
• Alpha-1 anti-trypsin activity (for deficiency)

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4. Liver Biopsy
• Liver Biopsy is a procedure in which a small piece of liver
tissue is removed and examined microscopically to determine
the cause and severity of disease.
• Indications:
1. Acute hepatitis of unknown cause
2. Chronic liver disease
3. Diagnosis and grading of alcoholic liver disease
4. accurate staging of advanced cases of primary biliary
cirrhosis etc.

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 • Methods of obtaining liver biopsy:

1. Percutaneous liver biopsy

- Percutaneous Blind liver biopsy
- Percutaneous guided liver biopsy
- Percutaneous plugged liver biopsy
2. Transvenous liver biopsy
3. Laproscopic liver biopsy

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1. Intrahepatic Cholestasis:
- In intrahepatic cholestasis reveales milder degree of cholestasis than
the extrahepatic disorders.
- The biliary canaluculi of the hepatocytes are dilated and contain
characteristic elongated green brown Bile Plugs.
- Cytoplasm of affected hepatocytes shows feathery degeneration.
2. Extrahepatic Cholestasis :
- In case of extrahepatic cholestasis shows marked changes of cholestasis.
- Since the obstruction is in the extrahepatic bile ducts, there is
progressive retrograde extension of bile stasis into intrahepatic duct
system. This is results in dilatation of bile ducts and rupture of canaliculi
with extravasation of bile producing Bile Lakes.

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Approach to the Patient:
JAUNDICE
Initial Evaluation: History
• History: In history Colicky pain in right quadrant of sudden
onset suggests Choledocholithiasis
- History of arthralgia, myalgia predating jaundice suggests
hepatitis either viral or drug induced
- In case of alcoholic liver disease patient gives typical history of
alcohol consumption since long time
- Color of urine and stool helps in diagnosing conjugated or
unconjugated bilirubinemia
- History of long term use of any medications is seen in case of
drug induced jaundice.
Initial Evaluation: Physical Examination
• In General examination Poor nutritional status , muscle wasting
suggests long standing disease like Cirrhosis or Pancreatic cancer.
• Signs of end stage liver disease (cirrhosis)
• Ascites, splenomegaly, spider angiomata, and gynecomastia
• Jaundice evident first underneath the tongue, also evident in sclerae
or skin
• Courvoisier’s sign = painless, but palpable or distended gallbladder on
examination
• Could indicate malignant obstruction
When the pattern of the liver tests suggests a cholestatic disorder, the
next step is to determine whether it is intra- or extrahepatic cholestasis

• Appropriate test is an ultrasound

• Biliary dilatation indicates extrahepatic cholestasis – SURGICAL
JAUNDICE
• Absence of biliary dilatation suggests intrahepatic cholestasis
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 Treatment
• Treatment mainly depends on the cause of the underlying condition leading to jaundice and any
potential complication related to it.
• Symptomatic treatment includes –
- Rest
- High protein diet
- Medical treatment with intravenous fluids, medications, antibiotics

• Treatment according to cause of jaundice:

1. Hepatocellular jaundice is treated with anti- viral medications and steroids along with
supportive treatment.

2. In case of Hemolytic Jaundice – anemia is treated with blood transfusion in case of thalassemia,
sickle cell anemias. Supportive treatment with iron supplements is also helpful
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3. Obstructive jaundice is treated with surgery to remove the obstruction like
stent placement, cholecystectomy etc according to cause of jaundice - followed
by medication

4. For medication induced jaundice – causative medications should be

discontinued and alternative medicines are prescribed.

5. In case of alcoholic liver disease alcohol consumption must be stopped or

reduced and high protein diet or nutritious diet should be started.

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 Case Scenario

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 Case – 1
• 40 years old, fat female, presents with intolerance to fatty foods, pain in the right side of
abdomen, yellowing of eyes and passage of clay colored stool.
• Laboratory data:
Total Bilirubin – 20 mg%
Direct Bilirubin – 16 mg%
ALP – 800U
SGPT – 90 IU/L
Urine: color – deep yellow
Bilirubin – present
Urobilinogen – absent
Stool: Clay colored
stercobilinogen – absent
Probable Diagnosis????
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 Obstructive jaundice due to Gall Stones

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Case – 2
• A 50 years old woman had 8 day history of loss of appetite, nausea and flu like
symptoms. She had noticed that her urine had been dark color over the past
two days. On examination she had tenderness in the right upper quadrant
• Laboratory Investigation:
Serum total bilirubin – 4.5 mg%
Direct Bilirubin – 2.5 mg%
Indirect bilirubin – 2.0 gm%
Serum AST – 40 IU/L
Serum ALT – 115 IU/L
Serum ALP – 20 units
What is probable diagnosis??????
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 Viral Hepatitis

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Case – 3
• Rh negative mother delivers a baby who develops jaundice immediately after birth
• General examination revels:
Heart rate 80/min
Icterus +
Irritability +
Liver – Papable
• Laboratory investigations
Serum Bilirubin Total – 10 mg%
Indirect – 7 mg%
Direct – 3 mg%
Alkaline Phosphatase – 50 U/L
Urine: Urobilinogen +
Feces: Stercobilinogen +
What is your likely diagnosis ??????
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 Hemolytic jaundice due to Rh Incompatibility

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 Hyperbilirubinemia

Unconjugated Hyperbilirubinemia Conjugated Hyperbilirubinemia

Bilirubin accumulation Bilirubin Conjugation Liver damage Cholestasis

Hemolysis Dyserythropoiesis E.g. Gillbert Syndrome E. g. Hepatitis E.g. Gallstones

Pathogenesis: Prehapatic Intrahepatic Extrahepatic
Laboratory findings: Prehapatic Intrahepatic Extrahepatic
Indirect bilirubin: ++ + Normal
Direct bilirubin: Normal + ++
Urinary bilirubin: - + +
Urinary urobilinogen: + Normal Normal/+ Low
AST, ALT: Normal ++ Normal/+
AP, ƴ-GT: Normal + ++
Other findings: Hb , Reticulocytes Hb , Reticulocytes Medical History Clinical findings Abdominal
Ultrasound

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References:
1. Robins Basic pathology – Kumar Abaas Aster(10th edition)
2. Textbook of Pathology – Harsh Mohan (7th edition)
3. Essentials of Clinical Pathology – Shirish M Kawthalkar ( 2nd
edition)
4. Harrison’s principles of Internal Medicine - Jameson Fauci Kusper
Hauser Longo Loscalzo (20th edition)
5. Henry’s clinical diagnosis and management by laboratory methods
- Mc Pherson , Pincus (23rd edition)

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 THANK YOU
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