Jaundice

A Presentation by SS-32
Muhammad Shoyab
Tahmina Sultana Rumi
Asim Kumer Das
5th Year MBBS
Sir Salimullah Medical College
Mitford, Dhaka
15 June 2009

WHY JAUNDICE?

WHY
AGAIN
JAUNDICE?

Jaundice is shrouded
in misconceptions
and superstitions

Definition
Jaundice may be defined as
yellowish discoloration of the
sclera,
skin
and
mucous
membranes.

Guyton

Clinical Classification
Clinical jaundice

> 3 mg / dL
(> 51 mol / L)

Latent jaundice

1 3 mg / dL
(17 51 mol / L)

Normal serum bilirubin upto 1 mg / dL

(17 mol / L)
Conjugated
0.1 0.4 mg / dL
Unconjugated
0.2 0.7 mg / dL
Kumar & Clark | Samson Wrights

Bilirubin Metabolism

Cecil

Mechanisms of
Hyperbilirubinaemia

Excess production

Reduced hepatocellular uptake

Impaired conjugation
Decreased secretion from
hepatocyte into bile canaliculi

Impaired bile flow

Robbins

Classification of Jaundice
Haemolytic / Pre-hepatic

Reduced hepatocellular uptake

Impaired conjugation
Decreased secretion from
hepatocyte into bile canaliculi

Impaired bile flow

Hepatocellular

Excess production

Obstructive / Post-hepatic

Classification of Jaundice
Excess production
CONJUGATED

Reduced hepatocellular uptake

Impaired conjugation
Decreased secretion from
hepatocyte into bile canaliculi
UNCONJUGATED

Impaired bile flow

Classification of Jaundice
Excess production

Haemolytic / Pre-hepatic

Reduced hepatocellular uptake

Impaired conjugation
Decreased secretion from
hepatocyte into bile canaliculi

Hepatocellular

CONJUGATED

UNCONJUGATED

Impaired bile flow

Obstructive / Post-hepatic

Bilirubin
UNCONJUGATED

CONJUGATED

Insoluble in water
Tightly bound to
albumin
Cannot be
excreted in urine
Deposited in
tissues, with
special affinity to
lipids (hence
kernicterus)

Soluble in water
Weakly bound to
albumin
Can be excreted in
urine
Elevation for
prolonged periods
allows it to bind
tightly with albumin
Robbins | www.drsarma.in

Aetiology of Jaundice
PRE-HEPATIC

UNCONJUGATED

Haemolytic Disorders
Spherocytosis
Sickle cell anaemia
Thalassaemia
Haemolytic disease of the newborn
Autoimmune haemolytic anaemia
Microangiopathic haemolytic anaemia
Paroxysmal nocturnal hemoglobinuria
Cecil | Cuschieri | Harrison

Aetiology of Jaundice
HEPATOCELLULAR

CONJUGATED

Viral Hepatitis
Hepatitis A, B, C, D, E
Epstein-Barr virus
Cytomegalovirus
Herpes simplex virus

Alcoholic Liver Disease

Drug-induced Liver Disease
Paracetamol, Alpha-methyldopa, Isoniazid
Allopurinol, Ketoconazole, Chlorpromazine
Methotrexate, Phenytoin, Halothane
Harrison

Aetiology of Jaundice
HEPATOCELLULAR

CONJUGATED

Environmental Toxins
Aflatoxin
Carbon tetrachloride

Autoimmune Hepatitis
Congenital
Dubin-Johnson Syndrome
Rotors Syndrome
Gilbert's syndrome
UNCONJUGATED
Crigler-Najjar Syndrome

Neonatal jaundice

Cecil | Cuschieri | Davidson

Aetiology of Jaundice
POST-HEPATIC

CONJUGATED

Intrahepatic Cholestasis
Primary biliary cirrhosis
Primary sclerosing cholangitis
Cholestasis of pregnancy
Total parenteral nutrition
Benign postoperative cholestasis
Paraneoplastic syndrome

Harrison

Aetiology of Jaundice
POST-HEPATIC

CONJUGATED

Extrahepatic Cholestasis
Gallstones
Tumors of the head of the pancreas
Gallbladder cancer
Periampullary tumors
Portal lymphadenopathy
Congenital biliary atresia
Choledochal cysts
Infectious cholangiopathy (Leptospira,
Clonorchis sinensis, Ascaris lumbricoides,
Fasciola hepatica)
Cecil

At a Glance

Haemolytic
Jaundice

Haemolytic Jaundice
Mild
anaemia

Recurrent, mild jaundice

Positive
family
history
History of recurrent
blood transfusion
Short Cases, ABM A | ACP Board Review

Haemolytic Jaundice
CONTD . . .

Mongoloid facies

Hepatosplenomegaly
ACP Board Review

Haemolytic Jaundice
CONTD . . .

Serum bilirubin not

above 6 mg / dL
Microcytic
hypochromic
anaemia
Evidence of
haemolysis
Liver function tests
normal
No bilirubin in urine

Harrison

Haemolytic Jaundice
CONTD . . .

Prolonged
elevation of
unconjugated
bilirubin may lead
to kernicterus

B&L

Hepatocellular
Jaundice

Hepatocellular Jaundice
Anorexia, nausea
vomiting
Mild fever

Moderate jaundice

ACP Board Review | Macleod

Hepatocellular Jaundice
CONTD . . .

Enlarged tender
liver

Signs of chronic
liver disease may
be present

Hepatocellular
Jaundice CONTD . . .
Marked rise of
serum alanine
aminotransferase
(ALT)
Bilirubin appears
in urine

Obstructive
Jaundice

Obstructive
Jaundice
Deep jaundice
Pale, bulky,
frothy, sticky,
foul-smelling
stool

Dark urine
Itching

Obstructive
Jaundice CONTD . . .
Right
hypochondriac
tenderness
Gall bladder
may be palpable

Obstructive
Jaundice CONTD . . .
Marked rise of
serum alkaline
phosphatase
(ALP)
Bilirubin
appears in urine
No urobilinogen
in urine

More About
Viral Hepatitis

Sequelae of HBV Infection

100%

Subclinical Disease (65%)

Recovery

99%

Acute Hepatitis (25%)

Fulminant
Hepatitis

1%

Healthy Carrier (5%)

Persistent
Infection (4%)
10-33%

70-90%

Recovery
Cirrhosis

Death

20-50%

10%

Chronic Hepatitis
HCC
Robbins

Prevention of HBV Infection

Screen blood
donors
Health

Avoid sharing
needles, razors,
tooth brushes

education

Disinfection of

Use barrier

surgical and

contraceptive
Immunisation

laboratory
articles

HBV Immunisation
Active (preexposure HBsAg)
Patient requiring
repeated blood
transfusion
IV drug abuser
Homosexual male
Sex worker
Baby of HBV mother
Patient on dialysis
Medical, paramedical
and laboratory staff
Spouse of HBV
carrier

Passive (postexposure HBIg)

Surgeons, nurses
Laboratory

technicians
Newborn of carrier
mother
Sexual contacts of
HBV patients

Why is HCV More Dangerous?

Clinical features are less prominent
Hepatic enzyme levels unreliable

More chronicity
More chance of malignant
transformation
No vaccine available

When to admit
Jaundice alone is not criteria
for admission

If liver failure present or

suspected extrabiliary
compression then admit

Surgery consult if obstructive

Evaluation of a
Jaundiced
Patient

Approach to Jaundice
How to clinically evaluate the
patient?
What tests will help us in D.D?
What imaging modalities will be
useful?

How to monitor the progress ?

www.drsarma.in

Algorithm for Jaundice

JAUNDICE
YOUNG
Risk of hepatitis

Liver Biochemistry

VIRAL MARKER

History
Examination

OLDER
No risk of hepatitis
Weight Loss

ULTRASOUND

Liver Biochemistry
Viral marker

+ ve

ve
Viral
Hepatitis

Re-check drug history

Autoantibodies
Liver biopsy

CBD
dilated

SOL

+ ve

ve

CBD OK
Biliary
Obstruction

MRCP / ERCP

Viral
Hepatitis
Biopsy

K&C

History
Pain
Fever
Confusion
Weight loss
Sex, drugs
Alcohol
Pruritus
Malaise,
myalgias
Oedema

Dark urine
Abdominal girth
Other
autoimmune
disease
HIV status
Prior biliary
surgery
Family history of
liver disease

Important Clues From

History

Duration of jaundice Acute / Chronic

Abdominal pain vs painless jaundice
Fever Viral / bacterial / sepsis
Arthralgia, rash, glands; Pruritus obstructive
Appetite Hepatocellular / Malignancy
Weight loss Malignancy CAH
Colour of stools chalky white obstructive
Family history Hemolytic Inherited dis.
H/O transfusion, promiscuity, IDU
Alcohol abuse, Medications INH, EM,
Largactil
www.drsarma.in

Examination

BP / HR / Temp
Mental status
Asterixis
Abdominal
tenderness
Liver size
Splenomegaly
Ascites
Oedema

Spider angiomata
Hyperpigmentation
Kayser-Fleischer
rings
Xanthomas
Gynecomastia
Virchows left
supraclavicular
lymphadenopathy

Investigations
AST, ALT, ALP
Serum bilirubin
Serum albumin
Prothrombin
time
Blood glucose
Na-K-PO4, acidbase
Acetaminophen
level

CBC / platelet
Ammonia
Viral serologies
ANA-ASMA-AMA
Quantitative Ig
Ceruloplasmin
Iron profile
Blood cultures

Imaging
Ultrasound
CT
ERCP
MRCP

PTC

Imaging : USG

98% specific, 90% sensitive for GB stones and

dilated ducts
Portable, cheap, no radiation, no IV contrast

Imaging : CT

Better imaging of the pancreas and abdomen

Imaging : MRCP

Imaging of biliary tree

Useful for duct stones

Imaging : ERCP

Distal biliary obstruction

Brushing and biopsy for malignancy

Liver Function Tests (LFT)

Liver function test

Normal Range

Bilirubin
Total
Conjugated
Alkaline phosphatase

0.1 to 1.0 mg / dL
< 0.2 mg / dL

Aspartate transaminase (AST)

5-31 IU / L

Alanine transaminase (ALT)

5-35 IU / L

Albumin

3.5-5.0 g / dL

Prothrombin time (PT)

12-16 s

25-112 IU / L

www.drsarma.in

Utility of LFT
Test

Utility

ALT

ALT < AST in alcoholism

Albumin

Assess severity / chronicity

Alkaline phosphatase

Diagnosis of Obstructive Jaundice

AST

Early diagnosis of Liver disease,

Follow-up

Bilirubin

Diagnose jaundice and its severity

Gamma-globulin

Diagnosis and follow-up of chronic

hepatitis & cirrhosis

GGT

Diagnosis of alcohol abuse

Prothrombin time (PT)

Assess severity of disease

www.drsarma.in

HBV Serology
HBcAb
HBcAb
HBsAg IgM
HBsAb
IgG
Acute HBV

Resolved HBV

Chronic HBV

HBV vaccinated

Diagnosis of Alcoholic Liver

Disease
The history is the key 60 grams/day
Gynecomastia, parotids, Dupuytrens
Lab clues: AST/ALT > 2, MCV > 94
AST < 300

Anorexia, fever, jaundice,

hepatomegaly

Diagnosis of
Immune-Mediated Liver
Diseases
LFT Serology

Ig

Biopsy

AIH

ALT

ANA
ASMA

IgG

Portal inflammation
Plasmacytes
Piecemeal necrosis

PBC

ALP

AMA

IgM

Bile duct destruction

granulomas

PSC

ALP

none

normal

Periductal concentric fibrosis

Diagnosis of Autoimmune
Hepatitis

Widely variable clinical presentations

Asymptomatic LFT abnormality (ALT and AST)

Severe hepatitis with jaundice
Cirrhosis and complications of portal HTN

Often associated with other autoimmune

diseases
Diagnosis:

Compatible clinical presentation

ANA or ASMA with titer 1:80 or greater
IgG > 1.5 upper limits of normal
Liver biopsy: portal lymphocytes + plasma
cells

Diagnosis of Primary Biliary

Cirrhosis
Compatible clinical presentation
AMA titer 1:80 or greater (95%
sens/spec)
IgM > 1.5 upper limits of normal

Liver biopsy : bile duct

destruction

Diagnosis of Primary
Sclerosing Cholangitis
ERCP (now MRCP)
No autoantibodies, no elevated
globulins

Biopsy: concentric fibrosis around bile

ducts

Treatment of
Jaundice

Principles of Treatment
No specific treatment
Hospitalised for early detection of
fulminant hepatic failure, if at risk
Adequate protein and calorie in
diet

Avoid

hepatotoxic

drugs

sedatives, hypnotics, alcohol)

(e.g.

Principles of Treatment
Bed rest : 3 5 weeks

CONTD . . .

If constipated : lactulose
If diarrhoea : avoid milk and milk
products; maintain hydration

If severe vomiting : glucose and

IV fluid
Psychological support

Acute Viral Hepatitis

Follow the principles of treatment
Special advice for HBV and HCV
patients
Avoid blood donation
Use barrier contraceptive
Screen and vaccinate partner
Check HBsAg after 3 months

Treatment of Chronic HBV

No drug available to eradicate HBV
completely
If HBeAg +ve : pegylated interferon

for 6 months
If HBeAg ve : 12 months
Other options : lamivudine, adefovir,
liver transplantation

Treatment of HCV Infection

Follow the principles of
treatment
-interferon 3 M units thrice

weekly for 1 year

Fulminant Hepatic Failure

Hepatic encephalopathy characterised
by mental changes, confusion, stupor
and coma occurring within 8 weeks of
the precipitating illness, in the
absence of pre-existing liver disease.

Davidson

Causes of Fulminant Hepatic

Failure
Acute viral hepatitis

Hepatotoxic drugs
Toxins
Leptospirosis
Wilsons disease, Budd-Chiari
syndrome
Hepatic malignancies

Clinical Features of
Fulminant Hepatic Failure
Features of
encephalopathy
Features of raised
intracranial
pressure
General features

Clinical Features of
Fulminant Hepatic Failure
Features of
encephalopathy
Features of raised
intracranial
pressure
General features

Confusion,

disorientation,

slurred speech
Flapping tremor
Exaggerated
reflexes, extensor
plantar response
Constructional
apraxia

Clinical Features of
Fulminant Hepatic Failure
Features of
encephalopathy
Features of raised
intracranial
pressure
General features

Headache
Vomiting
Papilloedema
Fixed pupils
Myoclonus
Bradycardia
Profuse sweating

Clinical Features of
Fulminant Hepatic Failure
Features of
encephalopathy
Features of raised
intracranial
pressure
General features

Weakness, nausea,
vomiting
Right
hypochondriac
pain
Jaundice
Foetor hepaticus
Liver : initially
palpable, later not
Ascites, oedema

Treatment of Fulminant
Hepatic Failure
Admission into intensive care unit

Correct encephalopathy
No protein intake
Avoid sedatives, diuretics
High carbohydrate diet

For cerebral oedema : mannitol

Treatment of Fulminant
Hepatic Failure CONTD . . .
Correct hypokalaemia and
hypocalcaemia

To prevent GIT haemorrhage : tablet

ranitidine 150 mg 12 hourly

When to Refer to
Gastroenterologist
Unexplained jaundice
Suspected

obstruction
Acute hepatitis
severe or fulminant
Unexplained
abnormal LFTs
persisting for 6
months or greater
Unexplained

cholestasis

www.drsarma.in

Cirrhosis (in non-

alcoholic) for
consideration of liver
transplant
Suspected hereditary
hemochromatosis
Suspected Wilson's
disease
Suspected
autoimmune hepatitis
Chronic hepatitis C for

consideration of
antiviral therapy

Treatment of Alcoholic Liver

Disease
Abstinence
Nutrition
Prednisolone 40 mg/day x 28
days
contraindications: infection, renal
failure, GI bleeding

Pentoxifylline 400 mg PO tid x

28 days

Hepatotoxic Drugs
Hepatocellular
Paracetamol, INH, methyldopa, MTX

Cholestatic
chlorpromazine, estradiol, antibiotics

Chronic Hepatitis
methyldopa, phenytoin

Hypersensitivity Reaction
Phenytoin, allopurinol

Paracetamol Toxicity
Danger dosages (70 kg patient)
Toxicity possible > 10 gm
Severe toxicity certain > 25 gm
Lower doses potentially hepatotoxic
in:
Chronic alcoholics
Malnutrition or fasting
Dilantin, Tegretol, phenobarbital, INH,
rifampin
NOT in acute EtOH ingestion
NOT in non-alcoholic chr. liver disease

Features of Paracetamol
Toxicity

Day 1:

Nausea, vomiting, malaise, or

asymptomatic

Day 2 3:
Initial symptoms resolve
AST and ALT begin to rise by 36 hours
RUQ pain, tender enlarged liver on exam

Day 4
AST and ALT peak > 3000
Liver dysfunction: PT, encephalopathy,
jaundice. Acute renal failure (ATN)

Treatment of Paracetamol
Toxicity
CONTD . . .

Activated charcoal if < 4 hours from

ingestion : single dose 1 mg/kg PO or
NG
N-Acetylcysteine (NAC)

140 mg/kg loading dose PO or NG

70 mg/kg q 4 hours PO or NG X 17 doses
Continue longer until INR < 2.0 and
improved
OK to DC if acetaminophen levels
undetectable and normal AST at 36
hours

Treatment of Paracetamol
Toxicity
CONTD . . .
Indications for NAC therapy:
Above the line on the nomogram
Serum concentration > 10 mcg/ml
and unknown time of ingestion
Repeated excessive doses, risk factors
for acetaminophen hepatoxicity, and
serum concentration > 10 mcg/ml
Evidence of hepatoxicity and a history
of excessive acetaminophen dosing

Primary Biliary Cirrhosis

Cholestatic liver disease (ALP)
Most common symptoms: pruritus
and fatigue
Many patients asymptomatic, and dx
by abnormal LFT

Female : male ratio = 9:1

Treatment : Urodeoxycholic
acid 15 mg/kg

Primary Sclerosing
Cholangitis

Cholestatic liver disease (ALP)

Inflammation of large bile ducts

90% associated with IBD

but only 5% of IBD patients get PSC

Cholangiocarcinoma : 10-15% lifetime

risk
Treatment : Liver Transplantation

Manifestations of Wilson's
Disease
HEPATIC
CAH, Cirrhosis, Fulminant hepatitis
EARLY NEUROLOGICAL
Incoordination, dysarthria,
Resting and intention tremors

Excessive salivation, dysphagia

PSYCHIATRIC
Behavioral, organic dementia,
Psychoneurosis, manic-depressive
Schizophrenic psychosis
OPHTHALMIC

KF ring, sunflower cataract

Mask-like facies, ataxia

HEMATOLOGIC AND OTHERS

LATE NEUROLOGICAL

IV hemolysis, Hypersplenism

Dystonia, spasticity, Rigidity, TCS

Distal RTA, Osteomalacia, OS

Wilsons Disease
Autosomal recessive Cu
metabolism
Chronic hepatitis or fulminant

hepatitis
Diagnosis : ceruloplasmin,
urinary Cu

Treatment : d-penicillamine

Neonatal Jaundice
Neonatal jaundice is common
50% healthy term infants
Re-emergence of kernicterus
In utero bilirubin is handled by
placenta and mothers liver
After birth, neonate to has cope
with
increase
in
bilirubin
production and the immature
liver cannot handle for a few
days
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www.drsarma.in

90

Basis of Phototherapy
Unconjugated bilirubin is not water
soluble
Blue light converts the
unconjugated bilirubin into its
photoisomers
The photoisomers are water soluble
The soluble photoisomers pass
through the glomerular filter and
get excreted
Thus conjugation in liver is by
passed
www.drsarma.in

Icteric Leptospirosis
(Weils Disease)
Agent : Leptospira interrogens
Host : Rodents
Route of entry : intact skin, mucous
membrane, cuts and abrasions
Organs affected : kidneys, liver,
meninges, brain

Clinical Features of Icteric

Leptospirosis
Deep jaundice

Fever
Haemorrhage
Epistaxis, purpura, erythema
Haematemesis, melaena
Pleural, pericardial and subarachnoid
haemorrhage

Clinical Features of Icteric

Leptospirosis
Renal impairment
Oliguria, anuria
Albumin, blood and casts in urine

Associated uveitis, iritis,

myocarditis, encephalitis, aseptic

meningitis

Diagnosis of Icteric
Leptospirosis
Blood polymorphonuclear

leukocytosis
Liver function tests elevated
transaminases and prothrombin
time
Definitive : culture of blood (1st
week), urine (2nd week), ELISA, PCR

Treatment of Icteric
Leptospirosis
Oral doxycycline
Intravenous penicillin
Treatment of renal impairment

Control haemorrhage

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