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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)
Bilirubin Metabolism
Cecil
Mechanisms of
Hyperbilirubinaemia
Excess production
Classification of Jaundice
Haemolytic / Pre-hepatic
Hepatocellular
Excess production
Obstructive / Post-hepatic
Classification of Jaundice
Excess production
CONJUGATED
Classification of Jaundice
Excess production
Haemolytic / Pre-hepatic
Hepatocellular
CONJUGATED
UNCONJUGATED
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
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
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
Haemolytic Jaundice
CONTD . . .
Mongoloid facies
Hepatosplenomegaly
ACP Board Review
Haemolytic Jaundice
CONTD . . .
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
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
Recovery
99%
Fulminant
Hepatitis
1%
70-90%
Recovery
Cirrhosis
Death
20-50%
10%
Chronic Hepatitis
HCC
Robbins
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
technicians
Newborn of carrier
mother
Sexual contacts of
HBV patients
More chronicity
More chance of malignant
transformation
No vaccine available
When to admit
Jaundice alone is not criteria
for admission
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?
Liver Biochemistry
VIRAL MARKER
History
Examination
OLDER
No risk of hepatitis
Weight Loss
ULTRASOUND
Liver Biochemistry
Viral marker
+ ve
ve
Viral
Hepatitis
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
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
Imaging : CT
Imaging : MRCP
Imaging : ERCP
Normal Range
Bilirubin
Total
Conjugated
Alkaline phosphatase
0.1 to 1.0 mg / dL
< 0.2 mg / dL
5-31 IU / L
5-35 IU / L
Albumin
3.5-5.0 g / dL
12-16 s
25-112 IU / L
www.drsarma.in
Utility of LFT
Test
Utility
ALT
Albumin
Alkaline phosphatase
AST
Bilirubin
Gamma-globulin
GGT
HBV Serology
HBcAb
HBcAb
HBsAg IgM
HBsAb
IgG
Acute HBV
Resolved HBV
Chronic HBV
HBV vaccinated
Diagnosis of
Immune-Mediated Liver
Diseases
LFT Serology
Ig
Biopsy
AIH
ALT
ANA
ASMA
IgG
Portal inflammation
Plasmacytes
Piecemeal necrosis
PBC
ALP
AMA
IgM
PSC
ALP
none
normal
Diagnosis of Autoimmune
Hepatitis
Diagnosis of Primary
Sclerosing Cholangitis
ERCP (now MRCP)
No autoantibodies, no elevated
globulins
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
(e.g.
Principles of Treatment
Bed rest : 3 5 weeks
CONTD . . .
If constipated : lactulose
If diarrhoea : avoid milk and milk
products; maintain hydration
for 6 months
If HBeAg ve : 12 months
Other options : lamivudine, adefovir,
liver transplantation
Davidson
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
Treatment of Fulminant
Hepatic Failure CONTD . . .
Correct hypokalaemia and
hypocalcaemia
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
alcoholic) for
consideration of liver
transplant
Suspected hereditary
hemochromatosis
Suspected Wilson's
disease
Suspected
autoimmune hepatitis
Chronic hepatitis C for
consideration of
antiviral therapy
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:
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 . . .
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
Treatment : Urodeoxycholic
acid 15 mg/kg
Primary Sclerosing
Cholangitis
Manifestations of Wilson's
Disease
HEPATIC
CAH, Cirrhosis, Fulminant hepatitis
EARLY NEUROLOGICAL
Incoordination, dysarthria,
Resting and intention tremors
PSYCHIATRIC
Behavioral, organic dementia,
Psychoneurosis, manic-depressive
Schizophrenic psychosis
OPHTHALMIC
LATE NEUROLOGICAL
IV hemolysis, Hypersplenism
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
www.drsarma.in
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
Fever
Haemorrhage
Epistaxis, purpura, erythema
Haematemesis, melaena
Pleural, pericardial and subarachnoid
haemorrhage
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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