Jaundice and its
Investigation
Andrew M Smith
Jan 2011
Jaundice
"it looks like there's something wrong…
….with your television set.“
Matt Groenig, creator of
The Simpsons
Jaundice
• An elevation of serum bilirubin above
normal limit (9 mmol/l)
• Clinically evident at ~ 35 mmol/l
Objectives
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Review Liver Anatomy and Physiology
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Classification and causes of Jaundice
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Investigation of Jaundice
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Principles of Management of Jaundice
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Cases
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Summary
Gross Hepatic Anatomy
Liver Histological Structure
Functions of the Liver
1.Metabolism
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Fats
Proteins
Carbohydrates
Hormones
2.Storage
3.Metabolism and excretion bilirubin
4. Drug metabolism and excretion
Normal Bile Physiology
• 250-500 mg bile/day
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Water (98%)
Bile Salts
Bile pigments (Bilirubin)
Fatty Acids
Lecithin
Cholesterol
Normal Bilirubin Metabolism
RBC
Hb Degraded to
Globin + Fe + Bilirubin
Hepatocyte
Bilirubin bound to
albumin
Conjugated
Bilirubin Diglucuronide
Kidney
Portal Vein
Intestine
Urobilinogen
Urobilinogen
Bilirubin
Urobilinogen
Stercobilin
Major Causes of Jaundice
Pre-hepatic
Haemolysis
Ineffective erythropoiesis
Hepatic
Prematurity
Gilberts
Drugs
Hepatitis: viral, NASH
Alcohol / cirrhosis
Tumours
Extrahepatic sepsis
Post-hepatic
‘Obstructive’
Gallstones (in the lumen)
Bile duct stricture ( in the wall)
Ca pancreas (extrinsic)
Investigation Of A Jaundiced
Patient
• History
• Examination
• Tests
– Blood
– Urine
– Imaging
History
‘most important part of the evaluation of the
patient with jaundice’
History
1. Jaundice – onset
2. Pale stools, dark urine?
YES = POST HEPATIC
PAIN?
YES
Colicky
Fatty food
intolerant
NO
Wt loss
Back Pain
Non-specific
symptoms
GALLSTONES
MALIGNANCY
ASSOCIATED FEVERS / RIGORS?
Gram –ve Septicaemia
ADMIT
NO = PRE & HEPATIC
Pre-hepatic:
Family history of bleeding
disorders, tendency to bleed
Hepatic:
IV Drug abuse
blood transfusions
Travel
flu-like illness
Hepatitis
Excess alcohol intake
Cirrhosis/
Obesity
NASH
Drug History
Examination
• Stigmata Chronic Liver disease
• Hepatomegaly – texture,edge,
nodules
• Hepatosplenomegaly
• Ascites –shifting dullness
• Portal hypertesion
• Obvious iv drug use
Examination – obstructive
jaundice
• Temp
• Tachycardic +/- hypotensive
• Cachexia, Virchow’s
node,clubbing
• Murphy’s sign
• Courvoisier’s law ‘If in the presence
of jaundice the gallbladder is palpable then the
cause of the jaundice is unlikely to be gallstones’
• Urine
cholangitis
Investigations for jaundice
• Bloods
– General – Liver Function Tests
- Albumin, INR (give more info on function!)
– Specific
• Urine
• Imaging
• Histology
Ix Jaundice – Bloods
• Liver Function Tests
- really a test of hepatocyte damage
Alanine Transaminase ALT range <40iu/L
elevated cellular damage
AlkalinePhosphatase ALP range 70-300iu/KL
elevation post hepatic obstruction
Bilirubin range 5- 40 umol/L
Prehepatic
• Unconguated Bil ↑
• LFT’s N
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haptoglobins ↓
Reticulocytes ↑
Coombs test +ve
Clotting screen
• Urine urobilinogen↑
Hepatic
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ALT ↑ ↑ ↑
ALP N or ↑
Bil ↑
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Albumin ↓
INR ↑
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Hepatitis serology
Autoantibodies
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Caeruloplasmin ↑
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Anti-mitochondrial PBC
Anti-nuclear & antimicrosomal, Autoimmune
hepatitis
Wilson’s
γ-Globulins ↑
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Cirrhosis esp autoimmune
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Transferrin ↑ ↑
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α-foetoprotein, αFP ↑
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Haemochromatosis ↑
HCC in cirrhosis
Post - hepatic
• ALT N or ↑
• ALP ↑ ↑ ↑
• Bil ↑
• INR ↑
• CEA, Ca19.9 ↑
• Panc & cholangio Ca
Imaging - Ultrasound
• Key investigation
• Distinguish hepatic and post hepatic
• Identify gallstones
Imaging - Ultrasound
Key information from report
BILIARY DUCT DILATION
Calculi
Gallstones present, GB wall thickness
CBD diameter normal (<7mm)
No calculi
No gallstones, but CBD ↑ ? Pancreatic malignancy
NO DUCT DILATION
Texture of liver eg normal, fatty, micronodular
Lesions present
Imaging - CT Scan
Imaging MRCP + MRI
Imaging - Endoscopic ultrasound
CBD
CBD
PD
PD
Imaging ERCP
Imaging PET scan
Investigation Summary
• First line
• LFT’s & USS
• Second line
– If dilated ducts refer for stone or ? maligancy
management
– No ducts – parenchymal liver disease
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Ensure good alcohol history
Hepatitis serology
Hepatic autoantibodies
Ferritin
Case 1
• A 18 year old student comes to see you
and reveals that his mates taunt him as he
often appears to have yellow eyes?
• What do you do?
Gilbert’s disease
• Diagnosis of exclusion
• Good Hx. No family hx of sickle/G6PD defficiency
• no other risk factors
• Notes jaundice worsens on fasting
• Unconguated Bil ↑ and LFT’s N
• haptoglobins Reticulocytes both normal, Coombs test ve
5 -7 % population, reasssure.
Case 2
• A Samuel Smiths delivery man who enjoys
the companys perks to excess attends,
complaining of a distended abdomen
which is becoming painful?
• Diagnosis?
• Management?
Decompensated alcoholic
cirrhosis
History – confirms 100+ unit intake for 20 yrs
Examination – stigmata chronic liver disease
abdo, palpable liver and spleen
shifting dullness
Ix -
LFTs Bil ↑ , ALT ↑ ↑ ↑, ALP ↑
INR ↑
Albumin low
USS , cirrhosis, splenomegaly and ascites
Treatment – Cessation of alcohol
- treatment of withdrawal
- thiamine, folic acid
- low salt diet, spironolactone
- Liver bx when ascites settles
- Ix portal htn, OGD, banding, B –blocker, TIPs
Case 3
• You are asked to make a home visit to see a 53 yr old
man with severe abdominal pain . His notes show that
he had an episode of pancreatitis on holiday in Spain a
year ago.
• He tells you that the has had upper tummy pain, can’t
get comfortable and has had shakes and feels cold?
• What is the diagnosis?
• What action do you take?
Ascending Cholangitis
• Examination reveals fever, jaundice and a
tachycardia.
• He has Charcot’s triad – pain, jaundice,
fever, ie ascending cholangitis
• He needs an emergency admission,
significant morbidity and mortality
• iv access, analgesia
Ascending Cholangitis
At hospital, continue resuscitation, antibiotics, check and correct INR
Emergency ERCP and duct clearance
Laparoscopic Cholecystectomy, same admission
Gallstones
• Previous pancreatitis due to gallstones.
20% incidence of further complications
within 6 months once symptomatic
• In elective situation can avoid ERCP, by
performing a duct exploration at the time of
laparoscopic cholecystectomy
• On horizon of further sea change with
advent of NOTES (natural orifice
transluminal endoscopic surgery)
Case 4
• A 37 year old Chinese immigrant who has
just arrived in Leeds, presents frankly
jaundiced with a history of abdominal pain
and weight loss. On examination he is
clearly jaundiced and has a palpable liver.
• What do we do next?
• Can we make an educated guess from the
history?
Hep C and HCC
• LFT’s and USS – ALT, ALP and Bilirubin
grossly elevated.
• USS cirrhosis and multiple lesions.
Referred.
• CT and Hep C, aFP
Beyond transplant or resection
Rx Chemoembolisation / BSC
Case 5
Your senior partner has been seeing for a year a
previously fit 43yr old man with non specific
symptoms of fatigue. Two consecutive ALT’s six
months apart were elevated at 120, and 107 (
normal < 40). The rest of his blood work was
normal.
Do you act on this result?
Investigation isolated abnormal
LFT
Investigation isolated raised ALT
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Present > 6 months should investigate
Good Hx and Exam
FIRST WAVE TESTS
1 .Exclude drugs NSAIDs, antibiotics, statins, antiepileptic drugs anti-TB.
Herbal remedies. Paracetamol
2. Assess Alcohol excess
3. Hep B and C
4. Hereditary Haemochromotosis
5. NASH and steatosis
SECOND WAVE TESTS Refer
6. Thyroid/Coeliac/muscle disorders
THIRD WAVE – Definitely refer
What is the most likely cause of
jaundice that I will see?
•
South Wales, Gut 2002
Glasgow, Gut, 2002
Alcoholic liver disease
Gallstones
Malignacy
Summary
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Good history will direct rest of care
LFTs and USS initially
Admit cholangitis when suspected
Admit for symptom control
Hep B
• Send hepatitis serlogy .
• Will assess status to determine whether
immune/carrier or chronic infection
• HepBsAg, HepBsAb, HepBcAb
• chronic infection HepBsAG +ve + HepBcAb +ve
• immune
• HBV DNA
HepBsAb +ve , HepBcAb +ve
Hep C
• Hep C Antibody
• Then Hep C RNA, Hep C genotype and
liver biopsy
Haemochromotosis
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Frequency 5/1000
Fe and TIBC,
Fe saturation > 45% then ferritin
Ferritin > 400ng/ml
Liver biopsy
NASH
• NASH more common women and type 2
Diabetes
• Hep B/C/HCC negative USS to look for
steatosis
• Bx if stigmata chronic liver disese
Isolated Hyperbilirubinaemia
• Occurs – excess production or impaired
uptake
• Check conjugated vs unconjugated
• Assess Haemolysis
• No haemolysis, fluctuating bilirubin –
gilberts disease.
Isolated Alkaline Phosphatase
• Source – liver and bone
• Increased 3rd trimester and in women
between 30 and 50 yrs
• Determine source, gGT and
5’nucleosidase increases in bone disease
• Gel electrophoresis
• If Hepatic – USS, if no obstruction then
AMA for PBC
• Repeat the LFTs