Jaundice and its Investigation
Andrew M Smith
Jan 2011
JaundiceJaundice
"it looks like there's something wrong… ….with your television set.“
Matt Groenig, creator of The Simpsons
JaundiceJaundice
• An elevation of serum bilirubin above normal limit (9 mmol/l)
• Clinically evident at ~ 35 mmol/l
ObjectivesObjectives• Review Liver Anatomy and Physiology
• Classification and causes of Jaundice
• Investigation of Jaundice
• Principles of Management of Jaundice
• Cases
• Summary
Gross Hepatic AnatomyGross Hepatic Anatomy
Liver Histological StructureLiver Histological Structure
Functions of the LiverFunctions of the Liver1.Metabolism • Fats• Proteins• Carbohydrates• Hormones
2.Storage
3.Metabolism and excretion bilirubin
4. Drug metabolism and excretion
Normal Bile PhysiologyNormal Bile Physiology• 250-500 mg bile/day
• Water (98%)• Bile Salts• Bile pigments (Bilirubin)• Fatty Acids• Lecithin• Cholesterol
Normal Bilirubin MetabolismNormal Bilirubin MetabolismRBCRBC
Hb Degraded toGlobin + Fe + Bilirubin
HepatocyteHepatocyte
ConjugatedBilirubin Diglucuronide
IntestineIntestine
Bilirubin
Urobilinogen
Stercobilin
Portal Vein
Urobilinogen
KidneyKidney
Urobilinogen
Bilirubin bound to albumin
Major Causes of JaundiceMajor Causes of Jaundice Pre-hepatic Haemolysis
Ineffective erythropoiesis
Hepatic PrematurityGilbertsDrugsHepatitis: viral, NASHAlcohol / cirrhosisTumours 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
HistoryHistory
‘most important part of the evaluation of the patient with jaundice’
HistoryHistory1. Jaundice – onset
2. Pale stools, dark urine?
YES = POST HEPATIC NO = PRE & HEPATIC
PAIN?YES NO
ColickyFatty food intolerant
GALLSTONES
Wt lossBack Pain
Non-specific symptoms
MALIGNANCY
Hepatic:
IV Drug abuseblood transfusionsTravelflu-like illness
Excess alcohol intakeObesity
Drug History
ASSOCIATED FEVERS / RIGORS?
Gram –ve Septicaemia
ADMITADMIT
Pre-hepatic:Family history of bleedingdisorders, tendency to bleed
Hepatitis
Cirrhosis/ NASH
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 jaundiceInvestigations for jaundice
• Bloods– General – Liver Function Tests
- Albumin, INR (give more info on function!)
– Specific
• Urine
• Imaging
• Histology
Ix Jaundice – BloodsIx Jaundice – Bloods• Liver Function Tests - really a test of hepatocyte damage
Alanine Transaminase ALT range <40iu/Lelevated cellular damage
AlkalinePhosphatase ALP range 70-300iu/KL elevation post hepatic obstruction
Bilirubin range 5- 40 umol/L
Prehepatic
• Unconguated Bil ↑• LFT’s N
• haptoglobins ↓• Reticulocytes ↑• Coombs test +ve• Clotting screen
• Urine urobilinogen↑
Hepatic• ALT ↑ ↑ ↑• ALP N or ↑• Bil ↑
• Albumin ↓• INR ↑
• Hepatitis serology• Autoantibodies
• Anti-mitochondrial PBC• Anti-nuclear & antimicrosomal, Autoimmune
hepatitis
• Caeruloplasmin ↑ • Wilson’s
• γ-Globulins ↑• Cirrhosis esp autoimmune
• Transferrin ↑ ↑• Haemochromatosis ↑
• α-foetoprotein, αFP ↑• HCC in cirrhosis
Post - hepaticPost - hepatic
• ALT N or ↑• ALP ↑ ↑ ↑• Bil ↑
• INR ↑
• CEA, Ca19.9 ↑• Panc & cholangio Ca
Imaging - UltrasoundImaging - Ultrasound• Key investigation
• Distinguish hepatic and post hepatic
• Identify gallstones
Imaging - UltrasoundImaging - UltrasoundKey information from report
BILIARY DUCT DILATION
CalculiGallstones 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, micronodularLesions present
Imaging - CT ScanImaging - CT Scan
Imaging MRCP + MRIImaging MRCP + MRI
Imaging - Endoscopic ultrasoundImaging - Endoscopic ultrasound
CBDCBDCBDCBD
PDPDPDPD
Imaging ERCPImaging ERCP
Imaging PET scanImaging 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
– Ensure good alcohol history– Hepatitis serology– Hepatic autoantibodies– Ferritin
Case 1Case 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 diseaseGilbert’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 2Case 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 Decompensated alcoholic cirrhosiscirrhosis
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 3Case 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 CholangitisAscending 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 CholangitisAscending Cholangitis
At hospital, continue resuscitation, antibiotics, check and correct INR
Emergency ERCP and duct clearance
Laparoscopic Cholecystectomy, same admission
GallstonesGallstones• 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 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 HCCHep C and HCC
• LFT’s and USS – ALT, ALP and Bilirubin grossly elevated.
• USS cirrhosis and multiple lesions. Referred.
• CT and Hep C, aFPBeyond transplant or resection
Rx Chemoembolisation / BSC
Case 5Case 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 Investigation isolated abnormal LFTLFT
Investigation isolated raised ALTInvestigation isolated raised ALT
• Present > 6 months should investigate• Good Hx and Exam
FIRST WAVE TESTS1 .Exclude drugs NSAIDs, antibiotics, statins, antiepileptic drugs anti-TB.
Herbal remedies. Paracetamol2. Assess Alcohol excess3. Hep B and C4. Hereditary Haemochromotosis5. NASH and steatosis
SECOND WAVE TESTS Refer6. Thyroid/Coeliac/muscle disorders
THIRD WAVE – Definitely refer
What is the most likely cause of What is the most likely cause of jaundice that I will see?jaundice that I will see?
•
South Wales, Gut 2002
Glasgow, Gut, 2002
Alcoholic liver diseaseAlcoholic liver diseaseGallstonesGallstonesMalignacyMalignacy
SummarySummary
• Good history will direct rest of care
• LFTs and USS initially
• Admit cholangitis when suspected
• Admit for symptom control
Hep BHep 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 HepBsAb +ve , HepBcAb +ve
• HBV DNA
Hep CHep C
• Hep C Antibody
• Then Hep C RNA, Hep C genotype and liver biopsy
HaemochromotosisHaemochromotosis
• Frequency 5/1000
• Fe and TIBC,
• Fe saturation > 45% then ferritin
• Ferritin > 400ng/ml
• Liver biopsy
NASHNASH
• 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 HyperbilirubinaemiaIsolated 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