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