How to manage a case of jaundice in General Practice

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How to manage a case of jaundice in General
Practice

• Andrew M Smith
• Nov 2007

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Jaundice
"it looks like there's something wrong
.with your television
set. Matt Groenig, creator of The
Simpsons
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Jaundice

• An elevation of serum bilirubin above normal
  limit (gt40 umol/l)
• Clinically evident at x2 normal level

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Learning Objectives

• By the end of this talk participants will be able
  to
• understand normal liver anatomy and physiology
• Recognise the COMMON causes of jaundice and
  their classification
• take a history and perform an examination
  pertinent for jaundiced patients
• Select the appropriate investigations and
  understand who and when to refer
• opportunity to apply the above in selected case
  histories

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Gross Hepatic Anatomy
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Gross Hepatic Anatomy
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Liver Histological Structure
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Liver Histological Structure
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Functions of the Liver

• 1.Metabolism
• Fats
• Proteins
• Carbohydrates
• Hormones
• 2.Storage
• 3.Metabolism and excretion bilirubin
• 4. Drug metabolism and excretion

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Normal Bile Physiology

• 1500ml bile/day
• 2 roles 1. excretion
• 2. emulsification of fat
• Water (98)
• Bile Salts
• Bile pigments (Bilirubin)
• Fatty Acids
• Lecithin
• Cholesterol

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Normal Bilirubin Metabolism
RBC Hb Degraded to Globin Fe Bilirubin
Hepatocyte Conjugated Bilirubin Diglucuronide
Bilirubin bound to albumin
Kidney Urobilinogen
Portal Vein Urobilinogen
Intestine Bilirubin Urobilinogen Stercobilin
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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)

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Investigation Of A Jaundiced Patient

• History
• Examination
• Tests
• Blood
• Urine
• Imaging

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History

• most important part of the evaluation of the
  patient with jaundice

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History

• 1. Jaundice
• 2. Pale stools, dark urine?
• YES POST HEPATIC
  NO PRE HEPATIC

PAIN? YES NO
Pre-hepatic Family history of bleeding disorders,
tendency to bleed
Wt loss Back Pain Non-specific symptoms MALIGNANC
Y
Colicky Fatty food intolerant GALLSTONES
Hepatic IV Drug abuse blood transfusions Travel f
lu-like illness Excess alcohol intake (AUDIT
CAGE) Obesity Drug History
Hepatitis
ASSOCIATED FEVERS / RIGORS? Gram ve
Septicaemia ADMIT
Cirrhosis/ NASH
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Examination

• Stigmata Chronic Liver disease
• Hepatomegaly texture,edge, nodules
• Hepatosplenomegaly
• Ascites shifting dullness
• Portal hypertesion
• Obvious iv drug use

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Examination obstructive jaundice

• Temp
• Tachycardic /- hypotensive
• Cachexia, Virchows node,clubbing
• Murphys sign
• Courvoisiers law If in the presence of jaundice
  the gallbladder is palpable then the cause of the
  jaundice is unlikely to be gallstones
• Urine

cholangitis
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Investigations for jaundice

• Bloods
• General Liver Function Tests
• - Albumin, INR (give more info on
  function!)
• Specific
• Urine
• Imaging
• Histology

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Ix Jaundice Bloods

• Liver Function Tests
• - really a test of hepatocyte damage
• Alanine Transaminase ALT range lt40iu/L
• elevated cellular damage
• AlkalinePhosphatase ALP range 70-300iu/KL
• elevation post hepatic obstruction
• Bilirubin range 5- 40 umol/L

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Prehepatic

• Unconguated Bil ?
• LFTs N
• haptoglobins ?
• Reticulocytes ?
• Coombs test ve
• Clotting screen
• Urine urobilinogen

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Hepatic

• ALT ? ? ?
• ALP N or ?
• Bil ?
• Albumin ?
• INR ?
• Hepatitis serology
• Autoantibodies
• Anti-mitochondrial PBC
• Anti-nuclear antimicrosomal, Autoimmune
  hepatitis
• Caeruloplasmin ?
• Wilsons
• ?-Globulins ?
• Cirrhosis esp autoimmune
• Transferrin ? ?
• Haemochromatosis ?
• a-foetoprotein, aFP ?

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Post - hepatic

• ALT N or ?
• ALP ? ? ?
• Bil ?
• INR ?
• CEA, Ca19.9 ?
• Panc cholangio Ca

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LFTs and urine summary
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Imaging - Ultrasound

• Key investigation
• Distinguish obstruction
• from hepatic cause
• Identify gallstones

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Imaging - Ultrasound

• Key information from report
• Duct size
• CBD normally lt 7mm
• Are both intrahepatic and extrahepatic ducts
  dilated?
• If duct increased are calculi present?
• Gallstones present none seen in CBD but
  Gallbaldder abnomalities ie GB stones, SLUDGE,
  increased GB wall thickness
• No gallstones, but CBD ? ? Pancreatic malignancy
• No calculi
• Texture of liver eg normal, fatty, micronodular
• Dioscrete Lesions present

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Imaging - CT Scan
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Imaging MRCP MRI
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Imaging ERCP
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Imaging PET scan
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Management

• Good history, drives rest of management
• Investigations
• General LFTs and USS, Urine dipstix
• Determine obstruction or not
• Specific Directed at underlying cause

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Who to treat? Who to refer?

• Determining who to refer is easier
• Pragmatic approach
• EMERGENCY
• Any patient with evidence of ascending
  cholangitis
• Unwell eg fulminant hepatic failure, paracetamol
  OD,
• Decompensated cirrhosis
• Failure to cope/thrive
• 2 WEEK WAIT
• Evidence or suspicion of cancer

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Case 1

• An 18 year old first year med student comes to
  see you and confides that his mates take the
  mickey out of him as he intermittently appears to
  have yellow eyes?
• What do you do?

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Gilberts 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 LFTs N
• haptoglobins Reticulocytes both normal, Coombs
  test -ve
• 5 -7 population, normal lifespan, reasssure.

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Case 2

• One of your known recidivists attends,
  complaining of a distended abdomen which is
  becoming painful?
• Diagnosis?
• Management?

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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 - Nutritional
support - low salt diet,
spironolactone - Ix portal
HTN, OGD, banding, B blocker, TIPs
- If abstains, HCC surveillance
- contiuned abstinence, consider transplant
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Survival with Alcoholic Liver Disease
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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,
  cant get comfortable and has had shakes and
  feels cold?
• What is the diagnosis?
• What action do you take?

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Ascending Cholangitis

• Examination reveals fever, jaundice and a
  tachycardia.
• He has Charcots triad pain, jaundice, fever,
  ie ascending cholangitis
• He needs an emergency admission,
• significant morbidity and mortality
• If possible iv access, fluid, antibiotic,
  analgesia

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Ascending Cholangitis
At hospital, continue resuscitation, antibiotics,
check and correct INR Emergency ERCP and duct
clearance Laparoscopic Cholecystectomy, same
admission
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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)

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Case 4

• A 37 year old Chinese refugee who has just
  settled in Leeds, presents frankly jaundiced with
  a history of abdominal pain and weight loss. On
  examination he is clearly jaundiced.
• Can we make an educated guess as to the aetiology
  from the history?
• What do we do next?

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Hep C and HCC

• LFTs 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
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HCV

• Persistent infection in 85 individuals
• 170 million worldwide, 4 million USA
• Acute HCV hepatitis, rarely seen
• Progression of HCV is silent
• 20-30 cirrhosis, 2-3 HCC
• Treatment Interferon (Peg interferon and
  Ribavirin)

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Case 5

• Your senior partner has been seeing for over a
  year a previously fit 43yr old man with non
  specific symptoms of fatigue. Two consecutive
  ALTs six months apart were elevated at 120, and
  107 ( normal lt 40iu). The rest of his blood work
  was normal.
• Do you act on this result?

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Investigation isolated abnormal LFT
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Investigation isolated raised ALT

• Present gt 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

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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 HepBsAb ve , HepBcAb ve
• HBV DNA

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Hep C

• Hep C Antibody
• Then Hep C RNA, Hep C genotype and liver biopsy

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Haemochromotosis

• Frequency 5/1000
• Fe and TIBC,
• Fe saturation gt 45 then ferritin
• Ferritin gt 400ng/ml
• Liver biopsy

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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

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Isolated Hyperbilirubinaemia

• Occurs excess production or impaired uptake
• Check conjugated vs unconjugated
• Assess Haemolysis
• No haemolysis, fluctuating bilirubin gilberts
  disease.

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Isolated Alkaline Phosphatase

• Source liver and bone
• Increased 3rd trimester and in women between 30
  and 50 yrs
• Determine source, gGT and 5nucleosidase
  increases in liver disease
• Gel electrophoresis
• If Hepatic USS, if no obstruction then AMA for
  PBC

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What is the most likely cause of jaundice that I
will see?

South Wales, Gut 2002
Glasgow, Gut, 2002
Alcoholic liver disease Gallstones Malignacy
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Summary

• Good history will direct rest of care
• LFTs and USS initially
• Move to specific tests
• Admit unwell ie cholangitis
• Always available to discuss

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