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Jaundice and its Investigation

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)

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Jaundice and its Investigation

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  1. Jaundice and its Investigation Andrew M Smith Jan 2011

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

  3. Jaundice • An elevation of serum bilirubin above normal limit (9 mmol/l) • Clinically evident at ~ 35 mmol/l

  4. Objectives • Review Liver Anatomy and Physiology • Classification and causes of Jaundice • Investigation of Jaundice • Principles of Management of Jaundice • Cases • Summary

  5. Gross Hepatic Anatomy

  6. Liver Histological Structure

  7. Functions of the Liver • 1.Metabolism • Fats • Proteins • Carbohydrates • Hormones • 2.Storage • 3.Metabolism and excretion bilirubin • 4. Drug metabolism and excretion

  8. Normal Bile Physiology • 250-500 mg bile/day • Water (98%) • Bile Salts • Bile pigments (Bilirubin) • Fatty Acids • Lecithin • Cholesterol

  9. 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

  10. Major Causes of Jaundice Pre-hepaticHaemolysis Ineffective erythropoiesis HepaticPrematurity 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)

  11. Investigation Of A Jaundiced Patient • History • Examination • Tests • Blood • Urine • Imaging

  12. History ‘most important part of the evaluation of the patient with jaundice’

  13. History 1. Jaundice – onset 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 MALIGNANCY Colicky Fatty food intolerant GALLSTONES Hepatic: IV Drug abuse blood transfusions Travel flu-like illness Excess alcohol intake Obesity Drug History Hepatitis ASSOCIATED FEVERS / RIGORS? Gram –ve Septicaemia ADMIT Cirrhosis/ NASH

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

  15. 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

  16. Investigations for jaundice • Bloods • General – Liver Function Tests - Albumin, INR (give more info on function!) • Specific • Urine • Imaging • Histology

  17. 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

  18. Prehepatic • Unconguated Bil ↑ • LFT’s N • haptoglobins ↓ • Reticulocytes ↑ • Coombs test +ve • Clotting screen • Urine urobilinogen↑

  19. 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

  20. Post - hepatic • ALT N or ↑ • ALP ↑ ↑ ↑ • Bil ↑ • INR ↑ • CEA, Ca19.9 ↑ • Panc & cholangio Ca

  21. Imaging - Ultrasound • Key investigation • Distinguish hepatic and post hepatic • Identify gallstones

  22. 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

  23. Imaging - CT Scan

  24. Imaging MRCP + MRI

  25. Imaging - Endoscopic ultrasound CBD CBD PD PD

  26. Imaging ERCP

  27. Imaging PET scan

  28. 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

  29. 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?

  30. 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.

  31. 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?

  32. 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

  33. 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?

  34. 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

  35. Ascending Cholangitis Athospital, continue resuscitation, antibiotics, check and correct INR Emergency ERCP and duct clearance Laparoscopic Cholecystectomy, same admission

  36. 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)

  37. 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?

  38. 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

  39. 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?

  40. Investigation isolated abnormal LFT

  41. Investigation isolated raised ALT • 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

  42. What is the most likely cause of jaundice that I will see? South Wales, Gut 2002 Glasgow, Gut, 2002 Alcoholic liver disease Gallstones Malignacy

  43. Summary • Good history will direct rest of care • LFTs and USS initially • Admit cholangitis when suspected • Admit for symptom control

  44. 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

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

  46. Haemochromotosis • Frequency 5/1000 • Fe and TIBC, • Fe saturation > 45% then ferritin • Ferritin > 400ng/ml • Liver biopsy

  47. 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

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

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