2 Objectives Definition Anatomy of the hepatobiliary tree Biochemistry of bilirubinTypes of JaundiceOBSTRUCTIVE JAUNDICE:CausesClinical presentationLaboratory investigationsRadiological investigationsTreatment options
3 Definition of Jaundice Yellowish discoloration of the skin and other tissues (sclera, mucous membrane, deep tissues…) due to deposition of bile pigment(bilirubin) when serum level exceed 3mg/dl (50 µmol/L)Normal : Total serum bilirubin mg/dlDirect bilirubin- < 0.4 mg/dlThe cause of the yellowish discoloration is the accumulation of the bile pigments (bilirubin) in the skin.Most of the bilirubin in the blood is in the unconjugated form.
4 Anatomy of the hepatobiliary tree The gallbladder has 3 main parts the neck, Body and the fundus. The gallbladder has the function of concentrating the bile and has no role in the production process the bile. Cystic duct joins the common hepatic duct to form the common bile duct. And then the common bile duct will join the pancreatic duct and it will enter the second part of the duodenoum. The area of the insertion is called Ampulla of Vater.
5 Bilirubin Biochemistry 80% of bilirubin is formed by the degradation of ‘Heme’ from RBC.The remainder ‘Heme’ containing enzymes (cytochromes, catalase, peroxidase..) potentially toxic.Remains harmless by binding to albumin
6 Unconjugated Bilirubin- (indirect bilirubin) Insoluble in waterTightly complex to albuminNot filtered through renal glomeruliNot excreted in urineThe main form of bilirubin in the blood
7 Conjugated Bilirubin- (Direct bilirubin) Conjugated in the liver before its excretion into bileConjugated with glucuronic acidChanges bilirubin into water solubleCan be filtered through renal glomeruliPresent in low concentration in the blood
8 Con’tWhen the conjugated bilirubin reaches the terminal ileum and colon it will de-conjugated into urobilinogen and stercobillinogen. Urobilinogen controbutes for the enterohepatic circulation, and some will be filtered in the urine because it is slightly water soluble. Stercobillinogen will give the dark brown color of the stool.
9 Types of Jaundice Pre-hepatic Hepatic Post-hepatic (Obstructive) Physiologic jaundice, affect the newborn because of the down regulation of the glucoronyltransferase enzyme. The reason for the down regulation is during fetal life the bilirubin must be in the unconjugated form so it can pass placenta and cleared by the mother liver. So the fetus doesn’t need to conjugate the bilirubin so it will loss its function for a while. But it will gain its function later.
10 Pre-hepaticExcess extra-hepatic production of bilirubin raising unconjugated form.Haemolytic anemias: congenital spherocytosis, sickle cell disease
11 Hepatic jaundice Disability of liver to: Acute : Chronic : uptake/ conjugate bilirubin- (hepatocellular) orexcrete bile from the liver (cholestatic)Acute :Chronic :Viral hepatitis A, B, C..Other viruses: EBV, CMVDrugsDose-dependant e.g. paracetamolIdiosyncraticToxinsAutoimmune hepatitisAlcoholic hepatitisViral hepatitis B, CChronic AI hepatitisGenetic (Crigler–Najjar, Gilbert syndroms)End-stage liver disease (of any cause)AlcoholicHepatitis B, CAutoimmuneHaemochromatosisWilson’s diseaseHemochromatosis : it could be primary (HEF gene mutation) or secondary (multiple blood transfusions).
12 Cholestatic jaundiceCholestasis denotes a pathologic condition of impaired bile formation and or bile flow.Intrahepatic cholestasis (Intrahepatic biliary tree diseases or hepatocellular secretory failureExtrahepatic cholestasis (biliary obstruction) frequently is amenable to surgical correction.intrahepatic cholestasis (Intrahepatic biliary tree diseases or hepatocellular secretory failure cannot be treated surgically, and the patient’s condition may be worsened by an operative procedure. Thus, there is some urgency in identifying the cause of jaundice and cholestasis
13 Consequences of Cholestasis Retention of bile salt in liverDecreased hepatocyte functionDecreased Kupffer cell activityDecreased albumin & clotting factors synthesisDecreased collagen synthesis, impaired wound healingRetention of bile constituents in serumJaundice, dark urine and pruritusCVS depressionNephrotoxicityHypercholesterolemia, atheroma, Xanthoma
14 Consequences of Cholestasis Absence of bile in IntestineEscape of endotoxins into portal bloodMal-absorption of fats and Vitamin A, D, E & KClay colored stools
15 Intrahepatic cholestasis Cholestatic phase of AVHAlcoholic HepatitisDrug induced liver diseasePrimary biliary cirrhosisPrimary sclerosing cholangitisTPNCholestasis of pregnancySepsisBenign postoperative Cholestasis
16 Drugs that lead to Cholestasis Jaundice EstrogenTamoxifenAnabolic steroidAzathioprineChlorpromazineCarbamazepineAntibiotics- Erythromycin, Rifampicin
20 Malignant Carcinoma gall bladder Periampullary carcinoma CholangiocarcinomaCarcinoma of the head of pancreasObstruction due to metastatic LN
21 Clinical presentation RUQ pain/painless,Nausea, vomiting, fever, jaundice,Dark urine , pale stool, pruritusCharcot triad: pain, jaundice, feverReynold’s pentad: triad+ confusion, shockSkin xanthomasSymptoms of intestinal mal-absorptionDeficiency of fat soluble vitamins
22 Calculous obstruction: Younger patient, intermittent abdominal pain, fatty dyspepsia, fluctuant jaundice, dark urine, pale stool, pruritus (bile salt deposits)Neoplasia: Older age, painless/ mild discomfort, weight loss, progressive jaundice, dark urine, pale stool, pruritus, Courvoisier sign, hepatomegalyHepatocellular: Stigmata of CLD- liver palm, spider naevi, gynecomastia, signs of PH (splenomegaly, ascitis, caput medusae), hepatomegaly
23 Courvoisier’s law/sign If the CBD is obstructed due to calculus , the GB is usually not distended owing to previous inflammatory fibrosis.If CBD is obstructed due to malignant growth, the GB becomes distended in order to reduce the press. in the biliary system.In presence of enlarged g b associated with jaundice ,the cause is unlikely to be gall stone
24 Laboratory Investigations Blood test (Hemoglobin, WBC, Platelets)Coagulation Profile – PT, aPTT, INRHepatic profile (Bilirubin, transaminase, ALP, GGT, albumin)Hepatitis profile (HAV, HBV, HCV)Tumour markers (AFP, CEA, CA 19-9)Blood test (Hemoglobin, WBC, Platelets)? infections. HemolysisCoagulation Profile (PTT, INR,..)? in liver failure patients the tendency of bleeding is high, ( vit. K deficiency because this is lipid soluble vitamin so it will not be absorbed because of the live unable to produce bile which is responsible for lipid absorption. and unable to produce clotting factors)Antibody assay? rule out infectious and autoimmune diseasesSurface antigen? look for hepatitis virusTotal and fractional Bilirubin see the summery slide
26 Alkaline Phosphatase Liver, bone, placenta and intestine Used mainly as indicator of ductal causes: partial obstruction of bile ducts, primary biliary cirrhosis, sclerosing cholangitisElevated in all extra hepatic obstruction with values greater 3-5 times the normal
27 GGT Very sensitive for hepatobiliary diseases. Mainly it increases in ductal injuryIn case of increase in alkaline phosphatase, GGT is a good test to exclude the bone source of ALPHigh Alkaline Phosphatase, Normal GGT Bone source likelyHigh Alkaline Phosphatase, High GGT Hepatic source likely
28 AST & ALTAST (aspartate aminotransferase) : liver, cardiac muscle, skeletal muscles, kidneys, brain, pancreasALT (alanine aminotransferase) liver, skeletal muscleUsed as indicator of liver cell injuryALT is more specific
32 Imaging studies To determine: Extrahepatic obstruction Level of obstructionCause of obstructionStagingBest therapeutic approach
33 ULTRASOUNDBest imaging for biliary tree, non-invasive, cheap, high accuracy esp. in gallstones and biliary dilatation.Disadvantage: distal bile duct may be obscured by bowel gasAt PTC or ERCP, stents can be introduced (treatment during diagnosis)
34 ENDOSCOPIC ULTRASOUND (EUS) 98%diagnostic accuracy.Diagnostic tissue sampling (EUS-FNA)High sensitivity for- focal pancreatic mass (superior to CT).More specific to biliary stricture compared to MRCP.
35 Other Investigations CT : MRCP: ERCP: Detects primary and metastatic tumorsMRCP:Non invasive visualization of hepato biliary tree.ERCP:invasivetherapeutic (biopsy, brush cytology, Stone extraction or stenting)Complications: Pancreatitis, Cholangitis, Hge, Sepsislimitations: Unfavorable anatomy
36 HIDA Scan: useful in acute cholecystitis Diagnostic Laparoscopy PTC indications:when ERCP either is inappropriate or has failed.Drainage of biliary obstructions.HIDA Scan: useful in acute cholecystitisDiagnostic LaparoscopyAngiography: Rule out abnormal vascular anatomyTumor markers- CA19-9 , CEA
44 Preoperative preparation Oral H2 antagonistVit. K or FFPPeri-operative broad spectrum antibioticsRehydration and adequate diuresisFurosemide/ MannitolCatheterization & CVP monitoring
45 Carcinoma gallbladder: Radical Cholecystectomy with wedge resection & CBD excisionCholedocholithiasis:ERCP removal, CBD explorationCholangio carcinoma:Liver resection and or local excision of thelesion or Whipple operationor stenting by ERCP or PTCBiliary Stricture:Hepatico-jejenostomy
46 Whipple’s operation Periampullary Ca: Carcinoma head of pancreas: Bilio-enteric bypass for unresectable tumour