Obstructive Jaundice M K Alam MS; FRCS Ed

Objectives Definition Anatomy of the hepatobiliary tree Biochemistry of bilirubin Types of Jaundice Causes of OBSTRUCTIVE Jaundice. Clinical presentation Laboratory investigations Radiological investigations Treatment options

Definition of Jaundice Yellowish pigmentation of the skin and other tissues (sclera, mucous membrane, deep tissue…) due to deposition of bile pigment(bilirubin) when serum level exceed 3mg/dl (50 µmol/L) Normal Total serum bilirubin is 0.3-1.9 mg/dl Direct bilirubin < 0.4 mg/dl The 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.

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.

Bilirubin Biochemistry 80% of bilirubin is formed by the degradation of Heme from RBC. The reminder Heme containing enzymes (cytochromes, catalase, peroxidase..) Potentially toxic Remains harmless by binding to albumin

Unconjugated Bilirubin (indirect bilirubin) Insoluble in water Tightly complex to albumin Not filtered through renal glomeruli Not excreted in urine Toxic substance The main form of bilirubin in the blood

Conjugated Bilirubin (Direct bilirubin) Bilirubin conjugated in the liver before its excretion into bile Conjugated with glucuronic acid Changes bilirubin into water soluble Can be filtered through renal glomeruli Present in low concentration in the blood

Con’t When 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.

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.

Pre-hepatic Excess extra-hepatic production of bilirubin raising unconjugated form. Haemolytic anemias: congenital spherocytosis, sickle cell disease

Hepatic jaundice Disability of liver to uptake/ conjugate bilirubin (hepatocellular), or excrete bile from the liver (cholestatic) Acute : Chronic : Viral hepatitis A, B, C.. Other viruses: EBV, CMV Drugs Dose-dependant e.g. paracetamol Idiosyncratic Toxins Autoimmune hepatitis Alcoholic hepatitis Tumours Viral hepatitis B, C Chronic AI hepatitis Genetic (Crigler–Najjar, Gilbert syndroms) End-stage liver disease (of any cause) Alcoholic Hepatitis B, C Autoimmune Haemochromatosis Wilson’s disease Hemochromatosis : it could be primary (HEF gene mutation) or secondary (multiple blood transfusions).

Cholestatic jaundice Cholestasis denotes a pathologic condition of impaired bile formation and or bile flow. Intrahepatic cholestasis (Intrahepatic biliary tree diseases or hepatocellular secretory failure Extrahepatic 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

Consequences of Cholestasis Retention of bile salt in liver Decreased hepatocyte function Decreased Kupffer cell activity Decreased albumin & clotting factors synthesis Decreased collagen synthesis, impaired wound healing Retention of bile constituents in serum Jaundice, dark urine and pruritis CVS depression Nephrotoxicity Hypercholesterolemia, atheroma, Xanthoma

Consequences of Cholestasis Absence of bile in Intestine Escape of endotoxins into portal blood Mal-absorption of fats and Vitamin A, D, E & K Clay colored stools

Intrahepatic cholestasis Cholestatic phase of AVH Alcoholic Hepatitis Drug induced liver disease Primary biliary cirrhosis Primary sclerosing cholangitis TPN Cholestasis of pregnancy Sepsis Benign postoperative Cholestasis

Drugs that lead to Cholestasis Jaundice Estrogen Tamoxifen Anabolic steroid Azathioprine Chlorpromazine Carbamazepine Antibiotics- Erythromycin, Rifampicin

Post hepatic (Obstructive Jaundice)

Benign Choledocholithiasis* Primary sclerosing cholangitis Post-surgical stricture Pancreatitis Parasitic infections

Malignant Carcinoma gall bladder Periampullary carcinoma Cholangiocarcinoma Carcinoma of the head of pancreas Obstruction due to metastatic LN

History - Age, gender - Pain / painless ,onset , duration - Fever ,fatty dyspepsia - Jaundice, dark urine, pale stool - Alcohol, blood transfusion - Medication , drug abuse - Surgery(post op complication) - Hemolytic disorders - Weight loss, loss of appetite

Clinical presentation RUQ pain/painless, nausea, vomiting, fever, jaundice, dark urine , pale stool, pruritus Charcot triad: pain, jaundice, fever Reynold’s pentad: triad+ confusion, shock Skin xanthomas Symptoms of intestinal mal-absorption Deficiency of fat soluble vitamins

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, hepatomegaly Hepatocellular: Stigmata of CLD- liver palm, spider naevi, gynecomastia, signs of PH (splenomegaly, ascitis, caput medusae), hepatomegaly

Courvoisier’s law/sign If the CBD is obst. due to calculus , the GB is usually not distended owing to previous inflammatory fibrosis. If CBD is obstr. 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

Laboratory Investigations Blood test (Hemoglobin, WBC, Platelets)? Coagulation Profile Hepatic profile Hepatitis profile Tumour marker Blood test (Hemoglobin, WBC, Platelets)? infections. Hemolysis Coagulation 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 diseases Surface antigen? look for hepatitis virus Total and fractional Bilirubin see the summery slide

Laboratory Investigations Hepatic Profile: AST (10-40) ALT Alkaline phosphatase (40-100 U/L) Albumin (35-50 g/L) Total bilirubin (5-20 umol/L) Direct bilirubin (<5 umol/L) Indirect bilirubin (<12 umol/L)

Alkaline Phosphatase Liver, bone, placenta and intestine Used mainly as indicator of ductal causes: partial obstruction of bile ducts, primary biliary cirrhosis, sclerosing cholangitis Elevated in all extra hepatic obstruction with values greater 3-5 times the normal

GGT Very sensitive for hepatobiliary diseases. Mainly it increases in ductal injury In case of increase in alkaline phosphatase GGT is a good test to exclude the bone source of ALP High Alkaline Phosph. Normal GGT  Bone source likely High Alkaline Phosph . High GGT  Hepatic source likely

AST & ALT AST (aspartate aminotransferase) : liver, cardiac muscle, skeletal muscles, kidneys, brain, pancreas ALT (alanine aminotransferase) liver, skeletal muscle Used as indicator of liver cell injury ALT is more specific

Haemolytic jaundice High unconjugated (indirect) serum bilirubin No bilirubin in urine Normal liver enzymes

Obstructive jaundice ALP  Transaminases: normal/ moderately elevated Serum conjugated bilirubin > 50% of total: more suggestive of post hepatic than hepatic jaundice ALP  Transaminases: normal/ moderately elevated Fecal urobilinogen:  -incomplete obstruction , absent - complete obstruction Urobilinogen in urine: absent in complete obstructive jaundice with  bilirubinuria.

Case Scenario 82-yr old, male Presents with: Progressive jaundice Itching Loss of weight .

History of presenting illness Gradually progressive jaundice Recurrent episodes of itching White stools for 2 months Dark yellow urine Generalized weakness & fatigability- 6 months Weight loss - 1 year Reduced appetite No fever

Past illness Personal History No h/o DM, HT, TB, No past Surgical history Personal History Smoker – 25 yrs Non-alcoholic

Physical Examination Abdomen Pulse 88/min, BP 110/70 mmHg, afebrile Anemia +, Jaundice ++ No lymphadenopathy Scratch marks Abdomen Soft non-tender– Palpable gall bladder No free fluid

Investigations Hb. 11.7, Hct. 35 WBC: 6000, Platelet: 350,000 Serum creatinine: 1.2 mg Total bilirubin: 20 mg; (unconj. 2 mg, conj. 18 mg) Alkaline phosphatase: 990 U/L Total protein: 6.5 grams; CA 19-9: 350 units/ml

Imaging studies To determine: Extrahepatic obstruction Level of obstruction Cause of obstruction Staging Best therapeutic approach

ULTRASOUND Best imaging for biliary tree, non-invasive, cheap, high accuracy esp. in gallstones and biliary dilatation. Disadvantage: distal bile duct may be obscured by bowel gas At PTC or ERCP, stents can be introduced (treatment during diagnosis)

ENDOSCOPIC ULTRASOUND (EUS) 98%diagnostic accuracy in obstructive jaundice It allows diagnostic tissue sampling (EUS-FNA) High sensitivity for identification of focal pancreatic mass, superior to CT. More specific to biliary stricture compared to MRCP.

Imaging/ ERCP CT : MRCP: ERCP: Main role in malignancies for primary and metastatic tumors MRCP: Non invasive to visualize the hepato biliary tree. ERCP: invasive, therapeutic (biopsy, brush cytology, Stone extraction or stenting) Complications: Pancreatitis, Cholangitis, Hge, Sepsis limitations: Unfavorable anatomy

ERCP MRCP

Oral Cholecystography (OCG): PTC indications: when ERCP either is inappropriate or has failed. Drainage of biliary obstructions. Oral Cholecystography (OCG): useful with symptomatic patients with negative US HIDA Scan: useful in acute cholecystitis Diagnostic Laparoscopy Angiography: Rule out abnormal vascular anatomy Tumor markers- CA19-9 , CEA

Scenario case (cont.) USG- solid mass in distal CBD, dilated CBD, Intrahepatic Biliary distension and distended GB CT abdomen show grossly dilated intra and extra hepatic biliary channels with distended gall bladder. Possibility of periampullary mass. Advised ERCP.

Treatment options for obstructive jaundice Antibiotic therapy (if indicated for infection) Intravenous fluids Pain medications, nutritional support ERCP: biopsy, stone removal ,dilatation, stent placement Surgery: Curative resection, palliative by-pass Adjuvant therapy for cancer: chemotherapy, or radiotherapy

ERCP (Stone CBD, Periampullary carcinoma)

CBD stone extraction

Surgical Procedures for Obstructive Jaundice

Preoperative preparation Oral H2 antagonist Vit. K or FFP Perioperative broad spectrum antibiotics Rehydration and adequate diuresis Furosemide/ Manitol Catheterization & CVP monitoring

Carcinoma gallbladder: Radical Cholecystectomy with wedge resection & CBD excision Cholediocholithiasis: ERCP removal, CBD exploration Cholangio Ca: Liver resection, Whipple operation, Stenting by ERCP or PTC- palliative Biliary Stricture: Hepatico-jejenostomy/

Periampullary Ca: Whipple’s operation Carcinoma head pancreas: Whipple op. Bilio-enteric bypass (palliative)

Whipple’s Procedure

Postoperative management - Correct Fluid & Electrolyte imbalance - Correct hypothermia - Achieve CVS stability - Adequate analgesia & chest physiotherapy - Antibiotics + H2 receptor antagonist - Maintain urine output - Replace blood and blood products

Thank you!