Obstructive Jaundice Dr. Mohammed H. Alarawi Consultant General surgeon Al- Iman General Hospital FRCS, ED – ABCS

Objectives Case scenario Definition of Jaundice Bilirubin Biochemistry Anatomy of the Hepatobiliary Tree Types of Jaundice OBSTRUCTIV Jaundice. Clinical presentation Laboratory investigations Radiological investigations Treatment options

Case Scenario 82 yr old male patient presents with progressive jaundice, itching, loss of weight .

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

H/o 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 –Afebrile anemia +, Jaundice ++– No Lymphadenopathy Scratch marks Abdomen Soft non-tender– palpable gall bladder– No free fluid

Definition of Jaundice = icterus 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 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.

Bilirubin Biochemistry 80% of Bilirubin is formed by the degradation of Heme from Red blood cell. The reminder from Heme containing enzymes (cytochromes, catalase, peroxidase..) Is potentially Toxic Remains harmless by binding to albumin

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

Conjugated Bilirubin (Direct bilirubin) Bilirubin must be conjugated before its excretion into bile Bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase This changes the bilirubin into a water soluble and thus facilitates rapid excretion 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.

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.

Types of Jaundice Pre-hepatic Hepatic Post-hepatic (Obstructive)(cholestatic) Intrahepatic Extrahepatic 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. Physiologic Jaundice???

Pre-hepatic Excess extra-hepatic production of bilirubin raising unconjagated form. Haemolytic anemias - Malariae

Hepatic jaundice liver disability to uptake, conjugate or excecrete bilirubin, raising unconjugated bilirubin 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).

Post hepatic (Obstructive Jaundice)

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

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

Cholestatic jaundice Cholestasis denotes a pathologic condition of impaired bile formation and or bile flow. Extrahepatic cholestasis (biliary obstruction) frequently is amenable to surgical correction. Intrahepatic cholestasis (Intrahepatic biliary tree diseases or hepatocellular secretory failure 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

What are the Causes of Cholestasis: Intrahepatic & Extrahepatic

Intrahepatic cholestasis Cholestatic phase of AVH Alcoholic H Drug induced liver D Primary biliary cirrhosis Primary sclerosing cholangitis TPN

Intrahepatic cholestasis Cholestasis of pregnancy Sepsis Benign postoperative Cholestasis

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

Consequences of Cholestasis Retention of bile salt in liver Decreased hepatocyte function Decreased Kuffer 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

Clinical presentation of obstructive jaundice Jaundice, dark urine,pale stool, pruritus RUQ pain, Nausea and vomiting Fever Charcot Triad??? Skin xanthomas Symptoms related to intestinal mal-absorption and nutritional deficiency of fat soluble vitamins

History - sex - onset , duration - alcohol consumption - age - sex - onset , duration - alcohol consumption - blood transfusion - drug abuse - medication - recent surgery(post op complication) - history of hemolytic disorders - weight loss, loss of appetite - pain ,fever ,fatty dyspepsia - dark urine, pale stool. - yellow discoloration(skin , sclera) - symptoms & signs of chronic liver disease

Courvoisier’s law 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 (PTT, INR,..)? Hepatic profile Hepatitis profile 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)

AST & ALT AST found in liver, cardiac muscle, skeletal muscles, kidneys, brain, pancreas ALT found in liver, skeletal muscle Used as indicator of liver cell injury ALT is more specific

Alkaline Phos. Can come from 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 patients with extra hepatic obstruction with values greater 3-5 times the normal

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

ALP  cholesterol  Serum conjugated bilirubin > 50% of total: more suggestive of post hepatic than hepatic jaundice ALP  cholesterol  Fecal urobilinogen (incomplete obstruction) and absent (complete obstruction) Urobilinogenuria is absent in complete obstructive jaundice with  bilirubinuria.

Case scenario Con’t Hb: 11.7• Hct: 35• WBC: 6000; Plt: 350,000 Serum Creat: 1.2 mg• Total bil: 20 mg;B1(unconj): 2 mgB2 (conj): 18 mg• Alkaline phosphatase: 990 U/L• Total protein: 6.5 grams; CA 19-9: 350 units/ml

Radiology Determine: Extrahepatic obstruction level of obstruction Cause of obstruction Staging Best therapeutic approach

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

Radiology Ultrasound Best imaging for biliary tree – non-invasive, cheap, high accuracy esp in gallstones and biliary dilatation. Disadvantege: 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.

CT : 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: Unfaverable anatomy

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

ERCP MRCP

Scenario case con’t USG-Abd: 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 And possibility of periampullary mass ADVISE ERCP

Treatment options for obstructive jaundice Depends on the cause and severity . Antibiotic therapy (if indicated for infection) . ERCP, allows treatment of some bile duct problems including removal of gallstones causing obstruction Intravenous fluids , pain medications and Nutritional support . Surgery to repair anatomical defects or create alternative pathways for the flow of bile Treatment for cancer, which may include surgery, chemotherapy, or radiation therapy

What are the Surgical Procedures done for Obstructive Jaundice?

Ca GB: Radical Cholecystectomy with wedge resection and CBD excision Cholediocholithiasis: ERCP removal, mechanical lithotripsy , shock wave laser or CBD exploration Cholangio Ca: Liver resection and or local excision of the lesion or Whipple or stenting by ERCP or PTC Biliary Stricture: Hepatico-jejenostomy/

Periampullary Ca: Whipple’s Procedure Chronic Pancreatits with head Mass: Whipple/ bilio-enteric anastmosis

Whipple’s Procedure Pancreaticojejunostomy- end to end Hepatico-jejunostomy – end to side Gastrojejunostomy – end to side Feeding Jejunostomy

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

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