Jaundice Jaundice Bilirubin Metabolism Prehepatic Hepatic Posthepatic Jaundice

Jaundice

Jaundice Bilirubin Metabolism • Pre-hepatic • Hepatic • Post-hepatic

Jaundice Bilirubin Metabolism: Pre-Hepatic • Bilirubin is formed in reticuloendothelial system as breakdown product of hemaglobin. • • Heme group biliverdin bilirubin Bilirubin is insoluble in water, bound to albumin. Bilirubin circulates in the blood before uptake by the liver. Pre-hepatic jaundice = if not taken up by the liver/produced in excess, unconjugated bilirubin is deposited in extrahepatic tissues. – Kernicterus in newborns

Jaundice Bilirubin Metabolism: Hepatic • Bilirubin is taken up into hepatocytes and conjugated to glucuronic acid = bilirubin diglucuronide > bilirubin monoglucuronide > secreted into bile • The glucuronide conjugated form of bilirubin is water soluble and is excreted into bile. • Hepatic jaundice = disorders of bilirubin uptake or conjugation

Jaundice Bilirubin Metabolism: Post-Hepatic • Glucuronide-conjugated bilirubin degraded to urobilinogen. • Urobilinogen pathway: – may be reabsorbed by the gut and returned to the liver – converted to urobilin > reabsorbed into plasma for excretion by kidneys – May be acted upon by bacterial enzymes within the gut to form the bile pigment stercobilinogen > stercobilin>brown color of feces • Obstructive jaundice = failure of bilirubin to reach the gut > light colored stool, dark urine.

Jaundice DDX ↑production ↓transport or ↓conjugation Impaired excretion Biliary obstruction ↑ Unconjugated ↑ Conjugated Hemolysis Gilbert’s Rotor’s CH/CBD stone Transfusions Crigler-Najarr Dubin. Johnson Stricture Txfusion rxn Neonatal Cancer Tumor/Cancer Sepsis Cirrhosis Pancreatitis Burns Hepatitis PSC Hgb-opathies Drug inhibition Amyloidosis Pregnancy

Jaundice DDX: Conjugated Hyperbilirubinemia • Intrahepatic Cholestasis (impaired excretion) • Functional, obstructive – Hepatitis (viral, alcoholic, and non-alcoholic) – – – – Primary biliary cirrhosis or end-stage liver dz Sepsis and hypoperfusion states TPN Pregnancy Infiltrative disease: TB, amyloid, sarcoid, lymphoma Drugs/toxins i. e. chlorpromazine, arsenic Post-op patient or post-organ transplantation Hepatic crisis in sickle cell disease

Jaundice DDX: Obstructive Jaundice • Extrahepatic Cholestasis (obstructive jaundice) – Choledocholithiasis – Cancer/Neoplasm: • • • – – Pancreatic CA Cholangiocarcinoma (rare) Gallbladder CA Ampullary adenoma/adenocarcinoma Duodenal adenoma/adenocarcinoma Metastatic CA (and adenopathy of porta hepatis) Strictures after invasive procedures Acute and chronic pancreatitis Primary sclerosing cholangitis (PSC) Parasitic infections

Jaundice Evaluation: History • • • Fever/chills, RUQ pain (cholangitis) Use of alcohol Hepatitis risk factors Inherited disorders including liver diseases and hemolytic conditions H/O blood transfusion TPN use H/O abdominal surgery Travel history Use of drugs or herbal medications Exposure to toxic substances

Jaundice Evaluation: PE • Look for jaundice: under tongue, conjunctiva, skin (>1. 5 mg/d. L) • Signs of end stage liver disease (cirrhosis): ascites, splenomegaly, spider angiomata, and gynecomastia • Hyperpigmentation (hemochromatosis) • Kayser-Fleischer ring (Wilson’s disease) • Courvoisier’s sign = painless, palpable/distended gallbladder on exam (think of CA)

Jaundice Evaluation: Labs • CBC – infection, anemia • LFTs – Bilirubin (total/direct/indirect) – AST, ALT (AST/ALT) • Predominant increase in AST/ALT implies intrinsic hepatocellular disease – Alk Phos, GGT • ↑Alk Phos also seen in sarcoid, TB, bone • In this case, GGT is specific for biliary origin • INR/albumin • CA 19. 9 • AFP

Jaundice Evaluation: Additional Labs • Further specific labs. – Serologic tests for viral hepatitis – Antimitochondrial antibodies (for primary biliary cirrhosis) – Anti-nuclear anti-smooth muscle (sm), and liver-kidney microsomal (LKM) antibodies (for autoimmune hepatitis) – Serum levels of iron, transferrin, and ferritin (for hemochromatosis) – Serum levels of ceruloplasmin (for Wilson's disease) – Measurement of alpha-1 antitrypsin activity (for alpha-1 antitrypsin deficiency)

Jaundice Imaging for Obstructive Jaundice • RUQ U/S: Stones, wall thickening, edema, CBD diameter/obstruction • MRCP • ERCP – Direct visualization of biliary tree & pancreatic ducts – Procedure of choice for choledocholithiasis – Diagnostic & therapeutic • PTC – When ERCP not possible • CT scan: identification and description of obstruction • Endoscopic U/S: visualization of the common bile duct without the hindrance of overlying bowel gas

Jaundice Treatment • Start with ABCs & resuscitation • If obstructive jaundice: – Ascending cholangitis: IVF, ABX, decompression (medical emergency) – Stones: remove using ERCP or surgery – Benign stricture: stent vs. drainage catheter – Cancer: Stent vs. drainage +/- resection of CA • Primary goal = decompression

Jaundice Take Home Points • Jaundice DDX is extensive • DDX starting point: pre-hepatic, post-hepatic • Obstructive jaundice: choledocholithiasis, tumors, PSC, pancreatitis, stricture, parasites • Ascending cholangitis is an emergency that must be identified and treated promptly • Imaging: U/S, EUS, CT, ERCP, MRCP • Treatment of obstructive jaundice: decompression