Jaundice Tad Kim, M. D. UF Surgery tad. kim@surgery. ufl. edu (c) 682 -3793; (p) 413 -3222
Jaundice Overview • • Normal Physiology Pathophysiology Broad Differential Diagnosis DDx of Obstructive Jaundice Work-up for “Medical” Jaundice Work-up if Obstructive Jaundice Treatment of Obstructive Jaundice
Jaundice Normal Physiology • Bilirubin is from breakdown of hemoglobin • Unconjugated bilirubin transported to liver – Bound to albumin because insoluble in water • Transported into hepatocyte & conjugated – With glucuronic acid → now water soluble • Secreted into bile • In ileum & colon, converted to urobilinogen – 10 -20% reabsorbed into portal circulation and re-excreted into bile or into urine by kidneys
Jaundice Pathophysiology • Jaundice = bilirubin staining of tissue @ lvl greater than ~2 • Mechanisms: – ↑ production of bilirubin – ↓ hepatocyte transport or conjugation – Impaired excretion of bilirubin – Impaired delivery of bilirubin into intestine • “surgically relevant jaundice” or obstructive jaundice – “Cholestasis” refers to the latter two, impaired excretion and obstructive jaundice
Jaundice Broad Differential Diagnosis ↑production ↓transport or Impaired ↓conjugation excretion ↑ Unconjugate ↑ Conjugated Biliary obstruction ↑ Conjugated Hemolysis Gilbert’s Rotor’s CH/CBD stone Transfusions Crigler-Najarr Dubin. Johnson Stricture Txfusion rxn Neonatal Cancer Sepsis Cirrhosis Chronic pancreatitis Burns Hepatitis PSC Hgb-opathies Drug inhibition Amyloidosis Pregnancy
Jaundice DDx: Unconjugated bilirubinemia • ↑production – Extravascular hemolysis – Extravasation of blood into tissues – Intravascular hemolysis – Errors in production of red blood cells • Impaired hepatic bilirubin uptake(trnsport) – CHF – Portosystemic shunts – Drug inhibition: rifampin, probenecid
Jaundice DDx: Unconjugated bilirubinemia • Impaired bilirubin conjugation – Gilbert’s disease – Crigler-Najarr syndrome – Neonatal jaundice (this is physiologic) – Hyperthyroidism – Estrogens – Liver diseases • chronic hepatitis, cirrhosis, Wilson’s disease
Jaundice DDx: Conjugated Bilirubinemia • Intrahepatic cholestasis/impaired excretion – Hepatitis (viral, alcoholic, and non-alcoholic) • Any cause of hepatocellular injury – Primary biliary cirrhosis or end-stage liver dz – Sepsis and hypoperfusion states – TPN – Pregnancy – Infiltrative dz: 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 • This is the slide to remember for surgeons • Obstructive Jaundice– extrahepatic cholestasis – Choledocholithiasis (CBD or CHD stone) – Cancer (peri-ampullary or cholangio. CA) – Strictures after invasive procedures – Acute and chronic pancreatitis – Primary sclerosing cholangitis (PSC) – Parasitic infections • Ascaris lumbricoides, liver flukes • Just remember top 5 (not parasites)
Jaundice Initial Evaluation: History • Jaundice, acholic stools, tea-colored urine • Fever/chills, RUQ pain (cholangitis) – Could lead to life-threatening septic shock • Reasons to have hepatitis or cirrhosis? – Alcohol, Viral, risk factors for viral hepatitis • • • Exposure to toxins or offending drugs Inherited disorders or hemolytic conditions Recent blood transfusions or blood loss? Is patient septic or on TPN? Recent gallbladder surgery? (CBD injury)
Jaundice Initial Evaluation: Physical Exam • Signs of end stage liver disease (cirrhosis) – Ascites, splenomegaly, spider angiomata, and gynecomastia • Jaundice evident first underneath the tongue, also evident in sclerae or skin • Courvoisier’s sign = painless, but palpable or distended gallbladder on exam – Could indicate malignant obstruction
Jaundice Screening Labs • NL LFT r/o hepatic injury or biliary tract dz – Consider inherited disorders or hemolysis • ↑Alk Phos moreso than AST/ALT implies “cholestasis” (intrahepatic vs obstruction) – ↑Alk Phos also seen in sarcoid, TB, bone – In this case, GGT is specific for biliary origin • Predominant ↑AST/ALT implies intrinsic hepatocellular disease – AST/ALT ratio > 2 in alcoholic hepatitis • ↓albumin or ↑INR c/w advanced liver dz
Jaundice Subsequent Labs • If no concern for obstructive jaundice: – Viral (Hep B&C) serologies for viral hepatitis – anti-mitochondrial Ab (PBC) – anti-smooth muscle Ab (Auto-immune) – iron studies (hemochromatosis) – ceruloplasmin (Wilson’s) – Alpha-1 anti-trypsin activity (for deficiency)
Jaundice Imaging for Obstructive Jaundice • RUQ Ultrasound – See stones, CBD diameter • CT scan – Identify both type & level of obstruction • ERCP – Direct visualization of biliary tree/panc ducts – Procedure of choice for choledocholithiasis – Diagnostic –AND- therapeutic (unlike MRCP) • PTC useul of obstruction is prox to CHD • Endoscopic Ultrasound or EUS
Jaundice Treatment • If Medical, then treat the etiology • If Obstructive Jaundice: – Should r/o ascending cholangitis, ABC/resusc • For cholangitis: IVF, IV Antibiotics, Decompression – Stones (remove stones vs stent vs drainage) • Done via ERCP or PTC or open (surgery) – Benign stricture (stent vs drainage catheter) – Cancer (Stent vs drainage +/- resect the CA) • The key principle is decompression, either externally(drainage) or internally(stenting) the duct open to allow better drainage
Jaundice Take Home Points • Above is a comprehensive approach • For surgery clerkship, all you need to know is: – 1. Broad categories (no specific diagnoses) – 2. The four DDx of obstructive jaundice – 3. H&P (ask about fevers/chills, jaundice, acholic stools, dark urine, weight loss for CA), r/o ascending cholangitis = emergency – 4. Labs (LFT: ? cholestatic, CBC w diff, BMP) – 5. Imaging (U/S, CT, MRCP, EUS) – 6. Therapy (ERCP vs PTC vs surgery)