This document provides an overview of jaundice, including normal physiology, pathophysiology, differential diagnosis, evaluation, and treatment. It discusses the broad categories of causes of jaundice as increased bilirubin production, decreased transport or conjugation, impaired excretion, or biliary obstruction. For surgeons, the key differential diagnosis for obstructive jaundice are stones in the common bile duct, cancer, strictures, acute or chronic pancreatitis, and primary sclerosing cholangitis. Evaluation involves history, physical exam, liver function tests, and imaging like ultrasound or MRCP to identify the level and type of obstruction. Treatment depends on whether the jaundice is medical or obstructive, with obstructive

1. Jaundice
Jaundice
Tad Kim, M.D.
UF Surgery
tad.kim@surgery.ufl.edu
(c) 682-3793; (p) 413-3222

2. 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

3. 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

4. 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

5. Jaundice
Broad Differential Diagnosis
↑production ↓transport or
↓conjugation
Impaired
excretion
Biliary
obstruction
↑ Unconjugate ↑ Unconjugate ↑ Conjugated ↑ Conjugated
Hemolysis Gilbert’s Rotor’s CH/CBD stone
Transfusions Crigler-Najarr DubinJohnson Stricture
Txfusion rxn Neonatal Cancer Cancer
Sepsis Cirrhosis Cirrhosis Chronic
pancreatitis
Burns Hepatitis Hepatitis PSC
Hgb-opathies Drug inhibition Amyloidosis
Pregnancy

6. 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

7. 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

8. 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

9. 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 cholangioCA)
– Strictures after invasive procedures
– Acute and chronic pancreatitis
– Primary sclerosing cholangitis (PSC)
– Parasitic infections
• Ascaris lumbricoides, liver flukes
• Just remember top 5 (not parasites)

10. 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)

11. 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

12. 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

13. 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)

14. 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

15. 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

16. 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)