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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.
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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
↑ Unconjugated ↑ Unconjugated ↑ Conjugated
Biliary
obstruction
↑ Conjugated
Hemolysis
Gilbert’s
Rotor’s
CH/CBD stone
Transfusions
Crigler-Najarr
DubinJohnson
Stricture
Txfusion rxn
Neonatal
Cancer
Tumor/Cancer
Sepsis
Cirrhosis
Cirrhosis
Pancreatitis
Burns
Hepatitis
Hepatitis
PSC
Hgb-opathies
Drug inhibition
Amyloidosis
Pregnancy
Jaundice
DDX: Conjugated Hyperbilirubinemia
• Intrahepatic Cholestasis (impaired excretion)
• Functional, obstructive
– Hepatitis (viral, alcoholic, and non-alcoholic)
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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:
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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
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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
(>1.5mg/dL)
• 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, 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