Jaundice

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Jaundice
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Bilirubin Metabolism

• Pre-hepatic
• Hepatic
• Post-hepatic

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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 extra-hepatic tissues.
• Kernicterus in newborns

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Bilirubin Metabolism Hepatic

• Bilirubin is taken up into hepatocytes and
  conjugated to glucuronic acid bilirubin
  diglucuronide gt bilirubin monoglucuronide gt
  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

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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 gt reabsorbed into plasma
  for excretion by kidneys
• May be acted upon by bacterial enzymes within the
  gut to form the bile pigment stercobilinogen gt
  stercobilingtbrown color of feces
• Obstructive jaundice failure of bilirubin to
  reach the gut gt light colored stool, dark urine.

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DDX
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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

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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

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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

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Evaluation PE

• Look for jaundice under tongue, conjunctiva,
  skin (gt1.5mg/dL)
• Signs of end stage liver disease (cirrhosis)
  ascites, splenomegaly, spider angiomata, and
  gynecomastia
• Hyperpigmentation (hemochromatosis)
• Kayser-Fleischer ring (Wilsons disease)
• Courvoisiers sign painless, palpable/distended
  gallbladder on exam (think of CA)

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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

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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)

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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

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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

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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