Jaundice

Jaundice

Dr Monika Pathania
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Overview

• Definition
• Production & metabolism
• Measurement of bilirubin – serum & urine
• Approach to the patient
• Broad Differential Diagnosis
• Work-up for “Medical” Jaundice
• Work-up if Obstructive Jaundice
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Definition
• Yellowish discoloration of tissue resulting from the deposition of
bilirubin in hyperbilirubinemia.
• Detected by examining sclerae – ELASTIN
• Scleral icterus -serum bilirubin of 3.0 mg/Dl
• As serum bilirubin levels rise skin yellow in light-skinned &green if long-
standing, oxidation of bilirubin to biliverdin.
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Differential diagnosis for yellowing of skin :

• Drugs – quinacrine, phenols.

• Carotenoderma -ingest excessive amounts of carotene. palms, soles,
forehead, and nasolabial folds. sparing of the sclerae.
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Production and Metabolism of

Bilirubin :
• Bilirubin, a tetrapyrrole pigment.

Bilirubin

HEMOPROTIENS-
70-80%-senescent RBC
Myoglobin,cytochromes
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Production steps:

Formation of
1.Opening of heme
Biliverdin by
ring
Microsomal enzyme
Bilirubin formed in
RES
BILIRUBIN by
2.Biliverdin Cytosolic enz.
(Insoluble in plasma)
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• To be transported in blood, bilirubin must be solubilized by

noncovalent binding to albumin.
• Bilirubin + albumin= unconjugated bilirubin transported to liver.
• Bilirubin minus albumin enters hepatocyte.
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UNCONJ. Bilirubin Urobilinogen (80-90% excreted in feces)

10-20% portal circulation & reexcreted in liver

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Measurement of Serum Bilirubin

• van den Bergh reaction- direct- and indirect

• the normal serum bilirubin is <1 mg/dL
• Up to 30% of the total may be direct-reacting (conjugated) bilirubin
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Measurement of Urine Bilirubin

• Unconjugated bilirubin is always bound to albumin in the serum -not
filtered by the kidney-not found in the urine.
• Conjugated bilirubin is filtered at the glomerulus and the majority is
reabsorbed by the proximal tubules; a small fraction is excreted in the
urine
• Any bilirubin found in the urine is conjugated bilirubin. The presence of
bilirubinuria implies the presence of liver disease
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Approach to the Patient:

JAUNDICE
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History,physical
exam.,lab tests-
s.bilirubin,LFT,PT,
Albumin

Isolated
Bilirubin & LFT
hyperbilirubinemiia

Direct>15% - 1.Hepatocellular-
Indirect-DRUGS- ALT/AST>>ALP
Rifampicin, inherited disorders
e.g- Dubin johnson 2.CHOLESTATIC—
INHERITED – G syn.,Rotor’s syn.
ilberts,Crigler ALP>>>>ALT/AST
Najjar,,Hemolytic
dis..,
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Hepatocellular Conditions that May Produce Jaundice

Viral hepatitis – Viral serology, ALT>=AST

  Hepatitis A, B, C, D, and E
  Epstein-Barr virus
  Cytomegalovirus
  Herpes simplex
Alcohol – AST/ALT -2:1,AST rarely > 300
Drug toxicity
  Predictable, dose-dependent, e.g., acetaminophen
  Unpredictable, idosyncratic, e.g., isoniazid
Environmental toxins
  Vinyl chloride
  Jamaica bush tea—pyrrolizidine alkaloids
  Kava Kava
  Wild mushrooms—Amanita phalloides or A. verna
Wilson's disease – young adult males where no othr cause of jaundice found
Autoimmune hepatitis – middle aged females,
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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)
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• While ALT and AST values less than 8 times normal may be seen in
either hepatocellular or cholestatic liver disease, values 25 times
normal or higher are seen primarily in acute hepatocellular diseases.
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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
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When the pattern of the liver tests suggests a cholestatic disorder, the next
step is to determine whether it is intra- or extrahepatic cholestasis

• Appropriate test is an ultrasound

• Biliary dilatation indicates extrahepatic cholestasis – SURGICAL
JAUNDICE
• Absence of biliary dilatation suggests intrahepatic cholestasis
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Intrahepatic

A. Viral hepatitis

1. Fibrosing cholestatic hepatitis—hepatitis B and C

2. Hepatitis A, Epstein-Barr virus, cytomegalovirus

B. Alcoholic hepatitis

C. Drug toxicity

1. Pure cholestasis—anabolic and contraceptive steroids

2. Cholestatic hepatitis—chlorpromazine, erythromycin estolate

3. Chronic cholestasis—chlorpromazine and prochlorperazine

D. Primary biliary cirrhosis

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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
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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
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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
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DDx: Obstructive Jaundice

• 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
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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
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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)
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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
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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)
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Thanks