Jaundice

For neonatal jaundice please see the Neonatal jaundice page

Background

Cycle of heme breakdown and excretion.

• Bilirubin is end product of heme metabolism
• All bilirubin products in the body are initially unconjugated and is transported bound to albumin into hepatocytes t o becombined with glucuronic acid into conjugated bilirubin
• Conjugated bilirubin is then excreted into biliary tract
• Only conjugated bilirubin is water-soluble (present in urine)
• Normal bilirubin level is <1.1 (70% unconjugated)

Jaundice Types

Prehepatic (overproduction):

• Hemolysis
• Primarily unconjugated bili

Hepatic (inadequate processing):

• Viral, alcohol, toxin
• Primarily unconjugated bili

Posthepatic (underexcretion):

• Pancreatic tumor, choledocholithiasis
• Primarily conjugated bili

Clinical Features

Jaundice of the skin

Pediatric jaundice with icterus of sclera.

• Yellow skin, sclera
• +/- dark urine

Differential Diagnosis

Jaundice

Differential diagnosis of hyperbilirubinemia.

Indirect Hyperbilirubinemia

• Hemolytic
  • G6PD
  • Drug related
  • Autoimmune hemolytic anemia
• Hematoma resorption
• Ineffective erythropoiesis
• Gilbert's

Direct (Conjugated) Hyperbilirubinemia

• Choledocholithiasis
• Cholecystitis
• Ascending cholangitis
• AIDS cholangiopathy
• Stricture
• Neoplasm
  • Pancreatic head
  • Gallbladder
  • Primary liver (e.g. hepatocellular carcinoma)
  • Metastatic
• Obstructing AAA

Hepatocellular damage

Patient will have severely elevated AST/ALT with often normal Alkaline Phosphatase

• Viral hepatitis
• Fulminant hepatic failure
• alcoholic hepatitis
• Ischemic hepatitis
• Toxins
  • Isoniazid
  • Phenytoin
  • acetaminophen
  • Ritonavir
  • Halothane
  • Sulfonamide
• Autoimmune hepatitis
  • Primary biliary cirrhosis
• HELLP Syndrome
• Congestive Hepatopathy
  • CHF
  • Sepsis (Shock Liver)

Pregnancy Related

• HELLP syndrome
• Acute fatty liver of pregnancy
• Hyperemesis gravidarum
• Cholestasis of pregnancy

Transplant Related

• Transplant rejection
• Graft-vs-host disease

Pediatric Related

• Inborn error of metabolism
• Neonatal jaundice (physiologic)

Additional Differential Diagnosis

• Reye syndrome
• TPN
• Heatstroke
• Budd-Chiari (with acute ascites)
• Wilson's disease
• Sarcoidosis
• Amyloidosis

Masqueraders

Only bilirubin stains the sclera

• Carotenemia
• Quinacrine ingestion
• Dinitrophenol, teryl (explosive chemicals)

Evaluation

Evaluation algorithm

• Urine pregnancy
• CBC
• Chemistry
• LFTs
  • Hepatocyte injury: AST, ALT, alk phos
  • Hepatocyte catabolic activity: Bilirubin
• Coags
  • Hepatocyte synthetic function
• Albumin
  • Hepatocyte synthetic function
• Ammonia
  • Hepatocyte catabolic activity
• Acute hepatitis panel
• Lipase
• Urinalysis
• ?US vs. CT vs MRCP
• ?Retic count
• ?Haptoglobin/LDH
• ?APAP/ASA/Utox/ETOH

Liver function tests

Transaminases

• Transaminases in hundreds associated with mild injury; thousands suggests extensive injury
• Elevations <5x normal typical of alcoholic liver disease
• AST:ALT ratio > 2 common in acute alcoholic hepatitis (alcohol stimulates AST production)
• May be normal in end-stage liver failure
• ALT more specific marker of hepatocyte injury than AST

Alk phos

• Mild to moderate elevations accompany virtually all hepatobiliary disease
• Elevations > 4x normal suggest cholestasis

GGT

• Elevation in setting of hepatitis suggestive of alcoholic etiology

LDH

• Moderate elevations are seen in all hepatocellular disorders and cirrhosis
• Hemolysis results in elevation of LDH and unconjugated bili

Ammonia

• Elevation does NOT correlate with acute worsening of hepatic function in cirrhotic patient
• Serves as marker of generalized decline than as diagnostic tool or therapeutic end point

Coagulation Markers (PT/PTT/INR)

• Marker of synthetic function
• Correlation between PT prolongation and clinical outcome in fulminant liver disease

Albumin

• Marker of synthetic function
  • Half-life is 3 weeks so less useful than PT in evaluating fulminant liver disease
• Low levels also seen in malnutrition

Management

• Management is dependent on the diagnosis of either conjugated or unconjugated hyperblirubinemia and the severity of the elevation

Disposition

New Onset Jaundice Admission Criteria

• Transaminase >1,000 IU/L
• Tbil >10mg/dL
• Evidence coagulopathy

See Also

• Neonatal Jaundice
• Acute hepatitis
• Viral hepatitis
• Acute hepatic failure
• Cirrhosis
• Ascites