Jaundice: Difference between revisions

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''For neonatal jaundice please see the [[Neonatal jaundice]] page''
==Background==
==Background==
*Bilirubin is end product of heme metabolism
*Bilirubin is end product of heme metabolism
**All bilirubin products in the body are initially unconjugated
*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
**Transported from albumin into hepatocytes; combine with glucuronic acid into conj bili
*Conjugated bilirubin is then excreted into biliary tract
***Excreted into biliary tract in conjugated form
*Only conjugated bilirubin is water-soluble (present in urine)
*Only conjugated bilirubin is water-soluble (present in urine)
*Nl bilirubin level is <1.1, 70% unconjugated
*Normal bilirubin level is <1.1 (70% unconjugated)


===Jaundice Types===
===Jaundice Types===
*Prehepatic (overproduction)
'''Prehepatic (overproduction):'''
**Hemolysis
*Hemolysis
**Primarily unconj bili
*Primarily unconjugated bili
*Hepatic (inadequate processing)
'''Hepatic (inadequate processing):'''
**Viral, alcohol, toxin
*Viral, alcohol, toxin
**Primarily unconj bili
*Primarily unconjugated bili
*Posthepatic (underexcretion)
'''Posthepatic (underexcretion):'''
**Pancreatic tumor, choledocholithiasis
*Pancreatic tumor, [[choledocholithiasis]]
**Primarily conj bili
*Primarily conjugated bili


===Liver Function Tests===
==Clinical Features==
*Transaminases
 
**Transaminitis in hundreds a/w mild injury; thousands suggests extensive injury
 
**Elevations <5x normal typical of alcoholic liver disease
==Differential Diagnosis==
**AST:ALT ratio > 2 common in alcoholic hepatitis (alcohol stimulates AST production)
[[File:Classification of Hyperbilirubinemia.jpeg|thumb]]
**May be normal in end-stage liver failure
===Indirect Hyperbilirubinemia===
**ALT more specific marker of hepatocyte injury than AST
*Hemolytic
*Alk phos
**[[G6PD]]
**Mild to moderate elevations accompany virtually all hepatobiliary disease
**Drug related
**Elevations > 4x normal suggest cholestasis
**[[Autoimmune hemolytic anemia]]
*GGT
*Hematoma resorption
**Elevation in setting of hepatitis suggestive of alcoholic etiology
*Ineffective erythropoiesis
*LDH
*Gilbert's
**Moderate elevations are seen in all hepatocellular disorders and cirrhosis
===Direct (Conjugated) Hyperbilirubinemia===
**Hemolysis results in elevation of LDH and unconj bili
*[[Choledocholithiasis]]
*Ammonia
*[[Cholecystitis]]
**Elevation doesn't correlate w/ acute worsening of hepatic function in cirrhotic pt
*Ascending [[cholangitis]]
**Serve as marker of generalized decline than as diagnostic tool or therapeutic end point
*[[AIDS]] cholangiopathy
*Coags
*Stricture
**Marker of synthetic function
*Neoplasm
**Correlation between PT prolongation and clinical outcome in fulminant liver disease
**Pancreatic head
*Albumin
**Gallbladder
**Marker of synthetic function
**Primary liver (e.g. [[hepatocellular carcinoma]]
***Half-life is 3wk so less useful than PT in evaluating fulminant liver disease
**Metastatic
**Low levels also seen in malnutrition
*Obstructing [[AAA]]
===Hepatocellular damage===
''Patient will have severely elevated AST/ALT with often normal Alkaline Phosphatase''
*[[Viral hepatitis]]
*[[Acute liver failure|Fulminant hepatic failure]]
*[[alcoholic hepatitis]]
*Ischemia
*Toxins
**[[Isoniazid]]
**[[Phenytoin]]
**[[Acetaminophen (Tylenol) Toxicity|acetaminophen]]
**Ritonavir
**Halothane
**Sulronamide
*[[Autoimmune hepatitis]]
**Primary biliary cirrhosis
*[[HELLP Syndrome]]
*Congestive Hepatopathy
**[[CHF]]
**[[Sepsis]] (Shock Liver)
 
===Pregnancy Related===
*[[HELLP Syndrome]]
*Acute fatty liver
*[[Hyperemesis gravidarum]]
*[[Cholestasis of pregnancy]]
 
===Transplant Related===
*[[Transplant complications|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)


==Workup==
==Evaluation==
[[File:Evaluation of Hyperbilirubinemia.png|thumb|Evaluation algorithm]]
[[File:Ddx for jaundice by labs.gif|thumbnail]]
*Urine pregnancy
*Urine pregnancy
*CBC
*CBC
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*Acute hepatitis panel
*Acute hepatitis panel
*Lipase
*Lipase
*UA
*[[Urinalysis]]
*?US vs. CT
*?US vs. CT
*?Retic count
*?Retic count
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*?APAP/ASA/Utox/ETOH
*?APAP/ASA/Utox/ETOH


==Diagnosis==
===[[Liver function tests]]===
Masqueraders:
====Transaminases====
*Carotenemia
*Transaminases  in hundreds associated with mild injury; thousands suggests extensive injury
*Quinacrine ingestion
*Elevations <5x normal typical of alcoholic liver disease
*Dinitrophenol, teryl (explosive chemicals)
*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


NB: Only bilirubin stains the sclera
====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


==Differential Diagnosis==
==Management==
*Indirect >> direct: ('''Hematologic''') [near nl AST/ALT/Alk P/PT/PTT]
*Management is dependent on the diagnosis of either conjugated or unconjugated hyperblirubinemia and the severity of the elevation
**Hemolytic
***G6PD
***Drug related
***Autoimmune
**Hematoma resorption
**Infective erythropoiesis
**Gilbert's
*Direct >> indirect: Increased Alk P ('''Obstructive''')  [nl to mild inc AST/ALT]
**[[Choledocholithiasis]]
**[[Cholecystitis]]
**[[Ascending cholangitis]]
**[[AIDS]] cholangiopathy
**Stricture
**Neoplasm
***Panc head
***Gallbladder
***Primary liver
***Metastatic
**Obstructing [[AAA]]
*Nl Alk P ('''Hepatocellular/cholestatic''') [greatly elevated AST/ALT]
**[[Viral hepatitis]]
**Fulminant hepatic failure
**ETOH hepatitis
**Ischemia
**Toxins
***isoniazide
***[[phenytoin]]
***[[Acetaminophen (Tylenol) Toxicity|acetaminophen]]
***ritonavir
***halothane
***sulronamide
**Autoimmune [[hepatitis]]
***Primary biliary cirhosis
**[[HELLP Syndrome]]
**Congestive
***[[CHF]]
***[[Sepsis]]
 
===Pregnancy Related===
*[[HELLP Syndrome]]
*Acute fatty liver
*[[Hyperemesis gravidarum]]
*[[Cholestasis of pregnancy]]
 
===Transplant Related===
*Transplant rejection
*Graft-vs-host
 
===Peds Related===
*Inborn error of metabolism
*Physiologic neonatal
 
===Additional Differential Diagnosis===
*Reye's syndrome
*TPN
*[[Heatstroke]]
*Budd-Chiari (with acute ascites)
*Wilson's
*[[Sarcoidosis]]
*[[Amyloidosis]]


==Disposition==
==Disposition==
New Onset Jaundice Admission Criteria
===New Onset Jaundice Admission Criteria===
*Transaminase >1000IU/L
*Transaminase >1,000 IU/L
*Tbil >10mg/dL
*Tbil >10mg/dL
*Evidence coagulopathy
*Evidence coagulopathy
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==See Also==
==See Also==
*[[Neonatal Jaundice]]
*[[Neonatal Jaundice]]
*[[Acute Hepatitis]]
*[[Acute hepatitis]]
*[[Viral Hepatitis]]
*[[Viral hepatitis]]
*[[Acute hepatic failure]]


==Source ==
==References==
*Tintinalli
<references/>
*Rosen's


[[Category:GI]]
[[Category:GI]]
[[Category:Symptoms]]

Revision as of 18:31, 27 January 2019

For neonatal jaundice please see the Neonatal jaundice page

Background

  • 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):

Clinical Features

Differential Diagnosis

Classification of Hyperbilirubinemia.jpeg

Indirect Hyperbilirubinemia

Direct (Conjugated) Hyperbilirubinemia

Hepatocellular damage

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

Pregnancy Related

Transplant Related

Pediatric Related

Additional Differential Diagnosis

Masqueraders

Only bilirubin stains the sclera

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

Evaluation

Evaluation algorithm
Ddx for jaundice by labs.gif
  • Urine pregnancy
  • CBC
  • Chemistry
  • LFT
    • 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
  • ?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

References