Merck Manual

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Danielle Tholey

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Reviewed/Revised Sep 2023
Topic Resources

Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L).

Pathophysiology of Jaundice

Most bilirubin is produced when hemoglobin (Hb) is broken down into unconjugated bilirubin (and other substances). Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid to make it water soluble. Conjugated bilirubin is excreted in bile into the duodenum. In the intestine, bacteria metabolize bilirubin to form urobilinogen. Some urobilinogen is eliminated in the feces, and some is reabsorbed, extracted by hepatocytes, reprocessed, and re-excreted in bile (enterohepatic circulation—see Overview of Bilirubin Metabolism Overview of bilirubin metabolism The liver is a metabolically complex organ. Hepatocytes (liver parenchymal cells) perform the liver’s metabolic functions: Formation and excretion of bile as a component of bilirubin metabolism... read more Overview of bilirubin metabolism ).

Overview of Jaundice

Mechanisms of hyperbilirubinemia

Hyperbilirubinemia may involve predominantly unconjugated or conjugated bilirubin.

Unconjugated hyperbilirubinemia is most often caused by 1 of the following:

  • Increased production

  • Decreased hepatic uptake

  • Decreased conjugation

Conjugated hyperbilirubinemia is most often caused by 1 of the following:

  • Dysfunction of hepatocytes (hepatocellular dysfunction)

  • Slowing of bile egress from the liver (intrahepatic cholestasis)

  • Obstruction of extrahepatic bile flow (extrahepatic cholestasis)


Outcome is determined primarily by the cause of jaundice and the presence and severity of hepatic dysfunction. Hepatic dysfunction can result in coagulopathy, encephalopathy, and portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more (which can lead to gastrointestinal bleeding).

Etiology of Jaundice

Although hyperbilirubinemia can be classified as predominantly unconjugated or conjugated, many hepatobiliary disorders cause both forms.

Many conditions (see table ), including use of certain drugs (see table ), can cause jaundice, but the most common causes overall are


Evaluation of Jaundice


History of present illness should include onset and duration of jaundice. Hyperbilirubinemia can cause urine to darken before jaundice is visible. Therefore, the onset of dark urine indicates onset of hyperbilirubinemia more accurately than onset of jaundice. Important associated symptoms include fever, prodromal symptoms (eg, fever, malaise, myalgias) before jaundice, changes in stool color, pruritus, steatorrhea, and abdominal pain (including location, severity, duration, and radiation). Important symptoms suggesting severe disease include nausea and vomiting, weight loss, and possible symptoms of coagulopathy (eg, easy bruising or bleeding, tarry or bloody stools).

Past medical history should identify known causative disorders, such as hepatobiliary disease (eg, gallstones Cholelithiasis Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder. Gallstones tend to be asymptomatic. The most common symptom is biliary colic; gallstones do not cause dyspepsia... read more Cholelithiasis , hepatitis Causes of Hepatitis Hepatitis is inflammation of the liver characterized by diffuse or patchy necrosis. Hepatitis may be acute or chronic (usually defined as lasting > 6 months). Most cases of acute viral hepatitis... read more , cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more ); disorders that can cause hemolysis Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span... read more Overview of Hemolytic Anemia (eg, hemoglobinopathy Overview of Hemoglobinopathies Hemoglobinopathies are genetic disorders affecting the structure or production of the hemoglobin molecule. Hemoglobin molecules consist of polypeptide chains whose chemical structure is genetically... read more , glucose-6-phosphate dehydrogenase [G6PD] deficiency Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic defect common in people with African ancestry that can result in hemolysis after acute illnesses or intake of oxidant... read more Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency ); and disorders associated with liver or biliary disease, including inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more , infiltrative disorders (eg, amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more Amyloidosis , lymphoma Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis , tuberculosis Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more Tuberculosis (TB) ), and HIV infection or AIDS Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more Human Immunodeficiency Virus (HIV) Infection .

Drug history should include questions about use of drugs or exposure to toxins known to affect the liver (see table ) and about vaccination against hepatitis.

Surgical history should include questions about previous surgery on the biliary tract (a potential cause of strictures).

Social history should include questions about risk factors for hepatitis (see table Some Risk Factors for Hepatitis), amount and duration of alcohol use, injection drug use, and sexual history.

Family history should include questions about recurrent, mild jaundice in family members and diagnosed hereditary liver disorders. The patient’s history of recreational drug and alcohol use should be corroborated by friends or family members when possible.


Physical examination

Vital signs are reviewed for fever and signs of systemic toxicity (eg, hypotension, tachycardia).

General appearance is noted, particularly for cachexia and lethargy.

Head and neck examination includes inspection of the sclerae and tongue for icterus and the eyes for Kayser-Fleischer rings Kayser-Fleischer rings Wilson disease results in accumulation of copper in the liver and other organs. Hepatic or neurologic symptoms develop. Diagnosis is based on a low serum ceruloplasmin level, high urinary excretion... read more Kayser-Fleischer rings (best seen with slit lamp). Mild jaundice is best seen by examining the sclerae in natural light; it is usually detectable when serum bilirubin reaches 2 to 2.5 mg/dL (34 to 43 micromol/L). Breath odor should be noted (eg, for fetor hepaticus).

The abdomen is inspected for collateral vasculature, ascites Ascites Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more , and surgical scars. The liver is palpated for hepatomegaly, masses, nodularity, and tenderness. The spleen is palpated for splenomegaly. The abdomen is examined for umbilical hernia, shifting dullness, fluid wave, masses, and tenderness. The rectum is examined for gross or occult blood.

Men are checked for testicular atrophy and gynecomastia.

Neurologic examination includes mental status assessment and evaluation for asterixis (a characteristic flapping tremor of the hands).

The skin is examined for jaundice, palmar erythema, needle tracks, vascular spiders, excoriations, xanthomas (consistent with primary biliary cholangitis Primary Biliary Cholangitis (PBC) Primary biliary cholangitis (PBC; formerly known as primary biliary cirrhosis) is an autoimmune liver disorder characterized by the progressive destruction of intrahepatic bile ducts, leading... read more ), paucity of axillary and pubic hair, hyperpigmentation, ecchymoses, petechiae, and purpura.

Red flags

The following findings are of particular concern:

  • Marked abdominal pain and tenderness

  • Altered mental status

  • Gastrointestinal (GI) bleeding (occult or gross)

  • Ecchymoses, petechiae, or purpura

Interpretation of findings

Severity of illness is indicated mainly by the degree (if any) of hepatic dysfunction. Ascending cholangitis is a concern because it requires emergency treatment.

Severe hepatic dysfunction is indicated by encephalopathy (eg, mental status change, asterixis) or coagulopathy (eg, easy bleeding, purpura, tarry or heme-positive stool), particularly in patients with signs of portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more (eg, abdominal collateral vasculature, ascites, splenomegaly). Massive upper GI bleeding suggests variceal bleeding Varices Varices are dilated veins in the distal esophagus or proximal stomach caused by elevated pressure in the portal venous system, typically from cirrhosis. They may bleed massively but cause no... read more Varices due to portal hypertension (and possibly coagulopathy).

Cause of jaundice may be suggested by the following:

Other examination findings can also be helpful (see table ).



The following are done:

Blood tests include measurement of total and direct bilirubin, aminotransferase, and alkaline phosphatase levels in all patients. Results help differentiate cholestasis from hepatocellular dysfunction (important because patients with cholestasis usually require imaging tests):

  • Hepatocellular dysfunction: Marked aminotransferase elevation (> 500 U/L [8.35 microkat/L]) and moderate alkaline phosphatase elevation (< 3 times normal)

  • Cholestasis: Moderate aminotransferase elevation (< 200 U/L [3.34 microkat/L]) and marked alkaline phosphatase elevation (> 3 times normal)

Other blood tests are done based on clinical suspicion and initial test findings, as for the following:

Imaging is done if pain suggests extrahepatic obstruction or cholangitis or if blood test results suggest cholestasis.

If ultrasonography shows extrahepatic cholestasis, other tests may be necessary to determine the cause; usually, magnetic resonance cholangiopancreatography (MRCP) Magnetic resonance imaging (MRI) Magnetic resonance imaging (MRI) , endoscopic ultrasonography (EUS), or endoscopic retrograde cholangiopancreatography (ERCP) Endoscopic retrograde cholangiopancreatography (ERCP) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more Endoscopic retrograde cholangiopancreatography (ERCP) is used. ERCP is more invasive but allows treatment of some obstructive lesions (eg, stone removal, stenting of strictures).

Laparoscopy (peritoneoscopy) allows direct inspection of the liver and gallbladder without the trauma of a full laparotomy. Unexplained cholestatic jaundice warrants laparoscopy occasionally and diagnostic laparotomy rarely.

Treatment of Jaundice

  • Treatment of causes and complications

The cause and any complications are treated. Jaundice itself requires no treatment in adults (unlike in neonates—see Neonatal Hyperbilirubinemia Neonatal Hyperbilirubinemia Jaundice is a yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration). The serum bilirubin level required to cause jaundice varies with... read more ). Itching, if bothersome, may be relieved with cholestyramine 2 to 8 g orally twice a day. However, cholestyramine is ineffective in patients with complete biliary obstruction.

Geriatrics Essentials: Jaundice

Key Points

  • Suspect acute viral hepatitis in patients, particularly young and healthy patients, who have acute jaundice, particularly with a viral prodrome.

  • Suspect biliary obstruction due to cancer in older patients with painless jaundice, weight loss, an abdominal mass, and minimal pruritus.

  • Suspect hepatocellular dysfunction if aminotransferase levels are > 500 U/L and alkaline phosphatase elevation is < 3 times normal.

  • Suspect cholestasis if aminotransferase levels are < 200 U/L and alkaline phosphatase elevation is > 3 times normal.

  • Hepatic dysfunction is significant if mental status is altered and coagulopathy is present.

Drugs Mentioned In This Article

Drug Name Select Trade
7T Gummy ES, Acephen, Aceta, Actamin, Adult Pain Relief, Anacin Aspirin Free, Aphen, Apra, Children's Acetaminophen, Children's Pain & Fever , Children's Pain Relief, Comtrex Sore Throat Relief, ED-APAP, ElixSure Fever/Pain, Feverall, Genapap, Genebs, Goody's Back & Body Pain, Infantaire, Infants' Acetaminophen, LIQUID PAIN RELIEF, Little Fevers, Little Remedies Infant Fever + Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Infants, Mapap Junior, M-PAP, Nortemp, Ofirmev, Pain & Fever , Pain and Fever , PAIN RELIEF , PAIN RELIEF Extra Strength, Panadol, PediaCare Children's Fever Reducer/Pain Reliever, PediaCare Children's Smooth Metls Fever Reducer/Pain Reliever, PediaCare Infant's Fever Reducer/Pain Reliever, Pediaphen, PHARBETOL, Plus PHARMA, Q-Pap, Q-Pap Extra Strength, Silapap, Triaminic Fever Reducer and Pain Reliever, Triaminic Infant Fever Reducer and Pain Reliever, Tylenol, Tylenol 8 Hour, Tylenol 8 Hour Arthritis Pain, Tylenol 8 Hour Muscle Aches & Pain, Tylenol Arthritis Pain, Tylenol Children's, Tylenol Children's Pain+Fever, Tylenol CrushableTablet, Tylenol Extra Strength, Tylenol Infants', Tylenol Infants Pain + Fever, Tylenol Junior Strength, Tylenol Pain + Fever, Tylenol Regular Strength, Tylenol Sore Throat, XS No Aspirin, XS Pain Reliever
Locholest , Locholest Light, Prevalite , Questran, Questran Light
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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