Jaundice

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Overview

Jaundice, also known as icterus (attributive adjective: "icteric"), is yellowish discoloration of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). Usually the concentration of bilirubin in the blood must exceed 2–3 mg/dL for the coloration to be easily visible. Jaundice comes from the French word jaune, meaning yellow. Jaundice typically appears in a 'top to bottom' progression (starting with the face, progressing toward the feet), and resolves in a 'bottom to top' manner.

Neonatal jaundice

Neonatal jaundice can be physiological or pathological. Neonatal physiological jaundice is usually harmless: this condition is often seen in infants around the second day after birth, lasting until day 8 in normal births, or to around day 14 in premature births. Serum bilirubin normally drops to a low level without any intervention required: the jaundice is presumably a consequence of metabolic and physiological adjustments after birth. In extreme cases, a brain-damaging condition known as kernicterus can occur; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. Neonatal jaundice is a risk factor for hearing loss.

Jaundiced eye

It was once believed persons suffering from the medical condition jaundice saw everything as yellow. By extension, the jaundiced eye came to mean a prejudiced view, usually rather negative or critical. Alexander Pope, in 'An Essay on Criticism' (1711), wrote: "All seems infected that the infected spy, As all looks yellow to the jaundiced eye."

Pathophysiology

• Bilirubin is the major breakdown product of hemoglobin that is released from dying or damaged erythrocytes
• The normal bilirubin range is 0.3-1.0 mg/dL
• Jaundice is visible in conjunctiva, skin and mucosa when the serum bilirubin level rises above 2 mg/dL

Causes

When red blood cells die, the heme in their haemoglobin is converted to bilirubin in the spleen and in the hepatocytes in the liver. The bilirubin is processed by the liver, enters bile and is eventually excreted through feces.

Consequently, there are three different classes of causes for jaundice. Pre-hepatic or hemolytic causes, where too many red blood cells are broken down, hepatic causes where the processing of bilirubin in the liver does not function correctly, and post-hepatic or extrahepatic causes, where the removal of bile is disturbed.

Causes by Organ System

Cardiovascular	Eclampsia
Chemical / poisoning	1,2-Dibromoethane , 2-acetylamino-fluorene , 2-Nitropropane , 3,3-Dichlorobenzidine , 4-Dimethylaminoazobenzene , 8-Hydroxyquinolone , Acer rubrum, Acetates , Acetonitrile , Acetylene Tetrabromide , Acrylonitrile , Aflatoxin , Albitocin, Alicyclic Hydrocarbons , Aliphatic Amines , Aliphatic Hydrocarbons , Aliphatic hydrogenated hydrocarbons , Allyl alcohol , Amanita phalloides, Aromatic amines , Aromatic halogenated hydrocarbons , Aromatic Hydrocarbons , Arsenic , Arsine , Benzene , Benzyl chloride , Beryllium , Biliary colic, Bipyridyl pesticides , Black nightshade poisoning , Boron , Cadmium , Carbarsone , Carbolic Acids and Anhydrides , Carbon Disulfide , Carbon Tetrachloride , Chloramphenicol , Chlorate salts , Chlordane, Chlorinated benzenes , Chlorinated naphthalene , Chlorodiphenyls and derivatives , Chloroform, Chloromethane , Chloroprene , Chromium , Comfrey , Copper , Cresol , Cycasin, Cyclochlorotine , Dibromochloropropane , Diethylene Glycol , Dimethyl sulfate , Dimethylnitrosamine , Dinitrobenzene , Dinitrocresol , Dinitrophenol , Dinitrotoluene , Ethanolamines , Ethyl Acetate , Ethyl alcohol , Ethyl benzene , Ethyl Ether , Ethyl Salicylate , Ethylene chlorohydrin , Ethylene Dibromide , Ethylene dichloride , Ethylene oxide , Ethylenediamine , Germander , Germanium ,, Gold , Hafnium , Horse nettle , Hydrogen bromides , Hydrogen Cyanide , Icterogenin, Indospicine, Isopropyl acetate , Kepone pesticides , Lanthanides , Lead , Mercaptans , Mercury , Methoxyflurane , Methyl acetate , Methyl Bromide , Methy, Chloride , Methylene chloride , Methylene Dianiline , Metolachlor, Monomethylhydrazine, N,N-Dimethylformamide , Naphthalene, Naphthol , N-butyl acetate , Ngaione, Nickel , Niobium , Nitriles , Nitrobenzene , Nitromethane , Nitroparaffins , N-N-Dimethylacetamide , N-Nitrosodimethylamine , N-propyl acetate , Ochratoxin , Para-Dichlorobenzene , Phosphine , Phosphorus, Phthalic Anhydride , Picric Acid , Polybrominated biphenyls , Polychlorinated biphenyls , Polygonum multiflorum , Propylene dichloride , Psoralea Corylifolia , Pyrogallol , Pyrrolidizine, Ragwort, Rubratoxin , Safrole, Solanine, Solder , Sterigmatocystin , Stibine , Tellurium, Tetrachloroethane, Tetrachloroethylene , Tetramethylthiuram disulfide , Thallium, Thioxanthene, Thorium dioxide , Thorotrast , , Toluene , Trichloroethylene , Trinitrotoluene , Uranium , Vicia faba, Vinyl Chloride , White Phosphorus , Xylene
Dermatologic	No underlying causes
Drug Side Effect	No underlying causes
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	No underlying causes
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	No underlying causes
Musculoskeletal / Ortho	No underlying causes
Neurologic	No underlying causes
Nutritional / Metabolic	No underlying causes
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	No underlying causes
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	No underlying causes

Causes in Alphabetical Order

1,2-Dibromoethane 2-acetylamino-fluorene 2-Nitropropane 3,3-Dichlorobenzidine 4-Dimethylaminoazobenzene 5-Fluorocytosine 8-Hydroxyquinolone Aagenaes syndrome Absence of septum pellucidum and septo-optic dysplasia Accessory pancreas Acer rubrum Acetaminophen Acetates Acetonitrile Acetylene Tetrabromide Achrestic anemia Acinic cell carcinoma Acral dysostosis -- dyserythropoiesis Acrylonitrile Acute Cholecystitis Acute fatty liver of pregnancy Acute hepatitis Acute liver failure Acute meningitis Addison-Gull syndrome Aflatoxin Alagille syndrome Albitocin Alcoholic Hepatitis Alcoholic liver disease Aldolase A deficiency Alicyclic Hydrocarbons Aliphatic Amines Aliphatic Hydrocarbons Aliphatic hydrogenated hydrocarbons Allopurinol Allyl alcohol Alpha 1-Antitrypsin Deficiency Alprazolam Alveolar Hydatid Disease . Amanita phalloides Amineptine Amiodarone Amlodipine Amodiaquine Amphotericin Anabolic C-17 Angiosarcoma of the liver Aromatic amines Aromatic halogenated hydrocarbons Aromatic Hydrocarbons Arsenic Arsine Arthrogryposis -- renal dysfunction -- cholestasis syndrome Ascending cholangitis Aspergillosis Autoimmune hemolytic anemia Autoimmune Hepatitis Baber's syndrome Babesiosis Banti's syndrome Benign intrahepatic cholestasis Benzene Benzyl chloride Beryllium Bicalutamide Bile duct cancer Bile duct paucity, non syndromic form Bile plug syndrome Biliary atresia Biliary cirrhosis Biliary colic Bipyridyl pesticides Black nightshade poisoning Boron Breast cancer Breast feeding jaundice Breast milk jaundice Bromazepam Brown Recluse spider bite Budd-Chiari syndrome Buprenorphine Butyrophenones Byler Disease Cadmium Carbarsone Carbolic Acids and Anhydrides Carbon Disulfide Carbon Tetrachloride Caroli's Disease

Cefaclor Cephalhematoma Cephalosporins Chediak-Higashi syndrome Chloramphenicol Chlorate salts Chlordane Chlorinated benzenes Chlorinated naphthalene Chlorodiphenyls and derivatives Chloroform Chloromethane Chloroprene Chlorpropamide Cholangiocarcinoma Cholangitis Choledochal cyst, hand malformation Choledochal cysts Choledocholithiasis Cholestasis Cholestasis -- pigmentary retinopathy -- cleft palate Cholesteryl ester storage disease Chromium Chronic cholecystitis Chronic Hepatitis Cimetidine Cirrhosis of liver Clarithromycin Clavulanic acid Clindamycin Co-amoxiclav Colchicine Colorectal cancer Comfrey Congenital disorders of glycosylation Congenital TORCH infections Copper Cresol Crigler-Najjar syndrome Cycasin Cyclochlorotine Cyclopropane Cycloserine Cytarabine Cytomegalovirus Dantrolene Dapsone Daptomycin Deal-Barratt-Dillon syndrome Deracoxib Diazepam Dibromochloropropane Diethylene Glycol Diflunisal Dimethyl sulfate Dimethylnitrosamine Dinitrobenzene Dinitrocresol Dinitrophenol Dinitrotoluene Diphenoxylate and Atropine Disulfiram Docetaxel Doxepine Dubin-Johnson syndrome Duloxetine Dydrogesterone Eclampsia Embryonal rhabdomyosarcoma Eosinophilic gastroenteritis Erythromycin estolate Erythromycin Ethyl succinate Esophageal cancer Estrogen and Progestin Ethanolamines Ethionamide Ethyl Acetate Ethyl alcohol Ethyl benzene Ethyl Ether Ethyl Salicylate Ethylene chlorohydrin Ethylene Dibromide Ethylene dichloride Ethylene oxide Ethylenediamine Evans syndrome Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis Familial progressive intrahepatic cholestasis Familial Selective Vitamin B12 Malabsorption

Fanconi-ichthyosis-dysmorphism Fascioliasis Favism Fenoprofen Flucloxacillin Framycetin Fructose intolerance Fusidic acid Galactosemia Gallbladder cancer Gallstones Germander Germanium Gestational diabetes Gilbert's syndrome Glucose-6-phosphate dehydrogenase deficiency Glutaric aciduria Gold Goldstein-Hutt syndrome Graft-versus-host disease Griscelli disease Griseofulvin Growth hormone deficiency Hafnium Halothane Hashimoto-Pritzker syndrome HELLP syndrome Hemochromatosis Hemoglobin C homozygous (CC) Hemolytic anemia Hemolytic disease of the newborn Hemophagocytic lymphohistiocytosis familial Hemosuccus pancreaticus Hepadnaviruses Hepatic amyloidosis with intrahepatic cholestasis Hepatic encephalopathy syndrome Hepatic trauma Hepatic veno-occlusive disease with immunodeficiency Hepatoma Heptaosplenic T-cell Lymphoma Hereditary elliptocytosis Hereditary fructose intolerance Hereditary spherocytosis Hereditary xerocytosis Herpes Histoplasmosis HLH (Hemophagocytic lymphohistiocytosis) Hodgkin's Disease Horse nettle Hycanthone Hydrogen bromides Hydrogen Cyanide Hyperemesis gravidarum Hypopitutarism Hypothyroidism Ibuprofen Icterogenin Idiopathic liver cirrhosis Idoxuridine Imerslund-Najman-Grasbeck Syndrome Imipramine Indomethacin Indospicine Infectious mononucleosis Infective endocarditis Intrahepatic cholangiocarcinoma Intrahepatic cholestasis of pregnancy Iron Islet Cell adenoma Isoniazid Isopropyl acetate Itraconazole Kaposiform hemangio-endothelioma Kawasaki disease Kepone pesticides Ketoconazole Lábrea fever Langerhans Cell Histiocytosis Lanthanides Lead Leiomyosarcoma Lissencephalic syndromes Liver cancer Loprazolam Lorazepam Lormetazepam Lucey-Driscoll syndrome Lupus Lymphoma Lymphoproliferative syndrome, EBV-Associated, Autosomal

Malaria Malignant boutonneuse fever Manganese deficiency Marburg virus Mepacrine Mephenytoin Mercaptans Mercury Mesothelioma Methimazole Methoxyflurane Methyl acetate Methyl Bromide Methyl Chloride Methyldopa Methylene chloride Methylene Dianiline Metolachlor Metronidazole Minocycline Mirizzi's syndrome Mirtazapine Molybdenum deficiency Monoamine oxidase inhibitors Monomethylhydrazine Mosse syndrome Myelofibrosis-osteosclerosis N,N-Dimethylformamide Nanukayami Naphthalene Naphthol Naproxen N-butyl acetate Neonatal adrenal hemorrhage Neonatal hepatitis Neonatal physiological jaundice Neonatal sepsis Neuroma biliary tract Ngaione Nickel Niemann-Pick disease Niobium NISCH syndrome Nitriles Nitrobenzene Nitrofurantoin Nitromethane Nitroparaffins Nitrous Oxide N-N-Dimethylacetamide N-Nitrosodimethylamine Non-alcoholic fatty liver disease Novobiocin N-propyl acetate Obliterative portal venopathy Ochratoxin Omphalitis Organic acidemia Oxycodone p-aminosalicylic acid Pancreatic adenoma Pancreatic cancer Pancreatitis Pancreatoblastoma Papaverine Papillary stenosis Para-Dichlorobenzene Paroxetine Peliosis hepatis Penicillin Pernicious anemia Phenol Phenothiazine Phenylbutazone Phenytoin Phosphine Phosphorus Phthalic Anhydride Picric Acid Pneumonia Polybrominated biphenyls Polychlorinated biphenyls Polygonum multiflorum Porphyria Portal hypertension Postoperative Jaundice Premature birth Primary biliary cirrhosis Primary sclerosing cholangitis Progressive familial intrahepatic cholestasis (PFIC)

Propylene dichloride Pseudo-torch syndrome Psoralea Corylifolia Pyridine Pyrogallol Pyrrolidizine Pyruvate kinase deficiency Q fever Quinidine-induced Immune Hemolytic Anemia Quinolone Ragwort Ranitidine Relapsing fever Reye's syndrome Reynolds syndrome Rh deficiency syndrome Rh disease Rifampicin Rotor syndrome Rubratoxin Safrole Salicylate Sarcoidosis Sarcoma botryoides of common bile duct Secondary Biliary Cirrhosis Selenium deficiency Sepsis Sibutramine Solanine Solder Sotos syndrome Spectinomycin Spleen Cancer Sterigmatocystin Stibine Sulindac Sulphonamides Summerskill-Walshe-Tygstrup syndrome Syphilis Tamoxifen Tegaserod Telithromycin Tellurium Tetrachloroethane Tetrachloroethylene Tetracycline Tetramethylthiuram disulfide Thalassemia Thallium Thiabendazole Thioxanthene Thorium dioxide Thorotrast Thrombotic thrombocytopenic purpura Thyroid agenesis Toluene Transfusion Reaction Trazodone Trichloroethylene Trichomegaly cataract hereditary spherocytosis Trinitrotoluene Tuberculosis Tyrosinemia Uranium Valproic acid Vicia faba Vidarabine Vinyl Chloride Viral Hepatitis A Viral Hepatitis B Viral Hepatitis C Viral Hepatitis D Viral Hepatitis E Viral hepatitis X (non-A,-B,-C,-D,-E) Vitamin A overdose Vitamin B12 Deficiency Vitamin C Weil's disease White Phosphorus Wilson's Disease Wolman disease Xanthogranulomatous cholecystitis Xanthomatous biliary cirrhosis X-linked alpha thalassemia mental retardation syndrome (ATR-X) X-linked lymphoproliferative syndrome X-linked sideroblastic anaemia Xylene Yellow fever Zellweger syndrome Zieve's syndrome Zoxazolamine

Differential Diagnosis

• Abdominal mass
• Acute alcoholic hepatitis
• Alcoholic Hepatitis
• Alpha-1 Antitrypsin Deficiency
• Amyloidosis
• Annular pancreas
• Autoimmune hepatitis
• Autoimmunohemolysis
• Benign recurring cholestasis
• Bile duct tumor
• Biliary atresia
• Biliary tract obstruction
• Cholangitis
• Cholecystitis
• Choledocholithiasis
• Choledochal cyst
• Conditions following hemorrhage
• Congestive Heart Failure
• Crigler-Najjar Syndrome
• Cystic Fibrosis
• Cytomegalovirus (CMV)
• Decompensated cirrhosis
• Dubin-Johnson Syndrome
• Drugs and toxins
• Eclampsia
• Epstein-Barr Virus (EBV)
• Fetal erythroblastosis
• Following hemolytic disease of the newborn syndrome
• Galactosemia
• Gallbladder tumor
• Gilbert's Syndrome
• Glucose-6-phosphate dehydrogenase deficiency
• Graft-versus-host disease
• HELLP Syndrome (Hemolysis, Elevated Liver enzymes, Low Platelet count)
• Hepatic trauma
• Hepatitis
• Hepatotoxic liver damage
• Hyperbilirubinemia after heart surgery
• Hyperbilirubinemia after portocaval shunt insertion
• Hyperemesis gravidarum
• Hypermethioninemia
• Hypopituitarism
• Hypothyroidism
• Intrauterine viral infections
• Intrahepatic cholestasis of pregnancy
• Intrahepatic and extrahepatic biliary atresia
• Intravascular hemolysis
• Jaundice of newborn
• Liver abscess
• Liver allograft rejection
• Liver cell carcinoma
• Lucey-Driscoll Syndrome
• Lymphoma
• Malignancy
• Neonatal hepatitis
• Nonalcoholic steatohepatitis or non-alcoholic fatty liver disease
• Pancreatic cancer
• Pancreatitis
• Parasites
• Pernicious anemia
• Polycythemia vera
• Postoperative jaundice
• Primary biliary cirrhosis
• Primary hyperbilirubinemia
• Primary sclerosing cholangitis
• Rotor's Syndrome
• Sarcoidosis
• Sepsis
• Shock
• Sickle Cell Anemia
• Spherocytosis
• Storage diseases
• Strictures
• Thalassemia
• Total parenteral nutrition
• Transfusion reaction
• Trisomy 18
• Tuberculosis
• Tyrosinemia
• Viral hepatitis (A, B, C, D, E)

Diagnosis

History

The caregiver should ask questions regarding

• Alcohol/hepatotoxic medication use

Various Symptoms

• Alcohol Hepatitis

  • Aspartate aminotransferase:alanine aminotransferase ratio > 2 (AST:ALT)
  • Fever
  • Leukocytosis

• Viral Hepatitis

  • Anorexia
  • Dark urine
  • Fatigue
  • Hepatomegaly
  • Light-colored (acholic) loss stools
  • Nausea
  • Pruritis
  • Right upper quadrant (RUQ) pain
  • Nausea and Vomiting

Physical Examination

• Complete physical exam including evidence of:

  • Hepatomegaly
  • Splenomegaly
  • Palpable gallbladder
  • Signs of chronic liver disease

Appearance of the Patient Skin

• Jaundice is visible in conjunctiva, skin and mucosa when the serum bilirubin level rises above 2 mg/dL

Eyes

• Jaundice is usually best seen in the periphery of the ocular conjunctivae

Abdomen

• Hepatomegaly may be present

Neurologic

• A flap may be present

Laboratory Findings

• Total and unconjugated bilirubin
• Aspartate aminotransferase
• Alanine aminotransferase
• Albumin
• Alkaline phosphatase
• HIV serologies
• Hepatitis serologies
• Antinuclear antibody (ANA)
• Antimitochondrial antibodies
• Haptoglobin
• Reticulocyte count
• Lactic dehydrogenase (LDH)

'Pre-hepatic' -(or hemolytic) jaundice is caused by anything which causes an increased rate of hemolysis (breakdown of red blood cells). In tropical countries, malaria can cause jaundice in this manner. Certain genetic diseases, such assickle cell anemia and glucose 6-phosphate dehydrogenase deficiency can lead to increased red cell lysis and therefore hemolytic jaundice. Commonly, diseases of the kidney, such as hemolytic uremic syndrome, can also lead to coloration. Defects in bilirubin metabolism also present as jaundice. Jaundice usually comes with high fevers.

The laboratory findings include

• Urine: no bilirubin present, urobilirubin > 2 units (except in infants where gut flora has not developed).
• Serum: increased unconjugated bilirubin.

'Hepatic causes' include acute hepatitis, hepatotoxicity and alcoholic liver disease, whereby cell necrosis reduces the liver's ability to metabolise and excrete bilirubin leading to a buildup in the blood. Less common causes include primary biliary cirrhosis,Gilbert's syndrome (a genetic disorder of bilirubin metabolism which can result in mild jaundice, which is found in about 5% of the population) and metastatic carcinoma. Jaundice seen in the newborn, known as neonatal jaundice, is common, occurring in almost every newborn as hepatic machinery for the conjugation and excretion of bilirubin does not fully mature until approximately two weeks of age..

Laboratory Findings: Urine: bilirubin present, Urobilirubin > 2 units but variable (Except in children)

'Post-hepatic' (or obstructive) jaundice, also called cholestasis, is caused by an interruption to the drainage of bile in the biliary system. The most common causes are gallstones in the common bile duct, and pancreatic cancer in the head of the pancreas. Also, a group of parasites known as "liver flukes" live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct, biliary atresia, ductal carcinoma, pancreatitis and pancreatic pseudocysts. A rare cause of obstructive jaundice is Mirizzi's syndrome.

The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their color from bile pigments.

Patients also can present with elevated serum cholesterol.

Patients often complain of severe itching or "pruritus".

MRI and CT

• Abdominal CT scan may be helpful

Echocardiography or Ultrasound

• Abdominal ultrasound

Other Diagnostic Studies

• Endoscopic retrograde cholangio-pancreatography (ERCP)

Treatment

• Discontinue (and avoid) use of hepatotoxic medications
• Rehydrate
• Treat underlying etiologies

Acute Pharmacotherapies

• Steroids

Surgery and Device Based Therapy

• Cholecystectomy or ERCP

External links

- Children's Liver Disease Foundation: information on jaundice in infants

See also

• Cholestasis

External Links

• Beth Israel Deaconess Medical Center: Jaundice

References

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