Jaundice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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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.

Historical Perspective

Jaundice comes from the French word jaune, meaning yellow.

Classification

Neonatal jaundice | Prehepatic jaundice | Hepatic jaundice | Posthepatic jaundice

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.

Common Causes

Causes by Organ System

Cardiovascular Eclampsia, Alagille syndrome, Infective endocarditis , Lupus, Trisomy 18
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 , Methyl 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 ,Favism
Dermatologic Griscelli disease , NISCH syndrome , Hashimoto-Pritzker syndrome , Kawasaki disease , Deal-Barratt-Dillon syndrome , Lupus, Hemochromatosis
Drug Side Effect 5-Fluorocytosine , Allopurinol , Alprazolam, Amineptine, Amiodarone, Amlodipine, Amodiaquine , Amphotericin , Anabolic C-17 , Bicalutamide, Bromazepam, Buprenorphine, Butyrophenones, Cefaclor, Cephalosporins, Cimetidine , Clarithromycin, Clavulanic acid, Clindamycin, Co-amoxiclav, Colchicine , Cyclopropane , Cycloserine , Cytarabine , Dantrolene , Dapsone, Daptomycin, Deracoxib, Diazepam, Diflunisal , Diphenoxylate and Atropine, Disulfiram , Docetaxel, Doxepine, Duloxetine, Dydrogesterone, Erythromycin estolate , Erythromycin Ethyl succinate , Estrogen and Progestin, Ethionamide , Fenoprofen , Flucloxacillin, Framycetin, Fusidic acid, Griseofulvin , Halothane , Hycanthone , Ibuprofen , Idoxuridine , Imipramine, Indomethacin , Isoniazid , Itraconazole, Ketoconazole , Loprazolam, Lorazepam, Lormetazepam, Mepacrine , Mephenytoin , Methimazole, Methyldopa, Metronidazole , Minocycline, Mirtazapine, Monoamine oxidase inhibitors, Naproxen , Nitrofurantoin, Nitrous Oxide , Novobiocin , Oxycodone, p-aminosalicylic acid , Papaverine, Paroxetine, Penicillin , Phenol , Phenothiazine, Phenylbutazone , Phenytoin , Pyridine , Quinidine-induced Immune Hemolytic Anemia, Quinolone , Ranitidine , Rifampicin, Salicylate , Sibutramine, Spectinomycin , Sulindac , Sulphonamides, Tamoxifen, Tegaserod, Telithromycin, Tetracycline , Thiabendazole , Trazodone, Valproic acid, Vidarabine , Zoxazolamine ,
Ear Nose Throat Arthrogryposis -- renal dysfunction -- cholestasis syndrome
Endocrine Gestational diabetes, Growth hormone deficiency, Hypopituitarism, Hypothyroidism, Thyroid agenesis
Environmental No underlying causes
Gastroenterologic Accessory pancreas, Acinic cell carcinoma, Acral dysostosis -- dyserythropoiesis , Acute Cholecystitis, Acute fatty liver of pregnancy, Acute hepatitis, Acute liver failure, Addison-Gull syndrome, Alagille syndrome, Alcoholic Hepatitis, Alcoholic liver disease, Angiosarcoma of the liver , Arthrogryposis -- renal dysfunction -- cholestasis syndrome , Ascending cholangitis, Autoimmune Hepatitis , Baber's syndrome , Banti's syndrome, Bile duct cancer, Bile duct paucity, non syndromic form , Bile plug syndrome , Biliary atresia, Biliary cirrhosis , Budd-Chiari syndrome, Byler Disease , Caroli's Disease, Chlorpropamide, Cholangiocarcinoma, Cholangitis, Choledochal cyst, hand malformation , Choledochal cysts, Choledocholithiasis, Cholestasis , Cholestasis -- pigmentary retinopathy -- cleft palate , Chronic cholecystitis, Chronic Hepatitis , Cirrhosis of liver , Colorectal cancer, Crigler-Najjar syndrome, Eosinophilic gastroenteritis, Esophageal cancer, Gallbladder cancer, Gallstones , Gilbert's syndrome, Hemosuccus pancreaticus, Hepatic amyloidosis with intrahepatic cholestasis , Hepatic encephalopathy syndrome , Hepatoma , Hyperemesis gravidarum, Idiopathic liver cirrhosis , Intrahepatic cholangiocarcinoma , Intrahepatic cholestasis of pregnancy, Islet Cell adenoma, Liver cancer , Mirizzi's syndrome, Mosse syndrome , Neonatal hepatitis , Neuroma biliary tract , Non-alcoholic fatty liver disease, Obliterative portal venopathy , Pancreatic adenoma, Pancreatic cancer, Pancreatitis, Pancreatoblastoma, Papillary stenosis, Peliosis hepatis, Portal hypertension, Primary biliary cirrhosis, Primary sclerosing cholangitis, Sarcoma botryoides of common bile duct, Secondary Biliary Cirrhosis, Xanthogranulomatous cholecystitis, Xanthomatous biliary cirrhosis, Zieve's syndrome, NISCH syndrome , Benign intrahepatic cholestasis , Dubin-Johnson syndrome, Familial Selective Vitamin B12 Malabsorption , Hemochromatosis , Imerslund-Najman-Grasbeck Syndrome , Progressive familial intrahepatic cholestasis (PFIC) , Summerskill-Walshe-Tygstrup syndrome, HELLP syndrome , Heptaosplenic T-cell Lymphoma , Pernicious anemia, Alpha 1-Antitrypsin Deficiency , Viral Hepatitis A, Viral Hepatitis B, Viral Hepatitis C, Viral Hepatitis D, Viral Hepatitis E, Viral hepatitis X (non-A,-B,-C,-D,-E), Reynolds syndrome, Deal-Barratt-Dillon syndrome , Aagenaes syndrome , Infectious mononucleosis, Fanconi-ichthyosis-dysmorphism , Wilson's Disease, Cholesteryl ester storage disease, Chediak-Higashi syndrome , Weil's disease, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis , Zellweger syndrome, Trisomy 18
Genetic Aagenaes syndrome , Aldolase A deficiency , Arthrogryposis -- renal dysfunction -- cholestasis syndrome , Benign intrahepatic cholestasis , Chediak-Higashi syndrome , Cholesteryl ester storage disease, Dubin-Johnson syndrome, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis , Familial Selective Vitamin B12 Malabsorption , Galactosemia , Glucose-6-phosphate dehydrogenase deficiency, Glutaric aciduria , Hemochromatosis , Hereditary elliptocytosis , Hereditary fructose intolerance, Hereditary xerocytosis, Imerslund-Najman-Grasbeck Syndrome , Lucey-Driscoll syndrome, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Niemann-Pick disease , Porphyria, Progressive familial intrahepatic cholestasis (PFIC) , Pseudo-torch syndrome, Rotor syndrome, Sotos syndrome, Summerskill-Walshe-Tygstrup syndrome, Tyrosinemia, Wilson's Disease, Wolman disease, X-linked alpha thalassemia mental retardation syndrome (ATR-X), X-linked lymphoproliferative syndrome, X-linked sideroblastic anaemia, Zellweger syndrome, Griscelli disease , Hemoglobin C homozygous (CC) , Hereditary spherocytosis, Thalassemia, Fructose intolerance, Alpha 1-Antitrypsin Deficiency , Acral dysostosis -- dyserythropoiesis , Pyruvate kinase deficiency, Arthrogryposis -- renal dysfunction -- cholestasis syndrome , Alagille syndrome, Trisomy 18
Hematologic Achrestic anemia, Autoimmune hemolytic anemia, Evans syndrome, Fanconi-ichthyosis-dysmorphism , Favism , Hashimoto-Pritzker syndrome , HELLP syndrome , Hemoglobin C homozygous (CC) , Hemolytic anemia, Hemolytic disease of the newborn, Hemophagocytic lymphohistiocytosis familial ,Hepatic veno-occlusive disease with immunodeficiency , Heptaosplenic T-cell Lymphoma , Hereditary spherocytosis, HLH (Hemophagocytic lymphohistiocytosis), Hodgkin's Disease , Kawasaki disease , Langerhans Cell Histiocytosis , Lymphoma , Myelofibrosis-osteosclerosis ,Pernicious anemia, Rh deficiency syndrome, Thalassemia, Thrombotic thrombocytopenic purpura, Acral dysostosis -- dyserythropoiesis , Mosse syndrome , Zieve's syndrome, Aagenaes syndrome , Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis , Glucose-6-phosphate dehydrogenase deficiency, Sickle-cell disease, Hereditary elliptocytosis , Hereditary xerocytosis, Porphyria, X-linked lymphoproliferative syndrome, X-linked sideroblastic anaemia, Pyruvate kinase deficiency, Kaposiform hemangio-endothelioma , Goldstein-Hutt syndrome , Infectious mononucleosis, Rh disease, Kawasaki disease , Sickle-cell disease, Griscelli disease , Lymphoproliferative syndrome, EBV-Associated, Autosomal, Aldolase A deficiency , X-linked alpha thalassemia mental retardation syndrome (ATR-X), Lupus
Iatrogenic Post operative jaundice
Infectious Disease Alveolar Hydatid Disease ., Aspergillosis, Congenital TORCH infections, Fascioliasis , Infective endocarditis , Malignant boutonneuse fever, Nanukayami , Neonatal sepsis , Omphalitis, Pneumonia, Sepsis, Tuberculosis, Q fever, Relapsing fever, Syphilis, Weil's disease, Histoplasmosis, Malaria , Cytomegalovirus, Hepadnaviruses , Herpes, Infectious mononucleosis, Lábrea fever, Marburg virus, Viral Hepatitis A, Viral Hepatitis B, Viral Hepatitis C, Viral Hepatitis D, Viral Hepatitis E, Viral hepatitis X (non-A,-B,-C,-D,-E), Ascending cholangitis, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Acute meningitis
Musculoskeletal / Ortho Deal-Barratt-Dillon syndrome , Choledochal cyst, hand malformation , X-linked alpha thalassemia mental retardation syndrome (ATR-X), Fanconi-ichthyosis-dysmorphism , Myelofibrosis-osteosclerosis , Lupus, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis , Sotos syndrome, Cholestasis -- pigmentary retinopathy -- cleft palate , Alagille syndrome, Hemochromatosis , Aldolase A deficiency , Lupus, Trisomy 18, Arthrogryposis -- renal dysfunction -- cholestasis syndrome
Neurologic Absence of septum pellucidum and septo-optic dysplasia , Acute meningitis, Eclampsia, Hepatic encephalopathy syndrome , Pseudo-torch syndrome, Sotos syndrome, Wilson's Disease, Zellweger syndrome, Lissencephalic syndromes, Chediak-Higashi syndrome , Alagille syndrome, Arthrogryposis -- renal dysfunction -- cholestasis syndrome , Trisomy 18
Nutritional / Metabolic Breast feeding jaundice, Breast milk jaundice , Congenital disorders of glycosylation, Fructose intolerance, Manganese deficiency, Molybdenum deficiency, Organic acidemia, Pyruvate kinase deficiency, Selenium deficiency, Vitamin A overdose, Vitamin B12 Deficiency, Crigler-Najjar syndrome, Gilbert's syndrome, Cholesteryl ester storage disease, Galactosemia , Glutaric aciduria , Hereditary fructose intolerance, Lucey-Driscoll syndrome, Niemann-Pick disease , Tyrosinemia, Wolman disease, Acute fatty liver of pregnancy, Aldolase A deficiency
Obstetric/Gynecologic HELLP syndrome, Acute fatty liver of pregnancy, Eclampsia
Oncologic Breast cancer, Embryonal rhabdomyosarcoma, Kaposiform hemangio-endothelioma , Acinic cell carcinoma, Angiosarcoma of the liver , Bile duct cancer, Cholangiocarcinoma, Colorectal cancer, Esophageal cancer, Gallbladder cancer, Hepatoma , Intrahepatic cholangiocarcinoma , Islet Cell adenoma, Liver cancer , Neuroma biliary tract , Pancreatic adenoma, Pancreatic cancer, Pancreatoblastoma, Lymphoma , Zellweger syndrome, Mesothelioma
Opthalmologic Goldstein-Hutt syndrome , Cholestasis -- pigmentary retinopathy -- cleft palate , Chediak-Higashi syndrome , Absence of septum pellucidum and septo-optic dysplasia , Wilson's Disease, Alagille syndrome
Overdose / Toxicity Acetaminophen, Iron , Vitamin C , Vitamin A
Psychiatric No underlying causes
Pulmonary Alpha 1-Antitrypsin Deficiency , Mesothelioma, Sarcoidosis, Pneumonia, Tuberculosis
Renal / Electrolyte Arthrogryposis -- renal dysfunction -- cholestasis syndrome , Weil's disease, Alagille syndrome, Deal-Barratt-Dillon syndrome , Lupus
Rheum / Immune / Allergy Autoimmune Hepatitis , Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hemolytic anemia, Evans syndrome, Hemolytic disease of the newborn, Hepatic veno-occlusive disease with immunodeficiency , Sarcoidosis, Lupus
Sexual X-linked alpha thalassemia mental retardation syndrome (ATR-X), Lupus, Hemochromatosis
Trauma Cephalhematoma, Hepatic trauma
Urologic No underlying causes
Dental No underlying causes
Miscellaneous Brown Recluse spider bite , Neonatal adrenal hemorrhage, Neonatal physiological jaundice, Premature birth, Reye's syndrome

Causes in Alphabetical Order


Diagnosis

Symptoms

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. It was once believed persons suffering from the medical condition jaundice saw everything as yellow, but this is not true. 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." [1]

The caregiver should ask questions regarding

  • Alcohol/hepatotoxic medication use

Various Symptoms

Physical Examination

  • Complete physical exam including evidence of:

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


See also

References

  1. From "The Dictionary of Cliches" by James Rogers (Ballantine Books, New York, 1985).

Template:Skin and subcutaneous tissue symptoms and signs Template:Nervous and musculoskeletal system symptoms and signs Template:Urinary system symptoms and signs Template:Cognition, perception, emotional state and behaviour symptoms and signs Template:Speech and voice symptoms and signs Template:General symptoms and signs

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