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A 67-year-old man with type 2 diabetes presents to your primary care practice following 3 weeks of intermittent nausea and vomiting. His wife insisted he see a doctor because his skin and eyes are yellow. He has noticed that his pants are looser, but he has no other complaints.

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  • What are other important questions to ask this patient?
  • What is the differential diagnosis of jaundice? Of painless jaundice?

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Jaundice is a yellow discoloration of body tissues due to an excess of bilirubin, a pigment produced during the metabolism of heme. Normally, serum bilirubin should never exceed 1 to 1.5 mg/dL. Levels above 2 mg/dL result in detectable jaundice, first in the sclerae, next under the tongue and along the tympanic membranes, and finally in the skin. Thus, cutaneous jaundice implies higher levels of bilirubin than isolated scleral icterus.

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A thorough dietary and medication history can exclude the yellow skin discoloration of carotenemia, isotretinoin, or rifampin overdose, all of which spare the sclerae. Once these mimickers are excluded, jaundice must be recognized as a manifestation of advanced hepatocellular or cholestatic liver disease or, less commonly, hemolysis or abnormal bilirubin metabolism. The history should proceed in 2 parallel routes: (1) arrive rapidly at a likely diagnosis and (2) identify alarm features that may necessitate urgent intervention.

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Budd-Chiari syndromeHepatic vein obstruction, often due to an underlying hypercoagulable state (eg, oral contraceptives, polycythemia vera, paroxysmal nocturnal hemoglobinuria, antiphospholipid antibody syndrome); the acute form classically presents with tender hepatomegaly, jaundice, and ascites.
CholestasisRetention of bile in the liver, due to intra- or extrahepatic obstruction or biliary stasis.
Conjugated bilirubinFormed in the liver when unconjugated bilirubin is metabolized, then released into bile; may be filtered by the glomerulus and appear in the urine.
Fulminant hepatic failureOnset of hepatic encephalopathy within 8 weeks of liver injury, often accompanied by coagulopathy. Common causes include acute viral hepatitis, ingestions (eg, acetaminophen or Amanita mushrooms), and hepatic ischemia. Less common causes include Wilson's disease, autoimmune hepatitis, acute Budd-Chiari syndrome, other infections, and malignancy.
Hepatocellular jaundiceAccumulation of conjugated bilirubin in the serum due to hepatocyte dysfunction.
HyperbilirubinemiaElevated serum levels of bilirubin (> 1.2 mg/dL).
IcterusSynonymous with jaundice.
Infiltrative liver diseaseSubset of liver disease marked by cholestasis due to diffuse involvement within the liver including granulomatous disease (sarcoidosis, Wegener's granulomatosis, fungal and mycobacterial infections), amyloidosis, Wilson's disease, hemochromatosis, lymphoma, and metastatic cancer.
JaundiceYellow pigmentation of the skin and sclerae.
Nonalcoholic fatty liver disease (NAFLD)Parenchymal liver disease common in patients with the metabolic syndrome (phenotype is obese diabetic with hyperlipidemia but can also occur in obese patients without other comorbidities).
Obstructive jaundiceExcess conjugated bilirubin in the serum due to impaired bile flow in the intrahepatic or extrahepatic bile ducts.
Unconjugated bilirubinThe main circulating form of bilirubin, produced upon heme breakdown and delivered to the liver for further metabolism.

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