A 50-year-old male presents to the emergency department (ED) with nausea and vomiting, diminished appetite, and recent changes in his skin color, which he describes as turning “yellow.” This seemed to have worsened over the past few weeks, after which he began to worry and presented to the ED.
The patient’s vital signs are normal. His physical exam is positive for icteric sclerae, jaundice in the face and chest, and hepatomegaly. He is not tender to palpation on the abdomen. The rest of his exam is otherwise normal.
Jaundice is not a diagnosis, but a clinical manifestation of an underlying problem, specifically elevated serum bilirubin. Patients with Jaundice present with yellow discoloration of the skin, mucous membranes, and sclera. They can present to the ED with Jaundice in isolation or along with other symptoms. It is the Emergency Physician’s task to evaluate the patient, find the underlying cause, order the appropriate investigation and decide whether the patient requires admission to the hospital and consultation with other physicians.
Normal physiology of bilirubin metabolism
Bilirubin is the end product of heme metabolism. This occurs in three phases: pre-hepatic, hepatic, and post-hepatic phases. Approximately 75-80% of bilirubin comes from the catabolism of red blood cells. Initially, this bilirubin is unconjugated, which is insoluble in water and soluble in fat. Therefore, unconjugated bilirubin can easily cross the blood-brain barrier and the placenta .
Unconjugated bilirubin is actively transported to the liver by albumin and is conjugated by the enzyme glucuronosyltransferase. Subsequently, conjugated bilirubin is either stored in bile in the gallbladder or excreted through the biliary tract, where it eventually reaches the intestines and is excreted from the body [1,2].
Pathophysiology and differential diagnosis
The classic definition of jaundice is a serum bilirubin level greater than 2.5 to 3 mg per dL (42.8 to 51.3 µmol per L), with a clinical presentation of yellow skin and sclera . As described in the above section, bilirubin metabolism occurs in three phases, and dysfunction of any of these steps can lead to jaundice.
Unconjugated hyperbilirubinemia or elevated levels of unconjugated bilirubin before it reaches the liver can lead to jaundice. This can occur due to excessive heme metabolism from increased red blood cell breakdown (hemolysis) and the saturation of enzymes that conjugate it. A few underlying etiology for this include hemolytic anemia, sickle cell anemia, spherocytosis, glucose-6-PD deficiency, hemolytic uraemic syndrome, and transfusion reaction [1,3].
Any process that impacts liver functioning can lead to jaundice. Some of the hepatic causes of jaundice in adults include viral hepatitis, chronic alcohol consumption, autoimmune diseases such as primary biliary cirrhosis, genetic disorders such as Gilbert syndrome, hereditary metabolic defects such as Dubin-Johnson syndrome, and some drugs that can lead to drug-induced liver disease such as acetaminophen, oral contraceptives, estrogenic and anabolic steroids [4-6].
Any process that instigates post-hepatic obstruction can lead to jaundice due to elevated levels of conjugated bilirubin. Some of these include cholelithiasis leading to obstruction of the biliary duct system, biliary tract tumors, biliary duct strictures, and jaundice secondary to pancreatitis [1, 7].
History and physical examination
A good history and physical examination of patients presenting with jaundice to the ED is key in their diagnosis.
On history, the patient should be asked about alcohol and drug use, recent travel, sexual contact with a person with known or suspected hepatitis, recent tattoos or body piercings, and previous biliary surgery. A focused review of systems should also be conducted. For example, a history of fever and viral symptoms can point towards viral hepatitis, while the presence of constitutional symptoms such as weight loss and night sweat may point towards a malignancy .
The physical examination should comprise vital signs and a complete abdominal examination, assessing for right upper quadrant tenderness, ascites, hepatomegaly, splenomegaly, and ascites . Additionally, the physical examination should focus on evaluating encephalopathy by looking for asterixis and changes in mental status and underlying liver disease by assessing for bruising, spider angiomas, gynecomastia, and palmar erythema [1, 8-9]. Lastly, it is important to remember that the presence of painless jaundice and an abdominal mass may point towards obstruction from a malignancy.
First line serum testing should include a complete blood count (CBC) to check for hemolysis, bilirubin level with fractionation, aminotransferases (AST and ALT) to assess for hepatocellular injury (although these may be normal in chronic liver disease), alkaline phosphatase, prothrombin time and/or international normalized ratio, albumin, and protein to assess for liver synthetic function. If these tests come back normal, further tests may be needed to identify the underlying cause of the patient’s jaundice, such as hepatitis serology, autoimmune markers, and investigation for acetaminophen levels [1,8].
The majority of diagnostic imaging will be done outside of the ED. However, emergency physicians can conduct initial ultrasound screening to assess for bile duct dilation, biliary obstruction, and the presence of cholelithiasis. A CT scan can also be ordered to assess for intraparenchymal liver and pancreas disease [1,8]. Outside of the ED, investigation with Endoscopic Retrograde Cholangio-Pancreatography (ERCP), Magnetic Resonance Cholangio-Pancreatography (MRCP), and a liver biopsy may be warranted.
In the ED, emergency physicians are often involved in the initial investigation of a patient with jaundice in ruling out life-threatening conditions and to decide whether a patient should be discharged or admitted for further management. For example, physicians should first assess medical emergencies that can present with jaundice, such as ascending cholangitis, acute hepatic failure, and massive hemolysis. Timely diagnosis, resuscitation, treatment initiation, and emergent consultation of these conditions are critical in the ED. Additionally, patients with elevated AST/ALT levels should be admitted if there are any signs of sepsis, coagulopathy, altered mental status, and intractable pain and vomiting. The presence of hepatocellular injury, coagulopathy, and altered mental status may point towards fulminant liver failure and may require acute fluid resuscitation and hemodynamic monitoring in an acute care setting . Otherwise, depending on the underlying cause of a patient’s jaundice, surgical, gastroenterological or interventional radiological consultation may be required in an outpatient setting.
References and Further Reading
- Roche, S. P., & Kobos, R. (2004). Jaundice in the adult patient. American family physician, 69(2), 299-304.
- Wolfson, A. B., Hendey, G. W., Ling, L. J., Rosen, C. L., Schaider, J. J., & Sharieff, G. Q. (2012). Harwood-Nuss’ clinical practice of emergency medicine. Lippincott Williams & Wilkins.
- Sackey K. (1999). Hemolytic anemia: part 1. Pediatr Rev, 20,152-8.
- Pasha, T. M., & Lindor, K. D. (1996). Diagnosis and therapy of cholestatic liver disease. Medical Clinics of North America, 80(5), 995-1019.
- Schramm, C., Kanzler, S., Zum Büschenfelde, K. H. M., Galle, P. R., & Lohse, A. W. (2001). Autoimmune hepatitis in the elderly. The American journal of gastroenterology, 96(5), 1587-1591.
- Lewis, J. H. (2000). Drug-induced liver disease. Medical Clinics, 84(5), 1275-1311.
- Custis, K., Brown, C., & El Younis, C. M. (2000). Common biliary tract disorders. Clinics in Family Practice, 2(1), 141-154.
- Fargo, M. V., Grogan, S. P., & Saguil, A. (2017). Evaluation of jaundice in adults. American family physician, 95(3), 164-168.
- Winger, J., & Michelfelder, A. (2011). Diagnostic approach to the patient with jaundice. Primary Care: Clinics in Office Practice, 38(3), 469-482.
- Vaquero, J., & Blei, A. T. (2003). Etiology and management of fulminant hepatic failure. Current gastroenterology reports, 5(1), 39-47.