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The onset of jaundice usually prompts a patient to seek medical attention. Jaundice is a common medical finding in both inpatient and outpatient settings. Diagnosing the etiology of jaundice is an important training problem for medical students because accurate diagnosis requires prudent selection and interpretation of common diagnostic studies. Also, learning use of appropriate management strategies for jaundice is important because of its impact on patient morbidity and on health care cost.

The causes of hepatobiliary disease are many and can be quite overwhelming. A thorough understanding of a systematic approach to hyperbilirubinemia/jaundice is preferable to random knowledge of highly specific etiologies. The liver responds pathologically to injury in characteristic ways and knowledge of these patterns can also be very useful in differential diagnosis. Several etiologies of liver disease such as acute/chronic viral hepatitis and alcohol-induced liver disease are sufficiently common as to require specific attention. In addition, many liver diseases can result in cirrhosis and its complications and, therefore, understanding this end-stage development is important.

Required Skills/Procedures:

1. Perform situation-appropriate (problem-focused or complete) history and physical examinations
2. Interpret clinical information to formulate a prioritized differential diagnosis
3. Guide the creation of a patient-specific management plan

Appropriate Setting: Inpatient and Outpatient

Expected level of Responsibility: Direct supervision with real patients

Learning Topics during encounters with a patient with JAUNDICE can include:

Medical Knowledge Learning Topics related to JAUNDICE:

1. Pathophysiologic mechanisms that lead to jaundice including:

  • excess bilirubin production
  • decreased uptake and conjugation of bilirubin
  • intrahepatic cholestasis
  • hepatocellular disease
  • extrahepatic obstruction

2. Epidemiology, pathophysiology, symptoms, signs, and typical clinical course of hepato-biliary diseases including:

  • steatosis (fatty liver)
  • hepatitis
  • cirrhosis
  • infiltrative liver disease
  • intrahepatic cholestasis
  • extrahepatic cholestasis (obstructive jaundice)
  • alcohol-induced liver disease
  • portal hypertension
  • ascites
  • spontaneous bacterial peritonitis
  • hepatic encephalopathy
  • the hepatorenal syndrome
  • cholelithiasis and cholecystitis
  • the clinical syndrome of “ascending cholangitis”
  • autoimmune liver diseases such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis

3. Common causes of drug-induced liver injury

4. Distinguishing the type of bilirubin in each type of jaundice (unconjugated or conjugated) and the utility of a urine dip stick test for urobilinogen

5. Which type of bilirubin elevation (unconjugated or conjugated) goes with each of the 5 major pathophysiologic causes of jaundice

6. Genetic considerations in liver disease (i.e. hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, Gilbert’s syndrome)

7. Utility of laboratory tests including:

  • serum markers of liver injury (e.g. AST, ALT, GGT, Alk Phos) and function (e.g. bilirubin, ALB, PT/INR) in the diagnostic evaluation of hepatobiliary disease
  • which transaminase (AST vs ALT) is more specific for liver disease
    • what is meant by the “AST/ALT split” and why that may be important
    • two other sources of AST in the body
  • the clinical significance of asymptomatic, isolated elevation of AST, ALT, GGT, and/or Alk Phos
  • how to interpret a Direct Coombs test
  • the analysis of ascitic fluid and its use in the diagnostic evaluation of liver disease
  • tests that can help support a diagnosis of intravascular hemolysis

8. Time course for liver disease to affect:

  • transaminases
  • prothrombin time
  • albumin

9. Indications for and risks of paracentesis and liver biopsy

10. Causes of jaundice treated medically versus surgically

11. Reversing a prolonged prothrombin time with parenteral vitamin K in helping to refine the differential diagnosis of a conjugated hyperbilirubinemia

12. Method of parenteral vitamin K administration (IV, IM, or SC) is associated with anaphylaxis and reasons for avoiding that route

13. Medications that can cause jaundice

14. Recognizing the importance of an elevated alkaline phosphatase level in some patients with jaundice

15. Distinguishing between alkaline phosphatase elevations from bone disease and liver disease

16. Utility and indications of hepatobiliary imaging studies, including:

  • ultrasound
  • computed tomography
  • percutaneous transhepatic cholangiography
  • endoscopic retrograde cholangiopancreatography (ERCP)
  • magnetic resonance cholangiopancreatograpy (MRCP)
  • nuclear medicine studies

17. Distinguishing between acute and chronic hepatitis

18. Indications and efficacy of hepatitis A and B vaccinations

Diagnostic Evaluation Learning Topics related to JAUNDICE

1. Age-appropriate medical history that differentiates among etiologies of disease, including:

  • jaundice, discolored urine, pruritis, light-colored stool, unintentional weight loss, fever, nausea, emesis, diarrhea, altered mental status, abdominal pain, increased abdominal girth, edema, rectal bleeding, hematemesis
  • DM
  • an alcohol and drug use history, taken in a non-judgmental way, showing compassion for the patient
  • prescription, over-the-counter, and illicit drug use
  • transfusions and other sources of potential blood-born pathogen exposure
  • consumption of uncooked shellfish and other food items potentially contaminated with fecal matter
  • sexual history
  • vaccination history
  • family history of liver diseases

2. Physical exam establishing the diagnosis and severity of disease, including:

  • assessment of the size of a patient’s liver and spleen on physical exam
  • identification of signs of hepatic disease on physical exam
  • complete abdominal examination including findings consistent with ascites (e.g. bulging flanks, shifting dullness, fluid wave)
  • findings compatible with chronic alcohol use and portal hypertension (e.g. palmar erythema, spider angiomas, gynecomastia, testicular atrophy, Dupuytren’s contracture, muscle wasting, splenomegaly, ascites, edema, caput medusa, hemorrhoids)
  • findings compatible with hepatic (portosystemic) encephalopathy (e.g. disturbances of consciousness and behavior, fluctuating neurologic signs, asterixis)

3. Differential diagnosis recognizing specific history and physical exam findings that suggest a specific etiology. It is necessary to:

  • recognize physical exam findings related to jaundice and distinguish true jaundice from caroteneima
  • recognize a patient with scleral icterus on physical exam
  • recognize signs of intravascular hemolysis and explain why that would be important to determine the cause of jaundice.
  • recognize which kind of jaundice (unconjugated or conjugated) in which it is important to look for signs of intravascular hemolysis
  • recognize findings from a peripheral blood smear as intravascular hemolysis
  • recognize dark urine and pale stools as an important finding to help determine the type of bilirubin that is causing the jaundice
  • recognize the importance of identifying a small cirrhotic liver and how this relates to the differential diagnosis of jaundice
  • understand the importance of eliciting the findings of fever and peritoneal signs in a patient with jaundice and how that affects the treatment plans
  • be able to demonstrate shifting dullness and the fluid wave test to look for ascites

4. Ordering and interpreting diagnostic and laboratory tests both prior to and after initiating treatment based on the differential diagnosis. Consider test cost and performance characteristics as well as patient preferences. Laboratory and diagnostic tests should include, when appropriate:

  • CBC
  • electrolytes, BUN/Cr, GLC
  • ALB, TP, total bilirubin, direct bilirubin, PT/INR, AST, ALT, Alk Phos
  • hepatitis serology
  • ascitic fluid ALB, amylase, cell counts, staining, cultures, and the serum-ascites albumin gradient (SAAG)

5. Indications for and interpreting (with consultation) the results of:

  • ultrasound
  • nuclear medicine studies
  • CT
  • MRI
  • magnetic resonance cholangiopancreatography (MRCP)
  • endoscopic retrograde

6. Consideration of selected procedures

  • Assisting in performing a paracentesis after explaining the procedure to the patient
  • Performing a urine dipstick to look for urobilinogen
  • Taking a patient’s temperature

7. Identification of the patient’s problem from all of the problems listed in the differential diagnosis by combining scientific knowledge, information obtained in the clinical encounter and collective experience with similar patients

  • Diagnostic evaluation of asymptomatic, isolated elevation of the transaminases and/or Alk Phos
  • Diagnostic evaluation of patients with jaundice and unconjugated or conjugated hyperbilirubinemia
  • Determination of when to obtain consultation from a gastroenterologist, hepatologist, or biliary surgeon
  • Use of a cost-effective approach based on the differential diagnosis
  • Access and utility of appropriate information systems and resources to help delineate issues related to liver disease

8. Communication of the diagnosis to the patient

Management Plan Learning Topics related to JAUNDICE

1. Management of:

  • steatosis
  • hepatitis
  • cirrhosis
  • intra- and extra hepatic cholestasis
  • acute cholecystitis
  • ascites
  • portal hypertension
  • spontaneous bacterial peritonitis
  • hepatic encephalopathy

2. Preventive measures, including counseling and educating patients about sexual activity
4. Psychological support if indicated
6. Follow-up planning
7. Communication of the prognosis to the patient in a caring and compassionate manner
8. Communication of the treatment plan and follow-up plan to patient
9. Cost-effectiveness of the management plan
10. Public health role physicians play in the prevention of viral hepatitis
11. Empathy for patients faced with alcohol abstinence

Potential Differential Diagnosis Topics Includes:

The 5 major pathophysiologic causes of jaundice

Excess bilirubin production

  • hereditary spherocytosis/other RBC membrane defects
  • hemoglobin disorders – hemoglobinopathies
  • cytoplasm/enzyme disorders – G6-PD deficiency triggered by oxidative stress
  • pyruvate kinase difficiency
  • autoantibodies – autoimmune hemolytic anemia (Coomb’s positive)
  • abnormalites in the circulation/mechanical stresses – Artificial heart valves, Kasabach-Merritt syndrome, Hemolytic uremic syndrome (HUS), DIC, TTP, malaria

Decreased uptake and conjugation of bilirubin

  • Gilbert’s syndrome
  • Crigler-Najjar syndrome

Intrahepatic cholestasis, including problems at the:

  • intracellular level – hepatitis
  • canalicular level – estrogen
  • ductule level – phenothiazine exposure
  • septal ducts – primary biliary cirrhosis
  • intralobular ducts – cholangiocarcinoma

Hepatocellular disease

  • Viral hepatitis A, B, C, D, E
  • toxins – ETOH, drugs (tyelenol), solvents, heavy metals, mushrooms
  • infiltration: fatty liver, amyloid, sarcoid, hemachromatosis, Wilsons, Tb, fungal, lymphoma
  • autoimmune – Primary biliary cirrhosis, PSC

Extrahepatic obstruction

  • gallstones
  • strictures
  • masses (abscess, neoplasm)