Jaundice Agnieszka Dobrowolska- Zachwieja, MD, PhD
Jaundice definition Jaundice, as in the French jaune, refers to the yellow discoloration of the skin. It arises from the abnormal accumulation of bilirubin in body tissues, which occurs when the serum bilirubin level exceeds 3 mg/dl or 50 µmol/l. 1 Excess bilirubin causes a yellow tinting to the skin, sclera, and mucous membranes.
Jaundice The presence of jaundice can indicate a transient hepatitis, biliary obstruction, or progressive deterioration in a patient awaiting liver transplantation. Thus, the appropriate management of the patient with jaundice depends on localizing the site and nature of the problem.
Jaundice Hyperbilirubinemia is defined as a total bilirubin level greater than 1.5 mg/dl, an unconjugated level greater than 1 mg/dl, or a conjugated bilirubin level greater than 0.3 mg/dl.
Jaundice- Causes Of Hyperbilirubinemia- unconjugated Hemolysis Ineffective erythropoiesis Neonatal causes Uridine diphosphate glucuronosyltransferase deficiencies Gilbert syndrome Crigler-Najjar syndromes Miscellaneous causes (drugs, hypothyroidism, thyrotoxicosis, pulmonary infarct, fasting)
Jaundice- Causes Of Hyperbilirubinemia- conjugated Congenital causes Rotor syndrome Dubin-Johnson syndrome Choledochal cysts Familial disorders Benign recurrent intrahepatic cholestasis Cholestasis of pregnancy
Jaundice- Causes Of Hyperbilirubinemia- conjugated Hepatocellular defects Alcohol abuse Viral infection Cholestatic Primary biliary cirrhosis Primary sclerosing cholangitis Biliary obstruction Pancreatic disease
Jaundice- Causes Of Hyperbilirubinemia- conjugated Systemic disease Infiltrative disorders Postoperative complications Renal disease Sepsis Drugs
Jaundice Unconjugated hyperbilirubinemia exists if more than 80% to 85% of the total bilirubin is unconjugated. Conjugated hyperbilirubinemia exists if greater than 30% of the total bilirubin level is conjugated. Overproduction of bilirubin results in unconjugated hyperbilirubinemia. Mild hyperbilirubinemia may require blood or urine tests for detection, as jaundice usually does not become apparent until the bilirubin level exceeds 3 mg/dl.
Evaluation to the patient with jaundice The investigation of a patient with jaundice begins with a thorough review of the history of presentation, medication use, past medical history, physical examination, and evaluation of liver function tests.
Evaluation to the patient with jaundice Several questions must be answered initially: 1. Is the elevated bilirubin conjugated or unconjugated? In general, most jaundiced patients will not have an isolated unconjugated hyperbilirubinemia. 2. If the hyperbilirubinemia is unconjugated, is it caused by increased production, decreased uptake, or impaired conjugation? 3. If the hyperbilirubinemia is conjugated, is the problem intrahepatic or extrahepatic? 4. Is the process acute or chronic?
Evaluation to the patient with jaundice Patients with conjugated hyperbilirubinemia usually have acquired disease- identify an intrahepatic or an obstructive cause. Acute disease usually can be differentiated from chronic disease by the patient's history, physical examination (xanthelasma, spider angioma, ascites, or hepatosplenomegaly), and laboratory tests (hypoalbuminemia, thrombocytopenia, and an uncorrectable prolongation of the prothrombin time).
Evaluation to the patient with jaundice Chronic cholestasis may arise from such diseases as cirrhosis, primary sclerosing cholangitis, primary biliary cirrhosis, secondary biliary cirrhosis, or carcinoma or from drugs. Patients with chronic cholestasis usually do not have hepatitis or gallstones.
Evaluation to the patient with jaundice The presence of fever, right upper quadrant pain, tenderness, hepatomegaly, and new- onset bilirubinuria usually indicates acute disease. Patients older than 50 years of age with asymptomatic cholestasis and mild hepatomegaly may have carcinoma of the pancreas or biliary tree.
Evaluation to the patient with jaundice Women aged over 30 years of age are more likely to have choledocholithiasis. An adult with asymptomatic, isolated unconjugated hyperbilirubinemia who is not taking any drugs and has no evidence of hemolysis probably has Gilbert syndrome and can be monitored with bilirubin determinations for 12 months. If no abnormality develops, no further evaluation is needed.
Evaluation to the patient with jaundice Fever, leukocytosis, and hypotension point to ascending cholangitis Asterixis, confusion, or stupor may indicate severe hepatocellular dysfunction or fulminant hepatocellular failure
Clinical symptoms Fever Chills Weight loss Flu like symptoms Abdominal pain Anorexia Nausea, and vomiting Pruritus
Physical examination General appearance cachexia, muscle wasting, palmar erythema, Dupuytren contracture, abnormal nails, parotid enlargement, or xanthelasmas, gynecomastia, spider nevi, or dilated veins. The size and consistency of the liver shrunken, nodular liver - cirrhosis, a palpable mass - an abscess or malignancy. If the liver span is greater than 15 cm- fatty infiltration, congestion, other infiltrative diseases, or malignancy. Liver tenderness may denote acute disease but is generally not helpful. The presence of a friction rub or bruit suggests malignancy.
Clinical examination Spider angioma, palmar erythema, and distended abdominal veins Ascites in the presence of jaundice (cirrhosis, malignancy and severe acute disease, such as viral or alcoholic hepatitis) Splenomegaly (infections, infiltrative diseases, viral hepatitis, or cirrhosis) A palpable, distended gallbladder suggests malignant biliary obstruction. Asterixis in fulminant hepatic failure and end-stage liver disease. Patients with biliary colic or infection may have fever.
Laboratory tests TB (conjugated, unconjugated) AspAT, AlAT GGTP AP TP + (albumin, gammaglobulin) Prothrombin
Laboratory tests TCh AMA 5 -NT LAP Alfa1-antitrypsin antitrypsin Iron levels Ceruloplasmin Alfa-fetoprotein fetoprotein (AFP) Antinuclear antibody
Noninvasive tests US CT Radionuclide imaging is an excellent means of detecting cystic duct obstruction. It is the test of choice if acute cholecystitis is suspected, but it has little value in differentiating intrahepatic from extrahepatic causes of cholestasis.
Invasive tests ERCP - endoscopic retrograde cholangiopancreatography PTC - percutaneous transhepatic cholangiography liver biopsy
ERCP ERCP is 90% successful regardless of the presence or absence of ductal dilation and can localize the site of obstruction in more than 90% of patients. It is particularly helpful in diagnosing patients with common duct stones. Because it has therapeutic capabilities, it allows some patients to avoid surgery. ERCP is also helpful if a stricture due to chronic pancreatitis is suspected.
PTC PTC visualizes the biliary tree in 90% to 100% of patients with dilated ducts and localizes the site of obstruction in 90% of cases. It locates the obstruction in 50% to 90% of patients without dilated ducts, as determined by ultrasound. PTC is less expensive than ERCP and often is easier to perform. The patient must have a prothrombin time of less than 16 seconds, a platelet count greater than 50,000, and no ascites. Minor complications occur in 30% of patients. Major complications, including sepsis, bleeding, biliary leak, pneumothorax, arteriovenous fistula, hematoma, abscess, and peritonitis, occur in 1% to 10% of patients who undergo PTC.
Hepatocellular defects Viral hepatitis Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Hepatitis G
Hepatocellular defects Alcohol abuse Liver steatose (fatty liver) Hepatitis Cirrhosis of the liver
Cholestasis PBC PSC Biliary obstruction Pancreatic disease
PBC The clinical features include jaundice, pruritus, steatorrhea, xanthomas, and osteopenia. In advanced disease, signs of portal hypertension will occur with esophageal varices, ascites, and other conditions. Primary biliary cirrhosis is a chronic progressive cholestatic disorder typically, although not exclusively, found in women in the fourth to fifth decade of life.
PBC laboratory abnormalities: a characteristic isolated alkaline phosphatase elevation out of proportion to other liver function tests, Elevated serum IgM, cholesterol, antimitochondrial antibody (AMA).
PSC Progressive cholestatic liver disease, which is found mostly in men of middle age. Inflammation of both intrahepatic and extrahepatic bile ducts Clinically, patients present with recurrent abdominal pain, fever, and intermittent jaundice and later with symptoms of portal hypertension. Characteristic narrowing or "beading" occurs in the hepatic ducts, as demonstrated by cholangiogram.
PSC vs. UC Chronic inflammatory bowel diseases, such as ulcerative colitis, are associated in 30% to 75% of primary sclerosing cholangitis patients Of all patients with ulcerative colitis, 5% to 10% will have primary sclerosing cholangitis.