ICTERUS

JAUNDICE (Icterus)

Jaundice results from the accumulation of bilirubin—a reddish pigment product of heme metabolism—in the body tissues; the cause may be hepatic or nonhepatic. Hyperbilirubinemia may be due to abnormalities in the formation, transport, metabolism, and excretion of bilirubin. Total serum bilirubin is normally 0.2–1.2 mg/dL, and jaundice may not be recognizable until levels are about 3 mg/dL.

Jaundice is caused by predominantly unconjugated or conjugated bilirubin in the serum (Table 15–1). Unconjugated hyperbilirubinemia may result from overproduction of bilirubin because of hemolysis; impaired hepatic uptake of bilirubin due to certain drugs; or impaired conjugation of bilirubin by glucuronide, as in Gilbert's syndrome, due to mild decreases in glucuronyl transferase, or Crigler-Najjar syndrome, caused by moderate decreases or absence of glucuronyl transferase. In the absence of liver disease, hemolysis rarely elevates the serum bilirubin level to more than 7 mg/dL. Predominantly conjugated hyperbilirubinemia may result from impaired excretion of bilirubin from the liver due to hepatocellular disease, drugs, sepsis, hereditary disorders such as Dubin-Johnson syndrome, or extrahepatic biliary obstruction. Features of some hyperbilirubinemic syndromes are summarized in Table 15–2. The term "cholestasis" denotes retention of bile in the liver, and the term "cholestatic jaundice" is often used when conjugated hyperbilirubinemia results from impaired bile flow.

 

Manifestations of Diseases Associated With Jaundice

A. UNCONJUGATED HYPERBILIRUBINEMIA

Stool and urine color are normal, and there is mild jaundice and indirect (unconjugated) hyperbilirubinemia with no bilirubin in the urine. Splenomegaly occurs in hemolytic disorders except in sickle cell anemia. Abdominal or back pain may occur with acute hemolytic crises.

B. CONJUGATED HYPERBILIRUBINEMIA

1. Hereditary cholestatic syndromes or intrahepatic cholestasis—The patient may be asymptomatic; intermittent cholestasis is often accompanied by pruritus, light-colored stools, and, occasionally, malaise.

2. Hepatocellular disease—Malaise, anorexia, low-grade fever, and right upper quadrant discomfort are frequent. Dark urine, jaundice, and, in women, amenorrhea occur. An enlarged, tender liver; vascular spiders; palmar erythema; ascites; gynecomastia; sparse body hair; fetor hepaticus; and asterixis may be present, depending on the cause, severity, and chronicity of liver dysfunction.

C. BILIARY OBSTRUCTION

There may be right upper quadrant pain, weight loss (suggesting carcinoma), jaundice, dark urine, and light-colored stools. Symptoms and signs may be intermittent if caused by stone, carcinoma of the ampulla, or cholangiocarcinoma. Pain may be absent early in pancreatic cancer. Occult blood in the stools suggests cancer of the ampulla. Hepatomegaly and a palpable gallbladder (Courvoisier's sign) are characteristic, but neither specific nor sensitive of pancreatic head tumor. Fever and chills are far more common in benign obstruction and associated cholangitis.

 

LABORATORY STUDIES

Elevated serum aspartate and alanine aminotransferase levels (AST, ALT) result from hepatocellular necrosis or inflammation, as in hepatitis; ALT is more specific for the liver than AST, but an AST level at least twice that of the ALT is typical of alcoholic liver injury. In contrast, the ALT level is greater than the AST level in nonalcoholic fatty liver disease prior to the development of cirrhosis. In addition to signaling underlying liver disease, an isolated elevation of the serum ALT level may be the only clue to the diagnosis of celiac disease. Elevated alkaline phosphatase levels are seen in cholestasis or infiltrative liver disease (such as tumor or granuloma). Alkaline phosphatase elevations of hepatic rather than bone, intestinal, or placental origin are confirmed by concomitant elevation of g-glutamyl transpeptidase or 5'-nucleotidase levels.

LIVER BIOPSY

Percutaneous liver biopsy is the definitive study for determining the cause and histologic severity of hepatocellular dysfunction or infiltrative liver disease. In patients with suspected metastatic disease or a hepatic mass, it is performed under ultrasound or CT guidance. A transjugular route can be used in patients with coagulopathy or ascites.

IMAGING

Demonstration of dilated bile ducts by ultrasonography or CT scan indicates biliary obstruction (90–95% sensitivity). Ultrasonography, CT scan, and MRI may also demonstrate hepatomegaly, intrahepatic tumors, and portal hypertension. Spiral arterial-phase CT scanning, in which the liver is imaged during peak hepatic enhancement while the patient holds one or two breaths, improves diagnostic accuracy. Dual-phase spiral CT, CT arterial portography, in which imaging follows intravenous contrast infusion via a catheter placed in the superior mesenteric artery, MRI with use of ferumoxides as contrast agents, and intraoperative ultrasonography are the most sensitive techniques for detection of individual small hepatic lesions in patients eligible for resection of metastases. Use of color Doppler ultrasound or contrast agents that produce microbubbles increases the sensitivity of transcutaneous ultrasound for detecting small neoplasms. MRI is the most accurate technique for identifying isolated liver lesions such as hemangiomas, focal nodular hyperplasia, or focal fatty infiltration and for detecting hepatic iron overload. Because of its much lower cost, ultrasonography ($350) is preferable to CT ($1200– $1400) or MRI ($2000) as a screening test. Ultrasonography can detect gallstones with a sensitivity of 95%.

Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) identifies the cause, location, and extent of biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) appears to be a sensitive, noninvasive method of detecting bile duct stones, strictures, and dilation. ERCP requires a skilled endoscopist and may be utilized to demonstrate pancreatic or ampullary causes of jaundice, to carry out papillotomy and stone extraction, or to insert a stent through an obstructing lesion. Complications of ERCP include pancreatitis in 5% of cases and, less commonly, cholangitis, bleeding, or duodenathe most sensitive test for detecting small lesions of the ampulla or pancreatic head and for detecting portal vein invasion by pancreatic cancer. It is also accurate in detecting or excluding bile duct stones.

 

REFFERENCE

Federle MP (guest editor): Imaging of the liver. Semin Liver Dis 2001;21:133. (Entire issue devoted to all aspects of liver imaging.)

Janssen PL et al: Genes and cholestasis. Hepatology 2001; 34:1067. [PMID: 11731993] (Review of recently identified molecular defects in hepatocellular membrane transporters that account for various genetic hyperbilirubinemic disorders.)

Pratt DS et al: Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J. Med 2000;342:1266. [PMID: 10781624] (Useful review of causes and evaluation of elevated aminotransferase, alkaline phosphatase, and g-glutamyl transpeptidase levels.)

Rothschild JM et al: Abdominal cross-sectional imaging for inpatients with abnormal liver function test results: yield and usefulness. Arch Intern Med 2001;161:583. [PMID: 11252119] (Clinically significant findings were identified in 35% of cases and included biliary obstruction [25%], cholecystitis [20%], malignancy [20%], and cirrhosis [15%].)

Skelly MM et al: Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001;35:195. [PMID: 11580141] (With unexplained liver test abnormalities after a biochemical serologic evaluation, 35% had nonalcoholic steatohepatitis and 30% had fatty liver on liver biopsy; 5% had cirrhosis.)

SOURCESS : CURRENT MEDICAL DIAGNOSIS AND TREATMENT 2003