JAUNDICE

*As serum bilirubin levels rise, the skin will eventually become yellow in light-skinned patients and even green if the process is longstanding Darkening of the urine Another sensitive indicator of increased serum bilirubin w/c is due to the renal excretion of conjugated bilirubin Patients often describe their urine as tea or cola colored. Bilirubinuria indicates an elevation of the direct serum bilirubin fraction and therefore the presence of liver disease. Increased serum bilirubin levels occur when an imbalance exists between bilirubin production and clearance. Read: PRODUCTION AND METABOLISM OF BILIRUBIN MEASUREMENT OF SERUM BILIRUBIN MEASUREMENT OF URINE BILIRUBIN EVALUATION OF JAUNDICE The bilirubin present in serum represents a balance between input from production of bilirubin and hepatic/biliary removal of the pigment. The initial steps in evaluating the patient with jaundice are to determine (1) whether the hyperbilirubinemia is predominantly conjugated or unconjugated in nature, and (2) whether other biochemical liver tests are abnormal.

Yellowish discoloration of tissue resulting from the deposition of bilirubin. Tissue deposition of bilirubin occurs only in the presence of serum hyperbilirubinemia and is a sign of either liver disease or, less often, a hemolytic disorder. The degree of serum bilirubin elevation can be estimated by physical examination. Slight increases in serum bilirubin are best detected by examining the sclerae: have a particular affinity for bilirubin due to their high elastin content. DIFFERENTIAL DIAGNOSIS

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Carotenoderma Is the yellow color imparted to the skin by the presence of carotene. It occurs in healthy individuals who ingest excessive amounts of vegetables and fruits that contain carotene, such as carrots, leafy vegetables, squash, peaches, and oranges. Unlike jaundice, where the yellow coloration of the skin is uniformly distributed over the body, in carotenoderma the pigment is concentrated on the palms, soles, forehead, and nasolabial folds. Can be distinguished from jaundice by the sparing of the sclerae. Use of Quinacrine causes a yellow discoloration of the skin in 4 to 37% of patients treated with it. Unlike carotene, quinacrine can cause discoloration of the sclerae. Excessive exposure to Phenols -

Hyperbilirubinemia may result from: overproduction of bilirubin impaired uptake, conjugation, or excretion of bilirubin; or regurgitation of unconjugated or conjugated bilirubin from damaged hepatocytes or bile ducts. An increase in unconjugated bilirubin in serum results from either overproduction, impairment of uptake, or conjugation of bilirubin. An increase in conjugated bilirubin is due to decreased excretion into the bile ductules or backward leakage of the pigment.

ELEVATION OF SERUM BILIRUBIN WITH OTHER LIVER TEST ABNORMALITIES Evaluation of the patient with a conjugated hyperbilirubinemia in the setting of other liver test abnormalities. Divided into those with a primary hepatocellular process and those with intra- or extrahepatic cholestasis. This differentiation is made on the basis of the history and physical examination as well as the pattern of liver test abnormalities. History Complete medical history: single most important part of the evaluation of the patient with unexplained jaundice. Consider: the use of or exposure to any chemical or medication, either physician-prescribed or OTC, such as herbal and vitamin preparations and other drugs such as anabolic steroids.

Scleral icterus Indicates a serum bilirubin of at least 3.0 mg/dL. The ability to detect scleral icterus is made more difficult if the examining room has fluorescent lighting. If the examiner suspects scleral icterus, a second place to examine is underneath the tongue.

 Possible parenteral exposures, including transfusions, IV and intranasal drug use, tattoos, and sexual activity. Recent travel history, Exposure to people with jaundice, possibly contaminated foods, occupational exposure to hepatotoxins, alcohol consumption, Duration of jaundice Presence of any accompanying symptoms: arthralgias, myalgias, rash, anorexia, weight loss, abdominal pain, fever, pruritis, and changes in the urine and stool. Jaundice + sudden onset of severe RUQ pain and shaking chills suggests choledocholithiasis and ascending cholangitis History of arthralgias and myalgias predating jaundice suggests hepatitis, either viral or drug-related. Physical Examination Include assessment of the patient's nutritional status. Temporal and proximal muscle wasting suggests longstanding diseases such as pancreatic cancer or cirrhosis. Stigmata of chronic liver disease, including spider nevi, palmar erythema, gynecomastia, caput medusae, Dupuytren's contractures, parotid gland enlargement, and testicular atrophy are commonly seen in advanced alcoholic (Laennec's) cirrhosis and occasionally in other types of cirrhosis. An enlarged left supraclavicular node (Virchow's node) or periumbilical nodule (Sister Mary Joseph's nodule suggest an abdominal malignancy. JV distention a sign of right-sided HF, suggests hepatic congestion. Right pleural effusion, in the absence of clinically apparent ascites may be seen in advanced cirrhosis. Pts. w/ cirrhosis may have an enlarged left lobe of the liver, and an enlarged spleen. A grossly enlarged nodular liver or an obvious abdominal mass suggests malignancy. An enlarged tender liver could be viral or alcoholic hepatitis or, less often, an acutely congested liver secondary to right-sided HF. Severe RUQ tenderness w/ Murphy's sign suggests cholecystitis or, occasionally, ascending cholangitis. Ascites + jaundice suggests either cirrhosis or malignancy with peritoneal spread. -

The abdominal examination should focus on - size and consistency of the liver, - spleen is palpable - ascites present. Laboratory Tests LIVER FUNCTION tests: o total and direct serum bilirubin with fractionation, o aminotransferases o alkaline phosphatase o albumin o prothrombin time tests.

Enzyme tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)] are helpful in differentiating between a hepatocellular process and a cholestatic process. Hepatocellular process: > aminotransferases compared to the ALP. Cholestatic process: > ALP compared to the aminotransferases. * The bilirubin can be prominently elevated in both hepatocellular and cholestatic conditions and therefore is not necessarily helpful in differentiating between the two. Low albumin Normal albumin Elevated PT time Chronic process such as cirrhosis or cancer Acute process such as viral hepatitis or choledocholithiasis. Indicates either vitamin K deficiency due to prolonged jaundice and malabsorption of vitamin K or significant hepatocellular dysfunction. The failure of the prothrombin time to correct with parenteral administration of vitamin K indicates severe hepatocellular injury.

HEPATOCELLULAR CONDITIONS Hepatocellular diseases that can cause jaundice include: o viral hepatitis, o drug or environmental toxicity, o alcohol, and o end-stage cirrhosis from any cause.

Wilson's disease should be considered in young adults. Autoimmune hepatitis is typically seen in young to middle-aged women. Pattern of Aminotransferases Alcoholic hepatitis vs. viral Acute viral hepatitis and toxinand toxin-related hepatitis: related injury severe enough to produce jaundice: Patients with Aminotransferases alcoholic hepatitis greater than 500 U/L, typically have an with the ALT > or = AST:ALT ratio of at AST. least 2:1. The AST rarely exceeds 300 U/L. The degree of aminotransferase elevation can occasionally help in differentiating between hepatocellular and cholestatic processes. While ALT and AST values < 8x N may be seen in either hepatocellular or cholestatic liver disease, values 25x N or higher are seen primarily in acute hepatocellular diseases. Pts. w/ jaundice from cirrhosis can have N or only slight elevations of the aminotransferases. CHOLESTATIC CONDITIONS Determine: intra- or extrahepatic cholestasis. May be difficult. History, PE, & lab tests are often not helpful. The next appropriate test is an ultrasound.

If cholestatic,

intra- or extrahepatic?

All of these questions can be answered with History, PE, laboratory, radiologic tests and procedures.

ULTRASOUND inexpensive, does not expose the patient to ionizing radiation, and can detect dilation of the intra- and extrahepatic biliary tree. (-) biliary dilatation = intrahepatic cholestasis (+) biliary dilatation = extrahepatic cholestasis False-negative results occur in patients with partial obstruction of the CBD or in patients with cirrhosis or primary sclerosing cholangitis (PSC) where scarring prevents the intrahepatic ducts from dilating. CT and ERCP CT scanning is better than ultrasonography for assessing the head of the pancreas and for identifying choledocholithiasis in the distal CBD, particularly when the ducts are not dilated. ERCP is the gold standard for identifying choledocholithiasis. MRCP is a rapidly developing, noninvasive technique for imaging the bile and pancreatic ducts; this may replace ERCP as the initial diagnostic test in cases where the need for intervention is felt to be small.

SUMMARY The initial step is to obtain appropriate blood tests to determine if the patient has an isolated elevation of serum bilirubin. Inc bilirubin elevation fraction? increased unconjugated vs. conjugated

Hyperbilirubinemia + other liver test abnormalities, hepatocellular vs. cholestatic?