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PBL case objective
a)Differential Diagnosis of Jaundice
b)Biochemical basis for the diagnosis of acute liver disease
c) Biochemical basis for the diagnosis of obstructive jaundice
Clinical case 1: A 52-year-old man presented with a history of nausea, vomiting, abdominal pain, and icteric jaundice for one week. A physical examination revealed stable vital signs, and there was no evidence of hepatic encephalopathy. He had icteric sclera and right upper quadrant abdominal tenderness to palpation. The laboratory investigation results are presented below.
Total serum Bilirubin - 15.4 mg/dL
Direct bilirubun-11.5 mg/dl
Aspartate transaminase- 720 U/L
Alanine transaminase - 1625 U/L
Alkaline Phosphatase- 211 U/L
Total Protein- 7.3 g/dl
Serum Albumin- 3.8 g/dl
Prothrombin time : 12 seconds
Clinical Case 2. A 34-year-old woman presented with a history of jaundice, fever, and abdominal pain. Physical examination showed scleral icterus and right upper quadrant tenderness without inspiratory arrest at palpation. The laboratory investigation results are presented below.
Total Bilirubin: 5.2 mg/dL
Direct Bilirubin: 4.5 mg/dL
Alanine aminotransferase: 180 U/L
Aspartate aminotransferase:210 U/L
Alkaline phosphatase: 750 U/L,
gamma-glutamyltransferase: 999 U/L
Discussion:
Differential Diagnosis of Jaundice
Jaundice is defined as the discoloration of skin, eye, and sclera with serum bilirubin >3mg/dL. Based on the etiology, jaundice can be classified into pre-hepatic (hemolytic jaundice), hepatocellular jaundice, and post-hepatic (obstructive) jaundice. In pre-hepatic jaundice, the unconjugated bilirubin markedly increased in the serum because the production of bilirubin exceeds the conjugation capacity of the liver. In hepatocellular jaundice, the unconjugated and conjugated bilirubin is increased because of leakage of bilirubin from affected hepatocytes.
The increase in bilirubin is accompanied by markedly increased alanine transaminase and aspartate transaminase. Measurement of albumin and prothrombin time helps to differentiate chronic liver disease from an acute condition. In the case of obstructive jaundice, the conjugated bilirubin is increased due to obstructed biliary flow and regurgitation of bilirubin. An elevated serum alkaline phosphatase and 5'-nucleotidase activity are suggestive of obstructive jaundice.
Biochemical basis for the diagnosis of acute liver disease
Case 1: The clinical case presentation and biochemical test results are suggestive of acute hepatitis. The total and direct bilirubin are markedly increased. The transaminases are also elevated with ALT >20 times the upper reference limit showing that the viral infection may be caused by lysis of hepatocytes and leakage of bilirubin and transaminases. In addition, serum albumin and prothrombin time are within normal reference intervals suggesting the acute nature of the disease. To confirm the etiology and type of infected virus, the antibody detection assay against different class hepatitis virus, serological test, and PCR identification of virus serotype are recommended.
In chronic hepatic diseases, the ALT and AST are elevated (generally less than 7X URL), with a decrease in serum albumin and prolonged prothrombin time. The decreased serum albumin and prolonged prothrombin time are a result of compromised liver function.
Biochemical basis for a diagnosis of Obstructive jaundice
Case 2: The clinical case presentation and biochemical test results are suggestive of obstructive jaundice. The total and direct bilirubin mildly increased with significant hyperbilirubinemia. The transaminases (ALT & AST) are mildly elevated with approximately 4-5 X URLs with a marked rise in alkaline phosphatase and gamma-glutamyl transferase. The direct hyperbilirubinemia with elevated serum alkaline phosphatase and gamma-glutamyl transfer are suggestive of cholelithiasis. The enzyme activity of ALP is also elevated in Paget disease (bone) and cancer etc. GGT is also not the specific marker for obstructive jaundice and is elevated in patients with alcoholic liver disease. Therefore, measurement of 5'-nucleotidase and ultrasonography of liver and gallbladder area is preferable for confirmatory diagnosis.
Summary
The measurement of bilirubin, liver enzymes, and enzymes of biliary track enable the differential diagnosis of hepatocellular and obstructive jaundice. The measurement of albumin and prothrombin time provide additional evidence on the occurrence and duration of the disease. The detection and identification of viral serotypes in acute viral hepatitis are important for the treatment of viral hepatitis. Advancement in medicine has made the treatment of some type of hepatitis possible.
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| Differential Diagnosis of Jaundice (Adapted from Harrison's Internal Medicine-16th ed) |
Biochemical basis for the diagnosis of acute liver disease
Case 1: The clinical case presentation and biochemical test results are suggestive of acute hepatitis. The total and direct bilirubin are markedly increased. The transaminases are also elevated with ALT >20 times the upper reference limit showing that the viral infection may be caused by lysis of hepatocytes and leakage of bilirubin and transaminases. In addition, serum albumin and prothrombin time are within normal reference intervals suggesting the acute nature of the disease. To confirm the etiology and type of infected virus, the antibody detection assay against different class hepatitis virus, serological test, and PCR identification of virus serotype are recommended.
In chronic hepatic diseases, the ALT and AST are elevated (generally less than 7X URL), with a decrease in serum albumin and prolonged prothrombin time. The decreased serum albumin and prolonged prothrombin time are a result of compromised liver function.
Biochemical basis for a diagnosis of Obstructive jaundice
Case 2: The clinical case presentation and biochemical test results are suggestive of obstructive jaundice. The total and direct bilirubin mildly increased with significant hyperbilirubinemia. The transaminases (ALT & AST) are mildly elevated with approximately 4-5 X URLs with a marked rise in alkaline phosphatase and gamma-glutamyl transferase. The direct hyperbilirubinemia with elevated serum alkaline phosphatase and gamma-glutamyl transfer are suggestive of cholelithiasis. The enzyme activity of ALP is also elevated in Paget disease (bone) and cancer etc. GGT is also not the specific marker for obstructive jaundice and is elevated in patients with alcoholic liver disease. Therefore, measurement of 5'-nucleotidase and ultrasonography of liver and gallbladder area is preferable for confirmatory diagnosis.
Summary
The measurement of bilirubin, liver enzymes, and enzymes of biliary track enable the differential diagnosis of hepatocellular and obstructive jaundice. The measurement of albumin and prothrombin time provide additional evidence on the occurrence and duration of the disease. The detection and identification of viral serotypes in acute viral hepatitis are important for the treatment of viral hepatitis. Advancement in medicine has made the treatment of some type of hepatitis possible.
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