Deranged liver function tests (LFTs) may reflect muscle breakdown rather than a failing liver; therefore, checking a creatine kinase is important
Deranged liver function tests (LFTs) may reflect muscle breakdown rather than a failing liver; therefore, checking a creatine kinase is important: Excerpt from Avoiding Common Pediatric Errors
Author:
Caroline Rassbach, MD
What to Do - Interpret the Data
WhencheckingLFTs,itisimportanttoknowthatabnormalitiesmayreflecta
probleminadifferentorgan system."Liverfunction" isactuallyamisnomer,
as only prothrombin time (PT) and albumin are actual measures of the
liver's synthetic function. The other parameters are indirect measures of
liver function. Deranged LFTs may represent muscle injury rather than
liver damage, and checking a CK level is essential to determining the correct
etiology.
The aminotransferases include aspartate transaminase (AST) and alanine transaminase (ALT). These enzymes are found within hepatocytes,
are released during cell necrosis, and are the most sensitive tests of hepatocyte injury. Common insults include viral hepatitis, toxic injury (i.e.,
acetaminophen toxicity), and ischemic injury. The degree of elevation of the
aminotransferases does not necessarily correlate with the severity of liver
disease. The aminotransferases may rise slightly as a result of cholestatic
jaundice because bile is hepatotoxic.
Inaddition tobeing present inthe liver,ASTis also foundin cardiacand
skeletal muscle, erythrocytes, and kidney and pancreatic tissue. Elevations
of AST and ALT may represent muscle injury, with AST rising to a greater
degree than ALT. Even strenuous exercise can result in mild elevations in
the transaminases.
A CK level may be useful to help distinguish muscle disease from liver
disease when aminotransferase levels are elevated. CK is a sensitive marker
of muscle injury, as it is found predominately in skeletal and cardiac muscle.
CK is composed of three types of dimers: MM is found mostly in skeletal
muscle, MB in cardiac muscle, and BB is predominately in the brain and
intestine. An elevated CK level is highly sensitive for muscle injury.
Other enzymes may also be helpful when interpreting LFTs. Lactate
dehydrogenase (LDH) is present in blood cells and is elevated in hemolytic
conditions. It is also released from the liver early in the course of viral
hepatitis, and with space-occupying lesions of the liver. In addition, LDH is
found in the lungs, kidney, brain, and skeletal and cardiac muscle.
Alkaline phosphatase (AP) is present in the canalicular membrane of
hepatocytes and is elevated in obstructive jaundice. It rises to a lesser degree
as a result of hepatocyte injury. It is also present in bone, kidney, and small
intestine. During periods of rapid growth, AP will be elevated; therefore,
age-specific reference ranges are important.
Unconjugated bilirubin is produced as a result of red blood cell breakdown and is conjugated by the liver. The serum unconjugated bilirubin
may be elevated as a result of excess production, such as from hemolysis,
or delayed conjugation, as in physiologic jaundice, breastfeeding jaundice,
Crigler-Najjar syndrome, and hypothyroidism. Normally, bilirubin is conjugated by glucuronyl transferase in the liver and is excreted by the biliary
tree. Conjugated bilirubin levels are elevated with biliary tract obstruction
or infection.
Gamma-glutamyl transferase (GGT) is an enzyme present in the liver
and biliary tree that rises in response to cholestasis. The level may also rise
slightly in response to hepatocyte injury and to anticonvulsant drugs. It is
present in lower concentrations in the pancreas, spleen, brain, breast, small
intestine, and kidney. Because the GGT enzyme is very active in young
children, age-dependent normals should be used for reference.
The two most direct measures of hepatic synthetic function are albumin
and PT. Albumin is synthesized by hepatocytes, and levels fall as a result of
decreased liver function. Decreased albumin levels usually occur late in the
course of liver disease.
PT measures the time required for prothrombin (factor II) to be converted to thrombin. Because this conversion occurs in the liver, hepatocellular disease will result in a prolonged PT. The conversion of prothrombin
to thrombin is vitamin K-dependent; therefore, any process that impairs vitamin K absorption, such as biliary obstruction where bile salts do not reach
the intestine, will also result in a prolonged PT.
Finally, ammonia levels may be used to assess liver function. Ammonia
is created in the colon as a result of the breakdown of dietary proteins. It
is then eliminated by the liver under normal circumstances. An elevated
ammonia level signifies a poorly functioning liver. Assessing liver function
requires interpreting enzymes which are present in a number of tissues. It
is important to know which tissues release each enzyme so as to accurately
interpret the result. Specifically, when aminotransferase levels are elevated,
a CK level will distinguish muscle disease from liver disease.
Suggested Readings
Digestive system disorders. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook
of Pediatrics. 17th ed. Philadelphia: Saunders; 2004:
Ng VL, Balistreri W. Manifestations of liver disease. In: Behrman RE, Kliegman RM, Jenson
HB, eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders; 2004:1308–1314.
Neuromusculardisorders:evaluationandinvestigation.In:BehrmanRE,KliegmanRM,Jenson
HB, eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders; 2004:
D’Agata ID, Balistreri WF. Evaluation of liver disease in the pediatric patient. Pediatr Rev
1999;20(11):376–390.
Giboney PT. Mildly elevated liver transaminase levels in the asymptomatic patient. Am Fam
Physician. 2005;71(6):1105–1110.
Book Source Details
- Book Title: Avoiding Common Pediatric Errors
- Author(s): Anthony D Slonim MD, DrPH; Lisa Marcucci MD
- Year of Publication: 2008
- Copyright Details: Avoiding Common Pediatric Errors, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: Avoiding Common Pediatric Errors
Authors: Anthony D Slonim MD, DrPH; Lisa Marcucci MD
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7489-6
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