Liver Function Tests Flashcards by Ann Bagchi

What are the markers of liver injury?

alanine aminotransferase (ALT) - enzyme found mainly in the liver, but also in smaller amounts in the kidneys, heart, muscles, and pancreas => more specific to liver than AST
aspartate aminotransferase (AST) - enzyme normally found in red blood cells, liver, heart, muscle tissue, pancreas, and kidneys
alkaline phosphatase - enzyme made mostly in the liver and in bone with some made in the intestines and kidneys

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What are the markers of liver function?

albumin
prothombin time (PT)/International normalized ratio (INR)
bilirubin

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What is suggested if ALT/AST are elevated more than alkaline phosphatase?

injury to hepatocytes (cells of the main parenchymal tissue of the liver)

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What is suggested if alkaline phosphatase levels are elevated more than ALT/AST levels?

injury to cholangiocytes (epithelial cells of the bile duct) - suggests obstruction of bile flow

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What are common causes of injury to hepatocytes?

viral hepatitis
drugs affecting hepatocytes (Tylenol and Augmentin)
alcohol liver disease
non-alcohol liver disease
autoimmune hepatitis
hereditary diseases (hereditary hemochromatosis, Wilson disease)

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What are common causes of injury to cholangiocytes?

gallstones in common bile duct
pancreatic/hepatic mass
drugs affecting bile flow

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What are normal values for ALT and AST?

< 40 u/L

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Which enzyme is normally more elevated in the presence of liver injury?

ALT > AST

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What is the cause of liver injury if AST is elevated more than ALT (AST 2:ALT 1 or AST = 100-200 u/L)?

alcoholic liver disease

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What are the likely causes of liver injury if ALT > 1,000 u/L?

acute viral hepatitis (A/B), acute drug induced injury (acetaminophen >7.5 g/day) => order Hep A/B serology and check acetaminophen levels

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What are the likely causes of liver injury if ALT > 100 u/L?

Chronic viral hepatitis (B/C), drug-related injury (TB medications, antiepileptic, methotrexate, statins, amiodarone, acetaminophen, amoxicillin-clavulanate), non-alcoholic fatty liver disease, congestive liver disease, autoimmune hepatitis => order hepatitis B/C serology, autoantibodies (ANA), review medication history (obesity, T2DM, hyperlipidemia)

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What is the normal level of alkaline phosphatase?

< 120 u/L

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What are the causes of elevations in alkaline phosphatase?

cholestatic injury - requires evaluation of biliary tree (initial test = ultrasound, followed by MRCP to detect a stone or CT to detect a tumor)

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What is the implication if alkaline phosphatase is elevated and ultrasound shows ductal dilation?

extrahepatic cholestasis (common bile duct obstructed/compressed)

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What are potential causes of extrahepatic cholestasis?

=> choledocholithiasis - stone blocking the common bile duct (sharp pain)
=> pancreatic cancer compressing the bile duct (painless or dull pain)

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What is the implication if alkaline phosphatase is elevated and ultrasound shows NO ductal dilation?

intrahepatic cholestasis

What are potential causes of intrahepatic cholestasis?

=> metastatic disease (colon, prostate)

=> hepatocellular carcinoma

What is the most sensitive marker of liver function?

PT/INR (increase in either indicates decrease in synthetic liver function)

What are normal levels of PT/INR?

11-15 sec/< 1.0

Which is the best marker of acute liver injury?

PT - includes all clotting factors (including Factor VII, which has a half-life of 6 hours) => PTT will also be elevated but has a half-life of 20 days (does not include Factor VII), so does not increase as rapidly

What is a normal level of albumin?

3.5-5.3 g/dL - decrease indicates decrease in liver function => not as specific an indicator of liver function because it can also be decreased with nephrotic syndrome or malnutrition

What is a normal level for total bilirubin?

0.5-1.0 mg/dL - increases indicate decrease in liver function

At what level of bilirubinemia does jaundice become evident?

> 2 mg/dl

What is direct/conjugated bilirubin?

bilirubin that has been metabolized in the liver and is able to be excreted via the bile or the urine

What is indirect/unconjugated bilirubin?

bilirubin that has not yet been metabolized and that cannot be excreted => cannot be measured via blood tests

What is the implication of an increase in indirect/unconjugated bilirubin (e.g., total bilirubin increased but direct bilirubin normal)?

hemolysis - increased destruction of red blood cells => overwhelmed liver is unable to conjugate all unconjugated bilirubin

What is the implication of an increase in direct/conjugated bilirubin (e.g., total and direct/conjugated bilirubin increased)?

obstruction of the bile ducts or damage to the hepatocytes so that the usual amount of conjugated bilirubin cannot be excreted into GI tract (e.g., results in clay colored stools)

What are the types of extrahepatic jaundice?

intraluminal obstruction (stones or strictures) and extraluminal compression (tumors or strictures of common bile duct)

What are the types of intrahepatic jaundice?

compression of small bile ducts inside the liver (due to hepatitis, alcoholic liver disease, drug-induced liver injury, liver tumor)

What are some of the S and S of bilary tract obstruction (intra or extrahepatic)?

due to inability to excrete conjugated bilirubin, serum levels increase - since conjugated bilirubin is water soluble, it can be reabsorbed back into the blood and excreted in the urine (giving it a dark color = bilirubinuria) but cannot be excreted through the gut (resulting in clay-colored stools)

What are the S and S of jaundice due to excessive hemolysis?

elevation of unconjugated bilirubin - not water-soluble and cannot be excreted => urine and stool unaffected so no change in color (pale stool and dark urine virtually exclude pre-hepatic [hemolytic] jaundice)

What should be the first imaging test done for PTs with jaundice?

ultrasound (visualizes common bile duct, texture of liver, and gallbladder) => magnetic resonance cholangiography and endoscopic ultrasound can be obtained to further evaluate the intra and extrahepatic biliary tree

What should be the expected Dx if the common bile duct is dilated (> 4 mm) and jaundice is painless?

pancreatic tumor => should obtain CT scan of abdomen/pelvis to visualize the pancreas

What should be the expected Dx if the common bile duct is dilated (> 4 mm) and jaundice is painful?

stone obstructing the common bile duct

What should be the expected Dx if the common bile duct is not dilated on ultrasound?

intrahepatic compression

When should liver biopsy be conducted?

cases of jaundice in which Dx is unclear after initial evaluation => should only be performed if results will determine treatment or prognosis