Liver Function Tests

Question 1

What are the transferases as liver biomarkers and where are they found?

Answer 1

Transferases (aka transaminases) are AST and ALT. They found in the liver and can also be found in muscle.

Question 2

What enzyme is specifically made in the biliary tract?

Answer 2

Gamma glutamyl transpeptidase (GGTP) is specific to the biliary tract.

Question 3

What proteins are exclusively synthesized in the liver? What are their indications?

Answer 3

Albumin and clotting factors are only made in the liver. They are indications of hepatic synthetic function. Prothrombin time (INR) is a measure of hepatic function via blood clotting.

Question 4

What is the normal value of Total bilirubin? What of direct bilirubin? AST/ALT levels above what value are of concern?

Answer 4

Total: 0.3 - 1.2 mg/dL;
Direct 0 - 0.3;
AST/ALT > 40 are concerning

Question 5

What is the normal range of albumin in plasma? What of INR?

Answer 5

Albumin: 3.5 - 5.5 g/dL

INR = 1.0

Question 6

What does elevated levels of transaminases AST/ALT indicate?

Answer 6

AST/ALT > 40 indicates damage to liver cells (apoptosis is occurring).

Question 7

What is the most common cause of chronic liver disease? What condition is this associated with?

Answer 7

Non-alcoholic Steatohepatitis (NASH) which is associated with metabolic syndrome (HTN, hyperlipidemia) from a HIGH fat diet. Issue with fat metabolism.

Question 8

How does AST compare to levels of ALT in chronic liver disease (esp. in NASH)? Why?

Answer 8

AST > ALT in NASH and alcoholism. Since, healthy liver cells are rich in ALT compared to AST, a flip in this ratio can show liver disease as cells are being lysed.
“S for Sauced”

Question 9

What is Cholestasis? Is it the same as jaundice?

Answer 9

Cholestasis is the obstruction of bile flow. This is not the same as “jaundice” because pre-hepatic cholestasis from hemolysis is not always associated with a liver disease.

Question 10

What are the extrahepatic and intrahepatic factors that can lead to Cholestasis, respectively?

Answer 10

Extrahepatic cholestasis can occur from a tumor, stone or stricture. Intrahepatic can happen from a virus, drug or enzyme deficiency.

Question 11

What happens to bilirubin once it enters the liver cell?

Answer 11

Bilirubin is conjugated by UDP-GT (glucuronyltransferase) in the hepatocyte and leaves via the bile canaliculi to head downstream to Sphincter of Oddi.

Question 12

At what total bilirubin level can the yellow jaundice sign be seen?

Answer 12

At or above 3.0 total bilirubin is an indication of jaundice.

Question 13

A physician is measuring bilirubin levels to assess the hereditary cause of a patient’s jaundice. How can he distinguish Gilbert’s Syndrome from Dubin-Johnson Syndrome?

Answer 13

Gilbert’s syndrome involves a deficiency in UDP-GT resulting in elevated unconjugated (indirect) bilirubin. “Gilbert’s: Indirect”.
Dubin Syndrome involves a deficiency in MRP2 resulting in high conjugated (direct) bilirubin. “Dublin for Direct”

Question 14

What biomarker is also measured, if increased alkaline phosphatase is observed? Why do we measure this?

Answer 14

Gamma glutamyl transpeptidase (GGTP) should be gauged if Alk phos is high, to prove whether the issue is in the “biliary tree”. From there, we use imaging to pinpoint the holdup.

Question 15

What are the levels of bilirubin, alkaline phosphatase and transaminases (AST/ALT) from hepatocellular damage?

Answer 15

Hepatocellular damage:

low bilirubin, low Alk Phos, high transaminases

Question 16

What are the levels of bilirubin, alk phos and transaminases in Cholestasis?

Answer 16

Cholestasis:

high bilirubin, high Alk Phos, low transaminases

Question 17

What disease does low levels of albumin indicate? What signs/symptoms is this associated with?

Answer 17

Low albumin shows failure of hepatocyte synthetic ability from cirrhosis (liver cell death). This is linked to portal HTN, caput medussae (ascites) and edema.

Question 18

An alcoholic is admitted to the ER bleeding from a laceration at a bar fight While tending his wounds, the doc notices it takes longer than usual for what to occur? What might this indicate?

Answer 18

Longer than usual time to clot may indicate a lengthened prothrombin time (INR > 1.0) that can suggest chronic liver disease in this patient. This was probably brought about by liver damage leading to less clotting factors synthesized by the liver.

Question 19

What clotting factors are produced in the liver? Which one has a unique feature?

Answer 19

Clotting factors 5, 7, 9 and 10 are proteins of the extrinsic clotting cascade made in the liver. Factor 7 has a SHORT half life to which if it fails, can put the clotting cascade in disarray.

Question 20

List at least 5 differential diagnoses of a hepatocellular disease pattern.

Answer 20

Infectious hepatitis, yellow fever, drug overdoses, toxic amounts of Vitamin A, ischemia, (EB virus or autoimmune hepatitis too)

Question 21

What is the most common cause of cirrhosis in East Asian populations?

Answer 21

Hepatitis B infection = cirrhosis in East Asian populations

Question 22

Inflammation of the pancreas are indicated by elevated values of what enzymes?

Answer 22

Elevated Amylase and Lipase (at least 3x normal) = Markers for Pancreatitis

Question 23

Marked elevation of (AST/ALT) transaminases with barely an elevation in bilirubin nor alk phos is indicative of…

Answer 23

Hepatocellular disorder (HIGH AST/ALT)

Question 24

Marked elevation of BILIRUBIN and ALK PHOS with minimal elevation in transaminases suggests…

Answer 24

Cholestasis (not a tumor and not always jaundice)

Question 25

A low serum album level and disrupted production of clotting factors (abnormal INR) is indicative of…

Answer 25

Loss of Hepatocyte Synthetic function (low albumin and clotting factors)

Question 26

What are the 2 clinical situations of elevated bilirubin alone with normal levels of Alkaline phosphatase and ALT/AST?

Answer 26

1. Hemolysis of RBCs (thalassemia, sickle cell disease of spherocytosis)
2. Mild elevation of hyperbilirubinemia from congenital syndromes (Gilberts, Rotors or Dubin-Johnsons)

Question 27

What makes Craggier Najjar unique from other congenital hyperbilirubinemias?

Answer 27

This rare congenital disorder is associated with very HIGH bilirubin levels that is fatal at a very early age.

Question 28

Where is alkaline phosphatase found and what does its elevation suggest?

Answer 28

Alk p’tase is found in bile canalicular cells (primarily), bone, ovary and leukocytes. It rises due to an increased production by canalicular cells as a results of an underlying disease process.

Question 29

What makes intrahepatic cholestasis so unique in imaging and possible causes?

Answer 29

Intrahepatic cholestasis is more complex jaundice that would show liver and biliary ducts that are NOT DILATED. Possible examples include the cirrhosis patient with end-stage liver disease (disrupted liver cell architecture and high lipid content). This can also be caused by metabolic disruptions from viral infections, toxins or drugs.

Question 30

Acute liver failure is commonly caused by an ________ _____. This is indicated by a prolonged ____ which can alert the healthcare provider of a need for a ______ _____ in the affected patient.

Answer 30

Acute liver failure caused by Acetaminophen (Tylenol) overdose; Prolonged INR = low levels of Clotting factor = failing hepatic function; Emergent need for liver transplantation if > 80% of liver function is lost.