Module 1: Chapter 3 Flashcards
Liver enzymes are categorized as ___ or ___
hepatocellular or cholestatic
Hepatocellular liver tests. Where can you find these enzymes?
alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are enzymes in hepatocytes that are released into the blood when the liver is inflamed or damaged
The ALT is more specific to hepatocytes, as the AST is also located in muscle and to a lesser
extent in the kidney, brain, pancreas and red blood cells
Is AST is higher than ALT in hepatocellular liver tests, what does that indicate?
in alcohol related liver disease the AST is usually more than twice the ALT
In any other hepatocellular liver disease, where alcohol is excluded by history, if the AST
is higher than the ALT (AST/ALT>1) it may indicate that the patient has progressed onto cirrhosis
LDH indicators
As it is found in RBCs, it may be elevated in hemolysis, and it may also come from muscle, brain and kidney damage
It can be very high if the liver damage is due to ischemia or lack of blood flow (e.g. shock
liver after cardiac arrest) or with malignant infiltration from lymphom
Cholestatic liver tests include the Cholestatic liver tests include the___ ___ ___ which comes mainly from liver or bones (the normal range is higher in children due to bone growth)
Cholestatic liver tests include the alkaline phosphatase (ALP) which comes mainly from liver or
bones (the normal range is higher in children due to bone growth)
when can alp be elevated in addition to cholestatic issues
It can also be elevated in pregnancy, renal failure and ischemia of the bowel
ALP in the liver is synthesized by the canalicular membrane of the hepatocyte in response to
bile duct obstruction and may take some time to rise in the blood
____ is a very sensitive enzyme that is easily induced by drinking alcohol, being overweight
(fatty liver disease) or with certain medications (anticonvulsants or coumadin)
o Its main use is to distinguish the source of an elevated ALP, as___ is made in the ____, but
not the bones
GGT is a very sensitive enzyme that is easily induced by drinking alcohol, being overweight
(fatty liver disease) or with certain medications (anticonvulsants or coumadin)
o Its main use is to distinguish the source of an elevated ALP, as GGT is made in the liver, but
not the bones
In addition to the “Liver Enzymes” (ALT, AST, ALP, GGT) we often describe
___ ____ ___ as the “Liver Function Tests” as they provide more prognostic information about the
function of the liver, rather than just whether or not the liver is inflamed (ALT, AST) or if there is
a problem with bile flow (ALP, GGT)
In addition to the “Liver Enzymes” (ALT, AST, ALP, GGT) we often describe bilirubin, albumin &
INR as the “Liver Function Tests” as they provide more prognostic information about the
function of the liver, rather than just whether or not the liver is inflamed (ALT, AST) or if there is
a problem with bile flow (ALP, GGT)
↑ INR is very important for prognosis in both acute and chronic liver failure but can also be
seen due to ____ deficiency (especially in patients with cholestatic liver disease as bile
salts help us absorb ______) and after prolonged use of
____ (as bacteria produce vitamin K in the colon)
↑ INR is very important for prognosis in both acute and chronic liver failure but can also be
seen due to vitamin K deficiency (especially in patients with cholestatic liver disease as bile
salts help us absorb fat soluble vitamins A, D, E, and K) and after prolonged use of
antibiotics (as bacteria produce vitamin K in the colon)
Approach to Jaundice:
Pre-Hepatic jaundice is associated with ___ ____ bilirubin as the problem is before the conjugation of bilirubin in the hepatocyte by UGT and the other liver tests will be normal. It is due to:
Pre-Hepatic jaundice is associated with predominately unconjugated (indirect) bilirubin as the
problem is before the conjugation of bilirubin in the hepatocyte by UGT and the other liver tests
will be normal. It is due to:
- over production of unconjugated bilirubin due to hemolysis, ineffective erythropoiesis or resorption of a large hematoma ( blood clot)
- decreased uptake of bilirubin by transporters due to sepsis or drugs.
- Gilbert’s Syndrome: change in UGT enzyme that leads to jaundice during stress or periods of fasting
- rare deficiencies in UGT enzymes can lead to more significant jaundice in children.
If it is predominantly conjugated bilirubin this could either be due to a liver problem (____) or a blockage of ___ -___ outside the liver (______) and the next most important test is an abdominal ultrasound to see:
If it is predominantly conjugated bilirubin this could either be due to a liver problem (hepatic)
or a blockage of bile flow outside the liver (post-hepatic) and the next most important test is an abdominal ultrasound to see if the bile ducts are normal in size (hepatic jaundice) or dilated (post-hepatic jaundice)
Hepatic jaundice is usually accompanied by :
Post-hepatic jaundice is associated with :
Hepatic jaundice is usually accompanied by : abnormal liver tests, either hepatocellular or cholestatic
Post-hepatic jaundice is associated with : dilated bile-ducts and CHOLESTATIC ALP/GGT liver test elevation
Approach to Abnormal Liver Test:
Tests are either predominantly hepatocellular or cholestatic, as described by the elevation of
ALT or AST above the upper limit of normal (ULN) compared to the elevation of ALP above the
ULN
If cholestatic, the next most important test to order is an abdominal ultrasound (US) to examine the bile ducts:
The degree of the hepatocellular liver test elevation can help narrow the differential diagnosis
- Mild elevation of ALT is very common and the differential diagnosis is wide
- Moderate elevation should not occur from alcohol, NAFLD or alpha-1 antitrypsin deficiency
alone and it is uncommon for hereditary hemochromatosis to cause this level of elevation
- Severe elevation of ALT has a narrow differential diagnosis and when associated with
significant liver dysfunction, with an elevated blood clotting times (INR) and hepatic
encephalopathy (HE), is called acute liver failure (ALF) and these patients may need to be
considered for liver transplant (LT)
If cholestatic, the next most important test to order is an abdominal ultrasound (US) to
examine the bile ducts:
1. If bile ducts are dilated, it is extra-hepatic cholestasis due to intrinsic blockage (e.g. stone,
stricture) or extrinsic compression of the bile duct (e.g. pancreatic cancer
2. If the bile ducts are normal, the problem is in exporting bile out of the hepatocyte at the level of the bile duct canaliculus or intra-hepatic bile duct (intrahepatic cholestasis)
The degree of the hepatocellular liver test elevation can help narrow the differential diagnosis
- Mild elevation of ALT is very common and the differential diagnosis is wide
- Moderate elevation should not occur from alcohol, NAFLD or alpha-1 antitrypsin deficiency
alone and it is uncommon for hereditary hemochromatosis to cause this level of elevation
- Severe elevation of ALT has a narrow differential diagnosis and when associated with
significant liver dysfunction, with an elevated blood clotting times (INR) and hepatic
encephalopathy (HE), is called acute liver failure (ALF) and these patients may need to be
considered for liver transplant (LT)
*NOTE: some cholestatic liver diseases also cause elevation of ALT (mixed picture) and in late stages of many hepatocellular diseases (cirrhosis) many patients become more cholestatic
Screening test and confirmatory/additional tests for HBV and HCV
Screening: HBsAg
Confirmatory: HBVDNA, HBeAg, anti-HBe
Screening test and confirmatory/additional tests for Alcohol
Screening: history Confirmatory: biopsy
