OVERVIEW OF LIVER DISEASE AND LIVER FUNCTION TESTS Flashcards
What are the two vascular inputs into the liver?
The portal vein
The hepatic artery
What does the portal vein carry?
Anything absorbed via intestine
What is first part metabolism?
The fact that all medication will going via the liver and will begin to be metabolised before going to the rest of the systemic circulation via the heart
What makes up the common hepatic duct?
The left and the right hepatic ducts
What does the common hepatic duct join with at its distal end?
The cystic duct coming from the gall bladder
What do the common hepatic duct and the cystic duct join to form?
The common bile duct.
Where do the endocrine products of the liver get put into the circulation?
The hepatic vein
What is the exocrine product made by the liver?
Bile
Where is bile stored?
Gall bladder
How does bile get from the liver to the gall bladder?
It travels down the common hepatic duct and then retrogradely up the cystic duct
What are the cytotoxic blood factors of the liver?
AST (aspartate aminotransaminase)
ALT (alanine aminotransferase)
Albumin
PT
What are AST and ALT and why can they be used to recognise liver disease?
They are enzymes in the hepatocytes so when the hepatocytes die they are released into the circulation. This is similar to the cardiac enzymes that are used as markers of cardiac muscle death.
Will you always have high AST and ALT in liver failure?
No in the same way that you don’t see prolonged raise in troponin with heart failure following an MI.
Broadly, what does elevated AST and ALT signify?
Inflammation in the liver
Does AST have high or low specificity for the liver?
Low specificity
Which hepatocyte is AST found in?
Periportal hepatocytes.
Does ALT have high or low specificity for the liver?
High specificity
Will AST and ALT be elevated in chronic liver disease?
Often not. They are markers of acute injury.
What do AST and ALT tell you about residual function?
Nothing, they are purely markers of acute injury.
When AST and ALT start coming down, having been raised, is this always a good thing?
No. It could be a good thing because it could mean that the thing causing liver damage is no longer there, or no longer damaging the liver.
However, it could also mean that there are now significantly fewer hepatocytes to damages, indicative of nearing end stage liver failure.
AST and ALT tell you nothing about residual function.
Where is albumin made?
Liver
What is low albumin usually indicative of?
Chronic liver injury
Will albumin decrease in acute liver injury?
No. Because it has 20 day half life, so takes a while for levels to decrease.
What does an elevated INR tell you about whether liver injury is acute or chronic?
It doesn’t. INR may be elevated in both.
What is the most sensitive part of the liver function tests in terms assessing injury?
INR. This will be the first thing to change with acute or chronic injury.
What are the clotting factors produced in the liver that will contribute to the elevated INR in liver injury?
1 2 5 7 9 10
Does INR tell you the extent of liver injury?
Yes, unlike AST and ALT, INR is a good marker for residualt function.
Other than liver disease, what else might cause a patient to have an elevated INR?
Drugs such as Warfarin
Low vitamin K
Haemophilia
So as ALT is more specific to the liver than AST, which one is likely to be higher in acute liver injury?
ALT
ALT is usually higher than AST in acute liver injury, unless the liver injury is caused by…?
Alcohol
Alcoholic liver disease
What is the half life of albumin?
20 days
What part of the liver do AST, ALT, albumin and INR relate to?
The parenchyma of the liver
What are the two functions of bile?
Emulsifies fats
To get rid of the haem products
What part of the liver do the ALP, GGT, serum bilirubin and bile acids relate to?
Cholestatic part (common hepatic duct, cystic duct and common bile duct)
How long is the life of a red blood cell?
120
What form is the bilirubin in when it is released from blood cells?
Unconjugated bilirubin (indirect)
What does the liver do to bilirubin?
Conjugates it to conjugated bilirubin (direct)
Where does the liver excrete conjugated bilirubin?
Into the intrahepatic ducts which then follow out of the liver to be extrahepatic ducts
What form(s) of bilirubin can the kidney excrete?
Only the conjugated bilirubin
If there is a blockage in the hepatic ducts, what will blood test show in terms of unconjugated and conjugated bilirubin?
Most likely show an increase in both
If there is a blockage in the hepatic ducts, what will urine tests show in terms of unconjugated and conjugated bilirubin?
Conjugated bilirubin is the only form of bilirubin to be excreted by the kidneys.
What does bilirubinuria tell you about the nature of the elevated levels of bilirubin in the blood?
That the problem is either hepatic or post hepatic, not pre-hepatic. In pre-hepatic jaundice there is only an increase in the levels of unconjugated bilirubin (eg haemolysis)
What are the three things that can cause a rise in ALP?
Cholestasis
Pregnancy
Bone disease (bone growth, eg Paget’s disease)
What is ALP?
Alkaline phosphotase is an inducable enzyme which is released by biliary ductal cells of the intrahepatic bile ducts in liver damage.
What is GGT?
Gamma-glutamyltransferase
What causes a rise in GGT?
Cholestasis
Alcohol
Does bone disease increase GGT?
No
What is Gilbert’s syndrome?
Most common (5% of population) hereditary cause of increased bilirubin. The cause of this hyperbilirubinemia is the reduced activity of the enzyme glucuronyltransferase, which conjugates bilirubin and a few other lipophilic molecules
In Gilbert’s syndrome, is there an increase in unconjugated or conjugated bilirubin?
Unconjugated
In Gilbert’s syndrome, is there an increase in ALP?
No.
In hepaticellular jaundice, is there an increase of unconjugated or conjugated bilirubin in the blood?
Both. there is usually interference in all major steps of bilirubin metabolism—uptake, conjugation and excretion. However, excretion is the rate-limiting step, and usually impaired to the greatest extent. As a result, conjugated hyperbilirubinaemia predominates.
In an acute infection of hepatitis A virus, what will liver function tests reveal?
Increased ALT
Increased AST
ALT increased more than AST
Maybe increased INR
What do you look for in the blood in order to make a diagnosis of hepatitis A?
IgM anti-hepatitis A
In an acute infection of hepatitis B virus, what will liver function tests reveal?
Increased ALT
Increased AST
ALT increased more than AST
Maybe increased INR
What do you look for in the blood in order to make a diagnosis of hepatitis B?
Hepatitis B surface antigen
IgM Hepatitis B surface antibody
IgM Hepatitis B core antibodies
In an acute infection of hepatitis C virus, what will liver function tests reveal?
Increased ALT
Increased AST
ALT increased more than AST
Maybe Increased INR
What do you look for in the blood in order to make a diagnosis of hepatitis A?
IgM anti-hepatitis A
What do you look for in the blood in order to make a diagnosis of hepatitis B?
Hepatitis B surface antigen
IgM Hepatitis B surface antibody
IgM Hepatitis B core antibodies
What do you look for in the blood in order to make a diagnosis of hepatitis C?
IgM anti-hepatitis C
Hepatitis C RNA
In acute liver injury as a result of alcohol, what will liver function tests reveal?
Slightly increased ALT
Slightly increased AST
ALT and AST are raised about the same or AST could be higher
Maybe increased INR
In an acute bout of ischaemic liver injury, what will liver function tests reveal?
Huge elevation in ALT very sudden
Huge elevation in AST
Increased INR
How will liver function tests of someone with chronic hepatitis B differ from someone with an acute infection of hepatitis B?
They will be similar but ALT and AST won’t be as raised in the chronic case.
There will most likely be an increased INR in the chronic case
Albumin may be low in the chronic case
How will liver function tests of someone with chronic hepatitis C differ from someone with an acute infection of hepatitis C?
They will be similar but ALT and AST won’t be as raised in the chronic case.
There will most likely be an increased INR in the chronic case
Albumin may be low in the chronic case
In someone suffering from non-alcohol steatohepatitis (NASH/fatty liver disease), what will liver function tests reveal?
Increased ALT
Increased AST
ALT increased more than AST
Low albumin
In someone suffering from alcoholic liver disease, what will liver function tests reveal?
Increased AST
Increased ALT
AST increased more than ALT
Low albumin
In someone suffering from autoimmune hepatitis, what will liver function tests reveal?
Increased ALT
Increased AST
ALT increased more than AST
Low albumin
What do we look for in the blood in order to make a diagnosis of autoimmune hepatitis?
Anti-smooth muscle antibody
In someone suffering from hereditary haemochromatosis, what will liver function tests reveal?
Increased ALT
Increased AST
Low albumin
What do we look for in the blood in order to make a diagnosis of haemochromatosis?
Serum ferritin > 1000
Low or normal Total iron binding capacity
What is hereditary haemochromatosis?
An autosomal recessive genetic disease (found on chromosome 6) in which increased intestinal absorption of iron causes accumulation in tissues, especially the liver, which may lead to organ damage. Other organs that may be affected by iron deposits include the pancreas, joints, heart, skin and gonads.
In someone suffering from Wilson’s disease, what will liver function tests reveal?
Increased ALT
Increased AST
Low albumin
Low ALP
What sign seen on examination might indicate that someone has Wilson’s disease?
Kayser-Fleischa rings in their eyes
What do we look for in the blood in order to make a diagnosis of Wilson’s disease?
Low ceruloplasmin
Low ALP
In someone suffering from alpha 1 antitrypsin deficiency, what will liver function tests reveal?
Slightly increased ALT
Slightly increased AST
What will be seen in a histological assessment of liver biopsy in someone with liver disease as a result of alpha 1 antitrypsin deficiency?
PAS positive granules
What do we look for in the blood in order to make a diagnosis of alpha 1 antitrypsin deficiency?
Low levels of alpha-1AT
In someone suffering from primary biliary cirrhosis, what will liver function tests reveal?
Increased ALP Increased bilirubin (but later in the disease)
In someone suffering from primary sclerosing cholangitis, what will liver function tests reveal?
Increased ALP
Increased bilirubin
In someone suffering from large bile duct obstruction, what will liver function tests reveal?
Increased ALP
Increased bilirubin
What is the classic history of a patient with large bile duct obstruction?
Pain
Fever
Jaundice
