Liver Function Tests Flashcards
Explain how billirubin is metabolized and excreted both in a normal person and in a person with high levels of billirubin.
Billirubin is a breakdown product of heme. In the body, 85% of heme comes from the metabolism of old RBCs, but the remainder comes from recycling of myoglobin and enzymes that contain heme (cytochromes, catalases). The metabolism of heme to billirubin takes place in either macrophages or hepatocytes. Once billirubin is produced in these cells, it is secreted into the blood where it binds to albumin. Albumin carries it to the liver where the billirubin is actively uptaken into the hepatocyte and albumin is released back into the bloodstream. Once inside the liver cell, billirubin undergoes conjugation where it is made into glucuronide - billirubin by the enzyme UDP-glucuronide transferase. In a normal healthy person who does not have high levels of billirubin, conjugated billirubin is secreted from the liver in the bile and goes to the gallbladder. Once in the gallbladder, it is secreted as bile into the small intestine. In the GI tract, it is acted upon by bacteria in the colon which turn it into urobilogen. Urobilogen can be excreted in the feces (gives feces its brown color) or it can be absorbed into the blood and secreted in the urine. This is all normal.
When a person has high levels of billirubin in their blood, their liver is processing more billirubin than a normal person. As such, high levels of conjugated billirubin can accumulate in the liver and some of this can be secreted into the blood instead of the bile. Once in the blood, the conjugated billirubin is excreted in the urine, giving the urine a very dark yellow color. Additionally, when high billirubin is present in the blood, it’s possible that the person may not be able to uptake it all into the liver and you can see unconjugated billirubin in the blood. This cannot be excreted so it circulates and causes jaundice.
What are the risk factors for liver disease?
What liver pathology is seen here?
Cirrhosis that leads to obstruction of biliary secretion from liver so there is green nodules on liver due to build up of bile in liver
What liver pathology is seen here?
Fatty liver (alcoholism, diabetes, metabolic syndrome, obesity)
What liver pathology is seen here?
Ascites
What are the 3 classifications of jaundice?
- Pre-hepatic / hemolytic –> drug induced, hemolytic anemia, etc –> results in build up of billirubin in blood that is unconjugated b/c liver can’t conjugate fast enogh
- Hepatocellular –> damge to liver from toxins, infections, etc –> results in build up of both conjugated and unconjugated billirubin
- Post-hepatic –> liver function is fine but there is an issue getting bile from liver to gallbladder (cirrhosis, tumor, gallstones) –> results in build up of conjugated billirubin
If unconjugated billirubin is found in the serum, it is most likely due to […]
Hemolytic disorder
If conjugated billirubin is found in the serum, it is most likely due to […]
Liver and/or billiary tract disease
If a person has unconjugated billirubin in serum, will you find billirubin in their urine?
No - can’t be excreted
Billirubin found in the urine implies […]
That the billirubin is conjugated and the presence of hepatobilliary disease
What are the possible causes of unconjugated hyperbillirubinemia?
- What is different about seeing unconjugated hyperbillirubinemia in a newborn vs. an adult?
- What are the causes of this in a newborn?
- What is the treatment if it is found to be pathologic?
- What is the biggest consequence of untreated hyperbillirubinemia in a newborn?
- It is sometimes not pathologic in newborn b/c their hepatobiliary system is immature so in some infants it clears on its own as the liver develops more
- See slide for rest of questions
Why do we measure blood ammonia in relation to liver function?
There are several liver enzymes that can be tested for tin the serum. What does increased enzyme activity tell you?
Only tells you about liver dysfunction, not liver function
Let’s say a person has jaundice and you need to distinguish between the causes of jaundice. What 3 enzymes can be measured in serum to check for liver dysfunction that indicates hepatocellular damage?
AST
- Non-specific to liver, also in RBCs so can be high with hemolytic jaundice also
- Extramitochondrial and mitochondrial
ALT
- Found primarily in liver, if this is high it indicates liver damage
- Strictly extramitochondrial
LDH
- Cytosolic enzyme, has several isozymes throughout body so it has poor diagnostic sensitivity and specificity for liver disease
- Let’s say that a person has elevated levels of AST and ALT. How do you distinguish between elevation that signals liver disease and elevation that may not be due to liver disease?
- What does the ratio of AST:ALT tell you?
- Normal range in serum is 10-20 Units/Liter
- 20 U/L - 300 U/L is not specific to liver disease
- > 1000 U/L indicates extensive liver damage due to drugs, virus, toxins
- See image
Let’s say a person has jaundice and you need to distinguish between the causes of jaundice. What 3 enzymes can be measured in serum to check for liver dysfunction that indicates cholestasis or post-hepatic jaundice?
AlkPhos (ALP)
- Has isozymes in other parts of body, but is found near biliary cannaliculi in liver
- If elevated, and you don’t suspect other possible sources of elevation, it’s good indication of issue with biliary tract
Gamma glutamyl transpeptidase (GGT)
- Helps in DiffDx when ALP is elevated but you may suspect another cause of elevated ALP (bone disease)
5’-nucleotidase (5’-NT)
- Also found near bile cannalicular membrane, but not widely used clinically
In the image below, which liver enzymes would you expect to be elevated in the following types of jaundice?
Serum albumin is made exclusively by the liver. Is it a good measure of liver function?
It has a long half life (3 weeks) so if it is not normal it cannot detect acute disturbances to liver function. However, hypoalbuminemia is common in chronic liver disease like cirrhosis and reflects severe damage. However, you can also see hypoalbuminemia in other disorders. Important to measure other things too.
What does increased globulins in blood tell you?
Since albumin levels can’t detect acute liver damage, what other thing can you measure in the serum that can?
If you have cholestasis and can’t get bile into GI tract, you can’t absorb fat so you can’t absorb vitK which can lead to decreased clotting factors since many of these require vitK
Compare the utility of LFTs with their limitations.
What are the various ways in which alcohol is metabolized by the body?
Mostly liver, remainder occurs in brain, pancreas and stomach
Mechanisms of metabolism:
- 80% via:
- Ethanol –(alcohol dehydrogenase)–> Acetaldehyde –(aldehyde dehydrogenase)–>acetate
- Remainder via:
- Ethanol –(catalase)–>acetaldehyde –(aldehyde dehyrogenase)–> acetate
- Ethanol –(CytP4502E1)–>acetaldehyde –(aldehyde dehyrogenase)–> acetate
What are the consequences of a build up of acetaldehyde from alcohol metabolism?
Why would you see hypoglycemia in a person who abuses alcohol?
They are likely to be malnourished. Since they’re not taking in enough glucose because they likely get most of their calories from alcohol, they also are likely to have depleted glycogen stores. This puts them in a position to rely heavily on gluconeogenesis for new glucose to feed the brain. However, gluconeogenesis will be inhibited because of insufficient NAD+ that is needed to convert TCA precursors to pyruvate and the fact that any pyruvate that is made will be converted to lactate. Thus, they are at risk for hypoglycemia.
True or false: damge to the liver from alcohol consumption is always irreversible.
False - there is a point at which, once crossed, abstinance from alcohol use no longer allows for return to baseline. However, before this threshold is crossed, it is possible for the liver to recover.
What is hepatic encephalopathy?
What do each of these lab tests tell you about this patient and their chronic alcoholism?
What vitamin deficiencies would you expect in a person who is a chronic alcoholic?
