Liver Function Tests Flashcards
Function of the liver
Are AST and ALT liver function tests?
No, these enzymes can be normal while liver function is impaired
Three categories of liver function tests and what they measure
cholestatic, hepatocellular injury and hepatic synthesis impairment. One is associated with obstruction of the biliary tree (most often by a gallstone) that causes decreased bile excretion - we will call this lab pattern cholestatic. Hepatocellular injury is associated with damaged hepatocytes from ischemia, toxins or viruses). Synthetic dysfunction can be indirectly estimated by several tests that concern products of the liver and may be caused by acute or chronic liver injury.
Indications of Cholestasis
Cholestasis presents with an elevation of serum alkaline phosphatase and maybe bilirubin levels, approximately half of which is conjugated. It can be from anything that would block the flow of bile (commonly a gallstone in the common bile duct - known as choledocholithiasis). AST/ALT may also be elevated.
Hepatocellular injury indiciation
Hepatocellular injury is indicated by elevation of AST/ALT (aka transaminitis). It may occur from cholestasis (and in that case alk phos and bilirubin would also be abnormal) but is often seen alone with non-alcoholic fatty liver disease, viral or other insults.
When would you see combination of both cholestasis and hepatocellular injury
when the liver is diffusely injured: acute ischemia (sometimes called shock liver) or toxin-ingestion.
Non-hepatic causes of abnormal liver tests
What are the transaminases
Aspartate transaminase = AST
occasionally mentioned as SGOT
Alanine transaminase = ALT
occasionally mentioned as SGPT
Where else are transaminases found
cardiac muscle, skeletal muscle, kidney, brain, pancrease, lung, leukocytes, erythrocytes.
AST/ALT ratio > 2-3
AST is more commonly associated with alcohol-induced liver damage. When looking at the AST/ALT ratio, the classic proportion is AST 2-3 times highter than ALT when associated with alcohol as a cause
AST/ALT < 1
AST/ALT < 1 is likely in chronic viral hepatitis.
AST/ALT close to one
AST/ALT close to one is consistent with non-alcoholic steatotic hepatitis (NASH or fatty liver)
Levels of transaminase elevation and indication
Very mild elevation (up to 300) can be from slight injury (like a good workout).
> 1,000 U/L is most commonly from a viral hepatitis, toxin or drug-induced liver injury
>10,000 or the very highest is most likely from ischemic hepatitis, often in the setting of severe hypovolemia, sepsis or congestive heart failure-related ischemia.
What is Alkaline Phosphatase, and how to differentiate for liver
Group of isoenzymes distributed widely throughout the body (typically liver and bone).
The isoenzymes can be isolated to further determine the source of: intestinal, non-specific, placental, placental-like
These isoenzymes can be ordered, but a quicker, cheaper test to investigate whether elevated AlkP is of liver origin is GGT to see if it is associated with a hepatic cause.
Causes of Alk Phos elevation
This can be elevated during normal growth spurts in children or from placental development in the third trimester of pregnancy.
If this is all that’s elevated, it may be from a blockage like partial bile duct obstruction, infiltration (primary biliary cirrhosiss) or focal liver mass.
If it’s elevated along with bilirubin, and/or a mild elevated of transaminases, consider a process causing intrahepatic or extrahepatic cholestasis.
What is Gamma-glutamyl-transpeptidase
GGT is found in hepatocytes and biliary epithelial cells, as well as in the kidney, seminal vesicles, pancreas, spleen, heart, and brain.
It found in cell membranes of many organs, (including hepatocytes and cholangiocytes), but NOT bone (as Alk Phos is). Very sensititive for hepatobiliary disease, but not very specific
When is GGT elevated
Can be elevated with several conditions: COPD, Diabetes, renal failure; and also with certain agents: Alcohol, anetiepileptic medications. You probably already picked up on the fact that this would be a great test to further investigate a positive alkaline phosphatase (i.e. determine whether it is from bone or liver).
Elevated Alk Phos + Elevated GGT = suggests liver origin
Elevated Alk Phos + Normal GGT = unlikely liver origin (think about bone diseases/metastases)
What is bilirubin
Bilirubin is a breakdown product from heme which can be further tested (or fractionated) into two types: conjugated or unconjugated.
What does conjugated bilirubin mean?
Bilirubin when formed is lipid soluble and will not dissolve in water, so for transportation in blood, unconjugated bilirubin needs to be conjugated by binding to albumin.
What does direct/indirect bilirubin mean
Direct = conjugated
Indirect = unconjugated (this is indirectly calculated because the lab only reports total and direct bilirubin, subtracting those two will give you the indirect bilirubin).
What to order next if isolated hyperbilirubinemia
This can be seen with hemolytic anemia. So in working up isolated hyperbilirubinemia, we will often order CBC, peripheral smear, LDH and haptoglobin.
Recall that LDH would be elevated (from lysis of RBCs) and haptolglobin would be decreased a hemolytic anemia.
Congenital causes of Direct Hyperbilirubinemia
Dubin-Johnson: a rare genetic disease preventing bilirubin from moving into bile. See here for more info.
Rotor Syndrome
There can also be structural abnormalities that cause issues with biliary obstruction:
Alagailles (paucity of bile ducts) presents with cholestatic picture. In combination with other issues: butterfly vertebra, triangular facies, cardiac anomalies.
Familial hepatocellular cholestasis
Causes of Indirect Hyperbilirubinemia
What is LDH
Lactate Dehydrogenase (LDH) is a cytoplasmic enzyme present in tissues throughout the body and can be separated into isoenzymes. Remember that it is also present in RBCs so hemolysis can increase LDH in the serum.
Which coagulation factors were dependent on vitamin K?
II, VII, IX, X, protein C/S
What is Prothrombin Time (INR)
Looks at rate of coagulation
INR is the international normalized ratio - a corrected version for comparison across institutions. It is more often reported over a PT.
Vitamin K insufficiency can lead to both hypercoagulability and increased risk of bleeding. Monitoring liver failure associated coagulopathies with typical lab values (such as PT/PTT) can be misleading due to the involvement of Protein C/S. Typically even with an elevated INR, cirrhotic patients are prothrombotic.
What is albumin and what does it indicate
The most common circulating protein, made by the liver.
When it is low, either too little is coming in, too much is going out or not enough is being made: examples of these are malnutrition vs. nephrotic syndrome vs. cirrhosis.
Having decreased albumin synthesis can decrease oncotic pressure and cause swelling in patients with synthetic liver dysfunction.
What is ammonia and what does it indicate
Marker of metabolic function that is the product of gut bacteria and protein catabolism. It is cleared through the liver so with liver insufficiency may have hyperammonemia that can present with altered mental status due to hepatic encephalopathy.
What is a MELD score
This MELD score (model for end-stage liver disease) is a predictor of 5 year mortality that was initially used for liver-transplant but is now extrapolated into 5-year survival likelihood.
Dont need to know formula
How is creatinine impacted with liver disease
Creatinine may be impacted because as the liver becomes congested, it decreases renal blood flow and can lead to chronic kidney disease through various mechanisms (Hepatorenal Disease)
Pattern for chronic hepatitis
Hepatocellular (elevation in AST/ALT)
AST 3x > ALT more likely alcohol (Scotch over Liver)
ALT > AST more likely viral
Cholestatic (elevation in alkaline phosphatase, Bbilirubin)
often from gallstone or hereditary defect
Mixed picture of the above is also possible
What can cause very high enzymes
(most likely from acute injury)
Drugs (Tylenol) or supplements
Ischemic Hepatitis
Viral hepatitis
Hepatic artery ligation
Autoimmune hepatitis
Acute Budd-Chiari Syndrome
Rare causes: Obstruction, Wilson’s disease
Pattern for cirrhosis
AST > ALT
Decreased Platelets
Decreased Albumin
Increased Bilirubin
Increased PT/INR
Normal values
