Liver Function Tests Flashcards

1
Q

Function of the liver

A
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2
Q

Are AST and ALT liver function tests?

A

No, these enzymes can be normal while liver function is impaired

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3
Q

Three categories of liver function tests and what they measure

A

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.

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4
Q

Indications of Cholestasis

A

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.

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5
Q

Hepatocellular injury indiciation

A

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.

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6
Q

When would you see combination of both cholestasis and hepatocellular injury

A

when the liver is diffusely injured: acute ischemia (sometimes called shock liver) or toxin-ingestion.

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7
Q

Non-hepatic causes of abnormal liver tests

A
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8
Q

What are the transaminases

A

Aspartate transaminase = AST

occasionally mentioned as SGOT

Alanine transaminase = ALT

occasionally mentioned as SGPT

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9
Q

Where else are transaminases found

A

cardiac muscle, skeletal muscle, kidney, brain, pancrease, lung, leukocytes, erythrocytes.

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10
Q

AST/ALT ratio > 2-3

A

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

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11
Q

AST/ALT < 1

A

AST/ALT < 1 is likely in chronic viral hepatitis.

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12
Q

AST/ALT close to one

A

AST/ALT close to one is consistent with non-alcoholic steatotic hepatitis (NASH or fatty liver)

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13
Q

Levels of transaminase elevation and indication

A

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.

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14
Q

What is Alkaline Phosphatase, and how to differentiate for liver

A

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.

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15
Q

Causes of Alk Phos elevation

A

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.

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16
Q

What is Gamma-glutamyl-transpeptidase

A

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

17
Q

When is GGT elevated

A

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)

18
Q

What is bilirubin

A

Bilirubin is a breakdown product from heme which can be further tested (or fractionated) into two types: conjugated or unconjugated.

19
Q

What does conjugated bilirubin mean?

A

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.

20
Q

What does direct/indirect bilirubin mean

A

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).

21
Q

What to order next if isolated hyperbilirubinemia

A

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.

22
Q

Congenital causes of Direct Hyperbilirubinemia

A

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

23
Q

Causes of Indirect Hyperbilirubinemia

A
24
Q

What is LDH

A

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.

25
Q

Which coagulation factors were dependent on vitamin K?

A

II, VII, IX, X, protein C/S

26
Q

What is Prothrombin Time (INR)

A

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.

27
Q

What is albumin and what does it indicate

A

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.

28
Q

What is ammonia and what does it indicate

A

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.

29
Q

What is a MELD score

A

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

30
Q

How is creatinine impacted with liver disease

A

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)

31
Q

Pattern for chronic hepatitis

A

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

32
Q

What can cause very high enzymes

A

(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

33
Q

Pattern for cirrhosis

A

AST > ALT

Decreased Platelets

Decreased Albumin

Increased Bilirubin

Increased PT/INR

34
Q

Normal values

A