Liver function tests can be incredibly confusing, even for advanced practitioners. We’re going to simplify them today. There are five main liver function tests that we’ll cover: AST, ALT, CCT, ALK Phos and Total Bili.

First and foremost, you have AST and ALT, otherwise known as transaminases. Normal AST and ALT are about 35, ranging from 32 to 38. A normal Total Bilirubin is about one.

If you say “transaminitis,” that’s a fancy way of saying that AST and ALT are up. A transaminitis is an isolated elevation of AST and ALT. When someone has an elevation of their liver functions, any one of the five, you have to put it in one of two categories: hepatonecrotic or cholestatic. Hepatonecrotic indicates rapidly dying liver cells, while cholestatic means the bile isn’t moving.

It’s kind of like any time you have a leukocytosis. Any time someone’s white blood cell count is up, it’s one of two questions: is it infectious or not infectious? An elevated white blood cell count could be from an infection or it could be from a cortisol response. If cortisol spikes, that’s going to give you a leukocytosis. If you have someone with an elevated renal function, the question is, is it pre-renal, renal or post-renal?

So, if your liver functions are up, is it hepatonecrotic or cholestatic?

Picture This

Picture me standing in front of you. I have a 4’ by 4’ plywood box with a Plexiglas shield in front of it so you can look in. I take green balloons and pack the box with the balloons. You can see in and see all the balloons. Those green balloons are representative of hepatocytes. Within the hepatocytes is where AST and ALT live.

Next, I take a hose. If I rub my hands over it really quickly, I can feel little prickles on the hose. I take the hose and shove it down in between the balloons so the hose is sticking up out of the box. Because of the prickles on the hose, a few balloons pop. The balloons are your hepatocytes and the hose represents the ducts running through your liver. That hose is lined with two different cells, Alk Phos and GGT, and running through the hose is Total Bilirubin.

Hepatonecrotic Liver Functions

Now that you have this model in your mind, we can discuss how the labs sync together. I’m going to take a pin and start popping balloons. Would that put more pressure on the hose or take pressure off the hose? That would take pressure off the hose.

If you have a hepatonecrotic liver function, it is massive elevations of AST and ALT. When I say massive, I don’t mean 80 or 90; I mean 3,000, 4,000 or 5,000. Hepatonecrotic elevation of liver functions has minimal elevations of Alk Phos, GGT and Total Bili.

The problem is that the cells are popping. Hepatonecrotic means the liver took a hell of a hit; something really insulted the liver. Most commonly, it’s an acetaminophen overdose. It could also be someone who went into shock and the liver got really poorly perfused, resulting in a massive elevation of AST and ALT.

Look at Their PT INR

The physiology of the liver is a very important factor when it comes to looking at liver functions. Now, a lot of liver hits will survive fine. But think of it this way: if you have 99% of the factory go on strike and only one person at the factory is at work, that one percent is going to do the most essential functions of the factory. As soon as that one percent leaves the factory, it’s going to go to hell.

Same thing with the liver. If 99% of the liver is shot, one percent is doing the essential function. What is the most essential function of the liver? The liver makes clotting factors II, VII, IX and X. If someone’s liver is shot and their AST And ALT are really high, but the liver is still functional, clotting factors II, VII, IX and X are going to be okay.

How do you know that? The most sensitive lab test regarding the physiology of the liver is their PT INR. If someone has elevated AST and ALT of 4,000 or 5,000, but their INR is 1.2 or 1.3, their liver has a shot. It may survive. It their INR is six, their liver is done. They’re probably going to need a transplant.

Check Ammonia Levels

If the liver isn’t well, it’s not going to filter substrates well. Just like the kidney; if the kidney’s not working well it’s going to back up urea and creatinine. If the liver’s not working so well, it’s going to back up ammonia. When people’s ammonia gets high, they’re going to become somnolent. They’re going to be really sleepy, very similar to a hypercarbic patient who’s retaining carbon dioxide. What do we call that retention of ammonia? We call that hepatoencephalopathy and we treat it with lactulose.

When it comes to hepatonecrotic elevations, you’re going to expect massive elevations of AST and ALT. You’ve got to look at their PT INR and check their ammonia level, especially if they have an altered mental status. I don’t check it routinely if their mental status isn’t altered.

Cholestatic Liver Function

The second liver function pattern we’ll talk about is a cholestatic pattern. The best analogy to this is a common bile duct stone.

Let me explain: When it comes to understanding liver functions and cholestatic patterns, you have to understand the four diseases of the right upper quadrant. If you have a gallstone, four things can happen from that gallstone and you have to be able to identify each stage. It’s similar to understanding unstable angina versus non-STEMI versus STEMI. Think of it as a continuum.

Diseases of the Biliary Tract

There are four different diseases of the biliary tract. You have biliary colic, cholecystitis, choledocholithiasis and cholangitis. So, you have someone who’s got a gallstone and you know that 85% of all gallstones are cholesterol. If a stone pops out into the cystic duct, they’re going to have tremendous pain. Now who’s most likely going to get this? The most common demographic is 40-year-old, heavier set females.

Biliary Colic

Why does that stone move? It moves because of CCK and gravity. CCK is cholecystokinase, an enzyme from your pancreas. When someone eats a fatty meal, CCK squirts out and it makes the gallbladder go into contraction. Fatty meals provoke CCK to be secreted from the pancreas; therefore, it kicks out a stone. What else causes the gallstone to come out? Gravity. It’s mechanical. When someone is upright, the stone sits in the inferior pole of the gallbladder. When they lay down supine, the stone is closer to the cystic duct. That is why we tell someone with biliary colic to skip fatty meals and sleep with the head of the bed elevated.

If someone has biliary colic, the stone pops into the cystic duct and they have horrible pain. When the body tries to fit something through an orifice that it doesn’t normally fit through (gallstones, kidney stones, pregnancy, really bad constipation or a distended bladder from urinary obstruction), you have distension pain. That’s the worst pain you can have.

But if you biopsy the gallbladder, the gallbladder is not inflamed at all. If the gallbladder was inflamed, it would be the second stage. Biliary colic is someone with severe right upper quadrant pain from a stone, but there’s no inflammation of the gallbladder. If you see them in the acute care setting, you can typically send them home.


Cholecystitis is one step further. The gallbladder’s inflamed. Now, the gallstone goes into the cystic duct, it sits there for a while and the gallbladder becomes highly inflamed. How do you know that?

First and foremost, they’ll have a physical exam finding called Murphy’s sign. When someone’s got a right upper quadrant ultrasound going on, the tech will push the probe in and have the person take a deep breath and see if they splint. The tech will document that in the note, echographic or sonographic Murphy’s sign. We’re going to test it clinically, but the ultrasound tech is going to test it as well.

Someone who has cholecystitis will have a positive Murphy’s sign and their labs are going to be a little uglier. They’re going to have a higher white count than biliary colic. The ultrasound is going to show pericolic sludging or thickening of the bile wall or edema, or sludging within the gallbladder. That all tells me the gallbladder’s inflamed.

How do I tell it between biliary colic and cholecystitis? Well, the physical exam and an ultrasound will tell me. If you have someone with cholecystitis, they’re a little bit sicker and you really want to talk to a surgeon about this, depending on where they are on the spectrum. It’s not uncommon that these people get admitted to the hospital, cool down the gallbladder and then take it out.


Let’s say the stone does not get stuck in the cystic duct, but it goes all the way down into the common bile duct. Now you have choledocholithiasis.

With biliary colic, there is no infection and no inflammation. With choledocholithiasis, there is no infection and no inflammation. Now, you just have a common bile duct stone. If you have a common bile duct stone you cannot miss it, because it sets them up for cholangitis, a life-threatening infection. How do you know if someone has a common bile duct stone? We need to see it by a lab and then diagnose it with some kind of imagery.

I need a lab that tells me the Total Bilirubin is up, even just a little bit, to 1.6, 1.7 or 1.8. If I see a high Total Bilirubin, I want to see the duct using CAT scan or ultrasound. If the CAT scan or ultrasound shows common bile duct dilation with a Total Bilirubin, that’s a common bile duct stone until proven otherwise. Even without a fever or white count, they have to be admitted and put on high dose antibiotics, because if it gets infected, it’s a life-threatening anaerobic infection.


Cholangitis means the patient has a gallstone that’s stuck in the common bile duct and is infected. They’ll have ascending cholangitis. That’s the triad known as Charcot’s triad: right upper quadrant pain, fever and jaundice. This is life threatening.

If the patient gets septic, they’ll have hypotension and altered mental status. If you see hypotension, altered mental status and Charcot’s triad, we call that Reynold’s Pentad. This is a life-threatening infection and the pressure needs to be relieved using an ERCP or interventional radiology for a biliary drain. Nobody is going to use an ERCP; they’re going to get a biliary drain. When I say high-dose antibiotics, I mean something like Azocin 4.5 grams. Then, the patient needs to go to a hospital where an ERCP or interventional radiology are possible.

So, is it hepatonecrotic or cholestatic?

There are two major patterns of liver function elevations, hepatonecrotic and cholestatic. How do I know if it’s hepatonecrotic? You’ll have massive elevations of ALT and AST. You need to ask what caused it and assess their PT INT and ammonia levels.

If you have a cholestatic pattern of elevation, look at Total Bilirubin. That is going to be your primary number, but because there’s a blockage of the duct, other duct labs are going to be up as well. GGT and Alk Phos are going to be up because that hose is broken; AST and ALT will be up a little bit as well. The hose will swell and pop some balloons touching the duct, but not many. When you have someone with elevated Total Bilirubin, you want to image their gallbladder. That will comment on the common bile duct.

Let’s Review

You have four different diseases associated with the gallbladder: biliary colic, cholecystitis, choledocholithiasis and cholangitis.

  • Biliary colic: You’ll have right upper quadrant pain, relatively normal physical exam, normal labs, normal ultrasound. Send them home and tell them to sleep with the head of the bed elevated, skip fatty meals and follow up with a surgeon.
  • Cholecystitis: The physical exam is going to have a positive Murphy’s sign with more sinister lab results, a higher white count and low-grade temperature.
  • Choledocholithiasis: There’s typically no fever, but Total Bilirubin needs to be addressed and the common bile duct is dilated. Upper right quadrant pain needs an ultrasound. At night, a CAT scan will do.

Cholangitis: You’ll see Charcot’s triad with right upper quadrant pain, jaundice and fever, which is a life-threatening infection.

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