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RTL- Ep 85- Abnormal LFTs
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RTL- Ep 85- Abnormal LFTs
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[Dr. Smith] Welcome back to Run the List, a medical education podcast in partnership with McGraw Hill Medical. Our host are Dr. Navin Kumar, Dr. Walker Redd, Dr. Emily Gutowski, Dr. Joyce Zhou, and myself, Blake Smith. As a quick disclaimer, this podcast is meant for informational and educational purposes only and should not be understood as medical advice under any circumstances.
[intro music] [intro music] [intro music] Welcome back to another episode of Run the List. In the last two episodes we covered our approach to diarrhea, which led us down a path of differentiating the cause of inflammatory bowel disease and how to manage it.
But today we're going to turn towards a different topic, liver function tests or LFTs, and how to approach thinking about it. But first, I'll introduce the one, the only Dr. Navin Kumar, our gastroenterologist extraordinaire, RTL founder, and an attending GI at Brigham and Women's Hospital, associate medicine clerkship director at the Brigham and also at Harvard Medical School. Without further ado, Navin, are you ready to Run the List?
[Dr. Kumar] Thanks so much Blake, so happy to be back. I think I'm now on eight episodes in a row so going to try to finish strong today and then take a little holiday from Run the List. [Dr. Smith chuckles] That's okay with us. So I'll begin our case today. It is the case of a 58-year-old female in the emergency department who's presenting with a three day history of right upper quadrant pain, nausea and vomiting following meals.
She has a history of hypertension and recalled one prior episode of self-resolved afebrile right upper quadrant pain a couple of years ago. Her vitals are 99 degrees Fahrenheit, heart rate of 112, blood pressure of 135/85. She satting 99% on room air and a respiratory rate of 18. She takes lisinopril daily but has had no recent medication changes and no significant dietary changes or recent travel history or illness.
There are no notes in the EMR. She previously never had any hospitalizations. And on exam, the EM resident noted that the patient's afebrile, she has tenderness to palpation in the right upper quadrant with a positive Murphy sign. She appeared dry on exam with dry mucosa and some skin pallor and she has icteric sclera. Her labs were notable, she had a normal CRP of 8, ESR of 10 and mild white blood cell count of 10,000, but LFT showed a mild elevation in ALT of 60, AST 55, but LFT showed a mild elevation in ALT of 60, AST 55, and marked elevation in alk phos at 295 units per liter, the upper limit of normal here being 130, and a total bilirubin elevated at 4.2 mg/dL.
Her lipase was normal and urinalysis was positive for urobilinogen. So that is a lot Navin, but I'll pause there. Can you tell us how you start thinking about a common presentation, such as right upper quadrant pain? [Dr. Kumar] Yeah, absolutely. So with any acute abdominal pain complaint I like to use the framework from an anatomical standpoint. So with this being right upper quadrant pain, I like to think what organs are in the right upper quadrant of the abdomen.
And the two main organs I think about are the liver, and then the gallbladder/biliary tree. So thinking within those two major organs, we can start with the biliary system. I need to think about how can something in the biliary tract cause pain? And so we usually think about pain from the biliary system from gallstone and then it depends on where that gallstone is in terms of what kind of diagnosis we're dealing with and what kind of presentation we'll see.
So the first type of gallstone that can cause pain is a gallstone in the gallbladder where it is transiently blocking the cystic duct or the passage from the gallbladder into the common bile duct but it's transient, so the stone comes up into the cystic duct, causes symptoms for a few hours and then it falls off. And so those patients have what we describe as biliary colic or this really intense right upper quadrant pain usually with nausea, vomiting, and I think the hallmark feature is if you see a patient having biliary colic, you'll see that they just can't get comfortable.
They're moving around, they're not staying stationary, they're very uncomfortable. So that would be symptomatic cholelithiasis or biliary colic. Now if that same gallstone gets lodged in the cystic duct and does not fall off, then you deal with the issue of acute cholecystitis where the patient will again, have the right upper quadrant pain, but this will be constant and they'll also have oftentimes fever constant and they'll also have oftentimes fever as well as leukocytosis because behind that blockage of the stone in the cystic duct you're now getting an inflamed gallbladder wall.
So that's how I distinguish cholecystitis from cholelithiasis, honestly, it's a lot more of looking for systemic inflammatory responses in the cholecystitis which you don't see in the biliary colic patients. And then kind of just traveling down the biliary tree, if that stone, let's say, it gets through the cystic duct but it gets stuck in the common bile duct, then honestly, the presentation may be very similar to someone having biliary colic.
They have the pain, they may have some nausea, vomiting They have the pain, they may have some nausea, vomiting but they don't have the inflammation and so they generally don't have fever or an elevated white count, but they will have elevated liver enzymes because they're actually blocking the passage of bile from the liver. So that's one way to distinguish that from gallbladder disease.
And then on top of that stone, if they have inflammation behind the stone, so ascending cholangitis, then you start thinking about things like Reynolds' pentad where you have have fever, right upper quadrant pain and jaundice, and then- That's from Charcot's triad. Blake, let me put you on the spot. Do you remember the two others for Reynolds' pentad? Oh, I might get you here. [Dr. Smith chuckles] I think you did.
I remember that there were neurologic symptoms as well. [Dr. Kumar chuckles] Awesome, yeah, so there's altered mental status and then hypotension is the fifth one. And so when they have any of the conglomeration of those symptoms, you can start thinking about could this patient have cholangitis? But essentially, so with the biliary system you're thinking about could there be a stone? If there's a stone, where is it?
And is there anything happening proximally to it from an inflammatory standpoint? So that's one major category of causes of right upper quadrant pain are the biliary causes. And then the other main organ as I mentioned is the liver. And so the liver can cause pain usually in the setting of acute hepatitis where you have inflammation of the actual capsule surrounding the liver and that will cause pain.
And of those, there're many different causes, there can be toxic, metabolic, they're infectious there're autoimmune processes. So the differential is very wide for hepatitides, but certainly I'm thinking basically let's use the anatomical framework, let's think about the biliary tree and the liver, and then don't forget, sometimes patients have a very deep right basilar pneumonia that can then cause pruritus of that area, and sometimes those patients really present with right upper quadrant pain, even though the disease process is in their lung parenchyma.
[Dr. Smith] Yeah, I like that because in med school we learned right upper quadrant pain, we immediately think gallbladder but there are other anatomical organs in that quadrant of the abdomen. So it's good to think broadly, especially at this stage of working up the patient. So Navin, as you're further evaluating this patient, what else do you prioritize in your history taking and/or labs? And I'm willing to give you the labs again, if you need them.
[Dr. Kumar] No, that's great, Blake. And I think, you already did it initially in your presentation, so one thing I always want to ask about if I'm seeing abnormal liver enzymes, which we do in this patient is, was this patient recently started on a new medication? Medication is often a cause for change in liver enzymes. And so I'll always ask that, you mentioned that this patient only takes lisinopril and then gave the pertinent negative that there were no recent medication changes.
So that's very helpful. You also want to ask about non-prescription-based medications. Are they taking any supplements, herbal supplements, things over-the-counter or even off the counter that you would not normally ask about? That will be very helpful when looking at a patient with abnormal liver enzymes. And so with our patient, I'll just remind our listeners, so you mentioned they had a mild elevation of ALT of 60 and an AST of 55.
And so I always think about the ALT and AST together because those are our hepatocellular liver enzymes. So if those are elevated, that indicates that there is some inflammation damage happening at the hepatocellular level. And then you gave us correctly the alk phosphatase, alkaline phosphatase next, which was notably elevated at 295 units per liter where our upper limit of normal is 130, so more than twofold rise in the alk phos.
And the alkaline phosphatase is really helpful to think about cholestatic liver injury, so a different pattern of liver injury compared to hepatocellular. And then we finished with the T bili being elevated at 4.2 mg/dL, and although I think there is this tendency to use total bilirubin in conjunction with the alkaline phosphatase, you really should think about it separately because the T bili can be elevated in either hepatocellular or cholestatic processes.
So I think the key thing here is to think about AST, ALT as your hepatocellular enzymes, alk phos as your cholestatic, and then recognize that T bili can go up in either case. So once I've gone through that process which we just did here, right? we said mild hepatocellular injury but more significant cholestatic injury based on the alkaline phosphate being over twofold up the limit of normal.
I also like to objectively make sure that I am making the correct liver enzyme abnormality classification. And so to do that there is a helpful calculation you can do called the R factor which essentially differentiates between a cholestatic versus hepatocellular versus a mixed liver injury process. And so the actual calculation is taking the ALT over the upper limit of normal ALT and then dividing that by the alk phos over the upper limit of normal of alk phos.
And so what you're essentially doing is you're comparing the ratio of the rise in the ALT to the ratio of the rise in the alk phos. So if you think about it that way, your numerator being the rise of the ALT, your denominator being the rise of the alk phos, you can kind of actually just figure out which one will lead to hepatocellular, which one will lead to cholestatic process.
The actual numbers, the way they work out for this R factor is that if that R factor is above 5, then that's indicative of a hepatocellular injury. Basically that's saying that the proportion of the ALT rise is significantly more than the proportion of the alk phos rise. If it's less than 2, then that's a cholestatic liver injury basically showing that the alkaline phosphatase rise is proportionally higher than the rise of the ALT.
And then if it's between 2 and 5, then it's a mixed picture. And so we do that in this case, and the R factor comes back at 0.66, so less than 2, kind of confirms our initial feeling that this was a cholestatic liver injury. And then when you think about, okay, so we got a cholestatic liver injury, we got right upper quadrant pain, but no evidence of systemic inflammation, no fevers, no leukocytosis, at this point I'd be most concerned for a common bile duct stone.
[Dr. Smith] Thanks for that Navin. I feel like every specialty has their own calculator and we love incorporating math in Run the List. So thanks for walking us through your initial kind of diagnostic approach and really talking about how kind the numerator of ALT and the denominator of alk phos are kind of competing in these acute injuries and to think more of a hepatocellular injury or more of a cholestatic injury, and using this R factor to differentiate them.
So now that you're thinking about an acute biliary blockage, a CBD stone potentially causing cholestasis without the classic Charcot's triad or Reynolds' pentad as you liked to point out before, what additional workup would you send at this point for this patient? [Dr. Kumar] Exactly. So we've kind of honed in on this being an acute billary blockage and now we're trying to figure out where is that blockage.
So what I would first start out with is an ultrasound, an ultrasound being readily available, there's no radiation exposure and it very well may confirm our diagnosis. We generally at least want to see gallstones because it'd be surprising to see a gallbladder empty of stones even if they had a CBD stone. Generally, you see stones in the gallbladder and then hopefully some evidence that there is a stone in the common bile duct to confirm our diagnosis.
Now you could consider getting a CT scan after, but let's start with the ultrasound. Why don't you tell us what we see on the ultrasound then we can think about if we need any further imaging. [Dr. Smith] Yeah, definitely. So the right upper quadrant ultrasound demonstrated numerous gallstones within the gallbladder and a dilated common bile duct of one centimeter but no obvious CBD stone.
So would you order further imaging in this case? [Dr. Kumar] Yeah, exactly. So we see this presentation honestly quite a bit where clinically the patient is presenting with an acute biliary obstruction. We see gallstones when we do the ultrasound but we don't see a stone in the common bile duct. So imaging-wise, we don't confirm the presence of choledocholithiasis with the ultrasound.
And so oftentimes I think the next reflex is to get some cross-sectional imaging, be that either CT scan or MRI, but there's a very helpful prediction score that honestly I think this is probably more readily appreciated within the GI field, but there's an American Society of Gastrointestinal Endoscopy, ASGE and they have this really helpful algorithm for working up a patient with possible common bile duct stone.
And part of that algorithm is that if they have one of these three predictors of the CBD stone, the chance that they have a CBD stone is so high, that you basically treat them as such and you go directly to the intervention to relieve the CBD stone. So those three predictors are either seeing a CBD stone on ultrasound, so that's obvious, if they're presenting with ascending cholangitis so they have the features of biliary obstruction but also those other systemic features that we went through, the Reynolds' pentad that suggested they're cholangitic, then you're going to directly go to the procedure needed to relieve the biliary obstruction, or the third one which is honestly the one that we most commonly see in these patients is a total bilirubin above 4 mg/dL.
And so I remember, Blake, you said that her total bilirubin was 4.2. So that gives her a very strong predictor of having an underlying CBD stone. And so with that taken together, we would actually go straight to an ERCP to relieve that CBD stone straight to an ERCP to relieve that CBD stone rather than obtain more imaging before. [Dr. Smith] Awesome, thanks for that AGSE recommendation.
And again here, since we didn't see any CBD stones on ultrasound, but we did see a dilated CBD, we were kind of tipped off to the potential of this choledocholithiasis, and using the T bili, which in this case is above 4.0 based on your recommendations the patient does go directly to ERCP, or endoscopic retrograde cholangiopancreatography.
-: Got that. [Dr. Kumar chuckles] [Dr. Smith] And so the ERCP indeed shows several CBD stones found in the distal common bile duct which are cleared via balloon sweep of the duct. And then a sphincterotomy is performed to prevent recurrence of the CBD stones. In addition to monitoring her post ERCP for any complications, what else should be done before discharge? [Dr. Kumar] Yeah, so you mentioned in the ERCP they do a sphincterotomy so that's basically where they're making a cut through the ampulla so that it's for two reasons.
-: One, it gives easier access to remove the stones when they do their balloon sweep of the common bile duct, but two, because now they've actually made the ampulla- They've essentially dilated the ampulla by cutting it. If more stones were to form, they will come out more easily, they won't as readily get stuck, but the key thing to do for these patients before they go home is that you need to consult surgery to remove their gallbladder because if you leave the gallbladder in place, they're just at higher risk for forming more gallstones that can lead to future episodes of choledocholithiasis.
-: But then also with the gallbladder still in place, they're still at high risk for complications related to the gallbladder. They can still get cholecystitis from formation of future gallstones. I mean one thing to mention is that even if you take the gallbladder out, what then starts to happen is the common bile duct itself will start dilating in response to no longer having will start dilating in response to no longer having a gallbladder to hold bile.
-: And so with that common bile duct dilating, you still can form stones in the common bile duct, even without a gallbladder. So that's a good important point to remember for patients post-cholecystectomy who you're seeing with right upper quadrant pain, there still is the possibility that they formed a stone in their biliary tree. And then also a good reminder for oftentimes we get consults for dilated common bile duct, and one of the major reasons for that is that they're just post-cholecystectomy.
-: So just remember that after the gallbladder is removed, the common bile duct does tend to dilate a bit, but having that sphincterotomy is going to prevent recurrence hopefully of another if a stone were to form of it getting stuck in the common bile duct. And I just want to mention one thing. This case was nice and clean and the patient had that very strong predictor of a CBD stone with the T bili above 4, but oftentimes you don't have that very strong predictor and so they end up being in this intermediate risk category.
-: And so generally the patients with intermediate risk may have a total bilirubin of 1.8 to 4 or they have a dilated CBD like our patient did without that T bili above 4, and in these patients, when you have a clinical suspicion of them having a CBD stone but not enough to go straight to ERCP, that's when you get imaging. And the best imaging to get is either an MRCP which is basically an MRI with a dedicated protocol to look at the biliary tree very carefully for a CBD stone, or an invasive approach should be an endoscopic ultrasound.
-: So sometimes for these patients, what they end up doing just to save time is that they go for an EUS or an endoscopic ultrasound to look for the stone and if it's there then right in that same procedure you can convert and add on an ERCP. But if the EUS is negative, then the patient is all set and they're essentially done with their workup for a CBD stone. [Dr. Smith] That was awesome. Thanks for describing again some of the complications post-ERCP and potentially post-cholecystectomy and really discussing that intermediate case in patients that don't have one of these three diagnostic criteria for doing an ERCP.
-: So we talked a lot today about how to approach a set of abnormal liver function tests, labs in a patient who is afebrile with right upper quadrant pain. And we use that to really interpret how to guide patient care in this case. So before you go Navin, can you leave us with a few pearls? [Dr. Kumar] Yeah, absolutely, so number one is, with any patient presenting with abnormal liver enzymes, really spend a lot of time with the history.
-: Think about, were they exposed to any potential hepatotoxins? Are they recently started on any new medications? And also, do they have any associated symptoms that could explain their liver enzyme rise? I mean certainly, in our patient having right upper quadrant pain definitely pointed us towards the biliary tree. Although as we mentioned before, hepatitides can cause right upper quadrant pain as well.
-: So use your history to first start narrowing your differential. The next pearl is, once you see liver enzyme abnormalities try to put them into one of three categories, right? The hepatocellular liver injury, the cholestatic or the mixed, because once you get into one of these three buckets, you can further narrow your differential and your work-up from there. I really think the R factor can be a more objective measure of the injury type, I think we all do a kind of gestalt about, is the AST, ALT most elevated or is it the alk phos?
-: But to really kind of clench it objectively you can use the R factor, which is, again the ALT over the upper limit of normal ALT, and then divide that by the alk phos over the upper limit of normal of alk phos. And then lastly, for patients that like ours who had a very high risk of CBD stone, remember those ASGE guidelines, the high risk very strong predictors are either having a CBD stone seen on ultrasound, having ascending cholangitis, or having a T bili above 4, the next step is to go directly to ERCP, have the ERCP advanced endoscopist sweep the common bile duct, perform a sphincterotomy, and then consult surgery for a cholecystectomy before discharge to prevent future episodes of gallbladder-related stone disease.
-: [Dr. Smith] Awesome, that was so much. Thanks Navin for that and for reminding us about these calculators, like R factor, these guidelines the classic signs of right upper quadrant pain. And we hope that you guys enjoyed this episode, I know I did, as the host on this and hopefully you will join us again on another episode to Run the List. [Dr. Kumar] Awesome. Thanks, Blake.
-: [outro music] [outro music]