Fatigue Isn’t Just in Your Head: Understanding Fatigue Through Your Lab Test Results

Deandre White: Hi, I'm Deandre White from Diverse Health Hub and welcome to a conversation that could change the way you think about fatigue. So if you've ever been told your exhaustion is just in your head or if you've walked away from a doctor's appointment still wondering why you're tired, you're not alone.

Today we're joined with a true pioneer in laboratory science and patient education, Dr. Susan Leclair, to explore what your lab tests might be telling you about fatigue, anemia, inflammation, and so much more. This isn't just about numbers on a chart, it's about connecting the dots between what's happening inside your body and how you feel, something that should never be overlooked.

So whether you're a patient, a caregiver, or a clinician, this conversation is for you. So let's dive in.

Dr. Susan Leclair: Thank you, Deandre. I want to start by saying that one of the reasons that this conversation is for you, if you're a patient or a caregiver or a clinician, is because, well, you're probably having fatigue as you sit there and watch this.

Patients get fatigue from a variety of situations, both emotional, psychological maybe, and physical. So yes, there are times when those two streams of discussion with your physician are going to split. But that's an important place to have it split. If you're a caregiver, your fatigue is probably all emotional because of the worries that you have. And if you're a clinician, typically seeing 20 patients a day, you're tired too.

So let's talk about fatigue. One of the biggest things we have to talk about is that fatigue is a symptom. Well, what does that mean? It means that you and only you can feel this symptom. It is not the same as a sign, a blood pressure, a lab test, an x-ray. All of these are things that are externally generated by a machine or a person evaluating some particular phenomenon. It is an external kind of result. Physicians, caregivers in general, tend to look at signs.

Why? Because they can see them. They can hear your pulse. They can see your eye dilate or not. So they feel more comfortable with signs than they do with symptoms. When you say to them, I'm tired. Okay, what does that mean? I feel achy. How is a caregiver, a physician, a provider of any type, supposed to evaluate a symptom? It's hard to evaluate symptoms like fatigue. And so when you have a physician who's only got seven minutes to speak to you and you say to them, well, I just feel tired, it's very difficult for them to move on.

So it's important to look beyond just the word fatigue and look into what kinds of things might be evaluated and moved into a sign category, that would help support the concept of fatigue. Okay, so then we can say, well, what lab tests can we do that talk about fatigue?

Well, let's see. Fatigue can be caused by having difficulty getting your metabolism to move the way it's supposed to. Fatigue can also be caused by having your metabolism work so hard, it's exhausted. So there are two different ways of looking at this.

Let's then divide that concept of fatigue into things that are causing difficulty in letting me do my work and things that are causing me to work so hard that I can't do my normal metabolic work. In order to do that, I really have to look at what I'm going to call major screening tests. These will be tests, laboratory tests, that will try to split those two categories further apart. They will make them lead the caregiver, the health care provider, down a road of either not enough metabolic rate or too much metabolic rate.

When in doubt, one of the oldest tests that has been done in a clinical laboratory for the past, oh, 100 years or so, has been something called the complete blood count, or as we who like to live in the world of abbreviations likes to call it, the CBC.

What is the CBC? Well, the CBC is a way to count and evaluate the quality of your blood cells. Why do I care? Well, because the red blood cells, which is the largest number of cells in your bloodstream, carry something called hemoglobin. And hemoglobin brings oxygen to the cells. So if I need oxygen to make my cells work correctly and I'm not getting enough of it, well, then I'm going to have fatigue because the cells in my body are not getting sufficient oxygen to really do what they're supposed to do.

Okay, so how do I look at red cells? Well, the first thing I do is count them. Put a certain volume of them on a grid and count the number of them. Too few might suggest that I'm not getting enough hemoglobin in there. Too many might be that the hemoglobin's not working correctly or that something else is wrong.

So maybe I want to look at hemoglobin. How much hemoglobin do I have? Too much hemoglobin, sounds a little odd, might be contributing to fatigue if it's an abnormal hemoglobin. Too little hemoglobin, easy one. Not enough hemoglobin, not enough oxygen, not enough work for the cells to accomplish. Does that make sense?

Well, how can you have a hemoglobin that doesn't work? Well, there are mutations in hemoglobins, and no, we're not going to talk about them today. All I want you to know is that there are people out there who look like they've got great hemoglobin if all you're doing is looking at that number, but it doesn't work.

So I can look at hemoglobin. What else can I look at? Well, red cells are made in the bone marrow. They start with a fairly big cell, and over time they undergo mitosis. They divide and become double the number, so it's one, two, four, eight, and so on. If there is a problem with making the cells, then I might have cells that are too small, or I might have cells that are too big.

That might tell me, I have a few, lesser than normal, number of cells, but they're really big. Or I have a lot of cells, but they're too small. Now think for a minute of walking down a street or walking in a mall around Christmas time. If you're really small, you can slip through all of the people in the mall, in the corridors, in the hallways fairly quickly, but if you're really, really, really large, 7 foot 2, 400 pounds, then you're going to have a harder time moving through all of those people in the hallways in the mall.

So changes in shape might mean that I have trouble putting that cell where it's supposed to go. So you get a sense here that by looking at the size, the amount of hemoglobin, the number of cells, I can develop a picture which the healthcare provider can look at and say, "Well, wait a minute, too few cells, but they're really big."

Turns out means that there's difficulty in making the cells in the bone marrow, and there are a couple of big reasons why that can happen. So if I've got a patient who's got a lower number of red cells and is complaining of fatigue, which means maybe they're not getting enough oxygen to their tissues, then maybe I should look at these two or three potential causes.

So the first part of the CBC, the red cell numbers and evaluation, can tell whether or not you are anemic and suggest to the healthcare provider what additional tests or follow-up needs to be done to determine if that fatigue is related to the lower numbers of red cells. Does that make sense?

Now, what's another one? A lot of people complain about loss of appetite, something I sincerely wish I could have at times, but never mind. You just don't feel like eating once a day, not a big thing. Twice a day, slightly bigger thing. Three days in a row, we got a problem.

What is going on that you might have a loss of appetite, which in turn means you're not getting enough glucose or protein into your system and therefore gives you fatigue? Well, maybe we should move out of the laboratory for a little bit and have the physician or the healthcare provider think about problems in your GI tract. That could be an easy one for them to do. That's outside of the laboratory. It's in imaging or it's in radiology, but there's a way to look at that as well.

Deandre White: I love that you said that, Dr. Leclair. I actually wanted to ask you, are there lab values that may appear normal on paper, but when taken together with patient symptoms and signs tell a different story? Because we can talk about normocytic, which is normal red blood cell sizes, versus macro and micro. But there might be other factors that it looks normal to the patient on paper, and the doctor might explain it that way, but there's a lot more going on.

Dr. Susan Leclair: Well, if you look at one of the things that I mentioned, the what is going on that is causing you to work really, really hard, one of the things that could happen is you make perfectly normal red cells. They are gorgeous. They're the exact size, the exact shape, the exact color that they're supposed to be. But it turns out that your bone marrow is working two, three, four times the normal amount to overcome some death or destruction of those cells on the other side.

So how can that happen? Well, for the teenagers who might be listening to this, how about you go outside. It's a summer day as it is right now. There's a beautiful blue sky out. The sun is shining. It's glorious. And the first thing you teenagers want to do is if you're a female, get down to your bathing suit and sit there, and pray to the sun god because you want a tan.

Well, maybe the first time you do that, you burn, like all over or a goodly chunk. What have you done to the red cells that are near your skin? You've burnt them. You've blistered them. They die. They must be taken out of the system. And now your red cell production in your marrow has got to go double or triple the amount to bring you back to where you were. Okay, that's a one-shot deal. You're not going to go out the next day and do the same thing all over again, I hope.

But at any rate, that's one example. By far and away, the much more frequent example is called medications. For every medication you take, there are a bunch of side effects. Some of them are called adverse drug reactions because they're bigger than what we want them to be. And every medication has got this.

Well, so what? I take an antibiotic because I have an infection, and in 10 days I stop that, and so, my bone marrow is a little stressed, but it'll get back to normal. Cool. I agree with that one. Problem is that some of these drugs that cause this damage to red cells, you take every day. Like blood pressure pills will do this. Not all of them, but some of them will. Certain kinds of cholesterol-lowering medications might do this.

There's a whole bunch of other medications that, when you take them, can destroy red cells. That's called hemolysis. When your bone marrow can compensate for it, we don't really see it in the numbers too easily. But if it becomes difficult for your bone marrow to compensate, then it's called hemolytic anemia. You have fewer cells. They look different. You might be able to pick that up quite easily.

But in that gray zone between your bone marrow is working as hard as it can and it's succeeding, and your bone marrow is working as hard as it can and it's not quite succeeding to compensate for this, there will be these very small changes that can show up in parts of the CBC, but if you're not looking for them, you won't find them.

Probably the best example of that is a test that on your report form is called the RDW, the red cell distribution width. You don't care how it's done. Just trust me on that. There are slight changes. All red cells are not like dimes, absolutely the same at all times in size. They vary ever so slightly, but they're not supposed to vary widely.

The wider, the bigger the number of the RDW, the more stress there is on the bone marrow. So a physician could look at all of the numbers, look, okay, your red cell numbers are fine, your hemoglobin's fine. The things that I was talking about in terms of size and shape, those are called the indices, those look fine. You got a little bit of an increase in your RDW. Okay, that's maybe something they should put in the back of their minds. To watch for, because you don't know what it's saying.

It's saying there's stress, but you don't know where and you don't know why. And it may be just because you spent the day yesterday or you spent the day four days ago in the kitchen all day long trying to make a huge Thanksgiving dinner and it was hot and you have burns up and down your arms, or at least I always do, because I never remember. I just opened the pot covers and there you go, there's another scald.

So, it could be that and we won't have to worry about it, but they will remember it and make a note that the next time that person comes in, they want to check that because it should have been taken care of and that RDW should have gone back to normal. So there are little things like that that can lead a physician in one direction or another.

Deandre White: Dr. Leclair, what tips or what advice could you give to physicians when it comes to addressing when a patient says, I have fatigue, and you're looking at the fact that you're talking to, let's say, a patient with cancer versus a patient with an autoimmune disorder versus a patient that you know just works outside a lot. How would you give them advice on how do I approach each patient differently and how they describe their symptoms to me from a qualitative standpoint?

Dr. Susan Leclair: Well, the first thing that I would probably ask is, for how long? If your grandmother's fatigue is the week before Thanksgiving, I probably wouldn't think that that would be a huge thing. On the other hand, if your grandmother's fatigue is two weeks after some big event like Thanksgiving or Christmas or some other holy or holiday, you could then wonder why that fatigue is there.

And if you are careful, and primary care physicians are trained to do this, to ask questions about when that fatigue increases or decreases over time, they will be able to develop a picture in their mind of what the next test should be.

If they think that this person is also saying, and my hands hurt all the time, well, that could be a chronic inflammation, and chronic inflammation always has fatigue. So let's go down the road of testing for chronic inflammation, you know?

If all of a sudden, in the course of the conversation about fatigue, they're talking about difficulty in breathing or pain in their back or some other thing that might suggest a more serious disease, then your testing is going to move to another direction.

But the thing about the CBC is it's almost always the first thing you do. The second class or grouping of tests that they almost always do is some variation on something that's called a metabolic panel. Now, a metabolic panel is exactly that. It's a group of anywhere between 7 or 12, 14, sometimes more, tests that are done in the chemistry lab.

So these are going to be on a different kind of report form, and they will be evaluating general questions like, how is your heart doing? How are your kidneys doing? How is your liver doing? The great part about this panel is it gives you a huge amount of information. The bad part about the panel, in a sense, is it gives you information in one point in time.

And what do I mean by that? Your laboratory specimen was collected at 10:45 on a Tuesday morning, the 3rd of July. That's when that data is real. It is not real for the same day at 4:45 in the evening or the next day. So what it gives the physician or the other health care providers, and I have to keep reminding myself to do that because NPs and PAs are so important in our health care delivery system, and I don't wish to omit them by saying physician just because it's an easier word.

What it does is it gives them this moment in time as a base. You may have to come back and do others to see how change occurs over time. But what is in that base evaluation?

Well, the first thing typically is blood glucose. What is glucose? Glucose is the active form of sugars or carbohydrates that we talk about a lot in the body. All carbs are broken down until they get to a point where there is glucose. Glucose then is given to each and every cell in the body. It travels around in the liquid portion of the blood, and then it empties into the cells if there is sufficient insulin to make it so.

So an increase, at first glance everyone is now saying, oh my God, they're looking for diabetes. Well, yes, but we're also looking for what's your diet been lately? Again, if I have a teenager, yes, teenagers, I'm going to dump on you for a while, you decide that in order to get into a size eight dress for the prom, you need to go on a diet of watermelon and vinegar for three weeks, your diet's not so good, your glucose is going to be low.

Yes, you may lose weight, but it's really not a good way of doing it. So glucose will be able to tell a physician, is your metabolism of glucose working correctly? One of the things we in the laboratory want you to do is to come to us to have the specimen taken after an eight hour fast. No foods, no stimulating liquids, water sounds like a really good idea.

Why? Because if everybody comes in after an eight hour fast, then the physicians and the NPs and the PAs will be able to look at those values and say, okay, I can look at a population statistic and determine whether all of these are correct. If you come in after going to a breakfast place for two pancakes, a two egg omelet with cheese and bacon, I have no idea what your value is going to look like because you're going to be breaking that stuff down, putting it into the bloodstream and moving it through.

So a very high number, it may just be that you just finished eating and digesting. So there's no real value value for that. So I want to know, are you getting enough glucose in so that your cells are not starving?

I want to know then, how good are your kidneys doing? You have two of them, but they're the only two you're going to have, mostly three. You want to protect them. So I want to know, how good are your kidneys working? Well, what do your kidneys do? They get rid of liquids that are considered waste.

Well, there's one test called a blood urea nitrogen, a BUN. Urea is a waste product. I want to know how much of it you can get out. And that should be really simple, particularly, you say, if you've come in after an eight hour fast. Ah, but what did you eat two or three days before? Because you could still be getting rid of the waste of some real high protein dinner.

It is the beginning of summer. You went to a friend's house and you had a 12 ounce sirloin. Or you're a football player. I have a grandchild who played football in high school. And when he was playing football, I always had to double the amount of food that I was going to cook for him. Because he was really using it a lot.

So that protein that he ate, a high protein meal, had to be broken down and the waste products, the urea of that protein breakdown, might have been high for him. But his physician would be able to say to him, so you working out for football season? Ah, then you interpret the value differently. That's very different from somebody like me or older who comes in with a high BUN and the physician can say, when was the last time you had a glass of water? Because if you don't get enough fluid, all of these values are going to be falsely increased.

We don't drink enough fluids. So it's a big question that physicians always have with them.

Deandre White: So these are questions that the doctor should know to ask the patient based on some lab values they'd see. They're trained for that. But from a patient's perspective who kind of doesn't know how to navigate the situation or doesn't know what to say, what advice would you give a patient who's feeling tired all the time but they keep hearing from their providers or from their caregivers that everything looks fine? What advice would you give them in terms of what they should be asking and what they should be looking for out of their visits?

Dr. Susan Leclair: Well, it is very hard for a lot of people to straighten on that horribly uncomfortable patient examining table, but I want you to sit up as straight as you can, look your provider in the eye and say, okay, that's nice that you don't think anything's going on. I'm telling you something is going on.

Question number one, what do you think it could be besides something that's in my head? And then wait, that's the hard part. Wait for them to answer because you're nervous and you just said something to somebody that you go to for your health and you're really on edge and so you just want to keep on talking because that's what you do when you're nervous. Wait for them to answer and they say, well, it could be this or this or this or this and then you take another deep breath and say, so, kemosabe, so what are you going to do about it?

Are there other tests that we could do besides just the CBC if that turned out to be fine? What are we going to do about it? What answers from the laboratory tests that you are going to select are you looking for?

Because if all of a sudden now I just turn my mask around and I am your physician, I'm going to say to you, well, it could be your thyroid, so we'll do thyroid studies. I want you to say then, okay, what answers should I be looking for? What should be within the printed reference range that's a guidepost for your provider? Which ones... And what are we going to do if they're, either too high or too low?

And then they'll say something mumbly about that. Well, if this is too high or this is too low, we'll go forward. You want to then ask just in case, if you don't get the answers that you expect, what's your second guess?

Because now you're asking them to do something that in reality they have already done. They have prioritized in their heads what they think is the most logical reason for your fatigue, what would be the second most logical reason, and what should be the third.

So that the next time you go to see your provider, you have those questions, you have the lab test results. You can go in, and in that seven and a half minutes, and this is where magic happens, you can say to your provider, okie dokie, you did do the thyroid studies, and they do suggest that you are correct, that it looked like my thyroid's not working as well as it should be. Now what are you going to do?

You can actually have then maybe five minute discussion on what medications, how they should be taken, when they should be taken, and what you should feel about it. So what you're doing is you're focusing maybe not on that very first examination, because you're giving your physician this world of choices that they then have to narrow down. You have now become an active partner in narrowing it down.

Does that answer that correctly?

Deandre White: It does.

Dr. Susan Leclair: Does that make sense?

Deandre White: So we've talked about the patient's perspective, we've talked about the physician's or the clinician's perspective, but how would you say that lab professionals can collaborate better with physicians to catch hidden causes of fatigue earlier with patients?

Dr. Susan Leclair: Oh, bless you, my child. It is a sad fact of life that in the United States and in some other countries, medical schools had to make some very hard decisions. Do I give you a three credit course or maybe more than that in the interpretation of laboratory medicine, or do I give you another course instead on the genetics of disease formation, or anatomy, or medications?

And so a lot of medical schools have said to their students, you're just going to have to pick up the laboratory tests as you go along in your clerkships and in your residencies.

Deandre White: I can attest to that.

Dr. Susan Leclair: Well, yes. And I'm going to tell you that everybody who works in the laboratory who may be hearing this just had a severe tightening in their throat because that means you don't know what we can do for you. And if you don't know what we can do for you, you're not going to ask. So we'll never be able to have that conversation.

For example, one of the most common tests that is done for the evaluation of fatigue is something called a serum ferritin. It's a storage compound that requires iron. If it is decreased, then it is possible that your fatigue is due to the single most common anemia in the world today, which is iron deficiency.

But there are other things that can mask that lab test result. It turns out, and again, this is fairly well-known, I hope, that ferritin will be increased even in the face of iron deficiency. It will be increased because it is something that is required in chronic inflammation.

So if I have a person who has rheumatoid arthritis... If I have an elderly person who has, shouldn't be, if I have a person who has rheumatoid arthritis, chronic inflammatory disease, and they are bleeding, which is a very common way to get to be iron deficient, they will have a situation in which their ferritin will appear normal, even though they have iron deficiency.

The correct treatment of that then by the provider requires them to know that little tidbit and then be able to address it correctly. And if they don't, then you're missing that particular anemia.

Many of the cholesterol-lowering medications that we have have impacts on liver function, on kidney function, and as it turns out, on the presence or absence of psoriasis. If a physician is not aware of that, and the psoriasis one is not that common, then the fact that this person is sitting there complaining of fatigue and has psoriasis and is also on these medications may not click in to a point that says, holy cow, maybe the fatigue is due to, and the liver function studies and the psoriasis are all tied together with this medication. And if they don't know that, then that psoriasis thingy never gets fixed.

So there are nuances to every single one of the test numbers that we give you. The reason we no longer call the range of numbers typically to the rate of your results on a report form, we don't call them normal values. We call them reference ranges or reference intervals because they're a population. I took a thousand people that were within the ages of X and Y, and I did their tests on them, and that looks like it's an acceptable value if it falls within that range.

But if you modify that testing by giving someone a medication that will interfere with it, then no matter how good I am at doing that test, the answer's wrong. It is a truth at one level, but it's not a truth at another level.

If a patient isn't told to fast for eight hours, and they come in chewing M&Ms, or you tell them don't exercise any more than this level of exercise for four days beforehand, and instead they bike in a 10-mile ride to get to the laboratory collecting station, well, their values are going to be off, and again, no matter how good I've done them, you're giving the wrong information.

So it is important to have these little nuances known to the physician, and we're not always sure that picking it up along the way is a good way of doing it. There is one condition that I'm intimately aware of. There are three clinical symptoms, and there's one laboratory test. The laboratory test is not a good one. Forty percent of the time, the negative is wrong. If you don't know that as a physician, then you're not going to treat that disease, even though the three clinical symptoms are there, and it can kill you.

So this is an important issue. Sorry, I get a little carried away on that one.

Deandre White: It's okay. So as my final question, what is one thing you wish every patient understood about the link between their lab results and their fatigue?

Dr. Susan Leclair: I want you to know, regardless of whether it is in your head or not, I want you to know it's real. And I want you to keep talking about it until you get some satisfaction, I guess. I want you to believe in yourself. Your body is trying to say something to you, whether it is because of depression, which is fairly common these days in the United States, or a disease like malignancy. Most cancers will give you a fatigue.

So let's use those as the goalposts in this. Both of those are real. At both times, you can have fatigue, and they are just as valuable a symptom as the other one is. So I want you to understand that you have a legitimate concern, and I want you to say every single time you walk in until you get an answer. So what are you going to do about this fatigue? How can you address my fatigue?

And if the answer is, I think your fatigue is coming from, fill in the blank, disease, well, then you can walk down that conversation with your provider to find out how to fix it. And if the answer is, I can't find anything that's causing that disease, then maybe they should suggest that you see someone else who understands fatigue. It might be a neurologist. It might be a psychologist. It might be them just talking to you, but to make sure that someone believes you, because you should be believed with fatigue.

Deandre White: Absolutely.

Dr. Susan Leclair: End of sermon.

Deandre White: Thank you so much, Dr. Leclair. This was a very, very insightful and compassionate discussion, very important for everyone to know that fatigue isn't just in your head. It's what your body is telling you, and it's telling you for a reason.

So remember, fatigue is real. That's the closing statement here, and it's not always visible, but it is real, and that's why understanding your lab results matters, because the answers you need might already be in the blood work for you. Thank you for watching, and take care.