- [voiceover] hey guys. this is dr. joe with medimmersion.com. i'm coming at you with another flash flood review series video where i cover the highest yield stuff for your board examsand clinical rotations in as little time as possible. this video is very conciseand right to the point, it's awesome.
if you've listened to alot of these introductions and you're tired of seeing the same thing over and over, go over to medimmersion.com, get an account, and in most cases, you'll skip right over these intros and a lot of the youtube advertisements on my videos and everybody else's videos
that i've linked to, and you'll just jump rightinto the meat of the lecture. today i'm gonna talk about anemia. it's going to be super cool, so let's jump into it. after a quick intro, i'm going to talk about red blood cells, then young red blood cells, also called reticulocytes.
then some calculations that we do to correct for the reticulocyte count, called the reticulocyte index, the reticulocyte production index. and then i'll jump intokind of an overview about diagnosing anemia and the two major approaches: the kinetic approach and the morphologic approach, okay?
let's do it. all right, dudes and dudettes, anemia work up is pretty common in your clinical rotations, whether it's in the hospital or in the, like thefamily medicine clinic. you're gonna need to know it. you're gonna see it several times, and so, it's high yield.
also, if you don't really know the cbc or the complete blood count, go check out that video first, because you need to understand the cbc in order to do an anemia work up. what the heck is anemia? well, strictly defined, it is a decrease in the total number of red blood cells, or a reduction in thetotal red blood cell mass
compared to what's normal by blood volume studies. however, a blood volume study is slow and expensive, so what you're going tosee in practical use, is you're going to get a cbc and you're going to look at the hemoglobin and the hematocrit. there's all kinds ofthings that cause anemia
and often times, when yousee a person with anemia they are sick in a lot of different ways. and so, there's often multiple factors that contribute to their anemia, but that's not how i'mgoing to teach it here. i'm just gonna teach it as if each cause is the only cause. okay, that's just howyou have to learn it. commonly, blood loss
and iron deficiency anemia are at the top of the list. you're gonna see those quite a bit. also b12 and folate deficiencies, or nutritional deficiencies, and then anemia of chronic disease and anemia of kidney disease are also pretty common. next up let's talk about a few things
to set the foundation or the scaffolding that you can build on to understand anemiaand how we work it up. and i'm gonna do that bycovering a couple of basics. if this is too basic for you, you can skip past it, that's no problem. i want to kind of talk just a minute about red blood cells. red blood cells live about 100
to 120 days in your system, okay? that means that you need to replace about 1/100th or 1/120th of your red blood cells every single day. the production of red blood cells is called erythropoiesis and it occurs in the bone marrow from stimulation by a hormonecalled erythropoietin, which is made in the kidneys.
and if you'll remember, i said one of the common causes of anemia is kidney disease and this is why. that the hormone thatstimulates the production of red blood cells is made in the kidneys. so the kidneys aren't happy, they're not making that hormone. also, healthy bone, with all of the required substrates
that it needs to make red blood cells, can make up to five timesmore red blood cells than you need or that you lose from daily losses, okay? that's quite a bit more. you have the ability to produce 500% more than you lose daily, but what would that look like? well, i guess you would see
a lot of immature bloodcells floating around, right? if you started making five times more red blood cells, well there'd be a lot of young juvenile or immature blood cells floating around. that makes sense, right? yeah it does and those are called reticulocytes, or immature red blood cells.
under the microscope, you can tell the differencebetween a reticulocyte or an immature red blood cell, because they are slightly larger than their more matureelder brothers or sisters, and also they have someintracellular structures or fragments of ribosomal rna still visible with inside them. this is called polychromasia.
makes sense so far? okay, what about this? if the reticulocytes took about a day to mature and we knowthat we lose about 1% of our red blood cells per day, what do you think the normal percentage of reticulocytes in your blood would be? you got it. about 1%. we should see about 1% reticulocytes
for a given number ofred blood cells, okay? following that logic, what would you think if i told you that youhad a normal hemoglobin and a normal hematocrit, but you had a very highreticulocyte count? what would that suggest mathematically? well, it would suggest that the lifespan of your red blood cells wassomehow shorter than 100 days.
if you had, i don'tknow, 5% reticulocytes, that would suggest thatyou have to replace 5% of your red blood cells per day. meaning that you're losing 5% of your red blood cells per day to maintain your normalhemoglobin and hematocrit. well, that works. that makes sense and we use that principle when we're working up anemias,
and i'm gonna build off this and i'll show you how it works. okay, let's move on. in the process of building you up, the first thing i need to do is explain that the reticulocyte is a great thing to know. i'm sorry, the reticulocyte count is a great thing to know,
but if you use it all by itself, it has some shortcomings when you're trying to figure out anemia and there's two thatwe need to correct for. the first one here is that in anemia, by the definition, we have a low number ofred blood cells, right? and the reticulocyte count is a percentage of those red blood cells.
that kind of gives us a falsely elevated reticulocyte count. we have to correct for that. the second thing we need to correct for is that when we are anemic our bone marrow is stimulated, at least healthy bone marrow is stimulated and it starts producing more reticulocytes and also starts releasingthem into the circulation
earlier and earlier intheir maturation process. so they come out even more and more juvenile essentially and it takes more time for them floating around in circulation to become healthy mature red blood cells. and to correct for that, we use a simple correction table. let's look at the calculationsfor these two steps
and what they're called in the next slide. first off, here at the topis the reticulocyte index and that corrects for thefalsely elevated percentage of the reticulocyte count just because there isless blood in the system. let's work through an example here. let's say the reticulocyte count is 1.0, which that's normal, right? in the couple of slides ago i told you
1% is normal. however, the hematocrit is 15. 15 is about 1/3 of what it should be, so 15 over 45, which is a normal value for hematocrit times the reticulocyte count of 1%, equals like 1/3 of a percent. that's definitely too low, okay? so does that make sense?
let's change it up. the reticulocyte count is now 3%. whoa, that's way toohigh, it shouldn't be 3%. hold on. hold on a second. what's the hematocrit? well the hematocrit is 15. normal is 45. the reticulocyte index is 1.0. we've corrected for the change
in the amount of blood in the system. awesome, but did we correct completely? the answer is no. we still need to correct for the maturation correction factor, which is from this table here. what do we do? well we say the hematocrit was 15%, so therefore we go overand we use the 2.5.
it takes 2.5 days for those reticulocytes that were released from the bone marrow to fully mature, which is 1 1/2 days longer than they should take to mature. what do we get now? well we get 1.0 divided by 2.5. thus the answer is 0.4.
the reticulocyte production index, or the correctedreticulocyte count is 0.4. what does that mean? what should it be? it should be greater thantwo or preferably three. in this case, even though we started with a reticulocyte count of three, the bone marrow is just notputting out enough blood. so, diagnostically,
where does that steer us? well that kind of steers us towards a bone marrow problem, doesn't it? see where i'm going with this? see where i'm taking it? pretty cool, right? let's do another example, but this time let's show an example where the bone marrow
is doing what it's supposed to do. and we are gonna start witha reticulocyte count of 18. 18 times the patient's hematocrit, which was 15, divided by 45 gives us 18 times 1/3 or six. the reticulocyte index is six. then we put six divided bythe maturation correction, which was 2.5, therefore the reticulocyteproduction index is 2.4.
perfect. the bone marrow is doing what it's supposed to do. our patient is anemic, but we know that the bone marrow at least is working theway it's supposed to. well, diagnosticallywhere does that steer us compared to the previous example? well that means that the problem
is happening in circulation. maybe we're losing blood. maybe we're lysing blood cells. but it points us away from the bone marrow to other diagnoses, right? yeah cool, huh? now that you arepractically a hematologist, let's move on and talk about the art of diagnosing anemia.
and it really is just that. it is an art and ittakes time and practice to get good at diagnosing anemia. in fact it takes time and practice to get good at diagnosing anything. the skillful interpretation of lab values and the work up of diseasesis a lifetime pursuit. don't forget that. it takes practice.
that's why we say thepractice of medicine, instead of the mastery of medicine, okay? diagnosing anemia takesmore than just lab skills, you also need a littlebit of clinical prowess. if you see melena in your patient, your diagnosis should be focused on the gi system and gi losses instead of hereditary spherocytosis or sickle cell disease, okay?
how do we approach the diagnosis? well there's two main thought processes and i think both ofthem have value for you. the first one is the kinetic approach and the second one isthe morphologic approach. all right, the kinetic approach. and listen guys, again this is by no meansgonna be comprehensive. this is very basic
and it's going to allow you to build on it in your clinical rotations. i just want you to understandthe thought process. so, the kinetic approach. this is kind of taking over. the kinetic approach is getting more and more popular and it's being taught in major hospitals all around the country.
it's kind of the waythat medicine is going, and i like it, it's awesome. the diagnosis is made is a process of solving for the mechanism of the anemia. and we do that by looking at the rpi, or the reticulocyte production index. and you'll remember fromwhat i've previously said that if the rpi is low,
then that suggests, and inthe anemic patient rpi is low, that suggests that maybe you've got an underproduction problem. your bone marrow just isn't putting out enough red blood cellsand so you're anemic. and if we go that way we end up in another flow chart that looks a lot likethe morphologic approach. i'm gonna bing, put a pin it right there
and we're gonna comeback to that in a second. let's flip over to the otherside of the flow chart. let's say you have a highreticulocyte production index and your patient is still anemic. well that suggests that your bone marrow is producing enough red blood cells. it's trying to keep up, but you're losing them somewhere else. like you're lysing them oryou're just losing them.
let's say, let's startwith hemolysis first. what would you do ifyou suspected hemolysis? what are some otherlabs that you could do? well you could get aperipheral blood smear, which can show you some schistocytes and that would point you in a direction. you could confirm thatyou're getting hemolysis or hemolysis by getting a bilirubin, which is going to be abreakdown product of heme.
a lactate dehydrogenase, which is an enzyme that spilled from a lot of different cells, but when you're lysinga lot of red blood cells that's gonna be elevated. and a haptoglobin. now haptoglobin isactually going to be low. haptoglobin is a protein that floats around in your blood stream.
it captures or binds tofree floating hemoglobin as a protective measure. and it's protectivemeasure because hemoglobin, free hemoglobin, can be dangerous. it can cause oxidativestress to other cells and also if we're not careful we could have renal losses of iron and other organisms would take advantage of iron in the system
and they would be ableto grow much easier. the direct coombs test, you could do that looking for an autoimmune disease, okay? and other things as well, but this is a good framework. what about blood loss? well, blood loss is going to be more of a clinical diagnosis.
you see a patient with melena. you're gonna go straight for gi causes. you see a patient with massive hematuria. you're gonna go for gu causes. what else? there's all kinds of things. you could have a rigidabdomen after a surgery. you could have a lot ofthings that would suggest that this patient is just plain bleeding
and they're losing bloodthat way, all right? let's switch around and go back over and look at the morphologic approach. the morphologic approach is a little bit more old school, however, still very useful. number one because it is part of the flow for the kinetic approach. you're gonna need to godown this route anyway,
if you have a lowreticulocyte production index. also, this is maybe alittle bit easier to do in a small clinic where you might not have a machine to count reticulocytes, but you can get a cbc and a mean corpuscular volume or an mcv. so there is still value here.
the diagnosis in the morphologic approach is made by observation of cell changes, versus the kinetic approach again, which was looking at the mechanism. the cell changes could be from a variety of different mechanisms, but the same cellularchanges would bee seen. let's start with macrocytosis. if we see large mcv,
or greater than 100 femtoliters, then we think what are the many things that could make my redblood cells too large or give me a macrocytosis? common things being common, you might think about folate deficiency, b12 deficiency, liver disease, alcoholism, or anything else thatcauses a reticulocytosis, because as i talked about before,
reticulocytes are just bigger than mature red blood cells. the machine will count them as being red blood cells, but it will just say that they're bigger, which will increase the mean and thus, give you an elevated mcv. the labs that you wouldfollow to diagnose those should be pretty straight forward, right?
folate, b12, we can check those. we can also send the blood off or do it ourselves andcount the reticulocytes. we could get a liver panel, we could find out the patient's history. are they abusing alcohol? and we could even ask them what kind of drugs they're on, because some of the drugsmight do that as well.
shifting over to the normocytic. let's say that we've got an anemic patient and the mcv is in the normal range. well shucks, that could be a wholelot of different things. we probably have some kind of blood loss or hemolysis going on in the system. we're gonna do a lot of the same labs that i talked about already.
you're gonna want ldh a bilirubin and a haptoglobin. you should ask for those right away. you should also get arenal function panel, because if you're notproducing enough erythropoietin you aren't gonna havestimulated bone marrow to make red blood cells. and again, you're probablygonna want to know the reticulocyte count.
what about microcytosis now? well the first thing thatyou're going to want to do, if you see small red blood cells or red blood cells that aresmaller than 80 femtoliters, you're gonna want to jump on your iron studies right away. reason number one for doing that is that iron deficiency anemia is a major cause of anemia in general,
so you might as well start there anyway. and number two, it's gonna narrow downthe field a little bit. let's say your ironstudies look like this. you've got a low iron, you've got a high totaliron binding capacity, or transparent iron binding capacity, and a low ferritin. well that just means youdon't have enough iron.
your serum iron is very low. the iron binding capacity is very high. and the ferritin, which is kind of like yourreserve iron, is also low. you just don't have any iron. this is iron deficiency anemia. here's some iron supplementsand a multivitamin. have a nice day. what if you got normal iron studies,
but your patient is still anemic and the cells are microcytic? well then you're probablygonna want to do reticulocytes and maybe a hemoglobin electrophoresis, looking for thalassemias. what about low serum iron, low tibc, meaning there's not a lot of room for extra iron in the blood, and a high ferritin,
meaning that there's a lot of iron left in the reserve system? well you could be looking at a case of anemia of chronic disease, which can be from awhole host of problems. maybe your kidneys aren't happy or your bone marrow isbeing interfered with in the production of red blood cells by a lot of cytokines orinflammation, things like that.
lastly, let's say you'vegot a high serum iron, normal tibc, a high iron reserve, or a high ferritin. maybe you should do a smear in this case and look at the red blood cells and see if you see anybasophilic stippling or ring sideroblasts. you could also think aboutdoing another liver study. this could be sideroblastic anemia
or liver disease, or even heavy metal poisoning, okay? again, guys you've gotten through this. i hope you have a better understanding of how to digest the information coming at you about an anemic patient. and maybe this givesyou a better framework or foundational understanding, so that you can really go in there
and knock it out of the park, all right? dudes and dudettes of youtube, thanks for watching this video. i love making these things for you and i hope that you're a little bit more comfortable on anemia now. show your support for medimmersion. if you like this video, leave me a comment,
subscribe to the channel, give me a like. in the upper right hand corner you can make a donation, if you'd like. any little bit helps. let's keep the lights turned on, so that would be awesome. and as always, hey good luck in school. you can do this.
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