Case Study - Patient Diagnosis

Felician University | hematology So with hematology, and we talk about alterations of the hematological function, we will focus on all the components, the cellular components. We're going to start with red blood cells, erythrocytes. Then we're going to talk about white blood cells, leukocytes, and then platelets and their problems, thrombocytes. And a quick refresher about red blood cells, we're going to start with that. Of course you all know, the hemoglobin is 12 to 14, in females 13 to 15, in males erythrocytes are filled up with a hemoglobin. Hemoglobin is a very good carrier of oxygen. And oxygen is important for the energy production found in the mitochondria and our ATP.

So any malfunction of red blood cells leads to less ATP, less energy, and many other things. And of course, the most important thing to start with would be anemia. When we talk about anemia, anemia I would like to define it as a reduction in the oxygen carrying capacity of the blood. This reduction could be for many reasons, either I have less red blood cells, or I have malfunctioning red blood cells, or maybe I have red blood cells that have been attacked by the body, hemolytic anemias. Or maybe the hemoglobin is the problem.

So the physical appearance of the red blood cell is different. And we're going to talk about all these different things. But let me define two important words, an isocytosis-- and that's when the erythrocytes come with different sizes. So when you're looking at a blood smear, you see different red blood cells with different sizes-- and another definition called poikilocytosis, in which they are with different shapes.

So when we classify these anemia types, we're going to talk about mainly the size of the red blood cell and be content of hemoglobin. So by looking at the table on page 514, you can see macrocytic anemia, where the red blood cell is large. Macro means large. Microcytic anemia, where the cells are small, and normocytic anemias. So we're going to comment on the size.

The second thing we're going to comment on is the amount of hemoglobin. So by looking at the table again, we see macrocytic normochromic, meaning you have the same amount, good amount of color in it. And then you see microcytic hypochromic, which is less hemoglobin, and normocytic normochromic, where everything is normal, but the problem here is the number of red blood cells.

When we talk about anemia, we need to understand that anemia is a disease that affects many things in the body. You have less oxygen in the blood. That's called hypoglycemia. As I said, anemia means reduction in the carrying capacity of oxygen. And when anemia starts, we see several manifestations. You've all seen patients with anemia. Maybe you have anemia. You all know that first of all, there's pallor, person is pale.

Another thing is a person is tired. Fatigue is a very important part. They just tell you, I'm just tired. I get up, and I want to sit down again. I do a little bit of effort, and I can't continue. I go up and down the stairs, and I start hearing my heart doing what? Pounding. And that's because the body needs to compensate, so it just throws in more fluid to help out. But actually, it is causing the heart to be more strenuous.

A person is dyspneic, too. They're breathing faster. They want to collect more oxygen into their body. And sometimes when anemia is very severe, we see other problems. We see colic. We see sometimes gait disturbances, and we also see nausea and vomiting.

So let's start our first type, which is macrocytic normochromic anemia. Macrocytic means large. Again, a normochromic means you have the same amount, the same amount of the color itself or hemoglobin.

Come to think about it, so what's the problem? If I have a larger red blood cell with a good amount of hemoglobin, why not? Well, the idea is this. It is not going to be viable for a long time. Who knows how long a red blood cell would live?

300?

120 days. After these 120 days, what happens?

It dies.

It is broken down and recycled in the spleen. And that's why we're going to see a lot of blood diseases that we're going to talk about today, they might have an enlarged spleen, splenomegaly. And even hepatomegaly, the liver enlarges to help out the spleen also.

So we're going to see that these will not continue to 120 days. But why are they big? When a person has anemia and we start looking for many things, sometimes we need to do a bone marrow biopsy just to look at the red blood cells. What's going on? The red blood cells increase in size for a certain reason. To make hemoglobin you need protein. You need heme, which is iron. And you need coenzymes to form the DNA and RNA.

The most important coenzymes that we know of are vitamin B12 and folic acid. If you don't have enough of these two, either/or, then you won't be able to make that size of the DNA. It's going to be super small, but it compensates with more RNA, and that's what makes the cell larger. So it's large, but the amount of hemoglobin is good. But these cells aren't going to live for 120 days.

So the idea is this-- I might have only deficiency in vitamin B12, or only a deficiency in folic acid. Either/or will cause this type of anemia. So when we look at this, the vitamin B12 problem will be called pernicious anemia.

So vitamin B12 is found in a lot of things that we eat-- green vegetables. Everything that's dark and green has vitamin B12, and many other products too. When we take this vitamin B12 in the food in the stomach, right away an intrinsic factor is produced by the mucosal lining of the stomach. If I don't have that intrinsic factor, there's no way that I'm going to absorb that vitamin B12. It's just going to pass through.

So if I try to think about it, what would make my mucosa unable to produce it? Many things. For example, you can have chronic gastritis. And we're going to talk about chronic gastritis later on. In the GI system, we're going to see that one of the things is this-- anemia.

Also, people go through surgeries, all types of surgeries now. Right? You hear about the sleeve, the bypass, this and that. So then we don't have that intrinsic factor anymore. And so, you either, you're not taking that vitamin B12, or you're not absorbing the vitamin B12. Either/or, hemoglobin drops down, low levels, down to 7 and 8, very low levels.

This person has all the different things that we talked about before-- the fatigue, the weakness, the difficulty walking, abdominal pain, weight loss, sore throat. They are well known to have red beefy tongue, like large, enlarged tongue. However, vitamin B12 deficiency, on top of all these different anemic signs and symptoms that we know of, on top of all that, they also have neurological symptoms. So the tingling and the numbness and parasthesia. We will only see that in patients who have vitamin B12 deficiency.

You won't see these neurological manifestations when we talk about folic acid. So how can we treat this patient? Easy. What can we do?

Vitamin B12.

Vitamin B12, but we give it parenteral injection. OK? And it's lifelong. The other type is your folate deficiency. In folate deficiency the same thing happens, but I don't need an intrinsic factor here. This is not my problem. Intrinsic factor is not my problem, but it is the absorption from the GI system.

And in the absorption of the GI system, what I have is actually, I do have problems either taking in enough folic acid or absorbing it. And that's easy to follow up with. Just give the tablets.

The idea behind anemia is to find out the cause, because most of us, when we hear about anemia we say, oh, you just need iron supplements. That's what you need. Well, that's one type. There are many types of anemia. You need to know what's causing this. Why is this person-- why is their hemoglobin down to the seven and the eight and the nine?

Our next type is the microcytic. In microcytic anemia, from its name, micro means small. I don't know if you've seen blood smears before, but they're very easy to form if you worked with blood before. Just a drop on the slide, and then you get another slide, and then smooth it through and look at the red blood cells. If you're interested in that, go to page 516 and you will see different blood smears. Let your eye go through these and know them for your own benefit later on. You can see sickle cell anemia, the macro, the micro, and all the different things.

So I'm going to point out the macrocytic, and that would be D. See how large they are? And also, the microcytic, which is B. And see how small they are compared with A, which is your normal red blood cells.

So when we go to microcytic, the first thing that hits our mind, we are not making enough red blood cell hemoglobin. That's because I don't have enough iron. And it's the most common cause. Iron Deficiency Anemia, or IDA, is the most common cause of having this. It could be iron or protein, because that's what hemoglobin is formed of. But the most common thing is IDA or Iron Deficiency Anemia. And we see that in a lot of countries around the world, especially with younger kids, and we see it's probably not enough dietary intake or maybe chronic blood loss. Maybe this person has a chronic method of losing blood, maybe heavy menstruation, maybe epistaxis, maybe rectal bleeding, anything in which there is chronic blood loss.

So it's a constant demand that we need iron. So although we are recycling some of the iron that we have in hemoglobin in the spleen, we still need iron because we lose some of it. It goes through stages. If you're interested you can read that, but we're not going to go into detail about it. I just want to pin point several things about a person with iron deficiency anemia. You're going to see pictures on page 518.

You can see pallor, and pallor is always seen in the hands and in the eyes. That's how pale a person could be. But if you look at the fingernails, we see something called koilonychia, in which is called spoon shaped. They're concave, and I've seen that before. You can actually see a concavity in the nails themselves, and that means that it is a severe case.

Also you can see inflammation in the tongue. It's called glossitis. The tongue is inflamed. And a person doesn't know it, but they're inclined to eat and crush a lot of ice. It soothes them. Ask a person who has anemia, they say yes, they love ice. Just crushing on the ice makes them feel better.

So we have to see the amount of iron in the blood, and focus on the amount there. Because if the amount of is high, we're going to talk about another disease right now in which there is a lot of iron, but not enough of hemoglobin. We're going to see why. So the first thing is to treat a person by replacement therapy of iron. And right away you're going to see how they are better-- fatigue and lethargy and all that, and they're going to feel much better right away.

Our next thing is to talk about sideroblastic anemia. Sideroblastic anemia is an inherited disorder in which we have anemia, although you have enough iron. But the iron is not incorporated in the hemoglobin. It's a very strange thing. So you do have iron, and the iron is in the red blood cell when it's forming in the bone marrow, but it is found around the nucleus forming a ring. We call them ring cells. They are the immature cells that are found in the bone marrow. They're called sideroblasts.

There is no uptake of iron. Iron is there, and the amount of iron is high in the body. But guess what? The body is not using it.

So there is the inherited type. There is the acquired type that we see. And we also see that there is one type called a reversible sideroblastic anemia seen most commonly in people who drink a lot of alcohol. But it's reversible in the sense that it can be reversed if a person stops drinking alcohol.

So the hereditary part is very important, and most probably you see that in males. And the anemia is found starting in infancy and childhood. We worry a lot about this because you are going to have extra iron, and this extra iron will be deposited somewhere. So in the kidney, in the heart, in the liver-- we call it hemochromatosis. That means an increase in iron, and eventually it will affect the organs function at the end.

So sometimes we think it's just that they're not making enough red blood cells. We call it hypoplastic. But then you understand how this is.

One of the things that we do for these patients is phlebotomy. So regular phlebotomy-- just to release the amount of iron that's found. Just remove the iron, because we don't want to deposit. And then there's a medication called pyridoxine. Sometimes that helps too. And what it does is helps for some time to lower the level of iron in the body with pyridoxine therapy.

So there are some advances and we try to, as much as possible, maybe give erythropoietin to help the making of the red blood cell. But we can't help it sometimes. It is a chronic disease that is found there.

So, when a person have this type of disease, do they end up producing more red blood cells?

No, not as a number, but the red blood cells themselves are defective. They are small. They are microcytic, and they are defective. They have less hemoglobin in them. So it's considered a type under microcytic hypochromic anemia. And the cause is there's not enough iron, although the level of iron is high. And that's why testing the amount of iron is very important.

So our next thing is, what if it's normocytic normochromic? Meaning that I have a good size and a good amount of hemoglobin, what is my problem now? It's probably the number. And there's a table on page 520 that lists all the normocytic normochromic anemias out there. So either I'm not making enough cells, or I'm making enough cells and they're being broken down or hemolyzed on the way, or I'm making enough cells, but the cells are being lost. And that could be through acute loss, for example, a person going through a surgery, an accident, or chronic loss by time.

So let's talk about this a bit. One of the most important causes would be that I'm not making enough red blood cells. And that's called aplastic anemia. So this is a problem with the stem cells. It is a rare disease, most commonly autoimmune disease, and we see that the stem cell population is altered in a certain way in which you're not making enough red blood cells. And it's usually part of a pancytopenia. So it's not only the red blood cells. It's your red blood cells, your white blood cells, and also the platelets. And a lot of times, the only way out is to do stem cell therapy for this.

Post hemorrhagic, we just talked about losing blood through hemorrhage, acute or chronic. And then hemolytic-- there are several hemolytic diseases. We're not going to go into their names, but a lot of them are autoimmune diseases, in which the body fights the red blood cells. One of these that we're going to discuss later on is Systemic Lupus Erythematosus, or SLV. It's a disease. It's an autoimmune disease--

Lupus?

Lupus, yes. That's a disease in which your body fights DNA, red blood cells, and others, and they have anemia. A lot of autoimmune diseases have anemia in them. Multiple sclerosis is one of them too.

Your own body attacks the--

Attack the cells.

Red cells?

Yes. Autoimmune disease. So when a person has anemia, so I draw blood, and I find it's a seven or eight or a nine, and I look for the iron. They have enough. I look for the vitamin B12. They are great. Folic acid, perfect. They don't have an autoimmune disease.

I'm left with one thing-- chronic inflammation. With chronic inflammation, we talked about inflammation last week when we actually talked about cancer. And we said, any chronic inflammation can alter what the cell looks like. Today, we're going to say that chronic inflammation can actually cause anemia. The production of red blood cells is lowered, and how do we know that this person has chronic inflammation? We do testing for certain inflammatory markers like c-reactive protein or ESR to find out what the person has. A person might have low-grade fever, any other problem, and we have to look for underlying causes of this.

So here we talked about all the different things that might cause anemia. What is the opposite of anemia? Something called polycythemia. And that's when I have a lot. That's when we have too many red blood cells. Your normal is five million per cc. So here in polycythemia, we find out that it might be relative. Relative means that I'm not really making a lot of red blood cells. It's just that what's going on is I actually have less plasma, because of dehydration. That's called relative. I'm not talking about that.

I'm talking about a real polycythemia, absolute polycythemia. Something that starts on its own-- abnormality in the stem cells. OK? And all of a sudden, this is your body producing a lot of it.

Or the last reason could be secondary polycythemia, meaning the problem is not in my blood-- in my bone marrow I mean. The problem actually comes from production of too much erythropoietin. maybe I live in a place that has a high altitude, and I'm producing a lot of erythropoietin because of the oxygen deficiency. Or maybe I have a tumor in my body that's making a lot of erythropoietin. That's called secondary. And you're going to hear me saying secondary a lot during this course. That means it comes from something else going on in the body.

But when I say primary, that means it started on its own. So I'm going to talk about the primary polycythemia now. It happens on its own. It has to do with a mutation in a certain gene called the JAK2 gene. And with this, it is a rare thing that happens, but we start seeing a lot of red blood cells. Usually it happens all of a sudden. Just imagine yourself with a lot of red blood cells in your body.

So with a lot of red blood cells, it becomes hypercoagulable. When it's hypercoagulable, that means I am prone to having a stroke, a heart attack. And that's where people are suddenly taken to the ER because of something sudden like this. The blood is very sticky, and it has a lot of red blood cells in it. And sometimes it can actually cause some mental changes, chorea-- chorea means sudden jerky movements-- and even visual disturbances also.

One of the symptoms that a person with PV would have, also very uniquely there, is when they shower, when they're exposed to water, they itch a lot. OK? So it's intensified by it, and they call it aquagenic pruritis when they start itching a lot. That's because of the amount of red blood cells that are in there.

Again, we can easily draw blood and find out the number and the hemoglobin in there, the number of red blood cells. Very easy to diagnose. And we consider it as something going on in the body, which we don't need. So we want to quiet it down. And one of the medications, called hydroxyurea, it's a myelosuppressive, meaning its job is to suppress my bone marrow, quiet it down, so that it doesn't do, or doesn't increase that function that much. And we see--

Like a chemo, right?

Like a chemotherapy, but it's targeting the bone marrow. And we see that with treatment, some can live for longer, like 10 to 15 years. But sometimes, if they're not properly treated, it's down to like 18 months, which is a very, very short time. We also see a potential of this PV turning into acute myeloid leukemia. We see that goes hand-in-hand with an increase in the white blood cells also. So it has to be treated right away.

Of course phlebotomy is the thing. Also, you want to rid the body from the amount that's going on, because we don't want it clogging in your blood vessels. It's a very interesting disease.

So we talked about how we can have an overload of iron. And if it's on its own, we call it hemochromatosis. But we found that it's really not only about having sideroblastic anemia. Some people have a genetic disease in which we call it hereditary hemochromatosis. They just have a lot of iron in their body.

So when you have this poly--

Cythemia?

--cythemia. Is this a possible contributing factor, because at time you see that some people have to go to-- they lose a lot of blood. And when they laugh, laughing really hard, they pass out?

No, no. No, that's not it. I haven't heard or read something that points to them together. No.

OK, because I have encountered several people like that. At one time I went to [INAUDIBLE].

OK. No. So in hereditary hemochromatosis, is it is an autosomal recessive disease in which a person accumulates a lot of iron in their body, and that affects the liver by cirrhosis. It also affects the heart, causes cardiomyopathy, and also in the skin, causing hyperpgimentation. And we see that happening later on in age, around 40 to 60. And we do the same thing, of course, phlebotomy of at least 500 mils as much as frequent as we can.

Maybe sometimes, phlebotomy can be weekly, and that's the amount that we have there. And alcohol should be used in moderation for these people. And also, we tell them to take iron vitamin C supplements, because they're losing a lot of their iron there. It's an important disease that sometimes we do not consider, but it is something that's important, because it can alter also, not only the liver and cause failure, but even the pancreas. And then you start seeing diabetes. And then you start seeing enzymatic problems or digestion problems, and you wouldn't know that it really comes from an increase in the iron amount in the body.

So let's see the answer for this question. Which of the following is characteristic of the megaloblastic anemia? Mega means large, so small size, decreased thickness, presence of macrocytes caused by increased folate. C, macrocytes. Megaloblastic, mega always means large, and blast means immature types of cells.

OK, our next thing is to go over leukocytic function, white blood cells. So we're done with red blood cells, and we're going into white blood cells. And just to give you an idea about white blood cells, just a refresher, there were five types of white blood cells-- neutrophils, eosinophils, basophils, NEB. These three have to have granules in their cytoplasm. We call them granulocytes. Then you have lymphocytes and monocytes.

What is the highest number of white blood cells? Which one has the highest numbers out of these five?

Neutrophils?

Neutrophils. And then it's lymphocytes. So neutrophils make up 60% to 65%. Lymphocytes make up 20% to 25%. And then the rest are like 1% to 3% each. Their jobs-- neutrophils have to do with acute infection. They are the first cells that leave the bloodstream and go towards the what? To the tissue, to the infection-- eosinophils have to do with--

Parasite?

--allergies and parasites. Very good. Basophils have to do with histamine. They're like mast cells. They have to do with inflammation. Very good.

Monocytes have to do with chronic inflammation. Their like neutrophils. They are macrophages that leave the bloodstream, but they're kind of slower. They're larger and slower. So you see them in chronic inflammation.

So if I'm looking at a section of a chronic inflammation, I will see monocytes there. Neutrophils are a done deal. They die early.

The last one is lymphocytes. What do lymphocytes do? They have to do with my immune system. OK. And they have to do with antibodies. And they also have to do with fighting viruses, cancer cells, and infections. That was a quick review.

So I have a quantitative problem, maybe the numbers are different, or qualitative, maybe I do have the numbers, but they're not doing their function. So all five of them are the defensive mechanisms to my body. When I have a lot of white blood cells, we call this leukocytosis. And that can happen. My numbers can go up a bit if I'm fighting a certain infection-- if it's allergy season, if I have a viral problem.

Leukopenia, on the other hand side is when the numbers go down. And that's not normal. I shouldn't have my numbers going down. What is the normal number of your TLC, Total Leukocytic Count?

5 to 10.

5 to 10. 5 to 10 is your norm. OK? So going up to 12, 13, that means it is a bit high. But that's not leukemias. Leukemias are up to 100,000, and 110,000. We're going to talk about that.

So we're going to talk about each and every cell out of the five and see when they go up and when they go down. And there is an amazing table that puts them all together. You can study from that table right away, page 524. It just tells you when you have more or less of each type of cell. You don't have to memorize the examples. It just gives you an idea.

So when you are at the bedside with some blood tests coming back for your patient and you see that their monocytes are up or their lymphocytes are down, you would understand why this is happening very easily. So first of all, neutrophils. When the amount of neutrophils goes up, we call it neutrophilia. What could cause neutrophilia, guys?

Infection.

Infection, an acute infection happening now. And we say it is a shift to the left. If you heard that before, shift to the left, meaning that this bone marrow is working very hard to produce these white blood cells. And because there is a very high demand, it starts to send out immature cells. That's called a shift to the left. So if I see a lot of immature cells, that means that factory is working what? Day and night very hard.

At the end of the infection, it goes back shift to the right. That means what's produced in there is your normal, not the immature type right there. When neutrophils attack bacteria, they die, and the bacteria die. And what I find at the end is pus. So pus is just dead bacteria and neutrophils.

So here's the shift to the left and the right. When neutropenia happens, when a lower number of neutrophils occurs, neutropenia, that's because there has been such a long time with this infection. There is exhaustion of neutrophils. There is reduced survival, or maybe it's part of a bigger disease in the bone marrow. What did we just say a while ago when your bone marrow is just not making cells? What did we call that? Aplastic anemia. Very good.

OK, so eosinophilia, what does it mean when my eosinophils are up? What did we just say a while ago? Either parasite or allergies. Very good. Eosinopenia, you'd be surprised to see the causes. Eosinopenia, I always remember it by anything that's really sudden and stressful. So that could be shock, surgery, trauma, burns, mental distress. That just eats up your eosinophils. And I think personally, that this has to do with cortisol. Remember, stress and cortisol and how it's an anti-inflammatory. It just like wipe downs things in your body as much as possible.

Basophils, we said those have to do with inflammation. They're related to your mast cells. They produce histamine. So I'm going to have basophilia when there is a need, an inflammation. And I will have basopenia, less, when a person is on steroid therapy for a long time. A lot of cortisol there, hypothyroidism for a long time. So all of these are just quieting down my basophils.

Monocytes, we said they're large, right? And monocytes are the macrophages. They leave the bloodstream, but we said they are connected to chronic infection. So we're going to see a lot of them in later stages of infection. And we don't know a lot about monocytopenia.

Lymphocytes, when would I have a lot of lymphocytes or lymphocytosis? We just said this a while ago-- viral infection.

[INAUDIBLE]

And we see an increase in the number. Lymphocytopenia is when the viral infection has exhausted the lymphocytes, or there is radiation or an immune deficiency. Any of these causes can lead me to that, and that's a big problem. Of course, lymphocytosis, because lymphocytes produce the antibodies, and they are the natural killers that I need in my body.

So let's look at this question. Which of the following terms best describes a higher than normal white blood cell count?

[INAUDIBLE]

It would be?

C.

C, leukocytosis. Is it normal to have some leukocytosis? Yes. Is it normal to have leukopenia? We said, no. So that was just like an introduction to white blood cells and what they are, just a reminder. But now we're going to go over diseases of the white blood cells.

And you will see that most of the diseases that are chosen by this book that we're going to talk about today, most of them actually focus on lymphocytes. Lymphocytes are very, very important. We have two types of lymphocytes-- B and T. The B are mature, or become mature in the bone marrow, hence B. T become mature in the thymus, hence T.

And we are going to focus on diseases. I don't know if it's by chance or what, that most of the diseases that are found in the book focus on B lymphocytes, or B cells. So our first disease is infectious mononucleosis, well known as mono.

So what happens in mono is the viruses-- and I say viruses because it's not only one virus type that affects it-- the virus attacks your B lymphocytes. And we see here the most common, 85% is Epstein-Barr, but there are other viruses. Your flu virus can attack it, your hepatitis, your HIV. And what it does, it attacks B cells specifically. This patient will show the normal signs and symptoms of a person who has maybe the flu with some sort throat, tired, sleepy, maybe a bit feverish, and swollen lymph nodes. Until now, it looked like a normal case.

But then after a week, which normally a person should feel better, after that week that person still feels very tired, very sleepy. Now, they're going to the doctor. And a simple test-- there is a test that's done-- you look for the antibodies of Epstein-Barr virus. It's called the Monospot test. And just by testing this person you find out that they have infectious mononucleosis.

How did they get the disease? They call it the kissing disease, but it really has to do with saliva. So drinking off someone else's glass, water, straw, using someone's tissue, makeup in a mall, lipstick, whatever, all that kind of stuff. Oh, yeah, people put that all the time. So any of this saliva, a person can get infectious mononucleosis.

Now, so what's going on with these B cells? These B cells are attacked by the virus, and now they become abnormal cells. So they're picked up by the spleen. You have to know that the spleen monitors whatever is in your blood. So if it sees a lot of malfunctioning cells, the spleen picks them up and recycles them, breaks them down and recycles them. So here, the spleen is doing extra work. So as soon as the spleen does extra work, it enlarges-- splenomegaly, and sometimes even hepatomegaly. The spleen enlarged is one of the important signs of infectious mononucleosis.

And we worry about the spleen that it might rupture in 5% of cases, so they always would say you need to rest. You need to rest, and then there's no antibiotic. We can't give you anything. What your body is going to do is just fight this infection. You'll be fine. But however, we are going to give some symptomatic treatment, and that's all for this disease.

Next is leukemias. And I'm sure you guys have seen people with leukemia, maybe a patient with leukemia, family member with leukemia, because it's very, very widespread now. We see a lot of leukemias. But I'm sure you heard names, different names, like acute versus chronic. You've heard myelogenous versus lymphatic. So what are the names, and how are we going to characterize them?

There's a chart in 527. Let's take a look at the chart. Up there, you see hematopoietic stem cells. So here is the stem cell for white blood cells, mainly white blood cells. And also erythrocytes and platelets. From there, we see branching. There is a lymphoid branch, and there is a myeloid branch. The lymphoid branch is the one that gives us the lymphocytes, only T cells and B cells. If there is cancer in this stem cell, this person will have either ALL if it's acute, or CLL if it is chronic. It is in that line only.

Take a look at the other line. The other line is myeloid. From myeloid you get another stem cell specifically for red blood cells, and another specifically for platelets. But let's focus on the basophilic, eosinophilic, monocytic, myelomonocytic, which can give me either monocytes or also neutrophils. So all of these together, if I have an increase in basophils, eosinophils, neutrophils, or monocytes, we call this either AML if it's acute, or CML if it is chronic.

So last summer, a friend of mine around this time, Mae, was diagnosed with leukemia. And then after a while they said, OK, you have been diagnosed with AML. What would that mean?

Acute?

Acute and it's myeloid. Is it with the lymphocytes or the other cells?

Other cells.

The other cells. So after a while we wanted to know, so what type of cell. And then we knew later on that it was her monocytes, I think. OK? So there are four different names here. I can either have acute lymphocytic leukemia or I can have chronic lymphocytic leukemia. I can have acute myelogenous leukemia or chronic myelogenous leukemia.

So what is the difference between acute leukemias and the difference between chronic? For both of them, the numbers are very high. But in acute leukemias, most of what I'm seeing in the bone marrow and blood is immature cells. In the chronic, I still have a lot, but what I'm seeing is mature.

So there's immature in the acute. There is mature in the chronic. So what if I have a lot of mature cells? That's good. I'm going to have more protection against disease. They are a lot. They are mature. But they're malfunctioning. So although a person has all these numbers of white blood cells cramming their bone marrow and their blood, it's still not enough for them.

Let's talk about acute first. When a person is diagnosed with acute leukemia, the first thing that you see, because it's acute so a couple of days or a week at most, you see the full blown sign and symptoms. I won't imagine this person-- usually a child, because acute leukemias happen in children-- so this is a child that all of a sudden has a fever, infection, sore throat, very tired, their bones hurt a lot, maybe an enlarged spleen, an enlarged liver, and there's bruising all over their body. Because when these white blood cells are cramming the bone marrow, all three types of cells are affected.

Red blood cells causing anemia and fatigue, white blood cells causing infection, and then also you have the platelets causing that bruising in the body because of the number of megakaryocytes. Bone hurts because these bones are stimulated. The bone marrow stimulated to produce a lot of these cells. So overall, the bone hurts also. So this is acute leukemia.

Take a look here, guys. So fatigue, bleeding, fever, weight loss, bone pain, enlargement of the liver and the spleen, and infections. But an acute leukemia you see all that developing together in a week's time. And of course, this is very difficult for a lot of people to see their child having this that quick.

So we see that acute leukemias, AML and ALL, are very fast growing, and we see that, thank god, now we can actually treat it. Chemotherapy children are very, very well responding to this, and we see a lot of times that we go into very good remissions. ALL is the most common in children, and ALL is usually in the B cells more than the T cells. We see that happening there with leukocytosis.

And AML, on the contrary, we see in older people, the meat age being 67. And ALL and AML are very similar in clinical manifestations, as we said. And neurological manifestations might occur with all that we just mentioned a while ago.

So these leukemias have to be diagnosed right away, chemotherapy started. Very promising now is stem cell. We find out that when children, as we said, it has very good and promising results. And adults, even with AML have a good survival rate, which is not bad at all. But we see in children, it is 54% to 91%, which is very, very good.

Chronic leukemia, on the other hand side, happens later in life and takes a slower procedure. We don't see it full blown that quickly at all. We see CLL and we see CML. CLL is slow growing, and it's in your white blood cells, specifically in the lymphocytes. And chronic leukemia is mostly in adults.

CML, we see usually genetic distinction there. Going back to the friend of mine that had leukemia last year-- and thank god she is doing great this year-- as soon as they found out that she had it, she had genetic testing done. As I said last week, genetic testing now is very important because you want to know what type of gene is affected. And once you give the chemotherapy, you go back to genetic testing again to see, did it really solve the problem or not. But if the mutation is there, then again, this will happen and the cycle will happen again.

They're showing you this, figure 21-9, with the pathogenesis of chronic myeloid leukemia. You can see what's going on in the chromosome and the translocation that happened producing the wrong type of protein there. CLL we see usually more and B lymphocytes than T lymphocytes. Again, it has some genetic background that we're not going to go into details about. But just to know, chronic leukemia, like acute, takes months and years, two to five years, during which these symptoms at the beginning are not that apparent. And then you start seeing some liver enlargement, spleen enlargement, a person starts to have some infections, weight loss, low-grade fever here and there, and it might proceed to acute features, but usually it stays like that.

Diagnosis has to be done, of course, with genetic testing. And we start with chemotherapy, and later on a stem cell therapy, if it's something that we can do also. So that was leukemias as our second disease. And we went over all the types, acute and chronic.

Now, we're going to go to a disease that has to do with lymphocytes, but it's where they live. You see, lymphocytes are produced in your bone marrow. Then they're taken to your bloodstream. And in your bloodstream, they're taken to live in lymph nodes. Lymph nodes are important. Just like I said, the spleen monitors whatever goes on in your bloodstream. Your lymph nodes will monitor whatever goes on in your lymph. So if they are cancer cells, viruses, cells that are atypical, they would stay in the lymph node, and they will be fought by the lymph node. And that's why lymph nodes will enlarge in cases of infection and cancer also.

So their enlargement is called lymphadenopathy. That could be generalized where a person has all their lymph nodes enlarged. And believe it or not, that could be benign or malignant. Or I can have localized lymphadenopathy, so an area that drains my head or the armpit auxiliary. So there's an infection going on, and that's why lymph nodes are enlarged here.

We are going to choose, in malignant lymphoma, Hodgkin's lymphoma. Let's go to Hodgkin's lymphoma. And because the lymphomas are classified into Hodgkin, and all the rest are called non-Hodgkin's lymphomas. In Hodgkin's lymphoma there is enlargement of the cervical lymph nodes. But that's not the rule. Not everyone with Hodgkin's lymphoma will present with cervical.

You can see that lady in page 533, and also see her here in the slides, in slide 48, but specifically when I look under the microscope, as you see in slide 47-- now, usually the lymphocytes have a very large, dark nucleus that fills up the cytoplasm with a very thin layer of cytoplasm. So all the lymphocytes that are found circulating, that inner part, are normal lymphocytes. But when I look in the center of the slides, I see larger cells that have foamy cytoplasm. And you also see a smaller, fainter nucleus. These cells are called the Reed-Sternberg cells. And this is one of the signs that this is Hodgkin.

Is it for sure Hodgkin? No. Sometimes you can find these cells and Hodgkin isn't there. So what else are we looking for in Hodgkin disease? There is a triad that goes together in several diseases, and this is weight loss, night sweats, and fever. We see this repeated in Hodgkin. We see it in other diseases too. But well known in Hodgkin, these three things together. And some textbook, like your textbook here, would add parotits also.

We could also see an enlargement in these lymph nodes in the lung and mediastinal. Again, I have someone that I know, age 18, 19, and we see Hodgkin a lot in that age, a lot, in adolescence, high school, and early college age. We see that a lot there. It was found in the mediastinal. And it started off by the feeling that there is difficulty swallowing. That was the first thing that we found there.

Again, the spleen is enlarged. And there are other types of lymph nodes that might show it. Here is a picture on page 49, whatever is in red would be common sides. So you see the auxiliary, cervical, inguinal, retroperitoneal. These are common sites for Hodgkin.

The uncommon would be the AP trochlear, in the elbow, mezenteric, around the intestine, and popliteal, at the knees. We see a lot of Hodgkin's disease very early in age, as I said before. And we see that it has certain stages. And it's interesting. For the stages, look at page 534, please, table 21-7. And the staging is where stage 1 is just one lymph node. Stage two, two or more on the same side of the diaphragm. On the same side either above it or below it. In stage 3 you see regions on both sides of the diaphragm. Stage 4, disseminated or involvement of extralymphatic organs also.

So how do we treat this? Of course, treatment early with chemotherapy and radiation is important, surgery if we need to remove it, of course, and newer treatment out there with stem cell transplant as usual. So just like we had the Hodgkin's lymphoma, there's non-Hodgkin. And we're not going to go into detail about them, but most of them have to do with environmental conditions. So because we are seeing more and more pollution, we are seeing more and more lymphomas out there.

So we're going to actually go over Burkitt lymphoma because it's very interesting. And just because we talked about Epstein-Barr a while ago-- what we talked about Epstein-Barr virus and how it can affect the pharyngeal infections also. So Burkitt lymphoma again, is a B-cell tumor. When we talked about it before we said that we can see it in certain diseases and infections. And what they did was they actually took a swab of patients who had Burkitt lymphoma, that type of cancer, and they found a lot of this type of virus, which is the Epstein-Barr virus. And that's why they linked viral infection to it. And you guys studied this for the exam today went over the link between this virus and Burkitt lymphoma.

But the thing about Burkitt lymphoma is it presents differently here in the United States and in overseas. United States you see it more in an adult age, and a lot of times mesenteric lymph nodes are affected more. Burkitt lymphoma overseas, you see it in children and around the jaw area. You can see this picture in the African-American in 536. You can see how the jaw is enlarged. OK? Fast-growing tumor either in the jaw, as we said overseas, or in the abdomen. And here, we see that. But a lot of these patients have been linked to Epstein-Barr virus, as I said.

And we know where it happens. If it's a genetically-determined thing, there's a translocation that happens from chromosome 8 to 14. We've seen that occur there. And that might have to do with it.

And we see it more in the B cells. So the B cells are the malignant type of cells there, and this lymphoma can be treated, of course again, by chemotherapy and radiation. Five-year survival in children is good, 80% to 90%. As usual, children are responding very well to chemotherapy these days. Thank god.

And another type of lymphoma would be-- or another type of cancer that affects our white blood cells, specifically lymphocytes, would be your multiple myeloma. Now, multiple myeloma is a type of cancer of a specific cell related to B cells. Now, we have B cells and T cells, guys. OK? When a B cell is activated, it transforms into another cell, which is called the plasma cell.

So multiple myeloma is the cancer of the plasma cell, a form of the B cell. As I told you, most diseases we're going to be talking about tonight or today would be about B cells. Now, these B cells, when they transform into plasma cells, the plasma cells will make antibodies. So one of the ways to test this disease is actually to draw blood and see if there is an increase in the antibodies produced.

Now, multiple myeloma is a disease that happens, usually a type of cancer that happens in older age. And a lot of times we don't know even anything about it. So this person is developing multiple myeloma, it's in the plasma cells, around the bone marrow area, and we know nothing about it. It's actually, what it does is it eats up the bone releasing calcium into the blood. So there is hypercalcemia, a lot of calcium. This calcium can form more stones, can [INAUDIBLE] kidney function, can actually cause a person to fall and break a bone. All that, and we don't know that this person has multiple myeloma.

So the first time they know, they're in the ER with an X-ray because they just fell down. And you see that the bone has been eaten up. That's when they start testing the person, and they find out that they have multiple myeloma. Or maybe they have kidney function problems. They test them for that too.

But the protein that we test for is the M protein, Bence Jones proteins, produced by these types of plasma cells. Take a look here and you can see what's going on in this bone destruction. Slide 56-- you can also see picture on page 537, which shows you a bone marrow aspirate and how the plasma cells are huge. Again, genetic testing has to be done, and we see that they are chromosomes 11, 12, and 6-- you don't need to know their numbers-- and even 13 are affected by this.

And maybe this is one of the things that you're going to find different from this book and the earlier version, they didn't do a lot of genetic testing before, but nowadays, we want to know which chromosomes have caused this. Remember, the M protein is tested and the Bence Jones protein also all related to antibodies. Proteinuria is found in these patients also and hyperviscosity of their blood, because of the amount of plasma cells that are found. Again, a lot of times it is diagnosed a bit later, and we see the infiltration happening.

So what we try to do is chemotherapy and radiation as much as possible, but we find that the prognoses of MM or multiple myeloma remains poor till now. We use, of course, dexamethasone and various types of chemotherapy to try with them as much as possible. But the rates of the cases are increasing every year. We don't know why. The death rates have decreased, but the incident has increased of multiple myeloma.

So now we have discussed red blood cells and their diseases, white blood cells and their diseases, and then we're going to go into our last part, which is thrombocytes and platelets. But what the book goes over here is relates the spleen. We've talked about the spleen several times, and we said when the spleen functions more than usual, splenomegaly will occur. That's just to tell you what splenomegaly means.

Now, your normal number of platelets is 150,000 to 250,000 cells. For them to function well, you have to be at that 150,000. If they go below the 50,000, you start to see hemorrhage from minor trauma. A person is hit, or trauma, and they start bleeding. And you go below the 15,000, now this is very dangerous. Now this is spontaneous. You start to see bleeding from many parts of the body, in the eyes, the nose, urea, urine, and hematuria, and all that. And then below the 10,000 is the severe bleeding.

So we want to know, what are the causes of thrombocytopenia. As usual, I leave you to go over just parts of the chapters on your own. And this is just what I'd like you to read. I'm going to emphasize for you certain important reasons for thrombocytopenia. But I'd like you to read thrombocytopenia and DIC. These are the two diseases that I'd like you to know about, specifically DIC, because you've seen that.

So the most common causes of thrombocytopenia, or a decrease in the number of platelets, is number one, HIT. We call it HIT, which is heparin-induced. Now, we used to say that the first and primary cause would be immune thrombocytopenia, or ITP, but now we say that it's HIT or heparin-induced.

So heparin is-- most common cause of it. We see a lot of patients who are treated with heparin might develop thrombocytopenia, because what heparin is doing-- what does heparin do?

[INAUDIBLE]

Yes, it stops them from forming. But as we're doing that, we're actually attacking the thrombocytes leading to this. And the release of additional will cause a decrease in the platelet count even a week after you start the heparin. So a decrease in the platelet amount has to be monitored very, very closely, and that's why anyone on blood clotting medication, their always have to be tested, their PT and INR, just to adjust the dose as much as possible. So because we might, without even intending, you might lead to a CVA or a myocardial infarction or any one of these. So it has to be detected right away.

The next cause would be your immune thrombocytopenic purpura, very common too, as an autoimmune disease when your body starts to fight the platelet. And it's not only fighting the platelet, but there is that sugary covering for the platelet, and that's what is attacked there. We see it a lot in individuals around 40s and 50s. That's when it hits, generally. Sometimes we see in children also, and sometimes we see it in lupus, because lupus is a disease, as I explained a while ago, in which the body attacks many things, platelets being one of them, red blood cells being another, DNA being again another.

So you have to monitor. Sometimes people have that chronic ITP. They have to go back to the doctor here and then to just monitor and see their number of platelets, and they're given IGGs needed if we need to do that just to-- they're given immunoglobulins to fight the IGGs that are combating the platelets.

So here is the HIT. Here is the immune thrombocytopenic purpura that happens due to the IGG combating the antibody-coated platelets. And we also have the thrombotic thrombocytopenic purpura, and that's when platelets aggregate due to a thrombus, and when they aggregate their numbers go down. And that could be a chronic or acute TTP and ITP.

The opposite can happen. Instead of having less number, we can have more. We can have over 400,000. And that's called thrombocytosis, where the defect is in the stem cell, the megakaryocytes that are making a lot of platelets. Again, a reminder, platelets are not cells. They are bits and pieces of cytoplasm of a larger cell called a megakaryocyte that resides in the bone marrow.

And of course, whenever there are problems with bleeding, then you start seeing either tiny little dots under the skin called purpura, bigger are called petechiae, larger would be called-- purpura, petechiae, ecchymossis, of course. And then you see the bleeding happening. Remember something very important, bleeding and clotting-- clotting is not only dependent on your platelets. It's various things together. It's your liver that functions well, vitamin K related, and all the genetically determined clotting factors that you're born with.

Like, hemophilia is a problem in one of them. They are from 1 to 10, in Roman numerals, you have a lot of these. And if one of them is missing, that is a clotting problem-- and your calcium, and your platelets. So it's vitamin K, liver, clotting factor, calcium, all of these together. Any problems with the liver disease, Vitamin K, any of these can cause coagulation problem.

The last thing in this chapter is DIC. And I'd like you to read DIC, very important, because it is a disease that is very peculiar in which endothelial damage is the initiator. And we have clotting and bleeding at the same time. It could be a fatal disease, and that's what we want to protect our patients from by detecting it early enough and treating it early enough.