Heme coloring book

I hope you find the coloring book useful! It’s totally optional, of course – so use it as much or as little as you see fit.

Here are the answers to the “While you’re coloring…” questions, in the order they appear in the book.

1. Hematopathology Basics

Hematopoiesis

Here’s my colored drawing, labeled with the cell names:

Questions:

  1. Do you know the names of all the cells (including the immature ones)? These are listed on the drawing above.
  2. Try coloring the nuclei of the lymphocyte, monocyte, and neutrophil so they have the right chromatin pattern (is it clumpy? Clumpy and smudgy? Raked?) Neutrophil chromatin is clumpy (there are well-defined white spaces between the chromatin clumps). Lymphocyte chromatin is clumpy and smudgy (there are chromatin clumps, but in between them, it’s kind of smudgy). Monocyte chromatin has a “raked” appearance, like you dragged a little Zen garden rake across the nucleus. I gave it a try in the drawing above 🙂
  3. See if you can do the same for the blast cells. Blasts have really fine chromatin, which means that it’s not clumpy at all – you can basically see right through it (that’s why there are visible nucleoli in blast cells).

Normal Blood Cells

Questions:

  1. What are the names of all the white blood cells? You guys know this, but: neutrophil, lymphocyte, monocyte, eosinophil, basophil.
  2. Which ones are called granulocytes, and why? Neutrophils, eosinophils, and basophils are all called granulocytes because they have special (or “specific”) granules that give each cell its unique abilities. Neutrophil specific granules, for example, contain bactericidal substances like lysozyme. Note that “agranulocytes” (lymphocytes and monocytes) actually do have a few granules – but these are small and boring so they don’t really count.
  3. In normal blood, which white blood cell makes up the largest percentage of the differential count? Neutrophil. Which cell is next most common? Lymphocyte.
  4. Which cell makes up the smallest percentage of the differential count? Basophil.

Normal Red Blood Cells

Questions:

  1. What are some of the components of the red cell cytoskeleton? Spectrin, ankyrin, and actin are the main ones.
  2. What do you think would happen to the shape of a red cell if it lost some of its membrane (but retained all of its contents)? It rounds up into a sphere (that’s what happens in hereditary spherocytosis, for example).

Some Important Stuff About Red Cells

Questions:

  1. What CBC (complete blood count) parameter tells you the average size of the red cells? The MCV (mean cell volume).
  2. What CBC parameter (other than the hemoglobin) tells you whether the cells are hypochromic or normochromic? The MCHC (mean cell hemoglobin concentration).

2. Anemias

Anemia of Blood Loss

Questions:

  1. What color are reticulocytes? Lavender.  Why? Because they still have a little RNA (which stains blue) in the cytoplasm.
  2. If these were actual blood smears taken at some point after the patient lost blood, when do you think the left one was made (minutes after blood loss? Hours? Days?)? Probably minutes (or maybe an hour), because it looks like there are a normal number of red cells (compare this side to the right side, where there are bigger spaces between the red cells), and there aren’t any reticulocytes. If it was hours after the blood loss, there would probably be fewer red cells, because the patient would have received IV fluids (or would have pulled tissue fluid into the vascular space) – and that dilutes the red cells so there are fewer per unit volume.
  3. How about the right one? Probably days, since there are now reticulocytes present.

MAHA

Questions:

  1. What are the pointy little red cells called? Schistocytes.
  2. What happened to make the red cells look like that? Usually it’s something in tiny vessels: fibrin strands, clumps of platelets, or blood clots (containing both platelets and fibrin). When the red cells go through those tiny vessels, they get snagged on that stuff and break into pieces. There are also some other, non-small-blood-vessel things that can cause red cells to split into schistocytes, like artificial heart valves, or even excessive running (this is called runner’s anemia).
  3. Which oddly-shaped red cell is the MOST SPECIFIC for this type of anemia? The triangulocyte.

Autoimmune Hemolytic Anemia

Questions:

  1. Which one is warm and which one is cold? The one on the left is warm, and the one on the right is cold.
  2. What happens in warm autoimmune hemolytic anemia? IgG binds to the red cell surface, and the red cells get removed from circulation by macrophages in the spleen.
  3. What happens in cold autoimmune hemolytic anemia? IgM binds to the red cell surfaces in cold parts of the body (and since IgM is a pentamer, it causes red cell agglutination). The IgM falls off in warm parts of the body. Complement sees the IgM bound to the red cells, and this entices complement components to stick to the red cells (and poke holes in them). 

Sickle Cell Anemia

Questions:

  1. What’s the underlying problem in the red cells that causes them to sickle? The beta chain has a point mutation which makes the hemoglobin polymerize when it deoxygenates, contorting the red cell into a sickle shape.
  2. What’s so bad about having sickled red cells? Sickled red cells are more fragile, so they bust open more easily. Also, and perhaps even more importantly, sickled red cells get stuck in little vessels. This can happen anywhere in the body, including in the spleen (which eventually has so many little infarcts and scars that it shrinks down into a little useless piece of fibrotic tissue). 

Thalassemia

Questions:

  1. Which one is thalassemia major, and which one is thalassemia minor? The one on the left is thalassemia minor: the red cells are all microcytic – but that’s about it – the anemia isn’t really bad. The one on the right is thalassemia major: there’s a severe anemia (you can tell because there are relatively few red cells per unit area), a huge amount of anisocytosis and poikilocytosis (see the tiny little oval-shaped red cells?), and even a bunch of nucleated red cells (because the marrow is trying really hard to release as many red cells as possible into the blood). There are also a bunch of target cells, which is common in thalassemia, especially in more severe cases.
  2. What’s the underlying defect in thalassemia? In alpha thalassemia, there aren’t enough alpha globin chains (because the patient is missing one or more alpha chain genes); in beta thalassemia, there aren’t enough beta globin chains (because the patient has mutations in one or both beta chain genes that result in decreased beta chain production).

Hereditary Spherocytosis

Questions:

  1. Which cells are spherocytes? The small round ones with no central pallor.
  2. What’s the underlying defect that makes the red cells turn into spherocytes? The patient has inherited a mutation in one of the components of the red cell cytoskeleton. This makes the red cell membrane unstable, and over time, the red cell loses bits of membrane. The contents of the cell don’t get lost that much, though – so eventually the cell rounds up into a sphere.
  3. If the disease is causing clinical problems, what can you do to relieve the symptoms of the disease? Splenectomy takes care of most of the symptoms, because the spleen is where the spherocytes are removed from the circulation. So if you take out the spleen, the patient still has spherocytes (because the genetic defect is still there), but the red cells won’t get removed from the circulation (so the patient won’t be nearly as anemic). Spherocytes are more fragile than normal red cells, though (they have a tendency to break apart when trying to squeeze through tiny spaces). So because of the spherocyte’s shorter lifespan, the patient will probably still have a mild anemia – but it will be much improved, since the spleen is the main site of destruction.

G6PD Deficiency

Questions:

  1. What do you call the weirdly-shaped red cells in this disease? Bite cells.
  2. How does a deficiency in G6PD cause the red cells to look this way? The red cells are deficient in G6PD, which means that they don’t have as much reduced glutathione around. So when the cell undergoes oxidative stress (which can happen after certain medications, or fava bean ingestion), the free radicals attack the bonds between heme and globin, and the globin chains ball up and stick to the inside of the red cell membrane (this is called a Heinz body). Splenic macrophages do a couple things: 1) sometimes they completely remove the Heinz-body-containing red cell, and 2) sometimes they just bite out the Heinz bodies, leaving little bite marks in the cell. 

Iron-Deficiency Anemia

Questions:

  1. What’s the MCV like in IDA (low, normal, or high)? It’s low (the cells are microcytic).
  2. Is there any anisocytosis in IDA? Yes. Why? Because as the patient’s iron stores dwindle, each successive wave of new red cells becomes smaller and smaller. So the patient has both older (larger) red cells and newer (smaller) red cells in the blood.

Megaloblastic Anemia

Questions:

  1. What’s the MCV like in megaloblastic anemia (low, normal, or high)? It’s high (the red cells are macrocytic).
  2. What are the two characteristic things you see in a blood smear from a patient with megaloblastic anemia? Oval macrocytes and hypersegmented neutrophils.
  3. What causes this type of anemia? B12 and/or folate deficiency. These nutrients are required for the production of DNA (but not RNA). So if you’re depleted in B12/folate, you’ll make DNA more slowly than RNA. This means the red cells aren’t produced as quickly, and they’re also bigger than normal (because it takes longer for them to undergo mitosis, and they are bigger as a result). Also, the nucleus appears more immature than the cytoplasm (this is called nuclear:cytoplasmic asynchrony).

Aplastic Anemia

Bone Marrow Questions:

  1. What is the normal cellularity of bone marrow? This is usually reported as a percentage (meaning the % of total bone marrow volume that is made up of hematopoietic cells). See the next question 🙂
  2. How does this change with age? The normal cellularity of the bone marrow varies a LOT with age. As a general rule of thumb, the marrow is almost 100% cellular at birth, and you lose about 10% every decade (so at 20 you’re about 80% cellular, and at 50 you’re about 50% cellular). It actually bottoms out at around 30% or so (so even if you get to be 90, you’ll still have a marrow that’s about 30% cellular). 

Blood Questions:

  1. What’s the word used to describe a decrease in all three major cell lines (red cells, white cells, and platelets)? Pancytopenia.
  2. What’s the MCV like in aplastic anemia? It’s normal. How about the reticulocyte count? It’s decreased.

3. Benign Leukocytoses

Toxic Changes

Questions:

  1. Label the toxic change in each of the neutrophils in the bottom row. Left neutrophil: toxic granulation. Middle neutrophil: Dohle bodies. Right neutrophil: toxic vacuolization.
  2. What’s the mechanism behind each of these toxic changes?
    • Toxic granulation happens because in a bacterial infection, the marrow is rushing to get neutrophils out into the blood. Promyelocytes normally undergo a few rounds of cell division before they mature into myelocytes. But when the marrow is in a rush to get neutrophils out, the promyelocytes just mature (instead of dividing first) – so their primary granules don’t get diluted out into daughter cells like they normally do! They are retained and you see them in mature neutrophils.
    • Dohle bodies represent super-active rough endoplasmic reticulum (for some reason, it stains a pretty blue color when it’s all geared up).
    • Vacuolization is a result of the neutrophil ingesting bugs – it makes little vesicles/vacuoles when it does that.

Downey Lymphocytes

Questions:

  1. Label the Downey cells. Top left: Downey 1. Top right: Downey 3. Bottom left: Downey 2.
  2. What disease usually has Downey cells in the blood? Infectious mononucleosis.

4. Leukemia

That Hematopoiesis Diagram Again

 

Acute vs. Chronic Leukemia

Questions:

  1. Which two leukemias are acute? The top two. Which two are chronic? The bottom two.
  2. Which two leukemias are myeloid? The two on the left. You can tell that the top left one is myeloid because it has Auer rods! The top right one could be AML too (some AMLs don’t have any Auer rods!) – but since we know there are two lymphoid ones, we’ll call the top right one ALL. Which two are lymphoid? The two on the right.

Blasts

Questions:

So here’s something to think about: If you have a blood smear (or bone marrow) that shows a ton of blasts, and some of the blasts have Auer rods, what does that mean? It means it’s a case of acute myeloid leukemia (AML). You don’t see Auer rods in any other disease. How about if you have a ton of blasts, and there are no Auer rods present – what does that mean? It could be acute lymphoblastic leukemia (ALL) since ALL doesn’t have Auer rods. It could also still be AML (since some cases of AML don’t have Auer rods).

Acute Promyelocytic Leukemia

Questions:

  1. What’s the cell in the middle called? A faggot cell (faggot meaning bundle of sticks).
  2. What translocation is present in this type of AML? t(15;17)

Acute Monoblastic Leukemia

Questions:

  1. What’s unusual about the clinical presentation of AMLs that involve cells of the monocyte lineage? They tend to have extramedullary involvement (CNS, gums, and skin are common sites).
  2. How does this relate to the function of monocytes? Monocytes turn into macrophages, which like to crawl out into tissues.

Myelodysplastic Syndromes

Questions:

  1. Can you describe what’s wrong with each of the neutrophils in the bottom row?
    • The left one doesn’t have any granulation. You can’t really tell that there’s no specific granulation (that’s the pretty pink granulation that shows up in myelocytes during neutrophil development) in this drawing, since I decided not to draw the specific granulation on all the neutrophils in this book (it would have looked too busy, and you can’t really see the individual granules on a blood smear anyway – it just looks pink). But you can tell that there’s no primary granulation (primary granules are the dark purple ones that show up in promyelocytes during neutrophil development – normally, there are a handful of primary granules in mature neutrophils, but this neutrophil doesn’t have any).
    • The middle and right neutrophil have abnormalities in nuclear lobation. The middle one only has two lobes, and the right one just has a single, round nucleus (no lobes).
  2. Extra credit: what’s the name for the Harry-Potter’s-glasses-nucleus in the middle neutrophil? (We didn’t talk about this in class – but as long as we’re having fun coloring, I thought I’d mention it…the answer’s online.) It’s called a pseudo-Pelger-Huet cell (or nucleus). There’s a hereditary disorder called Pelger-Huet anomaly in which the patient’s neutrophils all have just two lobes. They look like this:

It doesn’t affect the function of the patient’s neutrophils at all – it’s just kind of a cool looking variation. When you see neutrophils with two lobes like this in a disease (like in myelodysplasia), you call them pseudo-Pelger-Huet cells (because they look like Pelger-Huet cells but they don’t have the genetic abnormality).

Is this leukemia? (page 54)

Probably not. There are a total of 49 cells, 6 of which are blasts. That makes the blast count around 8%, which doesn’t meet the 20% cutoff for acute myeloid leukemia (AML). And usually, acute lymphoblastic leukemia (ALL) presents with a TON of blasts (there’s no 20% cutoff, but usually it’s not even a question – it’s just obvious that there are WAY WAY too many blasts). 

The full differential (in case you want to check your count) is:

  • Blasts: 6 
  • Promyelocytes: 2
  • Myelocytes: 4
  • Metamyelocytes: 4
  • Segmented neutrophils: 10
  • Proerythroblasts: 1
  • Basophilic erythroblasts: 1
  • Polychromatophilic erythroblasts: 6
  • Orthochromatophilic erythroblasts: 5
  • Lymphocytes: 10

Is this leukemia? (page 55)

Yes! There are a total of 50 cells, 23 of which (46%) are blasts. That makes the cutoff for AML. It could be ALL too (ALL doesn’t have a blast cutoff for diagnosis – but typically, there are just TONS of blasts and hardly any other type of cell – so this is probably AML). Either way, it’s leukemia.

The full differential (in case you want to check your count) is:

  • Blasts: 23
  • Promyelocytes: 2
  • Myelocytes: 4
  • Metamyelocytes: 5
  • Segmented neutrophils: 5
  • Proerythroblasts: 1
  • Basophilic erythroblasts: 1
  • Polychromatophilic erythroblasts: 4
  • Orthochromatophilic erythroblasts: 0
  • Lymphocytes: 5

Is this AML or ALL? (page 56)

It’s AML because there are Auer rods in some of the blasts! 

Here’s the full differential (total of 50 cells):

  • Blasts: 24 (4 with Auer rods)
  • Promyelocytes: 2
  • Myelocytes: 4
  • Metamyelocytes: 4
  • Segmented neutrophils: 5
  • Proerythroblasts: 1
  • Basophilic erythroblasts: 1
  • Polychromatophilic erythroblasts: 4
  • Orthochromatophilic erythroblasts: 0
  • Lymphocytes: 5

5. Lymphoma

Small Cell Lymphoma

Questions:

  1. This lymphoma is exactly the same disease as one of the leukemias…which one? Chronic lymphocytic leukemia (CLL).
  2. How do you know these cells are “small”? Because there’s a blood vessel on the left with red cells inside – so that gives you an idea of how big the lymphoma cells are (they’re roughly the same size as the red cells, which are around 7 microns).

Large Cell Lymphoma

Questions:

  1. What’s the relative prognosis for this lymphoma? Poor. Why? Because it tends to involve extranodal sites (like the spleen and bone marrow) quite early on in the course of the disease. So patients often present with stage IV disease at diagnosis.
  2. How do you know these cells are “large”? Because there’s a blood vessel at the top right of the field – so that gives you an idea of how big the lymphoma cells are (they’re way bigger than the red cells, which are around 7 microns). You can also see some small lymphocytes scattered around too (those are about the same size as the red cells).

Burkitt Lymphoma

Questions:

  1. What’s the name used to describe how Burkitt lymphoma looks in a lymph node? (Not-so-subtle hint on the facing page.) Starry-sky pattern. It looks that way in the bone marrow/tissue too.
  2. What do you call the four cells with the junk in them, above? Tingible-body macrophages.

Follicular Lymphoma

Questions:

  1. What’s the name of these cells? Butt cells.
  2. Don’t let anyone tell you pathology isn’t fun. I mean… Seriously.

SĂ©zary Syndrome/Mycosis Fungoides

Questions:

  1. The cells in Sézary syndrome totally look like brains! What’s the name for this? Cerebriform lymphocytes.
  2. What else is weird about this type of lymphoma? It’s a T-cell lymphoma (most non-Hodgkin lymphomas are B-cell), and it often involves the skin (that’s not very common in other lymphomas).

Hodgkin Lymphoma

Questions:

  1. What’s the name of the cell with the owl’s-eye nuclei? Reed-Sternberg cell.
  2. Which of the cells on the right are malignant? Just the Reed-Sternberg cell! All the other cells are benign bystanders. Weird.

 

 

Cardiovascular pathology II shortened

Cardiovascular Pathology III shortened 2

12 Cardiovascular Pathology short