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Bone marrow

Histological features of the bone marrow.

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From a very young age, we learn that we have bones in our bodies either by learning about them in school or if you’re unlucky, through the first-hand experience of breaking your arm or leg as a kid. But what is this soft stuff found in some of our bones called bone marrow? Why is it so important and why do we need to learn about it? In this tutorial, we’re going to look at the microscopic anatomy of bone marrow as well as touch on its function and significance.

First, we’ll look at its location – that is, where bone marrow can be found in the human body – then we’ll move on to the major contents of bone marrow and their functions. We’ll look at the bony frameworks supporting marrow and the vasculature supplying it. The marrow cavity is organized into three zones and we’ll look at how to identifying those as well. Then we’ll describe the characteristics of red and yellow bone marrow and discuss how bone is significant clinically.

In adults, bone marrow is found within flat bones and the shafts of long bones. It’s supported by a bony framework filled with blood cells and fat tissue and is the site of blood cell production also known as hematopoiesis. We’ll discuss hematopoiesis in more detail when we examine red bone marrow. Let’s begin by looking at the structure of the bone marrow cavity at a microscopic level.

Here we see a micrograph taken from bone and what you can see highlighted in green is part of the network of bony trabeculae that fills the medullary cavity. Bone marrow fills the spaces between trabeculae. Marrow is mostly made up of very loose fluid-like tissue and, therefore, needs support to keep its integrity. This support comes from the lattice-like network of bony trabeculae. Spongy bone tissue makes up this delicate network that is then surrounded by the hard cortical bone tissue you see when you look at the outside of a bone.

Bones are highly dynamic. They change shape and size throughout your life and are heavily influenced by the endocrine system. Because of this, they must have an extensive blood supply. Arteries enter the bones through nutrient foramina on the surface and course through the bone tissue ultimately reaching the bone marrow as small sinusoidal capillaries. We can see one small capillary here traveling through the marrow. These white circles are fat cells and the smaller purple spots are developing blood cells.

Although the tissue surrounding the capillaries is also filled with blood, the blood in the capillaries has a slightly different color than the marrow. The purple cells of the marrow are mostly white blood cells and developing red blood cells. The capillary has mature red blood cells who appears more pink than the surrounding tissue. The bony trabeculae are also pink in this image, however, they’re much larger than the capillaries.

Now that we’ve talked a bit about the support structures and nutrition of bone marrow, we can move on to look at how it’s organized. Bone marrow is separated into three zones determined by their location. Let’s take a look at how the zones are organized.

The outer surface of bones is covered by supportive double layer of connective tissue called the periosteum. This layer contains blood vessels, nerves and progenitor cells that contribute to the growth of bones. Similarly, a layer of connective tissue called the endosteum covers the surface of the spongy bone trabeculae within the medullary cavity. The endosteal zone is a thin region of bone marrow immediately adjacent to the outer covering of bony trabeculae.

The intermediate zone is an intervening region of bone marrow between the central zone and the endosteal zone. This region of bone marrow contains maturing myeloid cells as well as erythroid islands which play a role in proper erythroid development as it’s in these islands that erythroid cells proliferate, differentiate and nucleate.

The central zone is located near the central region of the marrow cavity. In this third and final region of bone marrow, we again find maturing myeloid cells and erythroid cells. Megakaryocytes and sinusoids are also found in the central zone of bone marrow.

Okay, now let’s look at the types of bone marrow that can be found in the medullary cavity. There are two types of bone marrow that are predominant in bones depending on the need for blood cell production. These are red bone marrow and yellow bone marrow.

Red bone marrow named for its reddish appearance and copious blood supply is a primary site of hematopoiesis or the production of blood cells. Red bone marrow is most abundant in infants and small children due to their large need for blood cell production as they grow. In adults that don’t require such rapid cell production, red bone marrow is mostly restricted to flat bones such as the sternum and pelvis and in the epiphysis of long bones. Although there are some fat cells present, red bone marrow is mostly made up of red and white blood cells at various stages of development and a network of supportive fibers. Let’s take a look at some of these features.

The hematopoietic cells reside in small clusters called hematopoietic cords. Hematopoietic cords are made up of developing blood cells supported by a network of branched reticular cells. Some mast cells and plasma cells may also be present among the reticular cells. Erythropoiesis, thrombopoiesis and leukopoiesis occur here – a list of long words that might not mean that much to you. Let me explain.

Erythropoiesis is the formation of red blood cells, thrombopoiesis is the formation of platelets, and leukopoiesis is the formation of white blood cells. Specifically, erythropoiesis occurs in erythroid islands also known as erythroblastic islands. Here, the precursors to red blood cells develop, proliferate and lose their nuclei. These pink cells here are mature red blood cells and the purple cells in the erythroid island are precursor cells that have not yet lost their nuclei.

Along with the spongy bone trabeculae, hematopoietic cells have another supporting structure – reticular cells. In this micrograph, you can see the cells are adjacent to large adipocytes. Reticular cells produce a special kind of type III collagen fiber called reticular fibers. The reticular fibers look like small curved lines within the bone marrow. They are very tiny and it takes a powerful microscope to see them in detail. Reticular fibers intersperse within the connective tissue of bone marrow and form a network to support the cells.

Now that we’ve talked about the regions and major structures of bone marrow, let’s look at some of the cells found in it.

Here we can see some erythrocytes. The word erythrocyte is the histological term for red blood cell. Let’s take a closer look.

In this micrograph, we can see erythrocytes at a higher magnification. They contain a protein called hemoglobin that has a high affinity for oxygen and gives erythrocytes their red color. About a hundred billion of these cells proliferate and differentiate within the red bone marrow every day. They have no nucleus or organelles, are shaped like biconcave discs, and live for only a hundred twenty days in circulation so they need to be replaced fast. Red blood cells leave the bone marrow to carry oxygen to other tissues throughout your body.

White blood cells called leukocytes also proliferate and differentiate within the red bone marrow. This cells is a special type of leukocyte called a macrophage. Let’s take a closer look.

These lighter-colored cells are red blood cells and this is a macrophage. These cells have large nuclei and a grainy appearance in a H&E stain. Macrophages are a type of immune cell that travels around your body engulfing pathogens and foreign bodies. Its name gives you a bit of a clue about its function given that it translates to “big eater”.

Outside of the blood, macrophages have specific names depending on their location. These cells here are called megakaryocytes. Megakaryocytes are large polyploid cells. Polyploidy simply means that they have multiple nuclei. They divide into fragments called platelets under the control of thrombopoietin produced by the liver and kidneys. The platelets then circulate through the blood and form clots when blood vessels are injured and need to be patched up.

We’ve finished looking at red bone marrow and some of the cells that could be found in it so let’s look at the other type of bone marrow – yellow bone marrow.

Yellow bone marrow mainly plays a supportive role for the neurovasculature within the marrow cavity. It’s not actively involved in blood cell development and is present more in adult bones as they are not growing quickly and do not need to produce as many new cells. Instead yellow bone marrow is filled with adipocytes or fat cells. These cells look like round white droplets between the bone spicules. They arise from mesenchyme and store lipids as an energy source. When needed, adipocytes release a hormone called leptin that suppresses appetite.

Now that we’ve gone over the structure and functions of the marrow cavity, let’s take a look at how bone marrow is used in medicine.

Sometimes, surgeons harvest bone marrow to use for therapy or diagnosis. To get the marrow, a needle is passed through cortical bone to reach marrow cavities. Because they are taking blood cells, the surgeons usually attempt to use the iliac crest because it contains red bone marrow. Mesenchymal stem cell therapy from cells in the bone marrow can be used to repair musculoskeletal tissues as an alternative to orthopedic surgery. Pathologists also use blood cells from the bone marrow to diagnose leukemia. This is a slide of cells taken from bone marrow that was analyzed to diagnose a pathology. The red blood cells are the numerous pink cells throughout the slide and white blood cells are the two blue ones in the middle.

To finish up, let’s go over some of the things that we’ve learned today.

In this tutorial, we explored the histology of the bone marrow cavity. We began by listing the location, contents and major functions of bone marrow. Next, we talked about two major features supporting the structure of the marrow cavity – the trabeculae that form a bony network within the cavity and specialized blood vessels called sinusoidal capillaries. We went on to talk about the organization of bone marrow into three zones – the endosteal zone closest to the bone, the intermediate zone that exists between the endosteal zone and the central zone, and the central zone near the middle of the marrow cavity.

We then talked about the two types of bone marrow – red bone marrow and yellow bone marrow. Red bone marrow is responsible for blood cell production that occurs in hematopoietic cords. Several types of blood cells develop within these cords. Erythrocytes also known as red blood cells which carry oxygen to the tissues around the body, macrophages a special type of white blood cell, and megakaryocytes that will divide to form platelets. Specifically, the development of red blood cells occurs in erythroid islands. The red bone marrow is supported by specialized connective tissue cells called reticular cells that secrete reticular fibers to form a mesh-like network. Yellow bone marrow plays mainly a supportive role. It’s mostly found in adult bones and is made up of fat cells called adipocytes that secrete leptin when needed.

Finally, we talked about bone marrow aspiration – a process in which bone marrow cells are collected to be used in stem cell therapy or to diagnose leukemia.

And now we’ve reached the end of our tutorial. I hope you enjoyed it. Thanks for watching and see you next time.

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