Write-up on Bone Marrow

What is bone marrow?

Bone marrow is soft, gelatinous tissue that fills the medullary cavities - the centers of bones. There are two types of bone marrow: red bone marrow (also known as myeloid tissue) and yellow bone marrow (fatty tissue).¹

Both types of bone marrow are highly vascular and enriched with numerous blood vessels and capillaries.²

Long bone cross-section showing both red and yellow bone marrow.

The bone marrow makes more than 200 billion new blood cells every day.⁸ Most blood cells in the body develop from cells in the bone marrow.⁵

Stem cells

The bone marrow has two types of stem cells: mesenchymal and hematopoietic. Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells, which are blood-forming stem cells. Yellow bone marrow contains mesenchymal stem cells, also known as marrow stromal cells, which produce fat, cartilage and bone.⁴

Stem cells are immature (primitive) cells. There are two main types in the bone marrow that hematopoietic stem cells give rise to - myeloid and lymphoid lineages. These derive from even more primitive cells called common pluripotent stem cells.

The most primitive of the stem cells is called the pluripotent stem cell, which is different from other blood cells due to the following properties:

• Renewal: can reproduce another cell identical to itself
• Differentiation: can generate one or more subsets of more mature cells.

The process of development of different blood cells from these pluripotent stem cells is known as hematopoiesis.¹¹

It is these stem cells that are needed in bone marrow transplant.

Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages (precursor or blast cells) before forming into fully formed (mature) blood cells. Stem cells rapidly multiply to make millions of blood cells each day.¹⁰

Blood cells have a limited life span and are constantly being replaced. The production of healthy stem cells is vital.¹²

The blood vessels constitute a barrier, inhibiting immature blood cells from leaving the bone marrow. Only mature blood cells contain the membrane proteins required to attach to and pass the blood vessel endothelium. Hematopoietic stem cells may also cross the bone marrow barrier, and may be harvested from blood.¹⁵

The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with their own job:

• Red blood cells (erythrocytes) - transport oxygen around the body
• White blood cells (leukocytes) - help fight infection and disease. White blood cells include lymphocytes - the cornerstone of the immune system - and myeloid cells which include granulocytes: neutrophils, monocytes, eosinophils, and basophils
• Platelets (thrombocytes) - aid with clotting after injury. Platelets are fragments of the cytoplasm of megakaryocytes, another bone marrow cell.

Once mature, these blood cells migrate from the marrow and are introduced into the bloodstream, where they provide important functions in keeping the body alive and healthy.⁷

Mesenchymal stem cells are found in the bone marrow cavity and differentiate into a number of stromal lineages, such as chondrocytes (cartilage generation), osteoblasts (bone formation), osteoclasts, adipocytes (adipose tissue), myocytes (muscle), macrophages, endothelial cells and fibroblasts.⁶

Red bone marrow

All blood cells in humans are formed in the red bone marrow, with the exception of lymphocytes, which are formed in the marrow but reach maturity in the lymphoid organs.¹

Red bone marrow also plays a role in the obliteration of old red blood cells, along with the liver and spleen.

Yellow bone marrow

Yellow bone marrow's main purpose is to act as a store for fats and serves to provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions, such as severe blood loss or fever, the yellow may revert to red marrow.¹

Yellow marrow tends to be located in the center-most cavities of long bones, and is generally surrounded by a layer of red marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.⁶

Bone marrow timeline

Bone marrow first occurs in the clavicle near the end of fetal life and becomes active about 3 weeks later. Bone marrow supersedes the liver as the major hematopoietic organ at 32-36 weeks' gestation.

Bone marrow remains red until around the age of seven as the need for new continuous blood formation is high. As the body ages, the red marrow is gradually replaced by yellow fat tissue. Adults have on average about 2.6kg (5.7lbs) of bone marrow, with about half of it being red.³

In adults, red marrow has its strongest concentrations in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, skull and at the metaphyseal and epiphyseal ends of the long bones of the arm (humerus) and leg (femur and tibia). All other cancellous, or spongy, bones and central cavities of the long bones are filled with yellow marrow.

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What does bone marrow do for your body?

The majority of red blood cells, platelets, and most of the white blood cells are formed in the red marrow while only a few of them are formed in the yellow marrow.

White blood cells survive anywhere from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. These cells must be constantly replaced by the bone marrow as each blood cell has a set life expectancy. Certain conditions may trigger additional production of blood cells.

When the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the number of red blood cells decreases, the kidneys produce and release erythropoietin, a hormone that stimulates the bone marrow to produce more red blood cells.

Similarly, the bone marrow produces and releases more white blood cells in response to infections, and more platelets in response to bleeding. If a person experiences serious blood loss, yellow bone marrow can be activated and transformed into red bone marrow.

Bone marrow's function is important for:

Blood cell formation from differentiation of hematopoietic stem cells in red bone marrow.

Circulatory system

The circulatory system touches every organ and system in the body. Red cells are carried in the circulation of blood to transport oxygen.

Hemoglobin

Hemoglobin protein is found within red blood cells and gives them their color. Hemoglobin collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. CO₂ waste product is also removed by hemoglobin and sent back to the lungs where it is exhaled.

Iron

Iron is an important nutrient within the body. It combines with protein to make the hemoglobin in red blood cells and is essential in the production of red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron needed each day for making hemoglobin comes from the recycling of old red blood cells.

Red blood cells

The production of red blood cells is called erythropoiesis. It takes about 7 days for a committed stem cell to mature into a fully functional red blood cell. As red blood cells age, they become less active and become more fragile.

Aging red cells are removed or eaten up by white blood cells (macrophages) in a process known as phagocytosis and the contents of these cells are released into the blood. The blood stream carries the iron from the hemoglobin of the destroyed cells to either the bone marrow for production of new red blood cells or to the liver or other tissues for storage.

Normally, around 1% of the body's total red blood cells are replaced every day. The number of red blood cells produced each day, in a healthy person, is about 200 billion cells.

White blood cells

The bone marrow produces many types of white blood cells, which are necessary for a healthy immune system. These cells both prevent and fight infections.

The main types of white blood cell or leukocytes are:

Lymphocytes

Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection caused by viruses that enter the body through the nose, mouth, or cuts and grazes. This takes place through recognizing foreign substances that enter the body and then sending a signal to other cells to attack them. The number of lymphocytes increases in response to these invasions. There are two major types - B- and T-lymphocytes.

Monocytes

Monocytes are also produced in the bone marrow. Mature monocytes have a life expectancy in the blood of only 3-8 hours, but when they move into the tissues, they mature into larger cells called macrophages. Macrophages can survive in the tissues for long periods of time where they engulf and destroy bacteria, some fungi, dead cells, and other material foreign to the body.

Granulocytes

Granulocyte is the family or collective name given to three types of white blood cells: neutrophils, eosinophils and basophils. The development of a granulocyte may take two weeks, but this time is shortened when there is an increased threat like a bacterial infection.

The bone marrow also stores a large reserve of mature granulocytes. For every granulocyte circulating within the blood, there may be 50-100 cells waiting in the marrow to be released into the blood stream. As a result, half the granulocytes in the blood stream can be available to actively fight an infection in the body within 7 hours of recognizing that an infection exists. Once a granulocyte has left the blood it does not return.

A granulocyte may survive in the tissues for as long as 4-5 days depending on the conditions, but it only survives for a few hours in the circulation.

Neutrophils

Neutrophils are the most common granulocyte. They can attack and destroy bacteria and viruses.

Eosinophils

Eosinophils are involved in the fight against many types of parasitic infections and against the larvae of parasitic worms and other organisms. They are also involved in some allergic reactions.

Basophils

Basophils are the least common of the white blood cells and respond to various allergens that cause the release of histamines and other substances.

These substances cause irritation and inflammation in the affected tissues.

The human body recognizes the irritation or inflammation and dilates the blood vessels allowing fluid to leave the circulatory system and enter the tissue in an effort to dilute the irritant. This reaction is seen inhay fever, some forms of asthma, hives, and in its most serious form, anaphylactic shock.

Platelets

Platelets are produced in bone marrow by a process known as thrombopoiesis. Platelets are critical to blood coagulation and the formation of clots to stop bleeding.

Sudden blood loss triggers platelet activity at the site of an injury or wound. Here, the platelets clump together and combine with other substances to form fibrin. Fibrin has a thread-like structure and forms an external scab or clot.

Platelet deficiency causes the body to bruise and bleed more easily. Blood may not clot well at an open wound, and there may be a greater risk for internal bleeding if the platelet count is very low.

Lymphatic system

The lymphatic system is made up of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen and lymph nodes.

All lymphocytes develop in the bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T-cells. Lymphocytes that mature in the bone marrow or lymphatic organs are called B-cells.¹⁴

Immune system

Our immune system protects the body from disease. It kills unwanted micro-organisms such as bacteria and viruses that may invade our bodies.

How does our immune system fight against infection?

Small glands called lymph nodes are scattered throughout the body. Once made inside our marrow, lymphocytes enter the lymph nodes. The lymphocytes travel between each node through channels called lymphatics. The lymphatic channels meet at large ducts that empty into a blood vessel. Lymphocytes enter the blood through these ducts.

There are three major types of lymphocytes, which play an important part of the immune system:

There are three types lymphocytes. T-lymphocytes, B-lymphocytes and natural killer cells.

B-lymphocytes (B-cells)

These cells originate in the bone marrow. They make proteins called antibodies which attach onto the surface of infection-causing microbes. These are Y or T-shaped. Each antibody reacts to different microbes by sticking to molecules called antigens, which sit on the surface of the microbe. It is this antibody-antigen binding that triggers B-cells to grow and produce more antibodies which fight infection.

T-lymphocytes (T-cells)

These cells mature in the thymus, a small organ in the upper chest, just behind the sternum. T-cells help B-cells make antibodies against invading bacteria, viruses, or other microbes. Unlike B-cells, T-cells engulf and destroy pathogens directly, after binding to the antigen on the surface of the microbe.

Natural killer (NK) cells

These are a type of lymphocyte that directly attacks cells which have been infected by a virus.

What are bone marrow tests?

Examination of the bone marrow is helpful in diagnosing certain diseases, especially those related to blood and blood-forming organs. Testing provides information on iron stores and blood production.¹

Bone marrow aspiration (the removal of a small sample of bone marrow through a needle for examination under a microscope) of a small amount (about 1 ml) of bone marrow is accomplished by suction through a hollow needle. The needle is usually inserted into the hip or sternum in adults and into the upper part of the tibia (the larger bone of the lower leg) in children.

The necessity for a bone marrow aspiration is ordinarily based on previous blood studies and is particularly useful in providing information on various stages of immature blood cells.

Disorders in which bone marrow examination is of special diagnostic value include:¹

• Leukemia
• Multiple myeloma
• Gaucher disease
• Unusual cases of anemia
• Other hematological diseases.