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Red blood cells

Red blood cells



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How can we classify red blood cells while they lack nucleus? From my point of view i find it difficult to be classified as we have all cells with nucleus, even prokaryotic cells which have no nucleus membrane but they have a nucleus material which is DNA. Maybe if we classify it as a type of cell which lacks nucleus and others are cells with nucleus


As with many types of blood cells, subsetting cell types in a heterogeneous population can be done by flow cytometry. This is really quite a nice paper because it explores the differences between erythroid lineage cells and other cell types. Based on their immunophenotyping at different stages of erythroid differentiation, you can see that the cells begin to lose discerning markers as they get closer to losing the nucleus.

Also for your reference, a chart on blood cell differentiation.

Take home point: I would classify them as erythroid cells, erythrocytes on the basis of CD235+, CD71-, CD45-, CD117- by flow cytometry. CD235 may not be present in non-primate blood (ref).

CD numbers are referred to as clusters of differentiation, or as you've described it, how do we know what a cell is if it's indistinguishable from a mixed bag? These markers are used routinely in immunology for cell classification, though as commented red blood cells are easy to spot. My only thought is you may mistake a reticulocyte for a RBC by conventional light microscopy without the appropriate stain, so it's worth being careful if you're new to viewing these cells in a microscope.

We don't need to create an entirely new classification of cell, however. Think of RBC as terminally differentiated blood cells.


The Functions of Red Blood Cells


Red blood cells, known also as RBCs, have several important roles to play in our bodies. The primary function of red blood cells is to carry oxygen from the lungs to the tissues around your body. As a secondary function, they are also a key player in getting waste carbon dioxide from your tissues to your lungs, where it can be breathed out. When red blood cells stop functioning properly, you can rest assured that many things are going to go wrong in your body.

In order to properly understand the function of a red blood cell, you have to understand something about the structure. A typical RBC is about 6-8 micrometers in diameter, about the same as the width of a spider web strand. An RBC is biconcave in shape. Think of it like a miniature donut, only the hole in the center doesn’t poke all the way through. This small shape and physical structure allows the RBC to squish in to the small capillaries where your blood vessels are the smallest. Without this ability to flex, they would easily get stuck and cause obstructions in your circulation.

The oxygen carried in your red blood cells is stored in a special protein known as hemoglobin. There are several different types of hemoglobin and the exact structure of this important protein is quite complicated, so this explanation will be something of a gross oversimplification. A single hemoglobin molecule is made of four identical sub-units. Each sub-unit has a heme component, aglobin chain and an iron atom bound to the heme section. Red blood cells are completely lacking in most other common cellular parts, such as a nucleus with DNA, or mitochondria.

Oxygen is able to bind to each of the iron atoms, meaning that a single hemoglobin molecule is able to carry up to four oxygen molecules at its maximum capacity. Interestingly, the structure of hemoglobin makes it such that the more oxygen that is bound to one of the sub-units, the more other oxygen molecules are attracted to the remaining iron atoms. Again, the details of this effect involve a lot of complex chemistry, but this effect it important to the proper functioning of a red blood cell in oxygen transport.

The ability of oxygen to bind to hemoglobin is effected by many factors. The acidity of the blood (pH) is a primary factor, as is the temperature. Fetal blood has a different ability to bind oxygen (it holds on to the oxygen more tightly). Other chemicals such as hydrogen sulfide, carbon monoxide, hydrogen sulfide and 2,3bisphosphoglycerate (there’s a mouth-full, eh?) also effect the ability of hemoglobin to carry oxygen.

Factors in binding such as pH and temperature are vital to hemoglobin function. Your red blood cells need to grab on to oxygen in the lungs and let go of it in the tissues. Subtle changes in the pH and temperature of your blood (along with some other effects) allow the hemoglobin molecules to catch and release oxygen at the proper times.

A huge amount of space in a red blood cell is taken up by hemoglobin. Well over 90% of the content of an RBC that is not water, is hemoglobin. Even taking water in to account, over a third of the mass of an RBC is hemoglobin.

The second important function, just as important as carrying oxygen although less commonly known, is the ability of red blood cells to carry carbon dioxide. CO2 is a waste product of metabolism in every cell in your body. You need some way of getting rid of it all the time, or you will die rather quickly. Red blood cells serve as the vehicle to rid your body of this waste.

The process by which your red blood cells transport carbon dioxide is different than oxygen transport. RBCs contain an enzyme called carbonic anhydrase. As the CO2 enters the RBC, this enzyme, with the help of some water, converts it into another chemical called bicarbonate. Bicarbonate is used to control the pH in your blood and it later excreted either via your lungs or your kidneys. Some CO2 is dissolved in your blood directly and a small amount is actually carried on the hemoglobin molecules, but the vast majority is converted to bicarbonate.

Because red blood cells are so important to your body, when they don’t work properly, it often leads to disease. Although there are literally dozens of diseases related to your blood, I’ll mention a couple of the more common (or at least interesting) ones.

Sickle cell disease is a common disorder of the red blood cells. It is a genetic disease found mostly in persons of African descent. The disease involves a single DNA mutation that causes the cell wall of the red blood cells to not form properly. The RBCs become misshapen. Instead of round and biconcave, they become long and thin. Because of this the RBCs do not carry oxygen as efficiently and can become stuck in small capillaries, causing tremendous pain. Interestingly, the presence of these misshapen red blood cells is not entirely a bad thing. People with this genetic defect are more resistant to malarial infections, which rely on normally shaped red blood cells to infect a person.

Carbon monoxide poisoning is another interesting problem related to red blood cells. Carbon monoxide (CO) is structurally very similar to oxygen, which is normally found as a pair of atoms. Hemoglobin doesn’t differentiate between CO and O2 very well. In fact, carbon monoxide is hundreds of times more attracted to hemoglobin than oxygen. This is a big problem if you inhale too much CO. The CO takes over the iron binding sites on the hemoglobin and doesn’t allow space for oxygen to hitch a ride. In essence, you end up suffocating because the oxygen you breathe in cannot be transported to the tissues in your body.

As you can see, red blood cells can be quite complex. There are many issues here that I’ve covered in very shallow detail. To learn more about how RBCs work, you can always apply to medical school and become a hematologist!


Red Blood Cells

Red blood cells, or erythrocytes, are one of the components of blood. (The others are plasma, platelets and white blood cells.) They are continuously produced in our bone marrow. Just two or three drops of blood can contain about one billion red blood cells – in fact, that’s what gives our blood that distinctive red color.

What Is the Function of Red Blood Cells?

Red blood cells carry oxygen from our lungs to the rest of our bodies. Then they make the return trip, taking carbon dioxide back to our lungs to be exhaled.

What Does a Low Red Blood Cell Count Mean?

A low red blood cell count, known as anemia, can cause fatigue, shortness of breath, dizziness and other symptoms. If untreated, anemia can lead to serious complications. In many cases, anemia occurs when we don’t eat a nutrient rich diet choosing foods that are rich in iron and other vitamins and minerals can help raise the red blood cell count. Learn about heme iron and which foods are considered rich in iron.

Anemia can also be caused by pregnancy and certain medical conditions such as bleeding disorders and kidney disease. Talk to your doctor to determine the best course of treatment.

How Are Red Blood Cells Used in Medicine?

Red blood cells are the most commonly transfused blood component. Patients who benefit most from receiving red blood cells include those with chronic anemia resulting from kidney failure or gastrointestinal bleeding, and those with acute blood loss resulting from trauma. They can also be used to treat blood disorders such as sickle cell disease.

How Are Red Blood Cells Collected?

Red blood cells are prepared from whole blood by removing the plasma (the liquid portion of the blood). Sometimes this is done after a person donates a pint of whole blood, resulting in multiple components (red cells, plasma and platelets) that can be given to different patients. Learn more about the different components that can be obtained from a whole blood donation.

Other times, it is done during the donation itself, using a process called apheresis. In this case, only the red cells are retained and the patient’s plasma and platelets are returned to them. Some donors say that this leaves them feeling more hydrated than giving a whole blood donation.

Red cells have a shelf life of up to 42 days, depending on the type of anticoagulant used when they are stored. They can also be treated and frozen for 10 years or more.

Why Donations Are So Important

Recent studies show that there is a need for blood transfusions every 2 seconds, all of which must be collected from volunteer donors. One powerful way to help is to donate what the Red Cross calls “Power Red.” By donating Power Red, you double your impact by contributing two units of red blood cells in just one donation.


3. Inactivated platelets are irregular disc-shaped structures. Activated platelets are round with projections.

Like red blood cells, platelets are derived from myeloid stem cells. Some of these stem cells develop into megakaryoblasts, which give rise to cells called megakaryocytes in the bone marrow. After a megakaryocyte has matured, pieces of its cytoplasm break away into cell fragments called platelets. A single megakaryocyte can produce 1000–3000 platelets. Because they are not cells, platelets don’t have their own nuclei. However, they do contain numerous granules (or vesicles).

The hormone thrombopoietin, produced by the liver and kidneys, regulates the production of megakaryocytes and platelets.

Platelets have different appearances in their inactivated and activated states. When inactivated, platelets are irregularly shaped discs. Activated platelets are spherical, with protrusions that allow them to stick to wound tissue and to other platelets to form a plug at the site of a blood vessel tear. Activated platelets also release chemicals from their granules to initiate clotting.

The life span of a platelet is about 10 days. Like red blood cells, old platelets are phagocytosed. Reserve platelets are stored in the spleen.


Blood cells

Blood is a connective tissue that flows through the body of many animals, transporting gases, nutrients, waste products and hormones around the body. Is it also important for a number of other functions such as regulating the fluid that surrounds cells, reducing fluid loss after injury, regulating body temperature and immunity defenses.

Relative to water, blood is a viscous fluid due to the amount of proteins, red blood cells and other compounds it contains. It owes its vibrant red color to haemoglobin, a protein found in the red blood cells that binds to oxygen and increases the efficiency of oxygen transport around the body.

The contents of blood can be separated into two groups one group is called the “formed elements” which is 99.9% red blood cells, but also includes white blood cells and platelets (important components of the immune system and the clotting of blood). The other half of the blood is known as plasma and contains around 92% water, plasma proteins and other solutes such as electrolytes and organic wastes.

Red blood cells

Red blood cells (RBC) are responsible for the transportation of oxygen around the body and their significance is proven by the fact that they account for almost half of the entire blood volume. They are chocked full with haemoglobin which makes up approximately 95% of the proteins found in red blood cells.

Structurally red blood cells are shaped like a doughnut without the hole. This shape creates a large surface area which helps to increase the efficiency of oxygen exchange between the blood and tissue cells. Their shape also makes it easier for them to travel through thin capillaries as they can bend more and stack together.

Another important feature of RBCs in mammals is that they don’t have a nucleus or any organelles, one of the only animal or plant cells to lack such features. There is a certain level of variation between mammal species but generally the nucleus and organelles are absent in the red blood cells.

Haemoglobin

Haemoglobin is one of the most important and common proteins in the body. It is a globular protein – shaped like a globe – and is formed from four sub-unit proteins, each with a haem group in the middle. The haem group is a molecule in the center of the protein and has an iron ion, Fe 2+ , in its center. The haem group is able to reversibly bond to oxygen which is why haemoglobin is so helpful for transporting oxygen around the body.

The Fe 2+ ion attracts oxygen but but the protein surrounding the Fe 2+ ion prevents the oxygen from bonding and becoming FeO, or rust. Changes in the shape of the protein affect how tightly or loosely oxygen binds to the haem depending how close the O2 gets to the iron within the haem molecule.

White blood cells

The white blood cells or leukocytes show a much greater variation than the red blood cells and they perform a wide range of functions, more often than not, that help boost the immune system. They differ significantly from red blood cells in that they have nuclei and other organelles and do not have any haemoglobin.

There are a number of different types of white blood cells such as neutrophils, basophils, eosinophils and lymphocytes. Each different type of white blood cell performs a different set of functions. Neutrophil cells are the most common and make up to 70% of the white blood cells. They are an important component of the inflammatory system and are the cells responsible for the formation of pus. Basophil cells release compounds, such as histamine that help the repairing process of damaged tissue.

Eosinophils are a type of cell known as phagocytes, which basically means they engulf substances, often foreign to the body, such as bacteria, but also the break down components of bodily compounds, such as dead cells. Each eosinophil has particular anti-bodies, compounds on the cells exterior that attract the cell to specific compounds, which may be found on the cells of bacteria or the break-down components of damaged tissue. Macrophage cells are large generalist phagocytes.

Lymphocytes are very specific defense cells and are crucial to the adaptive immune system of mammals and higher animals. Lymphocyte cells include T cells, B cells and Natural Killer cells.

Blood plasma

The blood plasma contain a number of important compounds such as proteins, water and electrolyes. The most common plasma proteins are the albumins which are responsible for maintaining the osmotic pressure of the blood. Without albumins the blood would be more like the consistency of water. Increasing the thickness of blood reduces the amount of fluid that enters into the bloodstream from outside the capillaries.

Globulins are the second most common protein in the blood plasma. These include the immunoglobins which are an important part of the immune system and are also important for transporting hormones and other compound around the body. Fibrinogen makes up the majority of the remaining proteins in the blood and is the compound responsible for the clotting of blood to help prevent blood loss.

Transportation of blood

Blood is transported around the body through arteries, capillaries and veins. Arteries carry the blood away from the heart, and veins carry it back. Capillaries are very fine blood vessels that transport blood through the different tissues of the body. Pressure and osmotic gradients between the capillaries and the fluid outside of the capillaries allow for the transfer of blood between the two.

When blood is pumped from the heart, the pressure within the capillaries is much greater than the external pressure and blood is forced out of the capillaries to reduce the pressure. As the blood moves through the body, the pressure gradually reduces due to the movement of blood out of the capillaries. The osmotic pressure forces fluid into the capillaries once the pressure within the capillaries is reduced.

New blood cells

Haematopoiesis is the formation of new blood cells. It begins with stem cells, known as hemocytoblasts, which have the potential to form any type of blood cell. The process occurs mostly in the bone marrow but some final differentiation can occur in the blood and tissue.

Each stem cell undergoes a number of phases, each phase producing a different precursor cell than the previous phase. The pathway that any given cell might take depends on the compounds present, such as hormones, which influence how a cell will differentiate. At the end of the process a fully differentiated red, white or thrombocyte cell is formed.

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Utilizing Blood Bank Resources/Transfusion Reactions and Complications

Abdul-Kader Souid MD, PhD , . Bouraɺ Bou Aram MD , in Pediatric Emergency Medicine , 2008

Packed Red Blood Cell (Red Cell Concentrate) Transfusion

Packed red blood cell (PRBCs) transfusions are used to improve blood oxygen-carrying capacity and restore blood volume. Units are prepared from whole blood by removing most of the plasma (producing an average hematocrit value of 70%). This procedure reduces the transfusion volume and the isoagglutinin load. Each unit usually contains approximately 200 ml of RBCs, 70 ml of plasma, and 100 ml of additive nutrient solution (e.g., citrate [as an anticoagulant], phosphate, dextrose, and ATP). Clinical citrate toxicity (hypocalcemia due to calcium chelation) is rare, occurring only with massive transfusions (e.g., exchange transfusion), and responds to calcium supplements. Prolonged storage produces a leakage of potassium into the plasma, which is usually clinically insignificant. Blood should be infused through a filter (170 to 260 μm) to remove debris caused by storage. 1, 2

Transfusion is usually given if the symptoms of anemia or blood loss are severe and further delay might result in significant disability or death. Selected indications for transfusion include acute bleeding, high-dose chemotherapy, severe prematurity, sickle cell disease (e.g., splenic sequestration, severe acute chest syndrome), thalassemia major, aplastic anemia, pure red cell aplasia, and severe autoimmune hemolytic anemia (using the most compatible unit). 2 Transfusing 10 to 15 ml/kg of PRBCs in a child raises the hemoglobin concentration by 2 to 3 g/dl and the hematocrit by 6% to 9% ( Table 132-2 ). 1, 5 Transfusion is usually given at 15 ml/kg over 2 to 4 hours. Faster transfusion may be necessary to replace acute blood loss. If the intention is to transfuse small amounts (e.g., in infants), a unit can be divided into several aliquots.

Leukocyte-reduced PRBCs are prepared by passing the unit through a filter that removes 85% to 90% of the white blood cells the procedure is frequently performed at the time of blood collection. This type of product produces fewer nonhemolytic febrile reactions, which are mediated by antibodies against the donor's white cell antigens as well as by cytokines produced during component storage. This product also produces less alloimmunization and viral (e.g., cytomegalovirus) transmission. It is indicated for patients who need chronic transfusion (e.g., children on chemotherapy or with hemoglobinopathy) or who have prior exposure to blood antigens (e.g., multiparous females). 1

Irradiated PRBCs are prepared by exposing the unit to 2500 cGy of radiation. This treatment inactivates the donor's T cells, which reduces the risk of a graft-versus-host reaction in the recipient. This type of product is recommended for immune-compromised patients (e.g., children on chemotherapy). 1

Washed PRBCs are prepared by washing red cells with 0.9% NaCl, which removes most of the plasma. This type of product is used for patients who have severe allergic reactions (e.g., cough, wheezing, swollen lips, and urticaria) to transfusion despite antihistamine administration. Immunoglobulin E antibodies against the donor's plasma proteins mediate this adverse reaction. This product is also used for patients with immunoglobulin A (IgA) deficiency who have developed IgA antibodies. 2


Functions and diseases of red and white blood cells

Red and white blood cells have two main functions: the carriage of oxygen and defence against microbial attack. The full blood count is one of the most frequently requested routine blood tests it provides key indices such as haemoglobin and the number of white cell subsets, and provides information to aid diagnosis of a range of conditions, including anaemia, infection, leukaemia, myeloma and lymphoma.

Citation: Blann A (2014) Routine blood tests 4: functions and diseases of red and white blood cells. Nursing Times 110: 8, 16-18.

Author: Andrew Blann is a consultant at City Hospital, Birmingham, and senior lecturer in medicine, University of Birmingham.

  • This article has been double-blind peer reviewed
  • Scroll down to read the article or download a print-friendly PDF including any tables and figures to see other articles in this series

Introduction

Red and white blood cells have two main functions: the carriage of oxygen and defence from microbial attack respectively. Together, red cells (erythrocytes) and white cells (leukocytes) are part of the full blood count (FBC), one of the most frequently requested haematology tests.

Red blood cells

A number of red cell blood tests are used in the diagnosis, treatment and management of anaemia, polycythaemia and erythrocytosis. These are:

  • Red cell count (RBC): haemoglobin is a protein found in the red cells that carries oxygen to the tissues for cellular respiration. The red cell count reveals how many red cells the blood contains this can vary between the sexes. Lower levels are present in menstruating women in post-menopausal women, levels are still lower than in age-matched men, who produce testosterone, which stimulates red cell production. See Table 1 for reference values
  • Haematocrit (Hct): this index shows the proportion of the blood made up of red cells. It is expressed as a percentage (for example 43%) or decimal (for example 0.43)
  • Mean cell volume (MCV): this is the size of the average red cell, and is important in many cases in defining the cause of many types of anaemia.

Anaemia

Patients who have difficulty fulfilling basic physiological and lifestyle demands due to fatigue may have anaemia (insufficient red blood cells or haemoglobin) (Box 1). More serious signs of the condition include jaundice, hepatomegaly, angina and cardiac failure, although these may arise from other conditions.

Box 1. Signs and symptoms of anaemia

  • Pallor (especially of the conjunctiva)
  • Tachycardia (pulse rate over 100 beats per minute)
  • Glossitis (swollen and painful tongue)
  • Koilonychia (spoon nails)
  • Decreased work and/or exercise capacity
  • Fatigue, lethargy, “Tired all the time”
  • Weakness, dizziness, palpitations
  • Shortness of breath (especially on exertion)

Anaemia can be classified in a number of ways the most common are described in Box 2. Red cells are produced in the bone marrow, so infiltration of the bone marrow by cancer or other cells will inevitably lead to low numbers and therefore anaemia. A poor diet, low in iron, vitamin B12 or folate, will lead to anaemia as these are essential for the production of red cells.

Box 2. Classification of Anaemia

Depressed red cell production from the bone marrow

  • Due to infiltrating cancer
  • Due to drugs, such as the chemotherapy used to treat cancer Diet deficiency

Haemoglobinopathy

Problems with organs may also contribute to anaemia:

  • Liver: this organ stores iron and vitamins, so liver disease may lead to anaemia (Blann, 2014)
  • Kidneys: the kidneys produce erythropoietin to stimulate the bone marrow to produce red cells, so anaemia may be present in chronic renal failure (Blann, 2014b)
  • Intestines: intestinal diseases in which iron and vitamins are unable to cross the gut wall (malabsorption) can lead to anaemia - these include gastric atrophy, inflammatory bowel diseases such as Crohn’s disease or diverticulitis surgery for gastric cancer or any cancer that requires excision of a section of bowel can also lead to anaemia.

Haemolytic anaemia is the bursting, destruction or inappropriate break-up of red cells: causes include high fever and infections such as malaria (Blann and Ahmed, 2014). The condition can also occur when antibodies erroneously bind to red cells - this is known as autoimmune haemolytic anaemia.

Red cells may be lost by an acute or chronic bleed, such as heavy menstrual periods. Hidden or prolonged internal bleeding can lead to chronic blood loss and therefore anaemia.

The most common congenital haemoglobinopathies are sickle cell disease and thalassaemia these genetic conditions are characterised by changes in haemoglobin that reduce its ability to transport oxygen.

The MCV can be used to classify anaemia. If the cells are larger than normal (macrocytes), the haemoglobin is low and the patient is symptomatic, macrocytic anaemia is present, for example in vitamin B12 deficiency.

Some haemoglobinopathies and iron deficient states cause cells to be small (microcytes), leading to microcytic anaemia.

Normocytic anaemia is associated with normal-sized cells (normocytes) but a lower overall haemoglobin level. A prime reason for a normocytic anaemia is the sudden loss of a large number of healthy red cells, perhaps by an accident or bleeding gastrointestinal cancer.

Treatment of anaemia

Anaemia and its symptoms cannot be treated without a full understanding of the aetiology of the condition.

For example, dietary iron supplements will not help anaemia caused by malabsorption, but intravenous iron may increase haemoglobin levels and so address symptoms such as fatigue and lethargy. Patients with vitamin B12 deficiency should receive regular injections of this vitamin.

Anaemia can be caused by certain drugs, such as methyldopa, some antibiotics and hydrochlorothiazide. This should resolve when the patient stops taking the drug, ideally as soon as possible - if necessary substituting it with an alternative drug. In some cases, such as in cancer chemotherapy, cessation or substitution may not be possible, so the anaemia and its symptoms are treated by blood transfusion.

Autoimmune haemolytic anaemia may be treatable with immunosuppression.

However, some forms of anaemia, such as those caused by thalassaemia and sickle cell disease, are effectively incurable (except by bone marrow transplantation) and symptoms are managed by specialist teams.

Increased levels of red cells

There are two types of disease where the concentration of red cells is higher than normal: both are characterised by raised haemoglobin and Hct.

  • Polycythaemia: this may arise from a rare malignancy of the bone marrow
  • Erythrocytosis: this is often a result of the bone marrow’s response to reduced circulating levels of oxygen, often caused by heavy smoking.

White blood cells

White cells (leucocytes) defend the body from viruses, bacteria and parasites at such times, cell numbers will be raised. High concentrations are also found in rheumatoid arthritis and cancer, and after surgery. There are five types of white cells:

  • Neutrophils: making up to 70% of the white cell count, these recognise, attack and destroy bacteria
  • Lymphocytes: the second most common white blood cell (approximately 20-25% of the white cell count), are divided into two types - B lymphocytes make antibodies, while T lymphocytes destroy cells infected with viruses
  • Monocytes: these have several functions, including bacteria removal, and are active in inflammation and in repair of damaged tissues
  • Eosinophils and basophils: these cells have roles in hypersensitivity and allergy.

White cells defend the body from most microbial pathogens through two processes:

  • Inflammation: this develops rapidly and is associated with high neutrophil numbers, but can lead to the body attacking its own tissues, leading to chronic inflammation
  • An immune response, where lymphocytes are active: this develops slowly, over days or weeks, and is focused on the invading pathogen.

Inflammatory and immune responses often cooperate. For example, lymphocytes make antibodies that bind to bacteria and yeast pathogens, making them more palatable to the neutrophils and monocytes, which aids their removal. Infections occur when either or both these processes become impaired. Antibodies can also cause autoimmune diseases such as rheumatoid arthritis and thyroiditis.

Low white cell count: leucopenia

Virtually all cases of leucopenia are associated with the use of cytotoxic drugs, which can destroy white cells, increasing patients’ risk of infections. In these cases, prophylactic antibiotics may be needed, and stringent infection prevention measures are essential.

High white cell count: leucocytosis

Leucocytosis can be a normal response to infections and surgery. Pathological states associated with it include inflammatory and autoimmune diseases such as rheumatoid arthritis. The most serious cases of leucocytosis occur in leukaemia.

Leukaemia and other malignancies

The high white cell count in leukaemia is due to changes to how cells develop in the bone marrow.

Leukaemic cells stop developing prematurely, entering the blood in an immature state and increased numbers. If this process develops slowly, perhaps over several years, it is said to be chronic rapid development, for example, over months, is said to be acute.

Acute leukaemias, frequently characterised by high numbers of immature cells, are often much more aggressive than the chronic condition, and survival (unless treated) can be as short as months.

If the major affected cells in the leukaemia are of the neutrophil lineage, it is described as myeloid when lymphocytes are predominantly affected, it is known as lymphocytic leukaemia. A leukaemia dominated by blast cells is called lymphoblastic.

As leukaemia arises in the bone marrow, the production of other cells is reduced. Thus anaemia and low levels of platelets (thrombocytopenia, with a risk of bleeding and bruising) are invariably consequences of leukaemia (Table 2).

In advanced disease, leukaemia may invade the lymph nodes, liver and spleen, making them swollen (lymphadenopathy, hepatomegaly and splenomegaly respectively). Treatments are aimed at reducing the tumour burden, and are generally cytotoxic drugs. More severe leukaemias need transplantation of bone marrow stem cells from a donor or patients themselves.

Differential diagnoses of leukaemia

White cell counts may also be raised in severe infections. The most dangerous and life-threatening is septicaemia (blood poisoning), where the blood itself is infected with bacteria. Patients with septicaemia are usually cared for in intensive care units on high doses of intravenous antibiotics.

Other lymphoid cancers

Lymphoma involves malignant lymphocytes taking over lymph nodes: principle examples are Hodgkin and non-Hodgkin lymphomas. Lymphomas often progress to affect more lymph nodes the spleen, liver and bone marrow (therefore possibly leading to anaemia) can become involved.

Important differential diagnoses of lymphoma are self-limiting cases of lymphadenopathy, which may occur in tonsillitis or a nearby infected wound.

Myeloma is a tumour of B lymphocytes, which normally make antibodies to attack pathogens it is found in the bone marrow. Myeloma cells may make large amounts of an incorrect type of antibody, causing a high erythrocyte sedimentation rate.

Key points

  • Red blood cells’ main function is transport oxygen to body cells using haemoglobin
  • Lack of red blood cells leads to anaemia, which can be acute or chronic and is associated with a number of diseases
  • White blood cells defend the body from infection with bacteria, viruses or parasites
  • Different types of white cells perform different functions
  • Raised levels of white cells can be a sign of infection or a malignant condition such as leukaemia

Also in this series

Blann AD (2014a) Routine blood tests 2: what is the purpose of liver function tests? Nursing Times. 110: 6, 17-19.
Blann A (2014b) Routine blood tests 1: why do we test for urea and electrolytes? Nursing Times 110: 5, 19-21.
Blann AD, Ahmed N (2014) Blood Science: Principles and Pathology. Chichester: Wiley Blackwell.

Further reading
Blann AD (2013) Routine Blood Tests Explained. Keswick: M&K Update.


Pumping up red blood cell production

Cambridge, MA — Red blood cells are the most plentiful cell type in our blood and play a vital role transporting oxygen around our body and waste carbon dioxide to the lungs. Injuries that cause significant blood loss prod the body to secrete a one-two punch of signals – stress steroids and erythropoietin (EPO) – that stimulates red blood cell production in the bone marrow. These signals help immature cells along the path to becoming mature red blood cells. In a healthy individual, as much as half of their blood volume can be replenished within a week. Despite its importance, scientists are still working to unravel many aspects of red blood cell production. In a paper published online February 28 in the journal Developmental Cell, Whitehead Institute researchers describe work that refines our understanding of how stress steroids, in particular glucocorticoids, increase red blood cell production and how early red blood cell progenitors progress to the next stage of maturation toward mature red blood cells.

These findings are especially important for patients with certain types of anemia that do not respond to clinical use of EPO to stimulate the final stages of red cell formation, such as Diamond-Blackfan anemia (DBA). In this rare genetic disorder usually diagnosed in infants and toddlers, the bone marrow does not produce enough of early red blood cell progenitors, called burst forming unit-erythroids (BFU-Es), that respond to glucocorticoids. In both healthy people and DBA patients, these BFU-Es divide several times and mature before developing into colony forming unit-erythroids (CFU-Es) that that, stimulated by EPO, repeatedly divide and produce immature red blood cells that are released from the bone marrow into the blood. But the lack of BFU-Es in DBA patients means that the glucocorticoid signal has a limited target, and the cascade of cell divisions that should result in plentiful red blood cells is contracted and instead produces an insufficient amount.

One of the standard treatments for DBA is boosting red blood cell production with high doses of synthetic glucocorticoids, such as prednisone or prednisolone. But the mechanisms behind these drugs and their normal counterparts are not well understood. By deciphering the mechanisms by which glucocorticoids stimulate red cell formation, scientists may be able identify other ways to stoke CFU-E production – and ultimately red blood cell production – without synthetic glucocorticoids and the harsh side effects that their long-term use can cause, such as poor growth in children, brittle bones, muscle weakness, diabetes, and eye problems.

For more than two decades, Whitehead Institute Founding Member Harvey Lodish, has investigated glucocorticoids’ effects on red blood cell production. In his lab’s most recent paper, co-first authors and postdocs Hojun Li and Anirudh Natarajan, describe their research, which helps decipher how BFU-Es progress through their maturation process.

For more than 30 years, scientists have thought that glucocorticoids bestowed BFU-Es with a stem cell-like ability to divide until an unknown switch flipped and the cells matured to the CFU-E stage. By looking at gene expression in individual BFU-Es from normal mice, Li and Natarajan determined that the developmental progression from BFU-E to CFU-E is instead a smooth continuum. They also found that in mice glucocorticoids exert the greatest effect on the BFU-Es at the beginning of the developmental continuum by slowing their developmental progression without affecting their cell division rate. In other words glucocorticoids are able to effectively compensate for a decreased number of BFU-Es by allowing those that do exist, while still immature, to divide more times, producing in mice up to 14 times more CFU-Es than BFU-Es lacking exposure to glucocorticoids.

Li and Natarajan’s work reveals previously unknown aspects of the mechanism by which glucocorticoids stimulate red blood cell production. With this better understanding, scientists are one step closer toward pinpointing more targeted approaches to treat certain anemias such as DBA.

This work was supported by the National Institutes of Health (NIH grants DK06834813 and HL032262-25) and the American Society of Hematology and was performed with the assistance of Whitehead Institute’s Fluorescence Activated Cell Scanning (FACS) Facility and Genome Technology Core facility. Styliani Markoulaki, head of the Whitehead Genetically Engineered Models Center, and M. Inmaculada Barrasa of Bioinformatics and Research Computing (BaRC) are also co-authors of the paper.

Written by Nicole Giese Rura

Harvey Lodish’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of biological engineering at Massachusetts Institute of Technology (MIT). Lodish serves as a paid consultant and owns equity in Rubius, a biotech company that seeks to exploit the use of modified red blood cells for therapeutic applications.

“Rate of Progression through a Continuum of Transit-Amplifying Progenitor Cell States Regulates Blood Cell Production”

Hojun Li*, Anirudh Natarajan*, Jideofor Ezike, M. Inmaculada Barrasa, Yenthanh Le, Zoë A. Feder, Huan Yang, Clement Ma, Styliani Markoulaki, and Harvey F. Lodish.


Red blood cells - Biology

Red blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing.
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Red blood cells are red only because they contain a protein chemical called . out and eventually die. The average life cycle of a red blood cell is 120 days. .
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Red blood cells are by far the most abundant cells in the blood. . of red blood cells is to transport oxygen from the lungs to the cells of the body. .
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Red blood cells (also called erythrocytes) are shaped like slightly indented, flattened disks. . the body produces new red blood cells to replace those that .
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. but what is it really? Find out about blood in this article for kids. . B, and O. Those letters stand for certain proteins found on the red blood cells. .
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Red blood cells are also known as RBCs or erythrocytes (from . 2 Evolutionary advantages of red blood cells. 3 Mammalian erythrocytes. 4 Human erythrocytes .
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red blood cell n. ( Abbr. RBC ) A cell in the blood of vertebrates that transports oxygen and carbon dioxide to and from the tissues
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An anemic person has fewer or smaller than normal red blood cells. . Each unit of packed red blood cells administered to an adult is expected to .
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red blood cells (RBCs) or erythrocytes. platelets or thrombocytes . Red blood cells have surface antigens that differ between people and that create .
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The capitalized term Red Blood Cells is the proper name in the United States for . The first person to describe red blood cells was probably the young Dutch .
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If red blood cells are also deficient in hemoglobin, then your body isn't getting enough iron. . Red blood cells can be lost through bleeding, which can .
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Red Blood CellsWith a diameter of .0003 of an inch and a rim thickness of only .00001 of an inch, normal red blood cells have a biconcave shape, and elasti.
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Online Medical Dictionary and glossary with medical definitions . for red blood cells is RBCs. Red blood cells are sometime simply called red cells. .
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The mature red blood cell (also known as an erythrocyte) carries oxygen attached . The number of red blood cells is determined by age, sex, altitude, exercise, .
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The primary function of the red blood cells, or erythrocytes, is to carry oxygen . Oxygen transfer is accomplished via the hemoglobin contained in red blood cells. .
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The scientific name for red blood cells is erythrocytes. . Red blood cells contain hemoglobin, a protein that carries oxygen. .
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Red blood cells contain hemoglobin, a complex iron-containing protein that . Since red blood cells have reduced amounts of plasma, they are well suited for .
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Red blood cell indices are measurements that describe the size and oxygen . An anemic person has red blood cells that are either too small or too few in number. .
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A red blood cell (an erythrocyte) is described in any of the following ways: . Transporting hemoglobin is almost the only thing that the red blood cell does. .
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The proportion of blood occupied by red blood cells is referred to as the . creates a mesh onto which red blood cells collect and clot, which then stops .
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Destruction of red blood cells

Survival of the red blood cell in the circulation depends upon the continuous utilization of glucose for the production of energy. Two chemical pathways are employed, and both are essential for the normal life of the red cell. An extraordinary number of enzyme systems participate in these reactions and direct the energy evolved into appropriate uses. Red cells contain neither a nucleus nor RNA (ribonucleic acid, necessary for protein synthesis), so that cell division (mitosis) and production of new protein are impossible. Energy is not necessary for oxygen and carbon dioxide transport, which depends principally on the properties of hemoglobin. Energy, however, is needed for another reason. Because of the tendency for extracellular sodium to leak into the red cell and for potassium to leak out, energy is required to operate a pumping mechanism in the red cell membrane to maintain the normal gradients (differences in concentrations) of these ions. Energy is also required to convert methemoglobin to oxyhemoglobin and to prevent the oxidation of other constituents of the red cell.