Erythrocytes (red blood cells or RBCs) are anucleate, biconcave cells, filled with hemoglobin, that transport oxygen and carbon dioxide between the lungs and tissues. They are produced in the red bone marrow by a process called erythropoiesis. During this process, stem cell derived erythroid precursors undergo a series of morphological changes to become mature erythrocytes.
These mature RBCs are released into the bloodstream, where they survive between 100 to 120 days. As you can see, erythrocytes describe the state of your health for the past 3 months, so they can’t be fooled easily! This is the basis for the glycated hemoglobin (HbA1c) test performed by diabetics every 3 months to check their blood glucose levels. After 120 days, old RBCs are recycled by the macrophages of the spleen, liver, bone marrow and lymph nodes (reticuloendothelial system).
Do not contain organelles (including nucleus)
Contain only hemoglobin
|Function||Gas exchange and transport between lungs, blood and tissues (oxygen and carbon dioxide)
Determining blood type
|Origin||Red bone marrow (flat bones)|
|Stages of erythropoiesis||Colony Forming Unit - Erythroid, proerythroblast, erythroblast, reticulocyte, erythrocyte|
|Clearance sites||Mainly in the spleen by eryptosis|
|Disorders of erythrocytes||Anemia, polycythemia|
This article will focus on erythrocyte histology, in order to explain the structure, functions and life cycle of these cells.
- Erythrocyte structure
- Erythrocyte function
- Life cycle of erythrocytes
- Disorders of erythrocytes
Erythrocytes have a consistent diameter of 7-8 µm, making them the perfect ‘histologic rulers’ during routine examinations. However, they have an atypical structure compared to the majority of human body cells. First of all, erythrocytes have a biconcave shape, which resembles a donut. This means that their periphery is thicker than their central part. This feature maximizes the total surface of the cell membrane, facilitating gas exchange and transport. In addition, erythrocytes do not have a nucleus (anuclear) or any other intracellular organelles, as they are all lost during erythropoiesis. The only two major structures left are the cytoplasm which is enclosed by a surrounding cell membrane.
The cytoplasm of RBCs is filled with hemoglobin, a protein that reversibly binds and transports oxygen and carbon dioxide. The acidophilia of hemoglobin makes erythrocytes to stain intensely red with eosin on tissue samples stained with hematoxylin and eosin (H&E).
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Hemoglobin is a tetramer that comprises four polypeptide subunits called globin chains. There are four types of globin chains (α, β, γ, δ) which can give rise to three main hemoglobin classes called HbA, HbA2 and HbF. By far, the most prevalent one in adults is hemoglobin HbA. Each globin subunit contains an iron atom bound to a molecule called heme. The iron plays the main role in binding gasses, therefore each hemoglobin can transport up to four molecules of oxygen or carbon dioxide.
The cell membrane of erythrocytes is a lipid bilayer that contains two types of membrane proteins: integral and peripheral. Integral membrane proteins are more numerous, stretching through the entire thickness of the cell membrane. They bind hemoglobin and serve as anchor points for the cytoskeletal network of RBCs. In addition, integral membrane proteins express the antigens of ABO blood groups. Various combinations of these antigens can yield four main blood types: A, B, O and AB. Besides ABO, the membrane can also contain the Rh antigen. If a person has Rh on their erythrocytes, their blood type will be Rh positive (e.g. AB+). If the Rh is absent, the type is Rh negative (e.g. AB-). These erythrocyte surface antigens are extremely important for blood transfusions.
Peripheral membrane proteins project only into the cytoplasm, being located on the inner surface of the plasma membrane. These proteins are interconnected by many intracellular filaments, forming a complex mesh-like cytoskeletal network along the inner cell membrane. This network imparts elasticity and strength to erythrocytes, allowing them to pass through even the smallest capillaries in our body without breaking.
So far you’ve seen the structure of RBCs, but what do they actually do? The main role of erythrocytes is transportation and exchange of gases (oxygen, carbon dioxide) between lungs and tissues. Here’s how this happens in real time:
- In lung capillaries, hemoglobin binds the inhaled oxygen, forming oxyhemoglobin. This substance gives erythrocytes, and hence arterial blood, a bright red colour.
- Oxygen rich erythrocytes then travel through the arteries until they reach tissue capillaries.
- In tissue capillaries, the oxygen is released from hemoglobin and diffuses into the tissues.
- Simultaneously, the carbon dioxide from the tissues binds to hemoglobin, forming deoxyhemoglobin. This substance gives RBCs, and venous blood, a purple blue colour.
- Carbon dioxide rich erythrocytes then travel via venous blood towards the heart, and then to the lungs.
- Within lung capillaries, the carbon dioxide is released from hemoglobin in exchange for a new dose of oxygen.
Learn more about the histology of blood vessels to find out how vessels permit the diffusion of gasses and test your knowledge with our learning materials and their integrated quizzes.
Life cycle of erythrocytes
The life cycle of erythrocytes involves three stages; production, maturity and destruction. Production of erythrocytes (erythropoiesis) is one of the sub-processes of hematopoiesis, happening in the red bone marrow.
Early phases of hematopoiesis result in the creation of an erythroid stem cell, called CFU-E (Colony Forming Unit - Erythroid). This marks the beginning of erythropoiesis, a process driven forward predominantly by the hormone erythropoietin. CFU-E cells are found within erythroid islands in the bone marrow, where they replicate and differentiate towards mature erythrocytes. The differentiation process produces several generations of cells; proerythroblasts, erythroblasts, reticulocytes and erythrocytes. Each new cell population histologically resembles erythrocytes more closely.
You will find everything you need to know about erythropoiesis in our hematopoiesis article, while the following table will provide you with a brief summary of all cell generations and their main histological features.
|Proerythroblast||Large euchromatic nucleus with a prominent nucleolus. It contains a lot of ribosomes for the synthesis of hemoglobin subunits.|
|Basophilic erythroblast||Intensely stained basophilic cytoplasm as it contains even more ribosomes that synthesize subunits of hemoglobin.|
|Polychromatophilic erythroblast||Basophilic cytoplasm with many acidophilic fields. The first shape that contains hemoglobin molecules (acidophilic fields).|
|Acidophilic erythroblast||Strong acidophilia from large aggregations of hemoglobin. It ends its differentiation by expelling the nucleus.|
|Reticulocyte||Anucleate cell which stains with brilliant cresyl blue. It contains polyribosomes.|
|Erythrocyte||Anucleate cell without any organelles, containing only hemoglobin molecules.|
In this study unit you can learn more about the histology of the blood and actively test your skills.
With the time spent in circulation, the cell membrane of erythrocytes gets damaged. Macrophages recognize this morphological blueprint of an old or unfeasible erythrocyte and phagocytose it. The primary site of erythrocyte clearance, called eryptosis, is the spleen. In a healthy organism, eryptosis is in balance with erythropoiesis, ensuring a physiological amount of RBCs.
If you recall, globin chains and iron containing heme groups are the two most important components of hemoglobin within an erythrocyte. Once phagocytosed by macrophages, these components are separated. The polypeptide globin chains are degraded into amino acids, while the iron is extracted from heme. The iron molecule is subsequently transferred to the bone marrow to be reused in new cycles of erythropoiesis, while heme is metabolized into bilirubin. With additional modifications in the liver and intestines, bilirubin is excreted through urine and feces.
Disorders of erythrocytes
Erythrocyte disorders include anemias and polycythemias. Anemias are a group of diseases that manifest with a low oxygen transport capacity in the blood. They are mainly caused by either a decreased number of erythrocytes, or by a reduced concentration of hemoglobin inside RBCs. Due to anemias, tissues don’t get enough oxygen supply, a situation which presents with pallor, fatigue, shortness of breath and lightheadedness.
Anemias can be classified into various types, depending on their causes:
- Hemolytic anemia - caused by increased degradation or destruction of erythrocytes.
- Sideropenic anemia, also known as iron deficiency anemia.
- Megaloblastic anemia is caused by deficiency of folate and/or vitamin B12. They are necessary for differentiation of erythrocyte precursors.
- Aplastic anemia is due to aplasia (destruction) of the red bone marrow. It can happen during chemotherapy.
The opposite of anemia is a condition called polycythemia, which is defined as an elevated RBC count. It is much rarer compared to anemias.