18. Erythrocytes - structural, ultrastructural and functional characteristics. Erythropoiesis.

RBCs are biconcave discs that are highly flexible and malleable as they can travel in narrow capillary lumina. They don't have a nucleus and are the highest number of cells in blood and have a lifespan in circulation of about 120 days. 

The number of RBC in men makes up on average 45% of blood and is 4.1 – 6.1 x10¹²(million) per cubic millimetre. 

In women RBCs make up on average 42% and 3.8-5.5 x10¹²(million) per cubic millimetre. 

In the human embryo, RBCs are initially nucleated, upon 7 weeks during development. During the final stages of erythropoietic development in the bone marrow, RBCs lose their nucleus and almost all of their organelles except the cytoskeleton and then enter the circulation. 

In standard blood smears, the RBC centre is a pale area which is surrounded by a thicker eosinophilic peripheral zone. 

A biconcave shape provides a large surface area for gas exchange: transporting O₂ from lungs to provide to the tissues and returning CO₂ from tissues to lungs for elimination. The protein containing iron, called haemoglobin in RBCs accounts for their red colour. Haemoglobin rapidly binds to O₂ for transport due to its high affinity. It is a conjugated protein containing the pigment heme and the protein globin.

RBCs are 2.3-2.6μм thick and in the centre they are 0.8-1.0μм thick. Their diameter is normally 7-8μм. Microcytes have a diameter of 6μм, Macrocytes = 9μм, & Megalocytes = 12μм.

The increased number of erythrocytes is called erythrocytosis and the decrease in number of erythrocytes is called erythropenia. 

Erythropoiesis is the production of RBCs and takes around 7-8 days. During the maturation of the myeloid lineage, large primitive cells become smaller. The nucleus of young cells are big in relation to the cytoplasm, these too become smaller. They become pyknotic and eventually extruded. 

The initial stem cell, hemocytoblast differentiates into a large, round proerythroblast, that has a diameter of 15-30 μm. It has a deep blue cytoplasm due to lots of ribosomal RNA. 

Lots of free ribosomes begin to synthesise haemoglobin. 

The erythroblast divides into two smaller (10-18 μm) basophilic erythroblasts, which have an intensely basophilic cytoplasm and a more heterochromatic nucleus. 

Ribosomes still continue to synthesise more haemoglobin. 

Basophilic erythroblasts undergoes two or three cell divisions, and forms the polychromatic erythroblast, with a diameter of 10-12 μm. The slate grey bit of its cytoplasm is due to the build-up of haemoglobin and decrease in ribosomes. Its nucleus has condensed chromatin but no nucleoli. With higher haemoglobin content, the cytoplasm becomes more eosinophilic, and the cell is now called an orthochromatic erythroblast. This 8 to 10 μm cell has a small, densely stained, pyknotic nucleus. After extrusion of the nucleus and loss of all organelles, the cell becomes biconcave and has a diameter of 7-10 μm to form an erythrocyte. Erythrocytes remain in the bone marrow for 2-3 days until they fully mature, then released into the peripheral circulation.

Overall results of erythropoiesis are; synthesis and accumulation of haemoglobin, extrusion of the nucleus and decrease in cell volume.