Hemoglobin Production and Reticulocyte Stage

Hemoglobin Production

• Hemoglobin production starts in polychromatophil erythroblasts
• In successive generations, cells fill with hemoglobin, and the nucleus and endoplasmic reticulum are reabsorbed
• The cell at this stage, called a reticulocyte, still has remnants of organelles and ribosomal RNA, allowing it to produce hemoglobin

Reticulocyte Stage

• Reticulocytes pass from the bone marrow to the blood capillaries via diapedesis
• Within 1-2 days, the remaining material disappears, and the cell becomes an erythrocyte
• Reticulocyte concentration among red blood cells is usually less than 1%

Functions of Red Blood Cells

• Gas transport function: Red blood cells transport respiratory gases like oxygen and carbon dioxide
• Hemoglobin, a protein in these cells, binds with oxygen and most oxygen in the blood is carried by it
• Red blood cells pick up oxygen in the lungs and deliver it to tissue cells in the body, and also transport about 20% of carbon dioxide back to the lungs
• Erythrocytes have three structural characteristics that help them transport gases effectively:
  • Small size and biconcave shape provide a huge surface area relative to volume (about 30% more surface area than comparable spherical cells)
  • Discounting water content, an erythrocyte is over 97% hemoglobin, the molecule that binds to and transports respiratory gases
  • Because erythrocytes lack mitochondria and generate ATP by anaerobic mechanisms, they do not consume any of the oxygen they are transporting, making them very efficient oxygen transporters

Structural Characteristics

• Erythrocytes or red blood cells (RBCs) are small, anucleate cells enclosed by a plasma membrane and shaped like biconcave discs with depressed centers
• They are about 7.5μm in diameter and maintain their shape through a network of proteins, particularly spectrin
• The biconcave shape provides a large surface-to-volume ratio and facilitates gas exchange
• The normal concentration of erythrocytes in the blood is approximately 3.9 to 5.5 million per microliter (μL, or mm3) in women and 4.1-6.0 million/μL in men

Maturation and Development

• Several proteins in red blood cells are important in maintaining their shape
• These include band 3, proteins 4.1, 4.2, α and β spectrin, ankyrin, protein 4.1, and actin
• Together, they form a lattice on the inside of the cell membrane
• Spectrin is the most abundant protein
• Abnormalities in these proteins can result in red blood cells with an unusual shape, such as hereditary spherocytosis and elliptocytosis

Red Cell Metabolism

• In this series of biochemical reactions, glucose that enters the red cell from plasma by facilitated transfer is metabolized to lactate
• For each molecule of glucose used, two molecules of ATP and thus two high‐energy phosphate bonds are generated
• This ATP provides energy for the maintenance of red cell volume, shape, and flexibility
• The Embden–Meyerhof pathway also generates NADH, which is needed by the enzyme methemoglobin reductase to reduce functionally dead methemoglobin containing ferric iron to functionally active, reduced hemoglobin containing ferrous ions

Origin of Blood

• The Luebering–Rapoport shunt, or sidearm, of this pathway, generates 2,3‐DPG, important in the regulation of hemoglobin’s oxygen affinity
• Hexose monophosphate shunt:
  • Approximately 10% of glycolysis occurs by this oxidative pathway in which glucose‐6‐phosphate is converted to 6‐phosphogluconate and so to ribulose‐5‐phosphate
  • NADPH is generated and is linked with glutathione which maintains sulphydril (SH) groups intact in the cell, including those in hemoglobin and the red cell membrane