Erythrocytes and Erythropoiesis

Erythrocytes

• Erythrocytes, also known as red blood cells (RBCs), lack a nucleus and organelles.
• Normal RBC count: Male - 5 - 5.5 x 10⁶ /µL; Female - 4.5 - 5 x 10⁶ /µL.
• RBCs are biconcave discs, measuring 7.5-8 micrometers in diameter and 2µm thick at the outer edge and 1µm thick at the center.
• RBC membrane is flexible to change shape as RBCs pass through narrow capillaries (5µm).
• Hemoglobin carries oxygen (O₂) and carbon dioxide (CO₂).
• Average life span of RBCs is 120 days.
• Old and abnormal RBCs are removed by the spleen.
• New RBCs are generated by bone marrow.

Erythropoiesis

• Erythropoiesis is the process of RBC production.
• Sites of erythropoiesis:
  • Fetus: first trimester - yolk sac; second trimester - liver and spleen; third trimester - bone marrow of all bones
  • Children: bone marrow of all bones
  • Adult: bone marrow of flat bones and proximal ends of long bones (humerus and femur). Red marrow in other bones is replaced by fatty yellow marrow.
• Major steps in Erythropoiesis involve a chain of cell development: Pluripotent stem cell → Myeloid stem cell → Erythroblast → Reticulocyte → Erythrocyte
• Steps of Erythropoiesis : reduction in size, disappearance of nucleus, acquiring hemoglobin
• Reticulocytes are immature RBCs without a nucleus having a granular appearance, which are visible with ribosomal RNA. Normal reticulocyte count (retic count) is 0.5 - 1.5%. Reticulocytes are also good indicator, showing recent bone marrow activity.

Hemoglobin

• Normal Hemoglobin concentration: Female - 14 g/dL; Male - 16 g/dL.
• Adult hemoglobin (type A1) has two parts:
  • Globin: a protein with four polypeptide chains (2 alpha & 2 beta chains). Each alpha chain has 141 amino acids, and each beta chain has 146 amino acids.
  • Heme: four iron-containing heme groups, each bound to one polypeptide chain.
• Hemoglobin transports O₂ and CO₂. 98.5% of O₂ is carried by hemoglobin.
• Hemoglobin carries one oxygen molecule per subunit and combines with oxygen and has higher affinity for carbon monoxide (CO) than O₂.
• Hemoglobin appears reddish when combined with O₂ (e.g., arterial blood) and bluish when deoxygenated (e.g., venous blood).
• Function of Hemoglobin: transports oxygen, transports carbon dioxide, acts as a buffer by combining with H+ ions.

Applied Aspects

• If bone marrow sample is required, it is usually taken from iliac crest or sternum.
• Synthetic erythropoietin is given to patients with kidney failure or cancer undergoing chemotherapy to help with RBC production.
• During blood donation, about 450 ml of blood is given. Plasma is replaced in 2-3 days. RBCs are replaced in 36 days (20-59 days), therefore, blood donation is recommeneded after 3 months.

Erythrocytes Breakdown

• Average lifespan of RBC is 120 days.
• When RBCs breakdown, macrophages break hemoglobin into heme and globin.
• Globin is degraded into amino acids.
• Released iron is returned to the blood.
• Heme is converted to bilirubin.
• Bilirubin is carried to the liver and excreted in bile.
• The spleen removes old and abnormal RBCs.

Clinical Applications

• Increased RBC destruction may cause jaundice (yellowing of eyes and skin).

Summary

• Sites and requirements for RBC synthesis, the most abundant type of adult hemoglobin, the hormone released by kidneys to control RBC synthesis, the maturation process of RBCs in bone marrow, the importance of reticulocytes, sites and products of RBC breakdown, and definition of jaundice were all covered, along with the case study of sickle cell anemia and associated questions.