Erythropoiesis and Red Blood Cell Lifespan

Definition of Erythropoiesis

• Erythropoiesis: The normal production of red blood cells (RBCs).
• Occurs in red bone marrow found in the epiphyses of long bones.

Triggers of Erythropoiesis

• Blood Loss: E.g., stab wounds or ulcers.
• Low Oxygen Levels: E.g., altitude sickness (climbing Mount Everest).
• Anemia: Low red blood cell count triggers the need for more RBCs.
• Overall cause referred to as hypoxia: Inadequate oxygen delivery to tissues.

Nutritional Requirements for Erythropoiesis

Essential Substances

• Iron: Critical for hemoglobin synthesis.
  • Absorbed through the gastrointestinal tract, particularly in the duodenum.
  • Process involves:
    • Reduction: Iron (Fe3+) is converted to Fe2+ by the enzyme duodenal cytochrome B.
    • Transport: Iron enters enterocytes via divalent metal transporter 1 (DMT1).
    • Storage: Iron binds to apoferritin to form ferritin.
    • Transport to Bloodstream: Iron exits enterocytes via ferroportin, converted back to Fe3+ by HEP-Haston, and binds to transferrin for transportation.
• Vitamin B12 and Folate (B9): Essential for DNA synthesis and cell maturation.
  • B12 binds to intrinsic factor in the stomach and is absorbed in the ileum.
  • Transcobalamin proteins transport B12 in the bloodstream.
• Amino Acids, Carbohydrates, and Fats: Required for hemoglobin synthesis and overall energy needs.

Regulation of Iron Levels

• Hepcidin: A hormone produced by the liver that regulates ferroportin; controls iron levels in the bloodstream.
• HFE Protein: Regulates hepcidin production; dysfunction leads to conditions like hemochromatosis, resulting in iron overload.

Erythropoiesis Process

1. Stem Cell: Starts with hemocytoblasts (pluripotent stem cells) in the bone marrow.
2. Myeloid Stem Cell: Differentiates from hemocytoblasts to produce RBCs.
3. Erythropoietin (EPO): Hormone stimulating myeloid stem cells to commit to RBC production.
4. Cell Lineage Development:
   • Proerythroblast → Basophilic erythroblast → Polychromatic erythroblast → Orthochromatic erythroblast.
5. Nuclear Ejection: Orthochromatic erythroblast ejects its nucleus, forming a reticulocyte, which matures into an erythrocyte (RBC).

Lifespan and Function of Erythrocytes

• Lifespan: RBCs live for about 100-120 days.
• Function: Transport oxygen from lungs to tissues and carry carbon dioxide from tissues to lungs.
• Lack of mitochondria ensures they do not use the oxygen they transport.

Nutritional Deficiencies and Anemia Types

• B12 and Folate Deficiency: Leads to macrocytic anemia (larger than normal RBCs).
• Iron Deficiency: Results in microcytic anemia (smaller than normal RBCs).
• Amino Acids, Fats, and Carbs: Essential for overall RBC health and hemoglobin synthesis.

Conclusion

• Erythropoiesis is a complex process requiring various nutrients and regulatory hormones to ensure adequate production and maintenance of healthy red blood cells.