18.2 Production of the Formed Elements

Hemopoiesis and Blood Cell Formation

Blood cell formation, called hemopoiesis, is the process by which all blood cells are produced from a single type of stem cell in the bone marrow. Understanding this process explains how your body maintains its blood supply, fights infections, and repairs itself after injury.

Process of Hemopoiesis

Hemopoiesis takes place primarily in the red bone marrow found within certain bones: the pelvis, sternum, ribs, vertebrae, and the ends of long bones. It all starts with hemopoietic stem cells (HSCs), which are multipotent, meaning they can differentiate into any type of blood cell.

HSCs reside in specialized microenvironments called stem cell niches, which provide the signals needed for self-renewal and differentiation. When an HSC divides, it can follow one of two major lineages:

• Myeloid lineage produces:
  • Erythrocytes (red blood cells), which develop from erythroblast precursors
  • Platelets, which develop from megakaryoblast precursors (megakaryocytes fragment into platelets)
  • Myeloblasts, which further differentiate into granulocytes (neutrophils, eosinophils, basophils) and monocytes
• Lymphoid lineage produces:
  • Lymphoblasts, which further differentiate into T lymphocytes, B lymphocytes, and natural killer (NK) cells

Between the HSC and the final mature cell, there are intermediate stages called precursor cells (also known as progenitor cells). Each blood cell type has its own specific precursor. As a cell moves through these stages, it becomes progressively more specialized and loses the ability to become other cell types.

Regulation of Blood Cell Production

The body doesn't produce blood cells at random. Production is tightly controlled by hemopoietic growth factors, which are cytokines that stimulate specific cell lines to proliferate and differentiate. Here are the major ones:

• Erythropoietin (EPO) stimulates red blood cell production. The kidneys release EPO when they detect low oxygen levels (hypoxia). This is why people living at high altitudes or those with chronic lung disease often have elevated red blood cell counts.
• Thrombopoietin (TPO) stimulates platelet production. It's produced mainly by the liver and kidneys.
• Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate granulocyte and monocyte production. These are produced by endothelial cells, fibroblasts, and other tissues, often in response to infection.
• Interleukins such as IL-3 and IL-7, along with other cytokines, regulate lymphocyte production. These are secreted by immune cells like T lymphocytes and macrophages.

Beyond these chemical signals, the hematopoietic microenvironment itself plays a role. Stromal cells and the extracellular matrix within the bone marrow physically support developing blood cells and provide local signaling that guides differentiation.

Sites of Blood Cell Formation

The location of hemopoiesis changes over the course of a human lifetime:

1. Early embryonic development (first few weeks): The yolk sac is the primary site of blood cell formation.
2. Second trimester through late fetal development: The liver takes over as the main hemopoietic organ. The spleen contributes in a minor role during this period.
3. After birth: The red bone marrow becomes the dominant site and remains so for life. In adults, the most active marrow is in the pelvis, sternum, ribs, and vertebrae.

If the body faces unusually high demand for blood cells, the liver and spleen can reactivate their blood-forming capacity. This is called extramedullary hemopoiesis and can occur in conditions like severe anemia or bone marrow disease.

Other hematopoietic organs also contribute to blood cell maturation. The thymus is where T lymphocytes mature, and lymph nodes serve as sites where lymphocytes encounter antigens and complete their activation.

Cell Turnover and Homeostasis

Your body produces roughly 200 billion red blood cells and 150 billion platelets every day just to replace those that wear out. Blood cell production must be carefully balanced with cell removal to maintain homeostasis.

Old or damaged cells are cleared primarily by macrophages in the spleen and liver. Apoptosis (programmed cell death) also plays a key role by eliminating cells that are defective, unnecessary, or have completed their functional lifespan. When this balance between production and removal is disrupted, conditions like anemia (too few red blood cells) or leukocytosis (too many white blood cells) can result.