Haematopoiesis

Definition

• Haematopoiesis refers to the formation of blood cells.

Sites of Haematopoiesis

• Haematopoiesis occurs at different sites during various developmental stages:

  1. Yolk Sac (Mesoderm): The first site of haematopoiesis.

  2. Liver (Hepatic): After the yolk sac, the liver takes over as a significant site.

  3. Bone Marrow (Myeloid): The primary site for blood cell formation from around six months gestation onwards.

Phases of Haematopoiesis

1. Mesoblastic Period (2 months)

   • Duration: First two months of fetal life.

   • Occurs in mesodermal clusters of cells known as blood islands found within the embryonic yolk sac.

2. Hepatic Period (2-6 months)

   • Duration: From the second to the sixth month of fetal life.

   • The liver serves as the major site pfor blood cell production, hence called the hepatic period.

   • The spleen also contributes to the production of lymphocytes and red blood cells during this time.

3. Myeloid Phase (6 months to birth)

   • Begins around six months' gestation.

   • The bone marrow becomes the major site for the production of blood cells, continuing through to birth.

   • Lymph nodes and thymus gland play significant roles in the production of lymphocytes during this period.

Extrauterine Haematopoiesis

• Occurs during the first five years of life where myeloid haematopoiesis happens in virtually all bone marrow.

• Following this period, a progression of replacement occurs in long bone marrow leading to blood-forming marrow reductions.

• Other sites take over, primarily in the bones of the trunk which include:

  • Vertebrae

  • Ribs

  • Sternum

  • Scapulae

  • Pelvis

  • Skull

Extramedullary Haematopoiesis

• In certain disease states where bone marrow supply of blood cells is insufficient to meet demand, blood cell formation may resume at locations outside of the bone marrow.

• Common sites include the liver and spleen.

• This phenomenon is referred to as extramedullary haematopoiesis.

Developmental Origin of Blood Cells

Stem Cells

• Blood cells originate from pluripotent or multipotent stem cells, also known as hemocytoblasts.

• These stem cells are capable of dividing and differentiating into committed stem cells when stimulated by specific hormones or ligands.

Stimulators of Stem Cell Differentiation

• Key factors include:

  • FLT-3: FMS-like tyrosine kinase 3

  • TNF-α: Tumor necrosis factor alpha

  • TGF-β: Transforming growth factor beta

  • IL-2: Interleukin 2

  • GM-CSF: Granulocyte macrophage colony-stimulating factor

  • SDF-1: Stromal cell-derived factor 1

  • SCF: Stem cell factor

  • EPO: Erythropoietin

  • M-CSF: Macrophage colony-stimulating factor

  • G-CSF: Granulocyte-colony stimulating factor

  • TPO: Thrombopoietin

Commitments in Blood Cell Lineages

1. Committed Stem Cells: These stem cells actively divide and differentiate into the first recognizable immature forms of blood cells, termed "blast" cells, when stimulated.

2. Blast Cells: These are the earliest discernible immature forms of blood cells that are still actively mitotic.

   • Main characterizing changes during their development includes:

     1. A decrease in mitotic activity.

     2. A decrease in cell size.

     3. The disappearance of nucleoli.

     4. Coarsening of nuclear chromatin.

     5. A decrease in RNA levels.

     6. Development of specific cytoplasmic inclusions like hemoglobin in red blood cells and granules in granulocytes.

Haematopoiesis refers to the formation of blood cells, occurring at the following sites during development:

1. Yolk Sac (Mesoderm): First site of haematopoiesis.

2. Liver (Hepatic): Major site from 2 to 6 months.

3. Bone Marrow (Myeloid): Primary site from around six months gestation.

Phases of Haematopoiesis

1. Mesoblastic Phase (first two months): Blood cell formation occurs in blood islands of the yolk sac.

2. Hepatic Phase (2-6 months): Liver produces blood cells, with the spleen contributing lymphocytes.

3. Myeloid Phase (6 months to birth): Bone marrow becomes the primary site for blood production.

Extrauterine Haematopoiesis

Takes place in the first five years, with blood-forming marrow gradually reducing in long bones.

Extramedullary Haematopoiesis

Occurs in conditions where bone marrow is insufficient, mainly in the liver and spleen.

Developmental Origin of Blood Cells

Blood cells originate from pluripotent or multipotent stem cells (hemocytoblasts) that differentiate into committed stem cells.

Stimulators of Stem Cell Differentiation

Key factors include FLT-3, TNF-α, TGF-β, IL-2, GM-CSF, SDF-1, SCF, EPO, M-CSF, G-CSF, and TPO.

Commitments in Blood Cell Lineages

1. Committed Stem Cells: Differentiate into blast cells.

2. Blast Cells: Early immature forms that decrease in size and activity as they develop, with notable changes like the appearance of hemoglobin in red blood cells.