Blood Tissue and Erythrocyte Life Cycle: An In-Depth Guide

Blood Tissue: Free Cell Populations

Free cell populations are cells not associated with forming a coherent, topographically specific, and well-circumscribed structure. This category includes blood cells and immunocompetent cells. These cells are part of diffuse cell systems distributed within the organism’s tissues.

A common functional feature of these cells is their mobility. Most are found in lymph and blood, occasionally referred to as immigrant cells.

Free cell populations are found in:

  • Circulating tissues (blood, lymph, cerebrospinal fluid)
  • Hematopoietic tissues (red bone marrow, lymphoid formations)
  • Other tissues (epithelial, connective, etc.)

Immunocompetent cells of the immune system, involved in specific defense mechanisms, are based in:

  • Hematopoietic marrow
  • Blood and lymph
  • Lymphoid formations

Hematopoiesis: Embryonic, Fetal, and Postnatal

Hematopoiesis occurs in hematopoietic tissues and organs. In adults, two foci of hematopoietic activity exist: myeloid tissue in the bone marrow and lymphoid tissue in lymphoid organs and formations.

During embryonic and fetal life, hematopoiesis has three distinct periods:

1. Prehepatic or Mesenchymal Phase

This phase occurs between the second and twelfth weeks of human development. Blood elements differentiate from extraembryonic mesenchyme lining the yolk sac, where Wolff and Pander islets are located.

2. Lymphoid Liver Phase

This phase begins in the second month of human development in the liver, spleen, thymus, and lymph nodes. Elements for all blood cell series are generated. Blood formation gradually shifts from the liver to the bone marrow from the sixth month onward.

3. Medullo-Lymphoid Phase

This phase is established in the bone marrow from the sixth month of development. Different blood precursors intermingle within the red marrow, forming myeloid tissue.

Myeloid tissue consists of:

  • Reticular connective tissue cells that support various blood cell series
  • Adipocytes in variable quantities
  • Endothelium-lined capillaries and large, winding sinuses that release mature blood elements

Competent Hematopoietic Stem Cell

The competent hematopoietic stem cell is a mesenchymal cell involved in differentiating elements belonging to different series: red blood cells, platelets, granulocytes, and lymphocytes.

The progeny of pluripotent stem cell lines must choose between various differentiation pathways. Before differentiation, all cells appear similar, making identification through morphology impossible.

A classic experiment demonstrating pluripotent stem cells in bone marrow involves:

  1. Irradiating animals with X-rays to destroy their bone marrow
  2. Transplanting bone marrow from a compatible donor to provide new hematopoietic tissue

After a few days, cell colonies develop. Genetic markers reveal that splenic nodules are clones derived from a single founder cell: the colony-forming unit-spleen (CFU-S). These cells are considered stem cells.

Committed Hematopoietic Stem Cell

A committed hematopoietic stem cell follows an irreversible differentiation pathway, becoming unipotential. This commitment is followed by cell divisions that amplify the pool of committed stem cells. Amplifying divisions undergo strict control to regulate the production of each blood cell series. Committed stem cells reside in bone marrow and lymphoid organs and formations.

Regulation of Hematopoiesis

Several factors regulate hematopoiesis:

1. Erythropoietin (EPO)

EPO is a hormone produced in the kidneys that stimulates erythropoiesis (red blood cell production).

2. Other Hormones and Erythropoietin Analogue Factors

These hormones are produced in response to the need for various white blood cells or platelets. Each glycoprotein precursor cell variant is believed to have a specific humoral factor.

Interleukins are humoral factors involved in hematopoiesis.

3. Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)

Neutrophil granulocytes and macrophages originate from the same committed precursor. This precursor relies on GM-CSF for survival. GM-CSF concentrations in the blood increase sharply after infection.

4. Other Factors

Other factors influencing hematopoiesis include hypothalamic hormones, pituitary hormones, adrenal hormones, iron, cobalt, vitamin B12, and folic acid.

5. Feedback Mechanisms

The number of mature blood elements in peripheral blood conditions feedback mechanisms that stimulate or inhibit the differentiation of precursors in hematopoietic organs.

Composition of Blood

Blood comprises:

1. Plasma (55-60%)

2. Formed Elements or Blood Cells (40-45%)

Formed elements include:

a) Corpuscles

  • Red blood cells, erythrocytes, or RBCs (4.5-5 million/mm3 in women and 4.5-5.5 million/mm3 in men)
  • Thrombocytes or platelets (150,000-300,000/mm3)

b) White Blood Cells or Leukocytes (5,000-7,000/mm3)

  • Granulocytes:
    • Neutrophils: band cells (1-3%) and segmented neutrophils (60-70%)
    • Eosinophils (1-3%)
    • Basophils (0.5-1%)
  • Agranulocytes:
    • Lymphocytes (20-40%)
    • Monocytes (2-6%)

Functions of Blood

Blood serves several essential functions:

  • Transporting nutrients from the intestines to tissues, liver, and back
  • Exchanging respiratory gases (oxygen and carbon dioxide) between the lungs and tissues
  • Transporting metabolic waste products to the kidneys, skin, intestines, and liver for excretion
  • Distributing regulatory hormones and other substances
  • Protecting against microorganisms
  • Maintaining acid-base and fluid-electrolyte balance
  • Regulating body temperature (thermoregulation)
  • Facilitating blood clotting (coagulation)

Life Cycle of the Erythrocyte: Mature Erythrocyte

Erythrocyte: Concept and General Characteristics

Red blood cells, or erythrocytes, are blood corpuscles responsible for transporting oxygen (O2) and carbon dioxide (CO2). Their biconcave disc shape maximizes surface area for efficient gas exchange. Cytoskeletal proteins like spectrin, actin, and tropomyosin maintain their shape and elasticity.

In humans, erythrocytes are 7-8 µm in diameter, with a thickness of 2 µm at the periphery and 1.5 µm in the center.

Structure

Erythrocytes have a simple structure: a cell envelope enclosing an eosinophilic, moderately electron-dense, amorphous, and homogeneous content consisting mainly of hemoglobin. They lack a nucleus.

Under normal conditions, about 1% of circulating red blood cells are reticulocytes, immature erythrocytes containing ribosome remnants and other organelles visible as a delicate network of basophilic clumps under a microscope.

Half-Life, Destruction, and Renewal

Erythrocytes have a lifespan of 120 days after entering the bloodstream. Old, defective, and worn-out red blood cells are destroyed primarily in the spleen and, to a lesser extent, in the liver and bone marrow. Macrophages engulf and degrade erythrocytes, recycling iron and amino acids from hemoglobin. This process is called eryptosis.

Red blood cell production, or erythropoiesis, occurs in the bone marrow.

Erythropoiesis

Erythropoiesis begins with the erythropoietic stem cell, which differentiates into the following cell types:

  1. Pronormoblasts
  2. Basophilic erythroblasts
  3. Polychromatophilic erythroblasts
  4. Orthochromatophilic erythroblasts (normoblasts)
  5. Reticulocytes
  6. Mature red blood cells

As they differentiate and mature, red blood cells decrease in volume, their nuclear chromatin condenses until the nucleus is expelled at the normoblast stage, hemoglobin synthesis increases, and they lose their organelles.