Hematopoiesis and Cell Cycle Overview

Blood cell formation involves production and development of cells.
Occurs primarily in bone marrow, with secondary sites including liver, spleen, lymph nodes, and thymus.
In normal adults, effective hematopoiesis takes place solely in bone marrow.
Daily production rate of cells: approximately 6 billion cells/kg body weight.
Breakdown of daily cell production includes 2.5 billion red blood cells (RBCs), 2.5 billion platelets, and 1 billion white blood cells.
The rate of hematopoiesis is adaptable and can vary based on physiological needs.

Totipotential stem cells: Present in the early days post-fertilization, capable of developing into any cell type, including entire organisms.
Pluripotential stem cells: Present several days after fertilization, can develop into any cell type except those needed to form a fetus.
Multipotential stem cells: Derived from pluripotent cells, found in adults, limited to certain cell types; essential for forming blood cells and other tissue types.

Hematopoiesis involves the development of different blood cell lineages and differentiation, characterized by the emergence of unique cell properties.
Commitment in hematopoiesis signifies that cells derived from a common precursor follow separate developmental paths, leading to maturation.

Development of hematopoiesis occurs through three stages: Mesoblastic, Hepatic, and Myeloid.
Mesoblastic phase: Occurs in yolk sac, primarily producing RBCs with embryonic hemoglobin.
Hepatic phase: Starts at approximately six weeks, with cell production in the liver along with fetal hemoglobin synthesis.
Myeloid phase: Initiated by the fifth month, with bone marrow becoming the primary production site, transitioning from liver and spleen involvement.

Stem Cells: Multipotential with high self-renewal capability, identifiable by the CD34 marker via flow cytometry.
Progenitor Cells: Committed to differentiating into specific cell lineages known as colony-forming units (CFUs).
Maturing Cells: Show recognizable morphological traits specific to their lineage.

Cytokines govern the survival, self-renewal, proliferation, and differentiation of precursor cells.
Lineage-specific growth factors support various blood cell types:
- BFU-E & CFU-E: Erythropoiesis regulation relies on EPO.
- CFU-GM: Essential for granulocyte and monocyte production, supported by IL-3.
- CFU-Meg: Induced by IL-11 and TPO for megakaryocyte production.

Major hematopoietic organ, located between trabecular spaces, serving as the primary site of blood cell formation.
Bone marrow stroma provides crucial support for hematopoietic cells, differentiating between red and yellow marrow.

A lymphopoietic organ located in the upper mediastinum, important for T lymphocyte maturation.
Contains a cortex densely packed with small lymphocytes, where precursor T cells differentiate.

Situated in the upper left abdomen, highly vascularized organ.
Functions include culling and destruction of old RBCs, immune defense, pitting of damaged RBCs, and storage of platelets (up to one-third).

Erythron encompasses the entire population of erythrocytes and their precursors, involved in production, release, and destruction of RBCs.
Oxygen tension is the primary regulator of RBC production; decreased tissue oxygenation signals the need for more red cells.

Stimulated by EPO, which accelerates commitment of pluripotent stem cells to CFU-E, promoting erythroid cell development.
Maturation involves accumulation of hemoglobin and changes in cell morphology, leading to decreased size and reduced nuclear to cytoplasmic ratio.

RBC membrane has a trilaminar structure: outer hydrophilic, central hydrophobic, and inner hydrophilic layers.
Composition includes integral proteins (e.g., glycophorin and Band 3) and peripheral membrane components, contributing to membrane stability.

Lacks organelles such as nuclei and mitochondria, limiting metabolic pathways.
Energy is generated via several pathways, including:
- Embden-Meyerhof Pathway: Main source of ATP, utilizing glucose.
- Hexose Monophosphate Shunt: Produces NADPH, vital for maintaining reduced glutathione and protecting against oxidant damage.
- Methemoglobin Reductase Pathway: Maintains heme iron in ferrous state.
- Rapoport-Luebering Shunt: Regulates 2,3-DPG for oxygen delivery.

Occurs primarily through extravascular hemolysis, with 90% of RBCs undergoing this process, particularly by macrophages in the reticuloendothelial system.
Intravasculature hemolysis accounts for 5-10% of destruction, resulting in free hemoglobin release.

Maintenance of tissue homeostasis is crucial, relying on proliferation, differentiation, and apoptosis of cells.
Apoptosis is a regulated cell death process, distinct from necrosis, which results from harmful external factors.