Unit 2: Hematopoiesis

What is hematopoiesis?

The physiological process through which all cellular blood components (erythrocytes, leukocytes, and thrombocytes) are produced, renewed, and regulated within the body.

Where does hematopoiesis primarily occur in healthy adult animals?

Within the active (red) bone marrow, specifically located at the ends of long bones (e.g., femur, humerus) and within flat bones (e.g., ribs, sternum, pelvis, skull).

What is the anatomical and functional difference between red and yellow bone marrow?

Red marrow is the site of active hematopoiesis, containing hematopoietic stem cells and precursors. Yellow marrow is largely composed of fatty, inactive tissue but can potentially revert to active red marrow under extreme demand.

Define extramedullary hematopoiesis. Is it normal?

The production of blood cells outside the medullary (bone marrow) cavity, typically occurring in the liver and spleen. It is considered an abnormal, compensatory response to severe, chronic demand or bone marrow failure.

Define medullary hematopoiesis.

The normal production of blood cells that occurs within the bone marrow cavity.

What is the ultimate progenitor cell for all blood cell lineages?

The pluripotent hematopoietic stem cell (HSC). This cell resides in the bone marrow and has the potential to self-renew or differentiate into any blood cell type.

What is the first critical step after a pluripotent stem cell is signaled to differentiate?

It divides asymmetrically. One daughter cell remains a pluripotent stem cell to maintain the bone marrow reserve. The other commits to differentiation, becoming a multipotent progenitor cell.

What determines the specific lineage commitment of a multipotent progenitor cell?

Specific chemical signals, primarily hormones and growth factors collectively termed "poietins." The body's needs (e.g., infection, hemorrhage, oxygen levels) dictate which poietins are released.

What are the two primary developmental pathways arising from the multipotent progenitor cell?

1. The Myeloid Pathway (Myelopoiesis). 2. The Lymphoid Pathway (Lymphopoiesis).

List all blood cell types produced via the myeloid pathway.

Erythrocytes (RBCs), Thrombocytes (platelets), Monocytes, and Granulocytes (Neutrophils, Eosinophils, Basophils). Essentially, all blood cells except lymphocytes.

Which cells are produced via the lymphoid pathway?

Lymphocytes, specifically B-cells and T-cells, which are central to adaptive immunity.

What is erythropoietin (EPO), where is it produced, and what is its stimulus?

A glycoprotein hormone primarily produced by peritubular interstitial cells in the kidney. Its release is stimulated by tissue hypoxia (low oxygen levels). It specifically stimulates the production of red blood cells.

What is thrombopoietin (TPO), and where is it mainly synthesized?

A glycoprotein hormone that is the primary regulator of megakaryocyte development and platelet production. It is produced mainly by the liver, with smaller amounts from the kidneys and bone marrow stroma.

What are leukopoietins? Are they a single substance?

Leukopoietins are not a single hormone but a collection of factors (including interleukins, colony-stimulating factors like G-CSF, GM-CSF, and other cytokines) that act in concert to stimulate the production and differentiation of white blood cells.

Describe the two primary mechanisms by which poietins accelerate the production of a needed blood cell type (e.g., neutrophils during infection).

1. Increase Proliferation: Stimulate more cell divisions in the committed precursor cell lines, increasing the total number of cells produced. 2. Decrease Maturation Time: Shorten the development time from stem cell to mature, functional cell, delivering them to the bloodstream more rapidly.

During a severe, acute demand for a specific cell type (e.g., neutrophils in bacterial sepsis), what might happen to the production of other cell lineages in the bone marrow?

Production of other lineages (e.g., RBCs, eosinophils) may be temporarily suppressed or reduced. This allows the bone marrow to divert its finite resources and space to prioritize the production of the critically needed cell type.

What diagnostic procedure is required to directly evaluate the composition, activity, and health of the bone marrow?

A bone marrow core biopsy and aspirate, examined by a clinical pathologist.

What is the functional role of the kidney in the feedback loop of erythropoiesis?

The kidney acts as the primary sensor for blood oxygen levels. Upon detecting hypoxia, it secretes EPO, which acts as the messenger to the bone marrow, stimulating RBC production to correct the oxygen deficit.

In the context of hematopoiesis, what does the term "committed progenitor cell" mean?

A cell that has progressed from a multipotent state and is now destined to develop into only one specific lineage (e.g., a colony-forming unit-erythroid (CFU-E) is committed to becoming only red blood cells).

What is the significance of the pluripotent stem cell's ability to self-renew?

It ensures a lifelong reservoir of stem cells is maintained within the bone marrow, allowing for continuous blood cell production and the potential to respond to injury or disease throughout an animal's life.