Mature blood cells have a limited lifespan and must be continuously replaced through

a process called hematopoiesis, which starts in the red bone marrow.

All formed elements of the blood derive from a common progenitor – the hematopoietic

stem cells, HSCs.

HSCs are multipotent, meaning they can differentiate to all types of blood cells.

They also have the ability to multiply constantly to maintain their numbers in the bone marrow.

Formation of blood cells from hematopoietic stem cells is a multi-step process, involving

several intermediate progenitors, and is regulated by a network of signaling molecules, known

as cytokines.

These cytokines control the proliferation, differentiation and survival or death of the

various progenitors.

By doing so, they maintain steady-state levels of blood cells in normal situations; and,

in response to certain stimuli, induce production of a particular cell type.

For example, in response to blood loss, production of red blood cells is accelerated.

Differentiation starts when progenitor cells develop surface receptors for a specific stimulating

factor.

Once this happened, the cells lose their potency and become committed to a certain cell type.

Production of red blood cells, RBC, or erythrocytes, is stimulated by erythropoietin, EPO.

During the differentiation process, the cells reduce in size, increase in number, start

making hemoglobin, and lose their nucleus.

EPO is produced predominantly by the liver during fetal development and by the kidneys

in adulthood.

Low levels of EPO are constitutively secreted and are sufficient to compensate for normal

red blood cell turnover.

When RBC count drops, such as during blood loss, the resulting oxygen-deficiency state,

hypoxemia, is detected by the kidneys.

The kidneys respond by increasing their EPO secretion, which leads to increased red blood

cell production by the end of 3 to 5 days.

People living at high altitudes usually have higher RBC count as a response to lower oxygen

levels.

Athletes whose demand for oxygen is more elevated, also have higher RBC counts.

Production of granulocytes and macrophages, the key players of the body’s innate immune

response, is controlled by several colony-stimulating factors, CSFs.

Normally, these cells are kept at a more or less constant number, by relatively low levels

of CSFs, but their production can increase greatly and quickly upon infection.

CSFs are commonly secreted by mature lymphocytes and macrophages, but can be produced, if needed,

by virtually any organ or cell type.

CSF production may increase a thousand-fold in response to indicators of infection, such

as bacterial endotoxins.

Production of platelets is stimulated by thrombopoietin, TPO, a hormone secreted by the kidneys and

liver.

TPO is responsible for formation of megakaryocytes – the gigantic cells that develop as a result

of multiple rounds of DNA replication without cell division.

A megakaryocyte gives rise to tens of thousands of platelets, which are essentially broken

fragments of its cytoplasm.

Production of platelets is subject to a classic negative feedback loop: reduced platelet levels

in the blood promote their production, while elevated levels inhibit it.