Human Physiology, 14th edition (2016)

Blood, Heart, and Circulation 411

normally stays in the bone marrow for the first 2 days and

then circulates in the blood on the third day. At the end of the

erythrocyte life span of 120 days, the old red blood cells are

removed by the liver and by macrophages (phagocytic cells) of

the spleen and bone marrow. Most of the iron contained in the

hemoglobin molecules of the destroyed red blood cells is recy-

cled back to the myeloid tissue to be used in the production of

hemoglobin for new red blood cells (see chapter 18, fig. 18.22).

The production of red blood cells and synthesis of hemoglobin

depends on the supply of iron, along with that of vitamin B 12

and folic acid.

also has been cloned, so that recombinant thrombopoietin is now
available for medical research and applications. In clinical trials,
thrombopoietin has been used to treat the thrombocytopenia (low
platelet count) that occurs as a result of bone marrow depletion in
patients undergoing chemotherapy for cancer.

Regulation of Leukopoiesis

A variety of cytokines stimulate different stages of leukocyte
development. The cytokines known as multipotent growth
factor-1, interleukin-1, and interleukin-3 have general effects,
stimulating the development of different types of white blood
cells. Granulocyte colony-stimulating factor (G-CSF) acts in a
highly specific manner to stimulate the development of neutro-
phils, whereas granulocyte-monocyte colony-stimulating fac-
tor (GM-CSF) stimulates the development of monocytes and
eosinophils. The genes for the cytokines G-CSF and GM-CSF
have been cloned, making these cytokines available for medi-
cal applications.

CLINICAL APPLICATION

Hematopoietic stem cell transplants help to restore bone

marrow function when the bone marrow stem cell popula-

tion has been depleted because of chemotherapy or radia-

tion therapy for cancer, or from other causes. These stem

cells can be obtained from aspiration of the marrow from

the iliac crest, but are now more commonly obtained from

peripheral blood after the person has been injected with

G-CSF and GM-CSF, which stimulate the marrow to release

more stem cells. Autologous transplants are obtained from

the same patient (before treatments that deplete the bone

marrow), whereas allogeneic transplants are obtained from

a different person, usually a sibling or someone else who is

genetically closely matched.

Regulation of Erythropoiesis

The primary regulator of erythropoiesis is erythropoietin, pro-
duced by the kidneys in response to tissue hypoxia when the
blood oxygen levels are decreased. One of the possible causes
of decreased blood oxygen levels is a decreased red blood cell
count. Because of erythropoietin stimulation, the daily produc-
tion of new red blood cells compensates for the daily destruc-
tion of old red blood cells, preventing a decrease in the blood
oxygen content. An increased secretion of erythropoietin and
production of new red blood cells occurs when a person is at
a high altitude or has lung disease, which are conditions that
reduce the oxygen content of the blood.
Erythropoietin acts by binding to membrane recep-
tors on cells that will become erythroblasts ( fig.  13.4 ). The
erythropoietin-stimulated cells undergo cell division and dif-
ferentiation, leading to the production of erythroblasts. These
are transformed into normoblasts, which lose their nuclei to
become reticulocytes. The reticulocytes then change into fully
mature erythrocytes. This process takes 3 days; the reticulocyte

Figure 13.4 The stages of erythropoiesis. The

proliferation and differentiation of cells that will become mature

erythrocytes (red blood cells) occurs in the bone marrow and

is stimulated by the hormone erythropoietin, secreted by the

kidneys.

Hemocytoblast

(stem cell)

Proerythroblast

Erythroblast

In bone marrow

(myeloid tissue)

Released

into blood

Stimulated by

erythropoietin

Nucleus expelled

Normoblast

Reticulocyte

Erythrocytes