280
U N I T 3
Hematopoietic Function
chemotherapy in persons with malignancies, and in the
treatment of anemia in human immunodeficiency virus
(HIV)-infected persons treated with zidovudine.
4
Because red blood cells are released into the blood as
reticulocytes, the percentage of these cells is higher when
there is a marked increase in red blood cell production.
In some severe forms of anemia, the reticulocytes (nor-
mally about 1%) may account for as much as 30% of
the total red cell count. In some situations, red cell pro-
duction is so accelerated that numerous erythroblasts
appear in the blood.
Red Cell Life Span and Destruction
Mature red blood cells have a life span of approximately
4 months, or 120 days.
3
Even though mature red cells do
not have a nucleus, mitochondria, or endoplasmic retic-
ulum, they have cytoplasmic enzymes that are capable
of metabolizing glucose and forming small amounts of
adenosine triphosphate (ATP). These enzymes also help
to preserve the pliability of the cell membrane, maintain
transmembrane transport of ions, keep the iron of the
cell’s hemoglobin in the reduced ferrous form that binds
oxygen, and prevent oxidation of the proteins. Even so,
the metabolic activity in the cell decreases as the red cell
ages, and the cell membrane becomes more and more
fragile, causing it to rupture as it passes through tight
places in the circulation. Many of the aged red cells self-
destruct in the spleen as they squeeze through spaces
between the trabeculae of the red pulp, which are only
about 3 mm wide, in comparison with the 8-mm width
of the red cell.
3
The rate of red cell destruction (1% per
day) normally is equal to the rate of red cell production,
but in conditions such as hemolytic anemia, the cell’s life
span may be shorter.
The destruction of red blood cells is facilitated by a
group of large phagocytic macrophages found in the
spleen, liver, bone marrow, and lymph nodes. These
phagocytic cells recognize old and defective red cells and
then ingest and destroy them in a series of enzymatic
reactions. During these reactions, the amino acids from
the globulin chains and iron from the heme units are sal-
vaged and reused (Fig. 13-6). The bulk of the heme unit
is converted to bilirubin, the pigment of bile, which is
insoluble in plasma and attaches to plasma proteins for
transport. Bilirubin is removed from the blood by the
liver and conjugated with glucuronide to render it water
soluble so that it can be excreted in the bile. The plasma-
insoluble form of bilirubin is referred to as
unconjugated
bilirubin
and the water-soluble form as
conjugated bili-
rubin.
Serum levels of conjugated and unconjugated bili-
rubin can be measured in the laboratory and are reported
as direct and indirect, respectively. If the rate of red cell
destruction and consequent bilirubin production exceed
the liver’s ability to remove it from the blood, unconju-
gated bilirubin accumulates in the blood. This results in
yellow discoloration of the skin, called
jaundice.
When red blood cell destruction takes place in the cir-
culation, as in
hemolytic anemia
, the hemoglobin remains
in the plasma where it binds to a hemoglobin-binding
protein called
haptoglobin.
1
Other plasma proteins, such
as albumin, can also bind hemoglobin. With extensive
intravascular destruction of red blood cells, hemoglobin
levels may exceed the hemoglobin-binding capacity of
haptoglobin and other plasma proteins. When this occurs,
free hemoglobin appears in the blood (i.e., hemoglobine-
mia) and is excreted in the urine (i.e., hemoglobinuria).
Kidney
Bone Marrow
Proliferation
Maturation
Release
Stem
cell
Committed
erythroid
precursor
Low tissue
oxygen
tension
Red blood cell mass
Mature
erythrocytes
Reticulocytes
Blood
Extruded
nucleus
O
2
Sensor
Erythropoietin
FIGURE 13-5.
Red blood cell development involves the proliferation and differentiation of
committed bone marrow cells through the erythroblast and normoblast stages to reticulocytes, which
are released into the bloodstream and finally become erythrocytes.
