Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

U N I T 3

Erythropoietin

Kidney

Blood

Proliferation

Maturation

Release

Bone Marrow

O 2 Sensor

Reticulocytes

Committed erythroid precursor

Stem cell

Low tissue oxygen tension

Extruded nucleus

Mature erythrocytes

Red blood cell mass

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.

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).