Figure 143

Summary of iron balance. The thickness of the arrows corresponds approximately to the amount of iron involved. In the steady state, the rate of gastrointestinal iron absorption equals the rate of iron loss via urine, skin, and menstrual flow.

Adapted from Crosby.

In the previous section, we stated that iron, folic acid, and vitamin B12 must be present for normal erythrocyte production. However, none of these substances constitutes the signal that regulates production rate.

The direct control of erythrocyte production (erythropoiesis) is exerted primarily by a hormone called erythropoietin, which is secreted into the blood mainly by a particular group of hormone-secreting connective-tissue cells in the kidneys (the liver also secretes this hormone, but to a much lesser extent).

Erythropoietin acts on the bone marrow to stimulate the proliferation of erythrocyte progenitor cells and their differentiation into mature erythrocytes.

Erythropoietin is normally secreted in relatively small amounts, which stimulate the bone marrow to produce erythrocytes at a rate adequate to replace the usual loss. The erythropoietin secretion rate is increased markedly above basal values when there is a decreased oxygen delivery to the kidneys. Situations in which this occurs include insufficient pumping of

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Circulation CHAPTER FOURTEEN

Circulation CHAPTER FOURTEEN

Decreased Oxygen Delivery

FIGURE 14-4

Reflex by which a decreased oxygen delivery to the kidneys increases erythrocyte production via increased erythropoietin secretion.

TABLE 14-2 Major Causes of Anemia

FIGURE 14-4

Reflex by which a decreased oxygen delivery to the kidneys increases erythrocyte production via increased erythropoietin secretion.

blood by the heart, lung disease, anemia (a decrease in number of erythrocytes or in hemoglobin concentration), and exposure to high altitude. As a result of the increase in erythropoietin secretion, plasma erythro-poietin concentration, erythrocyte production, and the oxygen-carrying capacity of the blood all increase; therefore, oxygen delivery to the tissues returns toward normal (Figure 14-4).

Testosterone, the male sex hormone, also stimulates the release of erythropoietin. This accounts, at least in part, for the higher hemoglobin concentration in men than in women.

Anemia Anemia is defined as a decrease in the ability of the blood to carry oxygen due to (1) a decrease in the total number of erythrocytes, each having a normal quantity of hemoglobin, or (2) a diminished concentration of hemoglobin per erythrocyte, or (3) a combination of both. Anemia has a wide variety of causes summarized in Table 14-2.

1. Dietary deficiencies of iron (iron-deficiency anemia), vitamin B12, or folic acid

2. Bone marrow failure due to toxic drugs or cancer

3. Blood loss from the body (hemorrhage) leading to iron deficiency

4. Inadequate secretion of erythropoietin in kidney disease

5. Excessive destruction of erythrocytes (for example, sickle-cell anemia)

Sickle-cell anemia is due to a genetic mutation that alters one amino acid in the hemoglobin chain. At the low oxygen concentrations existing in many capillaries, the abnormal hemoglobin molecules interact with each other to form fiberlike structures that distort the erythrocyte membrane and cause the cell to form sickle shapes or other bizarre forms. This results both in the blockage of capillaries, with consequent tissue damage and pain, and in the destruction of the deformed eryth-rocytes, with consequent anemia. Sickle-cell anemia is an example of a disease that is manifested fully only in persons homozygous for the mutated gene (Chapter 5). In heterozygotes, who are said to have sickle-cell "trait," the normal allele codes for normal hemoglobin and the mutated allele for the abnormal hemoglobin. The erythrocytes in this case contain both types of hemoglobin, but symptoms are manifest only when the oxygen concentration is unusually low, as at high altitude.

Finally, there also exist conditions in which the problem is just the opposite of anemia, namely, more erythrocytes than normal; this is termed polycythemia. An example, to be described in Chapter 15, is the poly-cythemia that occurs in high-altitude dwellers; in this case the increased number of erythrocytes is an adaptive response. As we shall see later, however, the existence of polycythemia makes the flow of blood through blood vessels more difficult.

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Essentials of Human Physiology

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