Nutritional anemia

1

What is nutritional anemia?

Anemia develops when a pathological decrease in the circulating red blood cell (RBC) mass reduces the oxygen-carrying capacity of blood below the physiologic requirements of the body. Anemia is clinically assessed by measuring the hemoglobin (Hb) concentration, hematocrit (packed cell volume), or RBC count in the peripheral blood. Nutritional anemia develops as a result of a deficiency of one or more essential nutrients, regardless of the underlying cause of such deficiency.

2

Worldwide, what are the predominant causes of pediatric nutritional anemia?

Globally, iron deficiency is by far the most common cause of nutritional anemia in infants, children, and adolescents. Deficiencies of vitamin B ₁₂ (cobalamin) and folate are much less common but account for most other nutritional anemia. In low- and middle-income countries, vitamin A deficiency, the leading cause of pediatric blindness and a major nutritional risk factor for severe infection and death, is a cause of anemia that interferes with iron utilization and immune responsiveness. Deficiencies of thiamine (vitamin B ₁ ), riboflavin (vitamin B ₂ ), niacin (vitamin B ₃ ), pantothenic acid (vitamin B ₅ ), pyridoxine (vitamin B ₆ ), vitamin C, vitamin E, copper, and selenium are recognized but uncommon or rare causes of nutritional anemia.

3

Describe the pathways of body iron absorption, utilization, and storage, in the absence of inflammation and infection.

The amount of body iron is determined by careful control of gastrointestinal (GI) absorption. Humans have no way to regulate iron excretion to avoid iron excess, and the minimal mandatory daily losses, less than 0.05% of the total body iron, are matched by daily absorption. Iron is efficiently recycled with approximately 80% of the flux carried by transferrin in plasma to the erythroid marrow for incorporation into Hb. Senescent RBCs, at the end of their life span of about 120 days, are phagocytized by specialized macrophages within the spleen, bone marrow, and liver (Kupffer cells), which rapidly recycle most of the iron back to plasma transferrin for return to the erythroid marrow. Any excess iron is stored within ferritin and hemosiderin in macrophages and hepatocytes. Transferrin-bound iron delivery to nonerythroid tissues in the body is balanced by the return from cellular turnover.

4

How does the body regulate the amount, absorption, utilization, and storage of iron?

The hepatic iron regulatory hormone hepcidin governs the amount and distribution of body iron by controlling the entry of iron into plasma for transport by transferrin ( Figure 6.1 ). Hepcidin binds to the sole known cellular iron exporter, ferroportin, and induces its occlusion or internalization, ubiquitination, and degradation, resulting in sequestration of iron within iron-exporting cells (enterocytes, macrophages, hepatocytes).

• Hepcidin increases with inflammation and iron loading, thereby inhibiting iron absorption by GI enterocytes, iron recycling by macrophages, and iron release from hepatocyte stores. Inflammation can increase circulating hepcidin to concentrations that critically restrict iron recycling and absorption and can cause severe anemia.

• Hepcidin decreases with reduced or absent body iron stores, increased erythropoietic demand, and hypoxemia. When inflammation and iron deficiency coexist, the increase from sufficiently severe inflammation can overwhelm the effect of absent body iron stores.

5

Describe the epidemiology of iron-deficiency anemia worldwide.

It is estimated that 25% of the global population is anemic, with more than 60% of the anemia caused by iron deficiency, which affects almost 2 billion people. Worldwide, the highest rates of iron deficiency are found among infants, preschool-aged children, and females of reproductive age.

6

Distinguish absolute from functional iron deficiency.

Absolute iron deficiency is a deficit in total body iron with absent or reduced iron stores that cannot meet iron requirements ( Figure 6.2 ). Functional iron deficiency develops with sufficient or increased body iron stores that are unable to meet iron requirements because of (1) iron sequestration produced by increased hepcidin or (2) increased erythropoietic demand resulting from endogenous (hemolysis) or exogenous (erythropoiesis-stimulating agents) causes. Absolute and functional iron deficiency may coexist.

7

Describe the successive stages of absolute iron deficiency.

The successive stages of absolute iron deficiency traditionally have been defined by the effects on the Hb concentration:

• 1.

  Storage iron depletion: Body iron stores are exhausted, but the iron supply for erythropoiesis is maintained and the Hb concentration is not decreased.

• 2.

  Iron-deficient erythropoiesis: Body iron stores are exhausted and limit the iron supply for erythropoiesis, but the resulting decrease in Hb concentration is insufficient to be detected by the standard used to diagnose anemia.

• 3.

  Iron-deficiency anemia: Body iron stores are exhausted and limit the iron supply for erythropoiesis sufficiently to decrease the Hb concentration below the standard used to diagnose anemia.

In addition to the effects on erythropoiesis, iron deficiency is a multisystem disorder with a variety of clinical manifestations, including signs and symptoms of adverse effects on developmental, neurological, cardiac, GI, and immunological functions ( Box 6.1 ).