[Anemia induced by cadmium intoxication]

Anemia is commonly induced by chronic cadmium (Cd) intoxication. Three main factors are involved in the development of Cd-induced anemia: hemolytic, iron-deficiency, and renal. Intravascular hemolysis can occur at the early stage of Cd exposure owing to the direct damaging effect on erythrocytes. In addition, Cd that accumulates in erythrocytes affects membrane cytoskeletons and decreases cell deformability, and these cells are then trapped and destroyed in the spleen. Iron deficiency can be detected in animals after an oral exposure to Cd, which competes with iron for absorption in the intestines, leading to anemia. However, an increase in body iron content along with anemia is often observed in cases of parenteral exposure or itai-itai disease. Therefore, it is estimated that Cd disrupts the efficient usage of iron in hemoglobin synthesis in the body. Renal anemia is observed during the very last phase of chronic, severe Cd intoxication, such as itai-itai disease, showing a decrease in the production of erythropoietin from renal tubular cells. Because the renal anemia is based on the same pathophysiology as Cd-induced osteomalacia, which is derived from the disturbance of mineral metabolism due to renal tubular dysfunction, it is reasonable to include renal anemia in the criteria for the diagnosis of itai-itai disease. Hemodilution could also contribute to the development of Cd-induced anemia. Bone marrow hypoplasia or the inhibition of heme synthesis might only be involved in Cd-induced anemia in severe cases of Cd intoxication.