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.