1. By means of phlebotomy to recover and measure accumulated iron and by determining the rate of replenishment of hemoglobin after induction of iron-deficiency anemia, it is possible to compute the rate at which iron is accumulated by absorption from the diet. Normal humans are presumed to be in iron balance and absorb iron only to replace what is lost; under these conditions they accumulate none. During recovery from induced iron deficiency a normal human accumulated iron at the rate of 5 to 6 mg. per day.
2. Patients with hemochromatosis were found to accumulate iron at the rate of 1.5 to 5 mg. per day. With iron deficiency the rate increased to 8 to 10 mg. per day. Because of uncertainty concerning the manner of onset of iron accumulation in hemochromatosis, whether gradual or abrupt, it is not possible by extrapolation to establish the time of onset in these patients. However, at the rates of accumulation established in this study there was an insufficient excess of iron to permit a conclusion that such rates had existed throughout the patient’s life. If the disease began early, the initial or interim rates were less than those found. If the disease began and continued at the rate found, its onset was 10 to 17 years prior to this study.
3. In a patient with hypochromic iron-loading anemia the rate of accumulation was about 2.5 mg. per day. It was not appreciably increased by iron deficiency except when the deficiency was severe and the plasma iron was quite low. While this patient was iron deficient the plasma iron became abnormally high even before the hemoglobin mass was completely reconstituted.
4. A patient with transfusion siderosis who had recovered from his anemia was phlebotomized to remove the accumulated iron. When iron deficiency finally developed the total amount of iron which had been recovered was less than half of the 32.5 Gm. given in the transfusions some years before. It was computed that during those years the patient was losing iron at a rate of about 4.0 mg. per day. The rate of iron accumulation during his recovery from the induced iron deficiency was the same as the normal: 5 to 6 mg. per day.
5. The ability to lose iron which is in excess of requirement is implicit in the demonstration of iron-laden deciduous cells such as the glandular epithelium of the stomach and duodenum and macrophages in the intestinal villi.
6. In hemochromatosis there is a failure of the intestinal mucosal block to prevent absorption of unneeded iron. When absorption exceeds the capacity of the iron excretory mechanisms, iron accumulation occurs. In iron deficiency the excretory mechanisms become less active so that the rate of iron accumulation is further increased.