Blood, 1950, Vol. 5, No. 11, pp. 983-1008.
© 1950 American Society of Hematology, Inc.
IRON METABOLISM
THE PATHOPHYSIOLOGY OF IRON STORAGE
CLEMENT A. FINCH M.D.1,
MARK HEGSTED PH.D.1,
THOMAS D. KINNEY M.D.1,
E. D. THOMAS M.D.1,
CHARLES E. RATH M.D.1,
DONALD HASKINS M.D.1,
STUART FINCH M.D.1, and
REX G. FLUHARTY PH.D.1
1 Medical Clinic, Peter Bent Brigham Hospital, Departments of Pathology, Biological Chemistry, and Medicine, Harvard Medical School, the Department of Nutrition, Harvard School of Public
Health, the Departments of Pathology and Medicine, Peter Bent Brigham Hospital, Boston, Mass.;
the Departments of Pathology of Western Reserve University School of Medicine and Cleveland City
Hospital, Cleveland, Ohio; the Department of Physics, Massachusetts Institute of Technology, Cambridge, Mass.
On the basis of experimental and clinical observations and a review of the
literature, a concept of the behavior of storage iron in relation to body iron metabolism has been formulated.
Storage iron is defined as tissue iron which is available for hemoglobin synthesis
when the need arises. This iron is stored intracellularly in protein complex as
ferritin and hemosiderin. It would appear that wherever the cell is functionally
intact, such iron is available for general body needs.
Iron is transported by a globulin of the serum to and from the various tissues
of the body to satisfy their metabolism. Surplus iron carried by this iron-binding
protein is deposited chiefly in the liver.
Storage iron may be increased in two ways. The first mechanism results from
the inability of the body to excrete significant amounts of iron. Because of this,
any decrease in circulating red cell iron (any anemia other than blood loss or iron
deficiency anemia) is accompanied by a shift of iron to the tissue compartment.
The total amount of body iron remains constant and is merely redistributed.
This is to be contrasted with the absolute increase in body iron and enlarged
iron stores which follow excessive iron absorption or parenteral iron administration. Enlarged iron stores in either instance may be evaluated by examination of
sternal marrow or determination of the serum iron and saturation of the iron
binding protein
In states of iron excess, differences in initial distribution are observed, depending
on the route of administration and type of iron compound employed. Iron absorbed
from the gastro-intestinal tract and soluble iron salts injected in small amounts
are transported by the iron-binding protein of the serum and stored predominantly
in the liver. Colloidal iron given intravenously is taken up by the reticulo-endothelial tissue. Erythrocytes appear to localize in greatest concentration in the
spleen, while greater amounts of hemoglobin iron are found in the renal parenchyma. These latter differences in distribution reflect the capacity of various body
tissues to assimilate different iron compounds, which while present in the plasma
are not carried by the iron-binding protein.
Over a period of time an internal redistribution of iron from these various sites
occurs through the serum iron compartment. The liver becomes progressively
loaded with iron. When the capacity of the liver to store iron is exceeded, the
serum iron increases and secondary tissue receptors begin to fill with iron. That
iron in large amounts is toxic to tissues is suggested by the occurrence of fibrosis
in the organs most heavily laden with iron. This sequence of events, whether
following excessive iron absorption or parenteral iron administration is believed
to be responsible for the clinical and pathologic picture of hemochromatosis.
