Lewis R. Weintraub

The Role of the Intestine in Iron Kinetics

The iron content of the body is small, amounting to about 60 parts per million (1). This quantity must remain within narrow limits to prevent the development of either siderosis or iron deficiency. It has been postulated that the metabolic balance of the bodys iron is maintained solely by controlled absorption and that excretion plays a minor role (2). Hahn and his associates proposed that the iron content of the intestinal mucosa controlled the quantity of iron absorbed by the body (3). More recent views are that the iron content of the gut is unimportant in the regulation of iron metabolism (4). This paper reports a study of the iron content of the intestine and its role in the regulation of iron equilibrium.

Absorption of hemoglobin iron: the role of a heme-splitting substance in the intestinal mucosa

The dog behaves like man in his ability to utilize dietary hemoglobin iron and, therefore, is an excellent model in which to study the mechanisms of absorption. Heme is taken up intact into the epithelial cell of the small intestine but the iron appears in the plasma in a nonheme form. A substance is present in mucosal homogenates which is capable of releasing iron from a hemoglobin substrate in vitro. This has a molecular weight greater than 64,000, and appears to behave as an enzyme. There is no difference in the in vitro, effective concentration of the hemesplitting substance in the mucosa of iron-loaded and iron-deficient dogs to explain in vivo changes in iron absorption. However, the rate at which the heme-splitting substance works in vivo appears to be increased by the removal of the nonheme-iron-end product from the epithelial cell to the plasma. Reduction of the heme-iron content within the epithelial cell may then enhance uptake from the lumen. These studies suggest that the labile nonheme-iron content of the intestinal epithelial cell determines its ability to accept heme as well as ionized iron from the lumen.

Interrelationship of iron and manganese metabolism.

A relationship between iron and manganese metabolism has been suggested by the observation of the incorporation of manganese into the porphyrin molecule of red cells and the increased gastrointestinal absorption of manganese in iron deficiency (1, 2). The present studies were performed to determine variations in the metabolism of each of these elements induced by deficiency or overload of the other. Methods. Male albino rats (Wistar strain) weighing 200-250 g were used. The animals were fed a standard rat diet (General Biochemicals, Chagrin Falls, Ohio) except that the iron and manganese content was modified from test to test as stated. Iron absorption was measured following a test dose of 0.5 μCi of ferrous-59 Fe citrate per 0.25 mg of ferrous sulfate per 0.5 ml of distilled water, administered through a 17-gauge endoesophageal tube to rats fasted for 16 hr. Whole body radioactivity (0.8 MeV —→ ∞) was measured in a small-animal, whole-body liquid scintillation detector (Packard Armac, LaGrange, Illinois), 3 hr and 7 days after dosing to determine the percentage of the test dose absorbed by the rats. An isolated intestinal loop technique was utilized to measure manganese absorption because of the significant hepatobiliary excretion of this element. The rat was anesthetized with sodium pentobarbital and the peritoneal cavity was exposed through a midline incision. A 6-cm closed loop of small intestine just distal to the ligament of Treitz was isolated with umbilical tape. One-half μCi of 54Mn per 1.0 mg of MnCl2 in 0.5 ml of saline was injected into the lumen of the loop and the abdominal wall was sutured together. One hr after the injection the animal was placed in the counter and the total radioactivity was measured.

Malabsorption of iron secondary to iron deficiency.

Abstract Intestinal absorption of 59Fe-labeled hemoglobin was measured in children with severe dietary iron deficiency and in iron-replete controls. Absorption was impaired in all the iron-deficient children and returned to normal after iron repletion. Studies of hemoglobin iron and inorganic iron were also performed in newly weaned dogs on an iron-deficient diet. A striking biphasic response was noted. Absorption of both forms of iron was initially increased over the control animals, reaching a maximum value at five months of age. Thereafter, there was a fall in absorption of both forms despite increasing severity of iron deficiency. Decreased levels of cytochrome oxidase and lactase were noted in the mucosa of the iron-deficient dogs. A decrease in iron-containing or iron-dependent enzymes in the mucosa of iron-deficient subjects may be responsible for a secondary malabsorption phenomenon.

Regulation of the Intestinal Absorption of Iron by the Rate of Erythropoiesis

PREVIOUS experimental work suggests that the utibation of iron for erythropoiesis is more important than the state of iron stores in the regulation of gastrointestinal absorption of iron. This has been demonstrated by: (I) increased absorption of iron in the iron-loaded animal following acute blood loss despite the presence of excess iron stores (Bothwell, Pirzio-Biroli and Finch, 1958; Weintraub, Conrad and Crosby, 1964a); (2) fdure of the direct reduction of iron by partial hepatectomy to stimulate increased absorption of iron (Weintraub et al., 1964a); (3) increased absorption of iron in experimentally induced haemolytic anaemia in animals with normal to increased iron stores (Bothwell et al., 1958; Chapelle, Gabrio, Stevens and Finch, 1955) ; and (4) before iron absorption is increased following acute haemorrhage there is a 4-5 day lag (Bothwell et al., 1958; Hahn, Bale, Ross, Balfour and Whipple, 1943) which has been demonstrated to correlate with onset of an increased plasma iron turnover (Weintraub et al., 1964b). To confirm the role of erythropoiesis one must also demonstrate that states in which erythropoiesis is depressed and the iron stores are normal or decreased are associated with a decreased iron absorption. The present experiments attempt to demonstrate this phenomenon using animals with physiologically induced polycythaemia. Reduction of the atmospheric pressure increases the rate of erythropoiesis, and polycythaemia results. If after this state has been attained the animals are returned to normal atmospheric pressure the stimulus to erythropoiesis is removed. The increased red-cell mass which is now no longer needed acts to depress erythropoiesis (Huff, Lawrence, Siri, Wasserman and Hennessy, 195 I ; Reynafarje, Lozano and Valdivieso, 1959; Weintraub, Gordon and Camiscoli, 1963). During this stage we performed our studies.

Circulating Iron-Containing Macrophages in Hemochromatosis

Abstract Iron-containing macrophages, present in various tissues in patients with iron-storage diseases, have been demonstrated to pass from the intestinal villus into the intestinal lumen, acting ...

Absorption of hemoglobin iron by the rat.

Summary In the rat the absorption of a test dose of hemoglobin or hemin iron59 was significantly less than a comparable dose of iron59 as FeSO4. That this is of physiologic significance was demonstrated by producing a state of iron deficiency in animals raised on a diet with hemoglobin as the only source of iron, These findings are in contrast to recent observations in man and suggest a difference between species as well as a difference in the epithelial cells”ability to sequester iron as the salt or in the heme ring.

Iron-loading anemia. Treatment with repeated phlebotomies and pyridoxine.

ABNORMALITIES in iron metabolism associated with anemia have been demonstrated in nutritional pyridoxine deficiency in several animal species.1 2 3 4 However, a similar condition in human beings ha...

Pseudoleukemia During Recovery from Dapsone-Induced Agranulocytosis

Abstract The case presented here illustrates how convincingly the recovery from agranulocytosis may mimic acute leukemia in both the peripheral blood and the bone marrow. The development of a leuke...

The Role of Hepatic Iron Stores in the Control of Iron Absorption

The mechanisms that regulate iron absorption l)y the gastrointestinal tract are not known. Clinical and experimental work suggests that decreased iron stores (1-3) or increased rate of erythropoiesis (2, 4) may be factors causing increased absorption of iron from the gut. The purpose of this paper is to describe the role of the hepatic iron stores as a stimulus to intestinal absorption of iron. In the rat subjected to partial hepatectomy, the liver returns to its original presurgical weight between the seventh and fourteenth postoperative days (5). This is due to a generalized hyperplasia of the remaining lobes rather than to the regeneration of the removed lobe or to growth of a new appendage. Thus there is a reduction in the total size and concentration of the hepatic iron stores without blood-letting or marrow hyperplasia.