Hematologic studies of severe undernutrition of infancy: I. The anemia of prolonged caloric deprivation in the pig

Extract: These studies were designed to define alterations in erythropoiesis that resulted from prolonged and controlled caloric deprivation. The caloric deprivation in the animal model chosen simulated that experienced by human infants receiving caloric intakes so restricted that infantile marasmus results. The model chosen was the young piglet receiving a diet that would support normal growth when given in adequate amounts. The intake of this diet was so restricted as to stabilize the weight of the animals at 5.0 to 7.0 kg from one to ten months of age. The studies of erythropoiesis in control piglets revealed a relatively high reticulocyte count associated with rapid growth and expansion of the red cell mass during the early months of life. The hematocrit and the hemoglobin levels increased with age, although there was a slight decrease in the total red cell mass per unit of body weight with increasing age. Iron kinetic studies were performed in normal growing pigs (table V). The mean values for plasma iron turnover (mg Fe/100 ml whole blood/24 h) were 2.07 at one month of age, 1.54 at two months of age, and 1.06 at three months of age. The mean percentage of injected Fe59 that appeared in the circulating erythrocytes seven days after injection was 95 at one month, 82 at two months, and 76 at three months of age. These findings are consistent with the presence of a decreasing rate of erythropoiesis and hemoglobin synthesis accompanying the relative decrease in growth rate with progressive age. Animals maintained on a very restricted caloric intake were found to have immediate alterations in erythropoiesis (table VI). Plasma iron turnover in these animals was 2.26 mg on the second day following dietary restriction and only 1.28 mg when measured four days after dietary restriction. After ten days, the value was reduced to 0.88 mg. A prompt decrease in urinary erythropoietin excretion was detected during this time and persisted throughout the period of observation while the animals were on the restricted diet (fig. 3). The appearance of iron in circulating erythrocytes seven days following the injection of Fe59 was found to be 100% when iron was given two days following dietary restriction. When the isotope was given four days following initiation of the restricted diet, 86.5% appeared in the circulating erythrocytes at seven days. A further decrease to 52% was observed in a study initiated ten days after dietary restriction. The alterations in erythropoiesis demonstrated by iron kinetic studies were also reflected by a decrease in the reticulocyte count and by an increase in the myeloid: erythroid ratio in bone marrow examined serially. The measurement of the Cr51 total erythrocyte mass prior to dietary restriction was 24.8 ml/kg (fig. 8). After thirty days on restricted caloric intake, the mean value was 25.8 ml/kg. Erythropoiesis, although decreased, continued at a rate sufficient to maintain a constant red cell mass during this immediate period of caloric restriction. Prolonged caloric deprivation produced a decline in hemoglobin levels and hematocrit in the experimental pigs (fig. 7). The reticulocyte count fell from the level of 5.6 to 1 % or less during the period of dietary restriction and was maintained at the low level of 1 % throughout the period of observation. Cr51 erythrocyte mass, which was maintained at a constant level during the first thirty days of dietary restriction, showed thereafter a progressive fall throughout the period of undernutrition and paralleled the fall in hematocrit (table VIII) . Levels of protein, folate, and iron in serum were maintained within the normal range throughout the period of caloric deprivation. Studies performed in pigs after five to seven months of dietary restriction found plasma iron turnover to be lower than that observed in the control animals and essentially the same as that observed after ten days of diet restriction. After six months of diet restriction, iron utilization was reduced to a maximum utilization of 3 1 to 64 % (fig. 9). After a period ofseven to eight months of dietary restriction, five animals were offered diet ad libitum. Within three to eight days, a prompt increase in erythropoietin excretion was seen; the reticulocyte count increased and, by six days after ad libitum feedings, had reached levels characteristic of normal, rapidly growing pigs. An increase in plasma iron turnover and per cent utilization of iron was measured ten days after initation of ad libitum feedings, and the myeloid: erythroid ratio reflected an increase in erythroid precursors soon after starting ad libitum feedings. The hematocrit decreased promptly after initiation of the ad libitum diet. The lowest level was reached in five days. The Cr51 total red cell mass had increased during the period of falling hematocrit, and the total plasma volume had also greatly increased at this time. The early fall in hematocrit was thus due to the increase in the plasma volume, rather than to any decrease in the circulating erythrocyte mass. Speculation: The availability of an animal model of prolonged caloric deprivation uncomplicated by infection, parasitism, or blood loss has demonstrated that caloric deprivation per se will result in a modest reduction in hematocrit and hemoglobin concentration that is paralleled by a reduction in the total circulating red cell mass. Such animals fail to demonstrate a deficiency of specific nutrients essential for normal erythropoiesis. The finding by others that caloric deprivation may be associated with a hypometabolic state suggests that anemia accompanying caloric deprivation may not be a primary consequence of inadequate nutrition but, rather, a reflection of an adaptive reduction in hemoglobin concentration in the face of a reduced demand for oxygen transport.