Erythropoiesis and Myocardial Energy Requirements Contribute to the Hypermetabolism of Childhood Sickle Cell Anemia

Abstract

Objectives-We hypothesized that an elevated hemoglobin synthesis rate (SynHb) and myocardial oxygen consumption (MVO 2 ) contribute to the excess protein and energy metabolism reported in children with sickle cell anemia.Patients and Methods-Twelve children (6-12 years old) with asymptomatic sickle cell and 9 healthy children matched for age and sex were studied. Measurements were whole-body protein turnover by [1-13 C]leucine, SynHb by [ 15 N]glycine, resting energy expenditure by indirect calorimetry and the systolic blood pressure-heart rate product used as an index of MVO 2 . Protein energy cost was calculated from protein turnover. Statistical analysis included Spearman correlations and partial correlation analyses.Results-Although body mass index was significantly lower for sickle cell versus controls (P < 0.02), children with asymptomatic sickle cell had 52% higher protein turnover (P < 0.0005). Proportional reticulocyte count, SynHb, MVO 2 and resting energy expenditure were also significantly higher in children with sickle cell (P < 0.01). Protein turnover correlated significantly with both SynHb (r = 0.63, P < 0.01) and reticulocyte percentage (r = 0.83, P < 0.0001). Partial correlation of these 3 variables showed reticulocyte percentage as the only variable to be significantly associated with protein turnover, even after adjusting for sickle cell anemia (P = 0.03). Partial correlation of log resting energy expenditure on MVO 2 was significant, controlling for protein energy cost, sex and age (P = 0.03).Conclusion-These results indicate that metabolic demands of increased erythropoiesis and cardiac energy consumption account for much of the excess protein and energy metabolism in children with sickle cell anemia. Homozygous sickle cell disease (HbSS) is characterized by severe chronic hemolytic anemia associated with increased rate of erythropoiesis (1). Resting energy expenditure (REE), whole-body protein turnover (Q) (2-6) and protein catabolism, via increased urea production rate (7,8), are concurrently elevated in patients with HbSS. These findings support the notion that patients with HbSS are hypermetabolic, requiring more dietary protein and energy, compared with healthy controls with normal hemoglobin (Hb) genotype (HbAA). Children with HbSS experience poor growth and development (9), often becoming short thin adults (10). This growth failure may be a direct consequence of inadequate dietary protein and energy. NIH Public AccessBecause protein turnover consumes energy, a direct link between increased REE and elevated erythropoiesis has been inferred; so far, no reports confirm this association (1). Cardiac output is estimated to account for 7% to 33% of REE in healthy adults (11-13), but its contribution to energy requirements of HbSS is not known. Buchowski et al. (14) showed that basal energy requirements were higher than normal for adolescents with HbSS and provided the following simple equation for predicting the REE based on body weight and Hb concentration:The components of this...

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Correlation between Body Mass Index and Hematological Indices in Young Adult Nigerians with Different Hemoglobin Genotypes

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