Sickle cell anemia (HbSS) includes chronic inflammation, but the origin is unclear. We hypothesized that in stable HbSS patients the inflammation was associated with hypermetabolism. We compared selected hypermetabolic and key immunomodulator indicators in HbSS versus control children and examined associations between measures of hypermetabolism and inflammation. Twelve fasting asymptomatic HbSS children 6-12 years and 9 controls matched for age, gender and fat mass (FM) were studied. Proportional reticulocyte count (retic%) and resting energy expenditure (REE) represented hypermetabolism, and C-reactive protein (CRP) indicated inflammation. Proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), chemokine monocyte chemoattractant protein-1 (MCP-1), and energy balance cytokine leptin were measured. Methods were indirect calorimetry, enzyme-linked immunosorbent assay, and radioimmunoassay. Statistical analysis included simple correlation and regression analysis. REE (51 ± 6 vs. 43 ± 12 kcal/kg per fat-free mass (FFM), mean ± SD), retic% (12 ± 4 vs. 0.7 ± 0.3%), CRP (5 ± 3 vs. 0.3 ± 0.4 mg/liter), and IL-6 (71 ± 40 vs. 20 ± 7 pg/ml) were significantly higher for HbSS than controls (P < 0.05). Conversely, leptin (0.1 ± 0.1 vs. 2 ± 1 µg/liter per kgFM) and MCP-1 (34 ± 5 vs. 41 ± 4 pg/ml) were significantly lower for the HbSS subjects (P < 0.01). TNF-α was not significantly different. There were no significant associations between REE or retic% and any cytokine measured. However, CRP was significantly associated with REE in HbSS (r = 0.8, P = 0.003) and an important predictor of REE/FFM. We provide new evidence for low circulating levels of inflammatory chemokine MCP-1 in stable HbSS children, confirm mostly low cytokine levels, inflammation, and hypermetabolism and demonstrate association of hypermetabolism with inflammation via CRP but not via cytokines.
The development of ACS during painful episodes is multi-factorial, but opioid selection may increase this rate. Patients on Nubain were less likely to develop ACS, and they had shorter hospital stays. These results were confounded by use of continuous analgesia infusion with PCA. However, Nubain may provide an alternative to morphine in the treatment of sickle cell pain episodes. A prospective clinical trial comparing these two analgesics would be a preferable next step.
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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