The effect of splenectomy for hypersplenism on whole body protein turnover, resting metabolic rate and growth in sickle cell disease

OBJECTIVE: To determine whether, in the same individual, an observed fall in whole body protein turnover following splenectomy in children with hypersplenism and homozygous sickle cell (SS) disease is associated with a measurable fall in resting metabolic rate (RMR) and an increase in rate of growth. SUBJECTS: Six children (5 SS disease, 1 S beta degree thalassaemia), aged 68 to 126 months, were studied before and after splenectomy for hypersplenism. DESIGN: Protein turnover was measured by the end product method using prime/intermittent oral doses of 15N-glycine and RMR by indirect calorimetry before preoperative transfusion and repeated at least eight weeks after splenectomy. Height and weight velocities were measured over six month periods before and after splenectomy. SETTING: University Hospital of the West Indies in Jamaica and the Medical Research Laboratories (Jamaica). RESULTS: After splenectomy protein turnover fell significantly by 30 percent and RMR by 34 kJ/kg/d. Mean weight velocity which was below normal before surgery, z = -2.3, improved significantly after surgery, z = 0.7, (p = 0.03). Height velocity increase in two children but the mean height velocity did not change following splenectomy. The reduction in protein turnover was estimated to account for 62 percent of the fall in RMR. CONCLUSION: This study confirms that there is a significant reduction in energy expenditure following splenectomy for hypersplenism in SS disease. A reduction in protein turnover was a major contributor to the saving in energy, although it is not clear whether it accounted for all. In the present group of children the energy saved was associated with an improvement in the wasting present before splenectomy.(AU)

Is there an energy deficiency in homozygous sickle-cell disease? - abstract

Low weight, reduced height for age, delayed skeletal maturation and retarded puberty in children with homozygous sickle-cell (SS) disease are consistent with chronic malnutrition. Voluntary energy intake in SS patients remains similar to that of controls with a normal (AA) haemoglobin genotype, despite a higher resting metabolic rate (RMR) suggesting a suboptimal nutritional state. Patients may therefore conserve energy by reducing physical activity and this hypothesis has been tested by comparing total daily energy expenditure (TDEE) in 16 SS adolescent boys with 16 AA controls matched for age, sex and pubertal stage. The RMR of SS patients (mean, SD:7.0 MJ/d, 0.9) significantly exceeded that of AA controls (6.3, 0.5; p = 0.018) but TDEE was greater in AA controls (mean, SD: 13.8 MJ/d, 4.9) than in SS patients (10.5, 2.2; p = 0.034). The physical activity level (TDEE/RMR was 45 percent greater in AA controls ( mean, SD: 2.2, 0.8) than in SS patients (1.5, 0.3), this difference being highly significant (p = 0.006). Reducing physical activity is a compensatory mechanism in normal children on low energy intakes and a similar adaptive response may occur in SS disease (AU)

Resting metabolic rate and body composition in stunted and non-stunted children - abstract

There is little information supporting the common assumption that stunted children have reduced energy requirements. Previously we found that stunted Jamaican children, aged 9-24 months, have higher energy intakes per kilogram body weight than non-stunted children. We hypothesized that this may be related to differences in basal metabolism and body composition, particularly in lean body mass (LBM) which is the major determinant of resting energy expenditure (RMR). We therefore compared the RMR (using indirect calorimetry) and body composition (using anthropometry amd impedance) in 34 stunted children (S) aged 7-8 years, with two groups of non-stunted controls matched for either age and sex (A), or height and sex (H). The RMR per kilogram body weight of S (58.9ñ6.9 kcal/kg) was significantly higher than A (52.5ñ6.0 kcal/kg; p <0.001), yet lower than the height controls (64.1ñ8.kcal/kg; p <0.01). However, after controlling for sex and weight or LBM in a multiple regression analysis, the RMRs of S and A were no longer significantly different, while the younger H continued to have significantly higher RMRs (p <0.001). No significant group differences were found in the proportions of body fat and LBM to total body weight. In conclusion, the LBM of stunted and non-stunted children of the same age and sex is proportionately and functionally the same, differences in their RMRs being accounted for by size. The lower RMR of stunted children compared to younger non-stunted children of the same size and body composition may be due to age-related changes in the composition of the LBM (AU)

Dietary intake and observed activity of stunted and non-stunted children in Kingston, Jamaica. Part II. observed activity

It is generally believed that activity levels are reduced in poorly nourished children. This may conserve energy, but may have a detrimental effect on mental development. However there are few data which support this hypothesis. No previous studies were found which looked at the activity levels of stunted children. In this study we modified the time and motion observation methods of Torun (1984) by using recording periods of 1 instead of 10 min. This significantly reduced the estimated time spent by young children in moderate and vigorous activities. Four hours of observing young children while they were awake, using the modified method, produced highly reliable data. The activity levels of a subsample of children described in part I were observed. The children were aged 12-24 months and were observed for 4 h on 2 d. Seventy-eight stunted children (height < -2 SD of median, NCHS) were compared with 26 non-stunted children (height >-1SD). The stunted children were significantly less active than the non-stunted children, although the difference in activity rating was small (3.4 percent). They spent more time in light activities (P < 0.001) and less time in moderate or vigorous activities (P < 0.01). Both groups slept a similar amount. Using Torun's values for the energy cost of activities it appears unlikely that the reduced activity would conserve energy to a great extent, but it may still be of biological importance, since it is comparable to the energy cost of growth at this age. Activity levels increased with age but were not significantly related to weight for height. The mechanism linking reduced activity to stunting requires further investigation.(AU)

The Kingston Project: VIII. Intrahousehold distribution of a therapeutic dietary supplement targeted at malnourished children in the community - abstract

The fate of a dietary supplement, high energy supplement (HES), was studied in 16 households of moderately malnourished children (7-32 months-of-age) attending a nutrition clinic in the slums of Kingston. Two methods were used in the study: observation of the consumption of the HES and a urine collection from all household members (on three occasions) to analyse the presence of D-Xylose, a tracer mixed in the HES. Households were observed during eight (8) four-hour periods by community health workers. The results showed that 60 percent of both adults and non-index children had positive urine results for xylose. However, adults were observed less often than the non-index children to consume the supplement (23 percent and 50 percent respectively). More children of large households (more than 6 members) consumed HES than those from small households. Both methods showed that sharing occurred during dietary supplementation. High energy supplements used in rehabilitation of malnourished children in this study are frequently shared by house-hold members; hence the index child will not receive sufficient nutrients required for full catch-up growth. This experience has led the public health service to focus more on fortifying existing menus in the households of malnourished children (AU)

Adaptation to a marginal intake of energy in young children

Six male children, aged 8-28 months, were studied for three consecutive periods of 1 week each. They were given diets that provided 1.7g protein/kg per d and supplements of minerals and vitamins, with a metabolizable energy intake during the 1st, 2nd and 3rd week of 419, 293 and 335 kJ (100, 70 and 80 kcal)/kg per d, diets 1, 2 and 3 respectively. All the food offered was consumed. Each child was weighed at the same time each day on an electronic balance. On the 6th and 7th day of each study period urine and stool were collected for 24h to assess nitrogen balance. Using linear regression analysis it was shown that all children gained weight on diet 1, 2.3(SD 1.3)g/kg per d, and five of six children gained weight on diet 3, the mean for the whole group being 2.7(SD 2.3)g/kg per d, not significantly different. On diet 2 all children lost weight, -5.4(SD 1.3)g/kg per d, highly significantly different from each of the other dietary periods. Using asymptotic regression analysis it could be shown that the rate of weight loss during the first part of the week on diet 2, -11g/kg per d, was greater than at the end of the week, -2g/kg per d, with a tendency towards a steady weight by day 7. Apparent N retention (mg/kg per d) was positive at the end of each of the three dietary periods: diet 1, 112(SD 25); diet 2, 54(SD 34); diet 3, 82(SD20). In five of the six children there was a marked reduction in stool frequency on diet 2 compared with diet 1, that was maintained to the period on diet 3. The findings suggest that during the period on diet 2 there was a saving of energy of the order of 105 kJ(25 kcal)/kg per d, which lasted through into the period on diet 3

Changes in red cell insulin receptors during recovery from severe malnutrition

Red cell insulin binding was studied in 13 Jamaican children (age range 4-24 months), while malnourished (MAL), during early recovery (GI), late recovery (GII), and after anthropometric recovery (REC). The rate of weight gain (RW), the energy intake (EN), and the protein intake (PR) were monitored at each phase of the study. Four-hour fasting blood samples were used, and the insulin binding characteristics were investigated in the physiological range of insulin concentrations (16.7-1670 pM). Analyses of variance were used to examine differences in the variables measured at the four phases. Red cell-specific insulin binding (SB) was lower in MAL than in GI (P<0.001) and in (GII) (P=0.026). SB in REC and MAL were not significantly different. Insulin receptor affinity (K) was also lower in MAL than in GI (P<0.001), GII (P<0.001), and REC (P=0.012). The insulin receptor number (S) appeared to be high in malnutrition and to decrease as recovery progressed; however, the decrease was not significant. Children with fever demonstrated high insulin binding. Plasma insulin (IN) rose during recovery, and was significantly higher in GII than in MAL (P=0.01). There was no difference in plasma glucose (G) at any phase of the study. The interrelationships among the variables measured were investigated longitudinally using multiple regression analyses. SB was positively associated with S (P=0.032), EN (P=0.029), and PR (P=0.0076). S was negatively associated with K (P<0.001). The associations of S and K with PR were positive and approached significance (P = 0.09 and P = 0.07 respectively). RW was positively associated with PR (P<0.001), and with EN (P=0.001). There were no significant relationships between G and any of the other variables longitudinally. However, correlations of the variables within phases demonstrated that in MAL, G was negatively associated with SB (P<0.05) and with K (P<0.05); but in REC, G was positively associated with SB (P<0.05). These results demonstrated that in severe malnutrition, the red cell insulin receptor affinity was low. During catch-up growth when protein and energy intakes were increased, both insulin receptor affinity and specific insulin binding were also increased. The negative relationship between insulin binding and plasma glucose during malnutrition may be related to carbohydrate intolerance (AU)

Whole body protein turnover and resting metabolic rate in homozygous sickle cell disease

Whole body protein turnover and resting metabolic rate were measured in six adults with homozyguous sickle cell disease (genotype HbSS) and in six normal adults (genotype HbAA) of similar age. Turnover was measured with prime/intermittent oral doses of [15N]glycine over 18 h and resting energy expenditure was measured by indirect calorimetry. In HbSS, nitrogen flux (0.9 ñ 0.08 g day-1 kg-1), protein synthesis (6.0 ñ 0.5 g day-1 kg-1) and protein degradation (5.6 ñ 0.5 g day-1 kg-1) were significantly increased compared with HbAA nitrogen (flux 0.5 ñ 0.02g day-1 kg-1, protein synthesis 3.2 ñ 0.2 g day-1 kg-1 and protein degradation 2.8 ñ 0.2 g day-1 kg-1). Resting energy expenditure was significantly higher in HbSS compared with HbAA when expressed per unit of body weight (115 ñ 3 and 94 ñ 4 kj day-1 kg-1 respectively) or weight 0.75(317 ñ 6 and 269 ñ 8 kj day-1kg-0.75, respectively). The increase in protein turnover and energy expenditure suggest that patients with HbSS exist in a hypermetabolic state that requires greater dietary energy compared with HbAA. (AU)

Whole-body protein turnover before and after splenectomy in children with homozygous sickle cell disease - abstract

Splenomegaly in sickle-cell disease is associated with excessive red cell destruction. We previously found whole body protein turnover and energy expenditure to be significantly higher in adults patients with sickle-cell disease compared to normals. The increase could be largely due to the increased turnover of the red cell, in particular the protein haemoglobin, in this disease state. We therefore measured whole body protein turnover in four children with sickle-cell disease, before and after splenectomy, to find out if the reduction in haemolysis that follows splenectomy would be reflected in a reduction in protein turnover. Protein turnover was measured with an oral primed intermittent infusion of 15N-glycine over 12-16 hours on the standard hospital diet. Isotopic excretion in urinary urea and ammonia were used to calculate protein turnover. (Table Included) Protein turnover was reduced by 23-47 percent after splenectomy. This reduction is presumably due to the fall in the excessive haemolysis that is associated with enlarged spleen. From a regression of protein turnover against energy expenditure in our previous study, it is estimated that the reduction in turnover after splenectomy could result in a theoretical saving of energy after splenectomy could be associated with the growth spurt that generally follow operation (AU)

Measurement of whole body protein turnover and basal metabolic rate in sickle cell anaemia

Whole body protein turnover and basal metabolic rate were measured in 6 patients with homozygous sickle cell disease, HbSS, and 6 normal controls. A technique using oral prime/intermittent infusion of 15N glycine as tracer, and enrichment in urinary urea and ammonia was used to measure protein turnover. The subjects received a priming dose containing 90æg15Nkg-1 followed, six hours later, by a continuous infusion at the rate of 5æg15Nkg-1 hr-1. Feeds were given intermittently along with the tracer. Plateau enrichments were mostly achieved by 9-12 hours in both ammonia and urea. Protein turnover in the sickle cell patients was 66-81 percent more than in the normals and represented an increase in synthesis and breakdown. A theoretical increase in haemoglobin turnover accounted for 20-26 percent of the increase in turnover. The average basal metabolic rate, as measured by oxygen consumption, was also significantly higher in sickle cell patients, despite subnormal nutritional status in 5 of the 6 patients. It was 7 percent (P<.05) more than in the normals and the difference was even greater when expressed in terms of body weight and muscle mass, being 22 percent, P<0.005 and 20 percent (P<.005) respectively. Protein turnover is an energy demanding process and with no other obvious cause, it seems that the process of protein turnover contributed to most of the increase in energy expenditure. With this assumption, protein turnover accounted for 40-44 percent of the energy expended in the sickle cell subjects compared to 27-32 percent in the normals. If the cost of protein turnover in normals is as much as 27-34 percent, this is further evidence that previous estimates based on the energy required for protein synthesis is significantly underestimated. The significant increase in protein turnover and energy expenditure indicates that there is a higher requirement for energy in HbSS compared to normal that could be relevant to the generalised poor growth, high susceptibility to infection, poor wound healing and the general ill health observed in the patients (AU)

Protein deficiency, energy deficiency, and the oedema of malnutrition

The role of dietary protein deficiency in kwashiorkor is uncertain, although it has been shown not to be involved in the famine oedema of adults. A study of six different diets given to 103 children with oedematous malnutrition showed that the rate of loss of oedema was strongly correlated with the dietary energy intake (r=-0.75) but not with the protein intake (r=0.03). 66 patients given a very-low protein diet (2.5 percent protein energy) lost oedema as fast as those given five times as much protein. The energy intake above which oedema accumulated was 245-270 KJ/kg/day. Because energy deficiency is not invariably associated with oedema it cannot be the only factor involved, and the other necessary dietary component(s) must therefore have been present in surfeit in all the therapeutic diets. This could be potassium together with factors necessary for its retention. The accessory ingredients must be low in foods associated with human and experimental nutritional oedema. It is suggested that protein deficiency is not the cause of the oedema of kwashiorkor and that there is no need to postulate a different pathogenesis for this oedema from starvation oedema of adults. (Summary)

Plasma zinc, rate of weight gain, and the energy cost of tissue deposition in children recovering from severe malnutrition on a cow's milk or soya protein based diet

Thirty-four malnourished children were rehabilitated on either a cow's milk or a soya protein based formula diet. The soya diet contained 25 percent less zinc than the cow's milk diet and 1.33 mmol/1 phytic acid. When the marasmic children were given either of these diets they had a dramatic fall in their plasma zinc concentration. Children given the soya formula had an even more profound drop in plasma zinc, to levels associated with acrodermatitis enteropathica. Plasma zinc remained low throughout the phase of rapid weight gain, but rose when a mixed diet was given and the children ceased gaining weight. There was a negative correlation between the rate of weight gain and the plasma zinc concentration, the rate of new tissue synthesis being the predominant modulator of the plasma zinc concentration. The energy cost of tissue deposition was initially low on the cow's milk diet and relatively high on the soya diet. Later, the energy costs rose in the cow's milk fed children. The rate of weight gain was less on the soya diet; however, the appetite, as measured by the ad libitum dietary intakes, did not differ between the diets, or correlate with the plasma zinc concentration. This may due to the relatively low protein content of the diets used. It is concluded that dietary zinc may limit the rate of weight gain during periods of recovery in body mass and may be a cause for the excessive deposition of adipose tissue. (AU)

Nutrition and protein turnover in man

The composition and homoeostasis of the body are maintained by the integrated action of all the tissues and organs. Therefore, although it is of interest to look at the component parts separately, each part has to be fitted functionally into a greater over-all framework. Whole-body protein turnover represents the integration of one fundamental activity of living organisms. Each individual protein has its own turnover rate, responding in a particular way to any change in metabolism. The turnover in the whole body is the resultant of these activities and in this sense has been likened to basal metabolic rate. The measurement of protein turnover in man has wide application, not only to the normal metabolic changes taking place during growth but also to disorders of metabolism in many clinical conditions. Although the standard nitrogen balance technique gives valuable information on net changes, it cannot indicate either the intensity of nitrogen metabolism or the mechanism by which changes are brought about. Nitrogen balance is the resultant of differences between synthesis and breakdown, which may change in the same or opposite directions in any given clinical state.(AU)

Fasting energy utilization in the smaller of twins with epinephrine-deficient hypoglycemia

The possible role of epinephrine deficiency in abnormal utilization of energy sources during fasting was investigated in three pairs of discordant identical twins with recurrent fasting hypoglycemia. The hypoglycemic twins, ages 2, 8 and 9 years, each had beens smaller at birth. Defective epinephrine responsiveness to hypoglycemia was established by administration of 2-deoxyglucose, 50 mg/kg, i.v. In the control twins, this resulted in a rapid increase of plasma glucose (+39 mg/100 ml), free fatty acids (+0.3 mM), and urinary epinephrine (+224 ng/mg creatine). These changes did not occur in the affected twins. Fasting metabolism in the epinephrine-deficient twins was compared to the unaffected twins as controls. Oxidation of carbohydrate and fat were estimated from hourly measurements of oxygen consumption and carbon dioxide production, and utilization of protein was determined from nitrogen excretion. PLasma glucose decreased more rapidly in the affected twins during the 8 hours prior to appearance of symptoms. During this period, carbohydrate was oxidized more rapidly than in the controls (average: 3.1 versus 1.7 mg/kg/min). Plasma á-hydroxybutyrate and free fatty acids was frequently less in relation to glucose. Symptoms occurred when the sum of both glucose and á-hydroxybutyrate was lower than in the controls. Urinary epinephrine excretion increased from an average baseline of 18 to a maximum of 134 ng/mg creatinine in the control twins. The average maximum urinary epinephrine reached in the deficient twins was only 51 ng/mg creatinine, in spite of lower glucose. Plasma insulin decreased in relation to glucose below 40 mg/100 ml in the control twins (r = 0.65), but this did not occur in the deficient twins (r = -0.38). Cortisol and growth hormone responses were similar in the two groups. THerefore, the consequences of inability to increase epinephrine when availability of glucose became acutely limiting were inappropriate persistent oxidation of carbohydrate, decreased circulating alternate substrates from fat, and lack of suppression of insulin. (AU)