Malcolm A. Holliday

Body Composition and Energy Needs during Growth

The study of body composition, dividing the body into component parts, is a logical step in the process of trying to correlate structure with function on a “whole-body” scale. Characterizing changes in body composition is a means for understanding the process of growth and change in function that affect nutritional needs as growth proceeds. Anatomic divisions are rather obvious, e.g., organ mass and muscle mass. Fluid–mineral divisions are less readily visualized. The body is divided into total body water and solids; total body water is further divided into an extracellular and intracellular phase. Extracellular fluid (ECF) includes plasma, interstitial fluid, and connective tissue fluids; intracellular fluid (ICF)—the fluid phase of cells—is mostly in organs and muscle (Widdowson and Dickerson, 1964). The functional aspects of body composition can be viewed in terms of organ function (brain, liver, etc.), locomotion (muscle mass), energy reserve (fat mass), environment for cells (extracellular fluid), and supporting structures (connective tissue and bone) (Figure 1). These functions, like their structures, are rather self-evident. The major organs and muscle constitute the bulk of cell proteins in the body. Of these, muscle protein is the principal reservoir for amino acids when diet is deficient or when there is a need for gluconeogenesis from amino acids. While glycogen and protein provide some reserve for energy, fat is the real reservoir for energy when the diet is deficient. Plasma and interstitial fluid are the environment and transportation system for the cells. Supporting structures—connective tissue and bone, etc., although containing protein, are not sources for protein during diet deficiency. The ECF of connective tissue is a reserve for interstitial fluid and plasma when dehydration occurs. Bone contains a reserve for calcium, phosphorus, and some other minerals.

Relation of calorie deficiency to growth failure in children on hemodialysis and the growth response to calorie supplementation.

Abstract To determine if a relation existed between calorie intake and growth of children on hemodialysis, linear growth rate was observed for periods of three to nine months in children on dialysis and compared to 50th-percentile growth rates taken from tables for normal children having the same age or comparable secondary sexual development. Five children (six observations) with calorie intakes of less than 67 per cent of Recommended Dietary Allowances (RDA) grew at an average rate of 34 per cent of normal (range, 0 to 59). Ten children (11 observations) with calorie intakes of greater than 67 per cent of RDA grew at an average rate of 117 per cent normal (range, 87 to 150). Therefore, in this patient population, only calorie intakes of approximately 70 per cent of RDA or more were compatible with normal growth.

The Relation of Metabolic Rate to Body Weight and Organ Size

The relation of metabolic rate to body size has been a subject of continuing interest to physicians, especially pediatricians. It has been learned that many quantitative functions vary during growth in relation to metabolic rate, rather than body size. Examples of these are cardiac output, glomerular filtration rate, oxygen consumption and drug dose. This phenomenon may reflect a direct cause and effect relation or may be a fortuitous parallel between the relatively slower increase in metabolic rate compared to body size and the function in question. The fact that a decrease in metabolism and many other measures of physiological function in relation to a unit of body size is observed in most biological systems. This phenomenon can be demonstrated by interspecies comparisons of mammals and birds, as well as within a species during growth or among matured members of a species that vary in size. Mice, for example, have a basal metabolic rate per kg (BMR/kg) approximately thirteen times that of elephants. In the case of humans during growth, the infant has a BMR/kg more than twice that of the normal adult. A normal adult may have a BMR/kg one and one-half times that of an obese adult. The purpose of this paper is to review this subject and propose reasons why there is a lower BMR/kg as body size increases. When applied to growing humans, the information developed should allow a greater precision in estimating BMR from body weight during growth. It will be seen that the factors responsible for the decline in BMR/kg during growth differ from the factors operative among different species. The equation describing the relation of BMR to body weight during growth also differs from the equation describing this relation among different species. Historical Background

Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

Rats were made acutely hyper- or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (Na(E) and Cl(E)). The following observations are noted: Brain Cl content varies directly with Cl(E) and brain Na content in the Cl space (Na(e)) varies directly with Na(E), indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (V(i)) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in V(i) in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) Na(E) is proportional to osmolality; (b) brain osmolality remains equal to plasma osmolality; (c) V(i) is osmotically active; and (d) there is no net gain or loss of solute from V(i). The validity of these assumptions is considered. When changes in osmolality are sustained, V(i) is much closer to control values than when in the acute phase. K content increases in hypernatremia and decreases in hyponatremia. The changes in K content can account for some of the adjustment in V(i) observed over the extended period of hyper- or hyponatremia. The regression of (Na + K)/v upon Na(E) describes a slope less than 1.0 and an intercept of (Na + K)/v equal to 40% of the control (Na + K)/v. These characteristics are interpreted to mean that significant quantities of Na and K in brain are osmotically inactive. The brain protects itself from acute volume changes in response to change in Na(E) by the freedom for Na and Cl to move from the Cl space, by V(i) not changing acutely to the degree predicted from osmotic properties of cells in general, and by significant quantities of Na + K in V(i) being osmotically inactive. With sustained changes in osmolality, V(i) approaches normal values and brain K changes to account for part of this later adjustment.

Expressing glomerular filtration rate in children

We have reviewed the studies that provide the current standards of reference for glomerular filtration rate (GFR) in normal children from 14 days to 12 years of postnatal age. These standards currently are presented as ml/min per 1.73 m2, i.e., adjusted to average adult body surface area. Children from birth to 1 year of age have adjusted values below the adult range, making comparisons of observed to reference values difficult. Currently, there is no accepted way of obtaining reference values that vary smoothly with age. An analysis of the absolute GFR values in normal children taken from published studies led to an equation that estimates average GFR in relation to weight and term-adjusted age from-2 months (7 months gestational age) to 12 years in children at least 14 days post delivery. When these data are transformed to percentage of normal (% nl) for age and weight (i.e., percentage of the estimated average), it is possible to describe approximate apparent lower limits of normal GFR as is now done for adults and older children. For children with loss of renal mass, GFR expressed as % nl for age and weight provides a convenient standardization which has several useful applications. First, results expressed as % nl for children of different ages, particularly under 1 year of age, can be combined with those of older children for summary purposes. Second, the course of GFR measured serially in children is more appropriately described using this method for expressing GFR. Reporting GFR in absolute values is also useful, particularly in patients whose body mass is significantly distorted or whose absolute GFR is low.

Fluid therapy for children: Facts, fashions and questions

Fluid therapy restores circulation by expanding extracellular fluid. However, a dispute has arisen regarding the nature of intravenous therapy for acutely ill children following the development of acute hyponatraemia from overuse of hypotonic saline. The foundation on which correct maintenance fluid therapy is built is examined and the difference between maintenance fluid therapy and restoration or replenishment fluid therapy for reduction in extracellular fluid volume is delineated. Changing practices and the basic physiology of extracellular fluid are discussed. Some propose changing the definition of “maintenance therapy” and recommend isotonic saline be used as maintenance and restoration therapy in undefined amounts leading to excess intravenous sodium chloride intake. Intravenous fluid therapy for children with volume depletion should first restore extracellular volume with measured infusions of isotonic saline followed by defined, appropriate maintenance therapy to replace physiological losses according to principles established 50 years ago.

A Rat Model for the Study of Growth Failure in Uremia

Extract: The growth of children with chronic renal disease is poor and the cause of this stunting is not known. Various factors have ben implicated and it is difficult to evaluate their relative importance in clinical studies. Accordingly, there is a need for an animal model, preferably one which enables the effect on growth of a number of factors to be studied separately and over a reasonably short period of time. The growth and food intake of male and female rats rendered uremic by 5/6 nephrectomy was observed between 40 and 70 days of age for male rats and between 35 and 70 days of age for female rats. Final mean body weight for males with uremia (243 g ± 32 g) was significantly less than for control males (323 g ± 24 g); final mean body weights for female rats were also significantly different (172 g ± 17 g; 223 g ± 21 g). The differences in body weight were apparent from 50 days onwards. Final tail length was significantly less in female uremic rats compared with their control subjects (173 mm ± 8 mm; 183 mm ± 7 mm). Uremic rats matched for body weight with control rats consumed significantly fewer calories; for both groups the average difference was about 15%. Multiple regression analysis of weight gain against age and calorie intake suggests that there may be an increase in the calorie cost of growth in rats with uremia, but these findings require confirmation in paired feeding studies.Speculation: These studies suggest that this rat model can be used for the investigation of alterations in energy balance, body composition, and metabolic functions in uremia. It should be possible to study the effects of single variables in the pathogenesis of growth retardation by appropriate manipulations halfway through the growth period.

HYPOPARATHYROIDISM, MONILIASIS, ADDISON'S AND HASHIMOTO'S DISEASES. HYPERCALCEMIA TREATED WITH INTRAVENOUSLY ADMINISTERED SODIUM SULFATE.

THE association of superficial moniliasis, idiopathic hypoparathyroidism, Addisons disease and Hashimotos thyroiditis in a single patient is previously undocumented. One purpose of this paper is ...

Extracellular fluid restoration in dehydration: a critique of rapid versus slow.

Abstract We compared current recommendations for treatment of severe dehydration by World Health Organization physicians and by the American Academy of Pediatrics Committee on Pediatric Gastroenterology with those in general textbooks of pediatrics, written mostly by pediatric nephrologists. The former recommend rapid (1- to 2-h) and generous intravenous restoration of extracellular fluid (ECF) volume followed by oral rehydration therapy (ORT) to replace potassium, current maintenance, and diarrheal losses – the rapid rehydration regimen. Oral feedings usually are resumed in 8–24 h. General textbooks of pediatrics usually recommend giving 20 ml/kg saline ”to restore circulation,” followed by the deficit therapy regimen to correct serum electrolyte abnormalities and replace remaining deficits of water, sodium, chloride, and potassium over 1–2 days. Mortality for hospitalized patients with dehydration treated with rapid rehydration was <3 per 1,000; no recent results are reported for patients treated by deficit therapy. The rapid rehydration regimen improves patient well being and restores perfusion, so that oral feedings are readily tolerated and renal function corrects serum electrolyte abnormalities in 6 h. Amounts of saline given correspond to amounts given for treating various forms of shock. Deficit therapy regimens provide less ECF restoration and are slower at restoring perfusion; tolerance for oral feedings is delayed. Two hundred pediatric nephrologists were surveyed, asking how they would treat a patient with severe dehydration and a patient with 40% burns. Only 30 of 200 responded; 29 used a deficit therapy regimen, with 20–40 ml/kg ECF replacement, while a majority rapidly and generously restored ECF volume in burn shock. We recommend that fluid therapy chapters should stop teaching deficit therapy for treating severe dehydration and instead teach the rapid rehydration regimen.

Extracellular fluid and its proteins: dehydration, shock, and recovery.

Abstract This review highlights characteristics of extracellular fluid (ECF) that are often overlooked. ECF has, in addition to plasma and interstitial fluid (ISF) surrounding cells, a third large compartment, the ISF of skin and connective tissue. This acts as a reservoir that gives up ECF to plasma volume (PV) in order to sustain circulation in the event of either shock or dehydration. While Starling forces drive filtration, ECF is returned to PV more by lymph and less by Starling forces than previously appreciated. Lymph return to PV is dependent on physical activity and muscle contraction to overcome gravity. Regional change in metabolic rate alters the need for oxygen and nutrients that is met by a regional increase in capillary blood flow. Blood flow is controlled by vasoactive compounds released in response to a drop in PO2; these relax capillary smooth muscle to increase blood flow and delivery of oxygen and nutrients. Plasma proteins, including albumin, are filtered into the interstitium through larger pores than those filtering ECF. The rate of protein filtration is set by size and charge of these larger endothelial pores and by size and charge of proteins. Charge of these pores, hence albumin permeability, is regulated by many of the same vasoactive compounds that control capillary flow. As a consequence, in response to gravitational stress and other forms of shock that reduce effective circulation, albumin as well as ECF is rapidly shifted from plasma and sequestered in ISF. When this has occurred, as in burn shock, restoration is better effected by generous expansion of ECF with Ringer’s solution alone, rather than with Ringer’s solution supplemented with human serum albumin or other colloid. Restoring both PV and ISF volume restores lymph circulation and returns sequestered albumin to PV.