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American Journal of Clinical Nutrition, Vol. 85, No. 1, 80-89, January 2007
© 2007 American Society for Nutrition


ORIGINAL RESEARCH COMMUNICATION

A whole-body model to distinguish excess fluid from the hydration of major body tissues1,2,3

Paul W Chamney, Peter Wabel, Ulrich M Moissl, Manfred J Müller, Anja Bosy-Westphal, Oliver Korth and Nigel J Fuller

1 From the Research and Development department, Fresenius Medical Care, Bad Homburg, Germany (PWC, PW, and UMM); the Institut für Humanernährung und Lebensmittelkunde, Christian Albrechts-Universität, Kiel, Germany (MJM, AB-W, and OK); and the MRC Childhood Nutrition Research Centre, Institute of Child Health, London, United Kingdom (NJF)

2 Data from the Institut für Humanernährung und Lebensmittelkunde were obtained through funding from Fresenius Medical Care.

3 Reprints not available. Address correspondence to PW Chamney, Research and Development, Fresenius Medical Care, Bad Homburg, Germany.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
Background: Excess fluid (ExF) accumulates in the body in many conditions. Currently, there is no consensus regarding methods that adequately distinguish ExF from fat-free mass.

Objective: The aim was to develop a model to determine fixed hydration constants of primary body tissues enabling ExF to be calculated from whole-body measurements of weight, intracellular water (ICWWB), and extracellular water (ECWWB).

Design: Total body water (TBW) and ECWWB were determined in 104 healthy subjects by using deuterium and NaBr dilution techniques, respectively. Body fat was estimated by using a reference 4-component model, dual-energy X-ray absorptiometry, and air-displacement plethysmography. The model considered 3 compartments: normally hydrated lean tissue (NH_LT), normally hydrated adipose tissue (NH_AT), and ExF. Hydration fractions (HF) of NH_LT and NH_AT were obtained assuming zero ExF within the diverse healthy population studied.

Results: The HF of NH_LT mass was 0.703 ± 0.009 with an ECW component of 0.266 ± 0.007. The HF of NH_AT mass was 0.197 ± 0.042 with an ECW component of 0.127 ± 0.015. The ratio of ECW to ICW in NH_LT was 0.63 compared with 1.88 in NH_AT. ExF can be estimated with a precision of 0.5 kg.

Conclusions: To calculate ExF over a wide range of body compositions, it is important that the model takes into account the different ratios of ECW to ICW in NH_LT and NH_AT. This eliminates the need for adult age and sex inputs into the model presented. Quantification of ExF will be beneficial in the guidance of treatment strategies to control ExF in the clinical setting.

Key Words: Excess fluid • tissue hydration • normal hydration • body composition • adipose tissue • ECW:ICW ratio


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
Diseases such as cardiac impairment and kidney failure often lead to an accumulation of excess fluid (ExF), increasing the body's state of hydration. ExF may be regarded as an expansion of the extracellular or total body fluid compartments of the body but is not required by the body to maintain homeostasis. In patients with kidney failure, it is essential to remove the ExF to avoid long-term cardiovascular mortality (1-4). Despite the occurrence of ExF, little progress has been made in the body-composition field to develop a method for its identification.

Well-established techniques, such as hydrometry (5, 6), dual-energy X-ray absorptiometry (DXA) (7-9), and underwater weighing (10, 11), are available to obtain estimates of fat-free mass (FFM). The major drawback with these methods, however, is that ExF cannot be distinguished from FFM. Although ExF may be reflected by a rise in ECW (12) or TBW, quantification of ExF is only possible once a hydration reference has been established. The hydration reference represents normal values of ECW and TBW found in healthy control subjects, although the proportions of ECW and TBW vary according to body composition. Where body composition is assumed constant in a given subject group, a hydration reference may be established allowing ExF to be calculated (13). The ratio of ECW to TBW also offers the basis of a hydration reference, and this approach has been applied in patients with corrections for age (14). The hydration of FFM (HFFM), although regarded constant at 0.73 (15), may be influenced by several health factors (16) thus limiting its use for quantification of ExF. Additionally, in more recent work, the hydration of lean soft tissue and its relation with the ratio of ECW to ICW was investigated (17).

One factor influencing the ratio of ECW to ICW (and hence its use as a reference) is the diversity of major body tissues such as the distinct adipose tissue and lean (nonadipose) tissue (18-20). To take into account the dissimilar hydration of relevant tissues and satisfy the need for a method to quantify ExF, we developed a new body-composition model.


    SUBJECTS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
Subjects and measurements
Data were used from 89 healthy adults recruited in Kiel, Germany. These data were supplemented with those from 15 healthy adults gathered in a previous study conducted in Cambridge United Kingdom (Morgan M, Madden A, Jennings G, Elia M, Fuller N, unpublished observations). Ethical approval was obtained from the ethical board of the Christians Albrechts Universität. The subjects were specifically chosen such that the full extent of the body composition range (in terms of percentage fat) could be investigated. The subject characteristics derived by combining the data (n = 104) from the 2 centers are reported in Table 1Go.


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TABLE 1 Characteristics of healthy control subjects1

 
Each subject fasted overnight for 10 h. At the end of this period, 5-mL venous blood samples were taken for assay calibration and to establish baseline concentrations of deuterium and bromide. A mixture of deuterium oxide (0.4g/kg body weight) and NaBr (50 mg/kg body weight) was administered to each subject. According to past studies, a homogenous distribution of deuterium is achieved within 4 h (5). During this equilibration period any ingestion of food or water was prohibited. At the end of the equilibration period, a second set of samples was taken. Plasma water was obtained from the resulting serum samples by ultrafiltration to remove plasma solids. In Kiel, the volume of TBW was determined from the concentration of deuterium in plasma water by using Fourier transform infrared spectroscopy (FTS 2000; Varian, Deutschland GmbH, Darmstadt, Germany). Deuterium space was corrected for nonaqueous exchange factors by multiplying by 0.945 (21). The same technique was used for analysis of deuterium in the Cambridge data (ATI Mattson Genesis, Cambridge, United Kingdom). Plasma water was assayed additionally for bromide concentration by evaluation of the peak area resulting from HPLC anion exchange chromatography (Waters GmbH, Eschborn, Germany). ECW was determined from bromide space as described by Miller et al (22) from the following equation:

Formula 1(1)
where MBr_Dose is the mass (in mmol) of bromide administered and CBr_4 h and CBr_Baseline are the concentrations (in mmol/L) of bromide after the 4-h equilibration period and at baseline, respectively. The factor 0.9 compensates for a small leakage of bromide into the intracellular space, and the factor 0.95 accounts for Donnan equilibrium effects. In the Cambridge data, ECW was determined by using a spectrophotometric fluorescein method with deproteinization. The assay was automated by using Cobas Fara (Roche Diagnostic, Welwyn Garden City, United Kingdom). The appropriate corrections were then applied (23). Before any further analysis, the whole-body volumes of TBW and ECW were converted to mass by the density of water, DBW, by using a value of 0.99371 kg/L at 36 °C (24).

Total body fat was measured by using DXA scanners (Hologic Inc, Waltham, Ma) models QDR-4500A V8.26a in Kiel and QDR-1000/W in Cambridge. Calculated values of body fat were also obtained from densitometry via Siri's equation (25) and by application of a 4-component (4-C) model (24) with the use of measurements of body volume obtained either by air-displacement plethysmography with a Bod-Pod (Life Measurement Instruments, Concord, CT) in Kiel or by underwater weighing in Cambridge. It was shown that these measurements of body volume are equivalent in healthy adults (26).

New 3-compartment model
Several authors have suggested that the body should be divided into adipose tissue (AT) and nonadipose body mass or adipose-free mass (AFM) (18-20, 27). The considerable disparity between the hydration of AT and AFM shown in these studies formed the basis of our new model. In the present study, it was assumed that in a state of health these 2 tissues could be considered "normally hydrated." A schematic of the new 3-component (3-C) tissue-based model is shown in Figure 1Go. It is consistent with the molecule level of the 5-level model classification described elsewhere (28), but modified to reflect the presence of excess fluid that may accumulate due to pathological reasons. It is clear from Figure 1Go that the mass of ExF is a subcompartment of AFM. Therefore, to avoid ambiguity, AFM is divided into "normally hydrated lean tissue" (NH_LT) and MExF. Similarly, the term "normally hydrated adipose tissue" (NH_AT) is used in place of adipose tissue to emphasize how adipose tissue should be regarded. The hydration properties of NH_LT and NH_AT are the cornerstones of the new model that provide the hydration reference against which ExF may be expressed. When ExF is present it may reside within adipose tissue or lean tissue raising the hydration of the respective tissue above the "normal" values, eg, edema. Alternatively, ExF may simply appear as a distinct compartment without altering the hydration of the major tissues, eg, ascites. Regardless of how ExF is manifested, for the purposes of calculation it is convenient to consider ExF as a compartment separate from normally hydrated tissue as represented in Figure 1Go.


Figure 1
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FIGURE 1. A: The new 3-compartment model comprising normally hydrated adipose tissue mass (MNH_AT), normally hydrated lean tissue mass (MNH_LT), and excess fluid mass (MExF). B: Relation between the compartments of the new model and standard measures of body composition in terms of lean mass, fat mass, and fat-free mass (FFM).

 
In the current model definition, NH_AT consists of stored lipids, essential lipids, water, and solids (some protein and nonosseous mineral). NH_LT tissue includes water, protein, osseous and nonosseous minerals, and essential lipids with some intracellular lipids. The ratio of bone mineral to total protein is assumed to be constant. An analysis of 3-C and 4-C models (24) shows that the error incurred as a result of this assumption is relatively small. Morse and Soeldner (20) concluded that the hydration parameters of adipose tissue and nonadipose tissue in healthy subjects (which is equivalent to NH_LT in the proposed new model) remain largely unchanged in obese or nonobese subjects. Consequently, our model was developed on the basis that in health a given mass of tissue could be associated with fixed proportions of intracellular water (ICW) and extracellular water (ECW) regardless of body composition. The consequence of these fixed hydration parameters is that the ratio of ECW to ICW is constant in a specific tissue. Fixed hydration parameters have the advantage that ExF can be identified by the new model by using 3 whole-body measurements of weight, ECWWB, and ICWWB. The details of this calculation are given in Appendixes A and B. During childhood, the water content of adipose tissue is considered to decrease significantly (29, 30). Therefore, the use of this model is limited, at present, to adults, although introduction of age-specific adipose tissue hydration parameters could extend applicability of the model to children.

In contrast with the current model, an estimate of ExF can be obtained by considering the expansion of either ECWWB or TBWWB. These methods generally assume a fixed ratio, such as ECWWB:ICWWB, reflecting normal hydration status for a given population and are given in Table 2Go.


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TABLE 2 Expressions for calculation of excess water assuming fixed whole-body hydration ratios1

 
Analysis
Because intracellular water (ICWWB) was not measured directly, the difference between TBW and ECWWB was used for calculations requiring the ICWWB. ExF was calculated from the new model with Equation B5 (derived in Appendix B). The tissue hydration parameters were calculated according to Equations C5, C6, and C9-12, which are shown in Appendix C. A summary of all abbreviations is given in Appendix DGo. Parameter value CIs were obtained through the bootstrap process. One-half of the data records (n = 52) were selected randomly from the total data pool. Each data record selected was replaced in the data pool enabling possible reselection. After retrieving 52 data records (one-half the total number of records), a set of hydration parameters was calculated. The process of random selection and parameter set calculation was repeated an arbitrary 2000 times. The CIs for the hydration parameters were obtained from the SD of the resulting distribution of each parameter.


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APPENDIX D Abbreviations

 
Box plots were used to identify significant statistical differences in HFFM, and the ratios of ECWWB to ICWWB and of ECWWB to TBW in different body composition ranges. Measurement precision was measured for each input measurement as SD/Formula 1 (where SD represents the SD of the intrasubject measurement reproducibility). This allowed the precision of ExF to be estimated by propagation of errors, based on a reference man weighing 73 kg and with 20% body fat (31).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
After normalization of fat, TBW, ECWWB, and ICWWB, a clear reduction in body water compartments was observed with increasing body fat content as shown in Figure 2Go. By linear regression of normalized TBW and ECWWB, as defined by Equations C4 and C8 against DXA fat mass, the following parameters were obtained: aTBW = –0.672, bTBW = 0.703, aECW = –0.185, and bECW = 0.266. By using these regression parameters, the tissue hydration parameters were calculated with Equations C5, C9, C11, and C12. The process was repeated by using fat mass calculated with the Siri equation and the 4-C model. However, these particular methods are not entirely independent of either body weight or TBW and so a small degree of mathematical coupling occurs, which slightly influences bias. The hydration parameters obtained with all 3 methods for fat determination are shown in Table 3Go along with those derived by using DXA for comparison. Literature values obtained with the use of in vitro techniques are shown in Table 4Go. By substitution of the DXA hydration parameters given in Table 3Go into Equation B5, the expression for the mass of ExF may be reduced to the following:

Formula 2(2)
Similarly, the mass of NH_LT given by Equation B2 may be simplified to the following:

Formula 3(3)
Rearrangement of Equation A1 leads to the mass of NH_AT, as follows:

Formula 4(4)
Finally, by combining the parameters HTW_NH_LT and KAR from Equation A8, the fat mass may be determined as follows:

Formula 5(5)
By using the parameters aTBW, bTBW, aECW, and bECW from the regression analysis, Equations C4 and C8 were denormalized to yield 17.2 L ECWWB and 24.7 L ICWWB for a reference man of 73-kg body weight and 14.6-kg fat mass. Under these conditions, input measurement errors (SDs) of 0.5 kg, 1 kg, and 0.1 kg were estimated for ECWWB, ICWWB, and MWB respectively. By propagation of these errors, the overall precision of the new method for calculation of MExF (Equation B5) was thus found to be {approx}0.5 kg.


Figure 2
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FIGURE 2. Relation of total body water (TBW), whole-body extracellular water (ECWWB), and whole-body intracellular water (ICWWB) with percentage fat measured by using dual-energy X-ray absorptiometry (DXA). A decline in normalized fluid volumes (NECW, normalized ECW; NICW, normalized ICW; and NTBW, normalized TBW) is observed after normalization of fluid volumes and fat mass to body weight as the proportion of body fat increases. The offsets of each regression line, where normalized fat = 0, reflect the total water, ECW, and ICW properties of normally hydrated lean tissue as indicated by HTW_NH_LT, HECW_NH_LT, and HICW_NH_LT, respectively. The slope of the regression lines for TBW and ECW are annotated with aTBW and aECW, respectively, from which total water, ECW, and ICW properties of normally hydrated adipose tissue (HTW_NH_AT, HECW_NH_AT, and HICW_NH_AT, respectively) can be obtained.

 

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TABLE 3 Hydration parameters of normally hydrated lean tissue (NH_LT) and normally hydrated adipose tissue (NH_AT) measured in vivo with 3 different methods1

 

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TABLE 4 Hydration parameters of normally hydrated lean tissue (NH_LT) and normally hydrated adipose tissue (NH_AT) from the literature1

 
The subjects were categorized into 1 of 3 body composition groups according to percentage fat: lean (<20%), normal (20–30%), and obese (>30%). Significant differences were found in the ECWWB-to-ICWWB and ECWWB-to-TBW hydration ratios at the extremes of body composition, as shown in Figure 3Go. HFFM did not differ significantly between the lean and obese subgroups but was accompanied by a relatively large variation.


Figure 3
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FIGURE 3. Comparison of hydration of fat-free mass (HFFM) and the ratios of whole-body extracellular water (ECWWB) to whole-body intracellular water (ICWWB) and ECWWB to total body water (TBW) in lean, normal, and obese subgroups. The boxes in each subgroup represent the interquartile range (50% of data) about the median value. The minimum and maximum values occurring within 1.5 times the interquartile range from the box edges are indicated by whiskers, and values falling outside this range (outliers) are represented by crosses. The notches in the boxes provide the 95% CIs. If the notches between any pair of boxes do not overlap, the difference between the subgroups is statistically significant. In this case, significant differences in the ECWWB:ICWWB and ECWWB:TBW occured between the lean and obese subgroups.

 
The bias occurring with the use of the different methods for calculation of MExF in the categorical body composition subgroups is shown in Table 5Go. The difference in MExF between the lean and obese subjects was not significant in results calculated from a fixed HFFM; however, the method was found to be subject to considerable variability within each body-composition group, which was apparent from the SD. Significant underestimation of ExF in lean subjects and overestimation of ExF in obese subjects was observed for methods involving fixed ECWWB-to-ICWWB and ECWWB-to-TBW ratios. In the new model, there was no significant bias between the lean and obese subgroups.


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TABLE 5 Comparison of different methods to calculate excess fluid (MExF) in lean, normal, and obese body-composition subgroups1

 
In order to obtain an impression of how the new model performed in pathologic cases, the Equation 2 to Equation 5 were applied to 3 groups of 11 malnourished patients from a previous study (32). The analysis exposed considerable quantities of ExF in these patients, as shown in Table 6Go. The results indicated an increasing prevalence of ExF with increasing degrees of malnourishment.


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TABLE 6 Application of the current model to malnourished subjects1

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
Central to the new model presented is the concept of normally hydrated lean tissue (NH_LT) and normally hydrated adipose tissue (NH_AT). The sum of these 2 tissues provides a hydration reference against which excess fluid (ExF) can be identified. In the current study, we used deuterium oxide and sodium bromide as the dilution references for TBW and ECW. An advantage of the model is that the hydration parameters in a group of healthy control subjects may be established by using any alternative dilution reference of choice such as total body potassium (TBK). Nevertheless, the hydration parameters obtained in our study for NH_LT and NH_AT were in the range reported in other studies (19, 20, 30, 33). NH_AT was found to have a much lower water content but a higher ratio of ECW to ICW than did NH_LT, which is consistent with the findings of others (19, 20). By definition, HTW_NH_LT cannot exceed HFFM because adipose water is included in FFM but not in NH_LT. Because the range of HFFM in healthy control subjects is 0.69–0.77 (16), the value of 0.8 for HTW_NH_LT obtained by Wang et al (19) may be slightly overestimated.

Although Morse and Soeldner (20) observed no difference in the hydration of NH_AT between obese and nonobese subjects, as seen in Table 4Go, a more recent study by Martin et al (33) indicated the contrary. This suggests that more detailed investigation of the hydration properties of adipose tissue may be necessary in differing degrees of obesity, not only in terms of total water content but also in terms of intra- and extracellular phases. The model developed in the present study assumed fixed hydration parameters for adipose tissue, and Figure 2Go indicates that this serves as a good approximation to the measured data. Furthermore, an improvement in the reproducibility of the measurement methods is necessary before a more complicated model of adipose tissue can be justified.

It is evident from Figure 2Go that whereas the ECWWB is clearly lower than the ICWWB when NH_LT dominates body weight, the converse is observed as NH_AT becomes the principle body weight component. This would appear to be the basis of the relative expansion of ECWWB in obese subjects observed in other studies (27). As the ratio of ECW to ICW in NH_AT is a least twice that of NH_LT, then the whole-body proportions of NH_LT and NH_AT would explain the significant differences in the ratios of ECWWB to ICWWB and ECWWB to TBW between the lean and obese subjects, as shown by categorical divisions of body fat (Figure 3Go).

Although the fat content of female subjects tends to be higher than that of male subjects, as seen in Table 1Go, these differences are reflected in the relative proportions of NH_LT and NH_AT. Therefore, there was no need to differentiate by sex in our model, because body composition (in terms of fat content) is taken into account from the input measurements of ECWWB, ICWWB, and body weight. It is also unlikely that age contributes fundamentally to the ratio of ECWWB to ICWWB, but is simply due to the proportions of NH_LT and NH_AT, as suggested by Wang et al (19). It can be argued that age-associated increases in fatness may lead to a higher proportion of NH_AT.

In our study, the mean value of HFFM was found to be 0.723, which is consistent with the findings of others (24, 34, 35). In circumstances where ExF accumulates, a rise in HFFM can be expected (16), but the lack of sensitivity of HFFM to variations in ExF has not been emphasized in past studies. This can be illustrated by considering, for example, a subject with 55 kg FFM and 40 L TBW, which leads to a HFFM of 0.727. If this subject now gains 5 kg ExF, HFFM rises to 0.750, a change of just 3%. It is clear that because ExF appears in both the FFM and the TBW, the effect of ExF largely cancels out in HFFM. This renders HFFM a poor choice for providing a reliable hydration reference against which any ExF can be detected.

A significant difference in the ECWWB-to-ICWWB and ECWWB-to-TBW hydration ratios was observed between the lean and obese subgroups, as seen in Figure 3Go. A similar rise in ratio of ECWWB to ICWWB has been observed in other studies with increasing BMI (27) and with increasing age (36). Therefore, any method for estimation of ExF that assumes fixed ECWWB-to-ICWWB or ECWWB-to-TBW values for the entire population will result in bias errors at extremes of relative fat, as shown in Table 5Go. In the method described by Lopot et al (14), such effects of body composition have been taken into account by introduction of corrections for age and sex in the ratio of ECWWB to TBW.

Considerable quantities of ExF were found to be present on application of the new model in a previous study of malnourished patients (32), as seen in Table 6Go. These results are reasonable given the high ratios of ECW to ICW resulting in these subjects coupled with the observation that a significant decrease in the ratio of plasma volume to ECW occurred in the severely malnourished subgroup (32). Methods to obtain the mass of LT or FFM via DXA, for example, do not differentiate ExF from these tissues (37). If a large proportion of the LT or FFM is occupied by ExF, the estimated protein content of these tissues will be reduced. This could lead to ambiguous conclusions regarding nutritional status. In the new model, by contrast, the mass of NH_LT applies regardless of the degree of ExF presented; that is, removal or accumulation of large volumes of fluid do not change the mass of NH_LT. It is proposed, therefore, that estimation of NH_LT mass may offer a more reliable alternative to measures such as LBM and FFM in disease.


    APPENDIX A
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
General model definitions
Whole-body mass (MWB) is given by the sum of the 3 compartments, namely normally hydrated adipose tissue mass (MNH_AT), normally hydrated lean tissue mass (MNH_LT), and excess fluid (ExF) mass (MExF), as follows:

Formula A1(EA1)
The total water (TW), intracellular water (ICW), and extracellular water (ECW) components of MNH_LT and MNH_AT are defined by Equations A2-A4 and A5-A7, respectively.

Formula A2(EA2)

Formula A3(EA3)

Formula A4(EA4)

Formula A5(EA5)

Formula A6(EA6)

Formula A7(EA7)
The fat mass (MFat) is related to the mass of normally hydrated adipose tissue (MNH_AT) with equation A8:

Formula A8(EA8)
where KAR is the ratio of residual adipose components (solids, mainly protein and mineral) to MNH_AT with a value of typically 0.05 (30, 33).


    APPENDIX B
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
Calculation of excess fluid
The sum of the intracellular components of MNH_LT and MNH_AT yields ICWWB, as given by Equation B1:

Formula 1(EB1)
Introducing the intracellular water mass fraction of normally hydrated lean tissue (HICW_NH_LT), substituting MNH_AT by Equation A1 and rearranging for the lean tissue mass MNH_LT leads to the following equation:

Formula 2(EB2)
By introducing relevant constants, the mass of excess water (MExW not to be confused with MExF) may be calculated as the difference between ECWWB and the sum of the extracellular components of NH_AT and NH_LT. By substitution of HECW_NH_LT and HECW_NH_AT in the respective tissues then gives the following equation:

Formula 3(EB3)
Because ExF contains dissolved proteins and minerals in addition to ExW, a factor HExF may be applied which denotes the ratio of the mass of excess water, MExW to the mass of excess fluid, MExF. A mean value for HExF of 0.98 was assumed in the current model as suggested by Wang et al (16). Introducing HExF to convert MExW to MExF and rewriting Equation B3 by re-expressing MNH_AT from Equation B1 leads to the following equation:

Formula 4(EB4)
Substituting the expression for MNH_LT (Equation B2) into Equation B4 and rearranging for MExF yields the following equation:

Formula 5(EB5)
where k is defined by the following:

Formula 6(EB6)


    APPENDIX C
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 
Calculation of principal body-composition parameters
The purpose of the following derivation was to extract the principal body-composition parameters defined by Equations A2-A7. To proceed, it was assumed that the ExF in healthy control subjects has a mean value of zero, ie, MExF = 0. By introducing Equation A1, the mass of total body water, TBW, may be expressed as follows:

Formula 1(EC1)
By rewriting Equation C1 in terms of measurable input quantities via Equations A1 and A8, with MExF = 0, then the following equation is obtained:

Formula 2(EC2)
The normalized TBW and fat, NTBW and NFat, respectively, are obtained by dividing Equation C2 by MWB, which leads to the following equation:

Formula 3(EC3)
By normalizing the measured MFat and TBW data to body weight, the following linear relation between NFat and NTBW was readily derived from regression analysis:

Formula 4(EC4)
where aTBW and bTBW are the regression coefficients. Because Equations C4 and C3 are equivalent expressions, the tissue parameters HTW_LT and HTW_AT could thus be solved by comparing coefficients, as follows:

Formula 5(EC5)

Formula 6(EC6)
HTW_NH_LT and HTW_NH_AT are obtained directly from Equations C5 and C6.

The ECW parameters were obtained in the same way by normalization of ECWWB and MFat to body weight. Taking the form of Equation C3 and making appropriate substitutions leads to the following equation:

Formula 7(EC7)
The equivalent regression equation involving ECW may be written as follows:

Formula 8(EC8)
By comparing coefficients of Equation C8 with those of Equation C7, then we obtain the following equations:

Formula 9(EC9)

Formula 10(EC10)
HECW_NH_LT and HECW_NH_AT are obtained from Equations C9 and C10. Finally, the parameters HICW_NH_LT and HICW_NH_AT can be readily found with the following equations:

Formula 11(EC11)

Formula 12(EC12)


    ACKNOWLEDGMENTS
 
The authors thank M Morgan, M Elia, A Madden, and G Jennings for the use of their Cambridge data.

PWC and PW developed the concepts for excess fluid calculation and prepared the manuscript. UMM contributed to technical aspects of the data analysis. MJM organized the study in Kiel and made a number of recommendations to simplify the manuscript. AB-W and OK undertook the studies in Kiel, performed all of the measurement assays and provided valuable scientific support. NJF contributed to refinement of the concepts, and input for alterations to the draft manuscript. PWC, PW, and UMM are employed at the Research and Development department at Fresenius Medical Care. None of the other authors has a conflict of interest to disclose.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 APPENDIX A
 APPENDIX B
 APPENDIX C
 REFERENCES
 

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Received for publication February 22, 2006. Accepted for publication August 23, 2006.




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P. Wabel, U. Moissl, P. Chamney, T. Jirka, P. Machek, P. Ponce, P. Taborsky, C. Tetta, N. Velasco, J. Vlasak, et al.
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