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A1 Measurement of Total Body Water

Total body water (TBW) is a fundamental component of body composition, which is influenced by many physiological and patho-physiological states. Knowledge of a patient’s TBW can contribute to diagnosis and management.

Rapid assessments of body fluid status can be made by Bioimpedance analysis (BIA) but the conversion of tissue reactance and resistance into absolute measures of body water, particularly in diseased states, can be unreliable.

Isotopic methods used to measure TBW provide well-validated results, but sample analysis by conventional methods has been expensive and time-consuming. Multiple sample acquisition, to analyse deuterium dispersal kinetics, has not been practical. Consequently, these methods have remained research tools.

Clinicians have used equations to estimate TBW. Whilst this approach works reasonably well for individuals with close to normal body composition, this cannot be said for malnourished, obese or fluid-loaded patients.

The DS-1 has been developed as a rapid, non-invasive tool for determining the deuterium abundance in breath water. When combined with conventional oral loading of deuterated water (2H2O, or D2O) this may be used to determine total body water. Additionally, the dispersal kinetics of deuterium throughout the body can be studied.

Protocol for TBW measurement

The baseline deuterium abundance in the breath of a subject should first be obtained by direct breath sampling from several consecutive exhalations (typically three).

The subject then drinks an accurately weighted amount of 99.9 % pure D2O in 200 mL of regular drinking water. The dose of D2O should be approximately 0.3 g/kg body weight. This is well within safe limits.

They immediately drink an additional 200 mL of water, in order to minimise the deuterium in the mouth mucosa, saliva and gullet.

The injested D20 will give rise to an increase in the measured ratio of 1H2HO (or HDO) to H2O. When the dispersal kinetics is to be studied, breath samples are analysed at approximately 3 minute intervals until equilibration in the breath deuterium is reached (usually within 2 hours). When just the TBW is required, it is sufficient to analyse the breath deuterium abundance 2 hours after ingestion.

Kinetics of dispersal of HDO in the body

Typical single-breath deuterium time profiles show rapid increases as the water vapour increases, followed by a relatively constant level during the alveolar portion of the breath exhalation. The abundance of deuterium in breath can be calculated for each exhalation.

A typical time variation of breath deuterium abundance during the two hours following ingestion shows three phases: an immediate and short increased level due to deuterium still present within the oral cavity: a rise to a second peak, which is usually reached 20 to 50 minutes following ingestion, due to the passage of HDO from the stomach and upper intestine into the blood stream: finally, decay towards an equilibrium value as the HDO disperses into the TBW.

It is possible to track the equilibration of deuterium between three distinct body compartments, the gastro-intestinal tract, the blood compartment and the TBW. A number of factors will determine the rates at which HDO will equilibrate in each case, including the rate of gastric emptying, the blood volume and the delivery of HDO to the tissues.

The transport of HDO can be modelled mathematically by considering diffusion (permeation) through the idealised interfaces between these model body compartments.

In the days following the test, water in ingested food and drink and even in inhaled humid air will dilute the HDO in the TBW. Measurements during this period can be used to estimate the total water intake.

Total body water volume is calculated from the volume of ingested D2O divided by the difference between the baseline deuterium abundance prior to ingestion and the asymptotic level of the final phase.

References

Spanel P, Smith D. Flowing afterglow mass spectrometry (FA-MS) for the determination of the deuterium abundance in breath water vapour and aqueous liquid headspace. In: Amann A, Smith D, eds. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Singapore: World Scientific, 2005.

Smith D, .el P. On-line determination of the deuterium abundance in breath water vapour by flowing afterglow mass spectrometry, FA-MS, with applications to measurements of total body water. Rapid Comm Mass Spectrom 2001; 15: 25–32.

Spanel P, Smith D. Accuracy and precision of flowing afterglow mass spectrometry for the determination of the deuterium abundance in the headspace of aqueous liquids and exhaled breath water. Rapid Comm Mass Spectrom 2001; 15: 867-872.

Davies Spanel P, Smith D. Rapid measurement of deuterium content of breath following oral ingestion to determine body water. Physiol Meas 2001; 22: 651-659.

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