Albert A. Plentl

THE ROLE OF THE FETUS IN THE WATER EXCHANGE OF THE AMNIOTIC FLUID OF NORMAL AND HYDRAMNIOTIC PATIENTS

In a preceding report on exchange mechanisms in pregnant monkeys (1), evidence has been presented that the water exchange between the maternal organism and the products of gestation can be represented by a kinetic model composed of three major compartments, all of which exchange with each other. The three compartments are defined as: 1) the amniotic fluid, 2) the maternal, and 3) the fetal body water. It could be shown that the introduction of a hydrogen tracer into fetus or amniotic fluid results in retention curves of predictable shape and that transfer rates for water can be calculated with reasonable accuracy when the amniotic fluid was used as the primary compartment. It should therefore be possible to devise methods whereby the transfer rates for the human could be calculated and to study the role which the fetus plays in the exchange of water between the amniotic fluid and the mother. For the calculation of transfer rates it is necessary to know the change in concentration of tracer as a function of time for each compartment. Continuous measurements on pregnant women are limited to the two accessible compartments: mother and amniotic fluid. In addition, a single sample of fetal or cord blood can be obtained at the time of delivery. Under these conditions there are two possible ways in which a time-activity curve for the fetal compartment can be calculated from available data. The first is based upon the

The lymphocyst: A complication of pelvic lymph node dissections

Abstract Nine of 55 patients with carcinoma of the cervix who were treated with pelvic lymphadenectomy 3 months after full radium and external radiotherapy developed retroperitoneal collections of fluid one to 6 months after operation. These lymphocysts were responsible for a large proportion of the morbidity and mortality resulting from this operation and constitute one of the major reasons for abandoning this procedure.

THE DYNAMICS OF THE AMNIOTIC FLUID

Over the past five years the investigations of my associates and myself have been concerned with the study of over-all exchange mechanisms between tlic products of gestation and the maternal organism. The stimulus to this project was the pioneer work of Flexner and his associates 011 the transfer of water m c l sodium i n the pregnant organism. 13y means of deuterium oxide and sotiium24, these investigators measured the transfer rxtes of water and sodium from the maternal organism to the fetus and also the transfer ratesfrom the maternal organism to the amniotic fluid. The “b:ickflow” or other exchange mechanisms were not considered in their calculations. It wits assumed, however, that an equal amount of the transferred species would be returned that was not and could not be substantiated under the conditions then prevailing. Despite t his shortcoming, the formulas used by Flexner, admittedly an approximation, were thought to he applicable. The analytic values carried a fairly large error, in some cases nearly 100 per cent, with no possibility of determining their magnitude since, for each individual patient, only one value for the tracer concentration could be obtained. Such data may be informative if based on a sufficiently large number of subjects of comparable age, parity, and length of gestation; Flexner’s data, however, are based on 5 patient,s whose gestational ages ranged from 14 weeks to term. These authors’ final conclusion that 34 per cent of the water of the amniotic fluid is exchanged per hour implies that the rate of equilibration for the amniotic fluid is considerably slower than that for the maternal organism. It was our thought that this difference should enable us to calculate transfer rates with a much higher degree of accuracy and to use the correct mathematical treatment of the data. The problern of water exchange of the amniotic fluid assumes considerable clinical significance under the pathological conditions of hydramnios and the rare oligohydramnios. The volume of the amniotic fluid varies throughout pregnancy for individual patients, and term pregnancies may be associated with aniniotic fluid volumes ranging from a few hundred to several thousand milliliters, I t would be desirable to know whether the exchange is effected in any manner and what its relation t o the varidil i ty of the amniotic fluid might be. A comparison of normal and abnormal conditions cannoi be based on the approximat ions used thus far, but requires much more precise and accurate measurement of transfer rates. Improvement in tracer analyses and i echniclues should lead to ;t higher degree of precision, and the more recent theoretic developments in the field of multic:ompartment systems Im)vidc the h i s for the c;ilculation of the hackflow from a minimum of dat;t. For reasons of expediency, our original studies were c~oncerned only wit ti the exchange between mother and amniotic h i d . This admittedly simplified system lends itself well to :I nxtthematicnl annlysis. In order to investigate

Total body water, sodium space, and total exchangeable sodium in normal and toxemic pregnant women.

Abstract 1. Simultaneous measurements of sodium space and total body water as well as total exchangeable sodium have been made on a series of toxemic patients and the values compared with the range obtained for normal pregnant women near term. 2. The relationship of total body water and body weight was found to be influenced by body build; i.e., lean pregnant women were found to have a higher (58.7 per cent body weight) and obese pregnant women a lower (45.4 per cent body weight) water content than the mean (53.3 per cent body weight). The ratio of sodium to water space showed no significant difference when lean, obese, and average normal pregnant patients were compared. 3. The mean sodium space of pre-eclamptic patients with and without hypertensive vascular disease constitutes a significantly higher percentage (56.0) of the total body water than the corresponding mean for normal (49.5) and hypertensive patients without pre-eclampsia (50.0). 4. The mean value for the total exchangeable sodium of pre-eclamptic patients is significantly higher (46.0 mEq. per kilogram) than that of normal pregnant patients (39.6 mEq. per kilogram) of comparable gestational age. 5. Additional evidence has been presented that normal pregnant women do not retain sodium beyond the limits for the nonpregnant state.

The role of the monkey fetus in the exchange of the water and sodium of the amniotic fluid.

Isotopic tracers allow for the expedient investigation of the exchange of elements or metabolic products between the maternal organism and conceptus. The quantity of carrier transferred per unit of time can be estimated from the behavior of tracers if the experimental data are subjected to the proper mathematical treatment. The general background and practical applications of the theory of multi-compartment systems to related biologic problems have recently been reviewed (1). Depending upon the aim of the investigation and the nature of the available experimental data, one can subdivide a given system into an arbitrary number of hypothetical compartments which exchange, or are assumed to exchange, their constituents at constant rates. If such a system is to be completely defined, time-activity curves for all compartments must be known and all must be accessible. Once the applicability of a certain kinetic model is established, the transfer rates can be calculated from a minimum of experimental data. It is the purpose of these investigations to test the applicability of a proposed kinetic model in order to provide the theoretical basis for further studies on clinical material. It is known that the human fetus participates in the exchange of water and electrolytes between amniotic fluid and mother (2), but because of its inaccessibility a quantitative formulation of these mechanisms is not easily accomplished. A knowledge of the tracer concentration in fetal blood as a function of time is a prerequisite for the calculation of transfer rates. Such a time-activity curve for the fetal compartment can be determined directly on some experimental animals where * This investigation was, in part, supported by a grantin-aid from the National Institutes of Health, Department of Health, Education and Welfare. samples of fetal blood can be obtained without disturbing the continuity of the system. The pregnant primate, a miniature model of the human maternal organism, should serve this purpose very well if it can be shown that the two species are comparable in the more pertinent aspects of water and electrolyte exchange. For the study of these problems three sets of experiments were carried out. The first was intended to show that the transfer rates of water in and out of the amniotic fluid compartment of pregnant monkeys at term are identical within the limits of error of the method. The second was intended to estimate the ratio of water to sodium transfer and to compare this ratio with values previously reported for the human. Finally, attempts were made to determine time-activity curves for all three compartments simultaneously and to estimate the overall transfer rates involving the fetus in utero.

THE TOTAL BODY WATER AND THE WATER TURNOVER IN PREGNANCY STUDIED WITH DEUTERIUM OXIDE AS ISOTOPIC TRACER

The status of pregnancy profoundly affects the maternal metabolism. By means of isotopic tracers over-all changes in metabolic rates of specific substances can, with certain limitations, be studied. This investigation is concerned with the demonstration of water turnover rates during various stages of pregnancy and an effort is made to define their physiologic and pathologic variations. Based upon clinical evidence, appreciable variations in the state of hydration are expected as pregnancy progresses and even greater variations may be anticipated under certain pathologic conditions. For this reason the water economy of the pregnant woman is of considerable interest to the clinician. Numerous investigations have been carried out to determine changes in specific fluid

Transfer of Water Across the Perfused Umbilical Cord.

Summary 1. Fresh human umbilical cords 20 cm in length were perfused with heparinized Group O blood while immersed in a solution the composition of which was similar to amniotic fluid. 2. Tritiated water was added to the perfusion fluid (blood) or the surrounding bath and the change in specific tritium activity determined as a function of time. 3. Rate of exchange of water between the 2 compartments was calculated to be 40.5 and 50.5 ml of water per hour. 4. Evidence is presented that the umbilical vessels and Whartons jelly play a significant role in the water exchange of the amniotic fluid.

Determination of deuterium exchange rates between maternal circulation and amniotic fluid.

Summary and Conclusions 1. Regarding the pregnant organism as a multi-compartment system the exchange rate of the water in amniotic fluid with the water of the maternal and fetal systems, was determined. By the application of trans-abdominal catheters, placed into the amniotic sac of pregnant women at term, amniotic fluid could be withdrawn at desired intervals without disturbing the continuity of the system. The mechanism of tracer (deuterium) exchange was demonstrated to be that demanded by theory, and the application of well known theoretic equations to the data so obtained permitted the calculation of absolute exchange rates. 2. In 2 experiments where the isotopic tracer was first placed in one compartment (mother) and then in the other (amniotic fluid) the exchange rates in both directions were found to be about 600 cc per hour. The observations of Flexner and his associates on the exchange rate of the water of the amniotic fluid are thus confirmed in principle.

Collection of C14O2 for scintillation counting by a modification of the Van Slyke procedure.

Abstract A method for the collection of CO 2 for scintillation counting is described in which a simple absorption unit is used as an accessory to the Van Slyke-Neill blood gas apparatus. Carbon dioxide is absorbed directly in the scintillation vial immediately after the determination of the total CO 2 content of the samples. The procedure was tested for varying sizes of samples and absorbents. Phenethylamine is superior to Hyamine as shown by statistical analyses of the data and the higher counting efficiency. The technique is applicable to standard procedures for blood and blood filtrates where labeled carbon dioxide may be liberated by chemical or enzymic means.

Hydrodynamic Model of A 3-Compartment Catenary System with Exchanging End Compartments

Summary A hydrodynamic model of a 3 compartment system analogous to the maternal organism has been constructed. Its schematic representation is that of a catenary 3 compartment system in which the end compartments exchange. The mathematical basis for this system has been reviewed and experimental “time-activity” curves for the 3 compartments used to calculate the transfer rates.