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Regulation of body fluid and salt homeostasis--from observations in space to new concepts on Earth.

The present manuscript summarizes recent discoveries that were made by studying salt and fluid homeostasis in weightlessness. These data indicate that 1. atrial natriuretic peptide appears not to play an important role in natriuresis in physiology, 2. the distribution of body fluids appears to be tightly coupled with hunger and thirst regulation, 3. intrathoracic pressure may be an important co-regulator of body fluid homeostasis, 4. a so far unknown low-affinity, high capacity osmotically inactive sodium storage mechanism appears to be present in humans that is acting through sodium/hydrogen exchange on glycosaminoglycans and might explain the pathophysiology, e.g., of salt sensitive hypertension. The surprising and unexpected data underline that weightlessness is an excellent tool to investigate the physiology of our human body: If we knew it, we should be able to predict changes that occur when gravity is absent. But, as data from space demonstrate, we do not.

Body Fluids↗

Epithelial magnesium transport and regulation by the kidney.

Magnesium is the fourth most abundant cation in the body and the second most common cation in the intracellular fluid. It is the kidney that provides the most sensitive control for magnesium balance. About a 80% of the total serum magnesium is ultrafilterable through the glomerular membrane. In all of the mammalian species studied to date, the proximal tubule of the adult animal reabsorbs only a small fraction, 10-15%, of the filtered magnesium. Unlike the adult proximal convoluted tubule that of young rats (aged 13-15 days) reabsorbs 50-60% of filtered magnesium along the proximal tubule together with sodium, calcium, and water. Micropuncture experiments, in every species studied to date, indicates that a large part (approximately 60%) of the filtered magnesium is reabsorbed in the loop of Henle. Magnesium reabsorption in the loop occurs within the cortical thick ascending limb (cTAL) by passive means driven by the transepithelial voltage through the paracellular pathway. Micropuncture experiments have clearly showed that the superficial distal tubule reabsorbs significant amounts of magnesium. Unlike the thick ascending limb of the loop of Henle, magnesium reabsorption in the distal tubule is transcellular and active in nature. Many hormones and nonhormonal factors influence renal magnesium reabsorption to variable extent in the cTAL and distal tubule. Moreover, nonhormonal factors may have important implications on hormonal controls of renal magnesium conservation. Dietary magnesium restriction leads to renal magnesium conservation with diminished urinary magnesium excretion. Adaptation of magnesium transport with dietary magnesium restriction occurs in both the cTAL and distal tubule. Elevation of plasma magnesium or calcium concentration inhibits magnesium and calcium reabsorption leading to hypermagnesiuria and hypercalciuria. The identification of an extracellular Ca2+/Mg2+ -sensing receptor located on the peritubular side of cTAL and distal tubule cells explains this phenomenon. Loop diuretics, such as furosemide and bumetanide, diminish salt absorption in the cTAL whereas the distally acting diuretics, amiloride and chlorothiazide stimulate magnesium reabsorption within the distal convoluted tubule. Finally, metabolic acidosis, potassium depletion or phosphate restriction can diminish magnesium reabsorption within the loop and distal tubule. Research in the 90's have greatly contributed to our understanding of renal magnesium handling.

Animals↗

Determination of body fluid compartments by electrical impedance measurements.

?The ratio of the LF and HF impedances appears to be an excellent and simple tool for investigation of liquid specimens, either of the total human body, taking into consideration global impedances, or of a particular organ, taking into consideration local impedances. We have sketched out in this communication a study of the global impedance ratio variations with age, but a large number of studies still remain to be undertaken in those cases of severe denutrition, as in all cases of metabolic illnesses. We can state that, in most cases, not only does the ratio decrease but that there is extreme difficulty in reestablishing normal values. Whatever action is undertaken, it seems that the intracellular liquid compartment remains insufficient with respect to that of the extracellular liquid compartment. It is as if the water will not enter in the cells or as if it were no longer retained within the cells. Finally, with this concept of impedance ratios of Zlf/Zhf a promising experimental method has been found which will, perhaps, enable better infestigations in a field which has often been left to one side.

Body Composition↗

Body volume changes during simulated weightlessness: an overview.

It has been hypothesized that many of the adaptive processes that occur in man during exposure to space involve the rapid headward shift of tissue fluids, blood, and other fluids during the first few hours of spaceflight. A total of 53 men and women between the ages of 22 and 55 years were tested during four bed rest studies lasting between 4 h and 7 d to define the segmental volume changes that took place during simulated weightlessness. Impedance plethysmography can be used to measure baseline resistance (Ro) changes of the calf, thigh, total leg, pelvic, torso, and arm segments before, during, and after each bed rest exposure. Records of Ro were analyzed to determine the fluid volume and volume change of each segment during each test sequence.

Adaptation, Physiological↗

Fluid shifts in weightlessness.

Studies of leg volumes in space by multiple girth measurements showed reductions of 1.9 L (12.8% of leg volume) with 1.1 L from the non-dominant leg on Skylab 4. On landing, 65% of postflight leg volume increase was complete at 1.5 h. Measurement of the dominant leg during the equivalent period on Shuttle showed a mean loss of 0.9 L which was 90% complete at 150 min. Postflight increases were 87% complete at 1.5 h postlanding. Mass measurements during and after Skylab 4 showed a loss of 2.5 kg over the first 4 d on-orbit with a gain of 2.7 kg over the first 4 d of recovery. These changes are assumed to be tissue fluids secondary to changes in hydrostatic pressures and are much greater than those seen in bed rest. Rate and magnitude of inflight and postflight changes have significant operational impact.

Arm↗

Space shuttle inflight and postflight fluid shifts measured by leg volume changes.

This is a study of the inflight and postflight leg volume changes associated with spaceflight on Space Shuttle missions. The results of this study show an inflight volume loss of 2 L from lower extremities, 1 L from each leg, representing an 11.6% volume change. The vast majority of this change appears to be a shift in body fluids, both intravascular and extravascular. The fluid shift occurs rapidly on Mission Day 1 (MD-1), with it being essentially complete by 6 to 10 h. The regional origin of shift and leg volume change shows a far greater absolute volume (708 ml vs. 318 ml) and percentage (69% vs. 31%) of the total change coming from the thigh as compared to the lower leg. Postflight, the return of fluid to the lower extremities occurs rapidly with the majority of volume return complete within 1.5 h postlanding. At 1 week postflight there is a residual leg volume decrement of 283 ml or 3.2% that is probably due to tissue loss secondary to atrophic deconditioning and weight loss.

Body Fluids↗