• DOI:10.7326/0003-4819-127-9-199711010-00020
• Corpus ID: 29854540

Language Guiding Therapy: The Case of Dehydration versus Volume Depletion

@article{Mange1997LanguageGT,
  title={Language Guiding Therapy: The Case of Dehydration versus Volume Depletion},
  author={Kevin C. Mange and Dean Matsuura and Borut {\vC}i{\vz}man and Haydee Soto and Fuad Ziyadeh and Stanley Goldfarb and Eric Neilson},
  journal={Annals of Internal Medicine},
  year={1997},
  volume={127},
  pages={848-853}
}

• K. Mange, Dean Matsuura, +4 authors Eric Neilson
• Published 1 November 1997
• Biology
• Annals of Internal Medicine

Patients presenting with orthostatic hypotension and normal plasma sodium concentrations are frequently admitted to the hospital with a diagnosis of dehydration. If they are fortunate, they receive fluids containing sodium chloride instead of free water to correct obvious extracellular fluid volume depletion. Confusing this diagnosis highlights the growing and pernicious habit of using the terms dehydration and volume depletion interchangeably at the bedside when the two describe clearly different disturbances. The heuristic value of describing discrete body fluid spaces affected by disorders of salt and water is a well-established bedside strategy [1-5]. It sprang from an early curiosity about the best treatment for fatal diarrhea [6] and seizures [7] and from classic experiments that formulated the volume behavior and osmolarity of cells [8, 9]. Adapting this information from cells to humans in the late 1930s required more conceptual thinking about the special role of vascular volume in the control of body fluids [2, 10]. The wartime assessment of potential fluid losses encountered by shipwrecked aviators and sailors in the early 1940s further enhanced our understanding of salt and water metabolism [11-13], as did the emerging role of cardiac performance [14, 15]. With the advent of radioactive tracers [16, 17], medical language in the latter part of the 20th century began to discriminate more carefully between dehydration associated with hypertonicity, a principal loss of body water from the intracellular and interstitial compartments, and extracellular fluid volume depletion, a fluid deficiency that clinically affects the vascular tree [3, 5, 18]. The proper use of the terms dehydration and volume depletion informs communication and should improve patient care. The Language of Salt and Water in Body Fluid Spaces At steady state, the hydration or water content of body fluids represents a physiologic balance achieved by the ingestion of water and its further distribution, evaporation, and clearance by the kidneys and gut [19, 20]. Total body water disperses in a well-defined pattern [8, 21, 22] across several elastic or virtual spaces [1, 3, 5, 22]. Approximately 66% of water is confined by solute to the intracellular compartment, whereas 33% is found in the extracellular space. Only 25% of this extracellular fluid, or 8% of total body water, resides within the vasculature [1, 4, 17], and eventually all spaces achieve identical osmolarity [23]. The concept of osmotic pressure derives from the fundamental gas laws of physical chemistry [2, 24]. Water moves down a concentration gradient generated by the osmotic properties of solutes bound by a semipermeable membrane to achieve equilibrium [2]. Simple osmosis of water across virtual body compartments is further amended by the Gibbs-Donnan effect of charge-bearing proteins [2] and, in blood vessels, by the hydrostatic attributes of Starling forces [10, 25]. Although measured osmolarity reflects all particles per volume of water, not all osmols influence transmembrane water flow [5]. The power to move water across cell membranes is a property of effective osmols [2, 26, 27]. Tonicity describes the volume behavior of such cells in solution and is modulated by the number of effective osmols, or osmotically active particles, that are restricted to one side of the cell membrane because of permeability characteristics, transmembrane pumps, or both [28]. Most effective osmols are extracellular sodium, chloride, and bicarbonate or intracellular potassium, chloride, and phosphate. Less abundant effective osmols are sugars, lipids, and proteins. Solutes such as urea or alcohol, however, freely move across cell membranes and are therefore ineffective osmols unable to effect transmembrane water flow [26]. Acutely, effective osmols in the intracellular space (particularly potassium salts) are relatively fixed, and thus the major influence on the location of water in this space is the effective osmolarity of the extracellular compartment [3, 26]. When water is lost from the skin, gut, or kidneys, the hypertonicity created in the extracellular space is directly transferred to the larger intracellular space [5]. Worsening hypertonicity therefore has its biggest impact on the size of the intracellular compartment and, to a lesser extent, on interstitial spaces. To dehydrate is to lose this intracellular water and stimulate thirst. The physiologic concept of dehydration, at first glance, might subsume the definition of volume depletion. This erroneous assumption, made by investigators early in this century [26, 29], was corrected by physiologists in the era after World War II [3, 18, 30] but today has insidiously resurfaced because volume depletion has become a shorthand for extracellular fluid volume depletion, and the first two words of the latter phrase make all the difference. The volume of the extracellular fluid space is principally regulated by the ingestion and excretion of sodium salts [31]. Sodium is largely confined to extracellular fluid because cell membrane pumps operate to actively exclude it from the intracellular compartment [28, 32]. Thus, the addition of sodium leads to a specific gain of effective osmols in extracellular spaces. If sodium is added isotonically to the extracellular compartment, no shift of water from the intracellular space will ensue and the volume increase of the extracellular space will equal the volume of isotonic infusate. If hypotonic or hypertonic sodium is added to the extracellular space, the volume of the intracellular space changes accordingly [26, 29]. Changes in extracellular volume can therefore be dissociated from changes in intracellular volume [5, 21, 33]. For example, a patient who bleeds will have a rapid decline in vascular volume but, in the absence of tissue injury or change in extracellular tonicity, will not have redistribution of water from intracellular spaces [3, 34]. Such a person will have a deficit of body water equal to the proportionately small water content of the lost blood. This can be illustrated quantitatively by considering the fate of an administrated infusate of 5% dextrose compared with an equal volume of fluid given as 0.9% saline (Table 1). Both infusates provide equal amounts of water, but their effect on plasma volume is vastly different. Table 1. Effect of a 1-L Infusion of Water or 0.9% Saline on Virtual Body Fluid Spaces Assessment of Body Fluid Spaces in Designing Effective Therapies Dehydration To best assess the state of hydration, one needs to ascertain the concentration of a marker substance whose content is constant and whose distribution is uniform throughout all virtual fluid spaces. Of course, surrogate markers were devised because no such natural substance exists [16]. Because sodium is the most abundant extracellular solute and its concentration (p[Na+]) influences water movement across cells, p[Na+] may be used as a surrogate at the bedside to gauge the relation between water and effective osmols in all body fluids [5]. Although anions and large molecules contribute to the property of tonicity, some intracellular anions are complex moieties that are not easy to formulate in simple terms; therefore, it is more convenient to estimate effective osmols in a representational shorthand that consists of cations. Equation 1 Formula [1] provides a conceptual framework with which to predict relative water deficit or excess determining tonicity [30]: (Equation 1) where TBNa+ is total body sodium, TBK+ is total body potassium, TBH2O is total body water, CM is cell membrane, ECH (2) O is extracellular water, and ICH2O is intracellular water. In this formula, extracellular total body sodium and intracellular total body potassium represent the principal effective osmols that partition total body water (0.6 L/kg of body weight in adult men and 0.5 L/kg in adult women) across cell membranes at equilibrium [21, 23, 27, 35]. The signs and symptoms of acute dehydration are thirst and, progressively, confusion, coma, and respiratory paralysis [28]. These complications may be mitigated if hypertonicity develops over time and if the brain and other tissues are allowed to adapt by generating new intracellular solutes (previously called idiogenic osmols) to minimize shrinkage [33, 36]. These new solutes include sodium chloride, amino acids, myoinositol, and methylamines [37, 38]. Isolated water deficits are corrected by water replacement and can be estimated [30], over and above any isotonic change in extracellular volume, by using Equation 8 formula [5] (for the derivation of Equation 8 formula [5], see Appendix): (Equation 2) The presentation of dehydration is well illustrated by the case of an elderly 70-kg woman with bipolar disorder and angina who was receiving lithium therapy and was admitted after a positive stress test result. Her blood pressure was 128/85 mm Hg, and her heart rate was 82 beats/min. Evaluation was unremarkable except for thirst and a p[Na+] of 150 mEq/L. Without orthostasis or evidence of decreased tissue perfusion, the patient was given a diagnosis of hypertonicity brought on by acute water deprivation superimposed on lithium-induced nephrogenic diabetes insipidus. She required intravenous water expansion with 5% dextrose before cardiac catheterization because the dye load and ensuing osmotic diuresis would have worsened the hypertonicity by producing urine with lower concentrations of sodium and potassium than are found in body fluids [39]. Assuming the expected restoration of p[Na+] to 140 mEq/L, the patient's free water deficit was calculated by using Equation 8 formula [5], as follows: (Equation 3) In addition, any urine output during treatment should be replaced in the same ratio of solute (sodium plus potassium) to water. If the patient's condition had actually been mislabeled as extracellular fluid volume depletion and 0.9% saline (154 mEq of Na+/L) had been administered inste