Derangement of Starling forces will promote fluid accumulation in the interstitial compartment, causing edema and ascites ( 34, 35, 46, 50). Heart failure, cirrhosis, and nephrotic syndrome induce renal water and salt retention. In high mineralocorticoid states and frequently in CKD, renal excretion of excess salt and fluid is impaired, causing a sustained increase in systemic arterial blood pressure. Acute exogenous mineralocorticoid administration induces renal salt retention and causes a transient increase in ECF and plasma volume in humans ( 10) and small animals ( 22, 53). Typically, CKD impairs salt (NaCl) and water excretion, causing a transient increase in plasma volume after salt intake ( 19, 29).
In contrast, chronic kidney disease (CKD), mineralocorticoid excess, heart failure, and cirrhosis commonly induce ECF expansion. An increase greater than 2% in plasma osmolality or a decrease greater than 10% in plasma volume trigger compensatory mechanisms through the release of vasopressin from the posterior pituitary, which induces water retention by the kidney, thirst, and vasoconstriction to maintain blood osmolality and blood pressure ( 9). Under these conditions, ECF volume depletion accounts for TBW loss, and the plasma volume decrease can reach 20% of TBW loss ( 9). Isotonic dehydration occurs when both water and sodium salts are lost at the same rate. Thus, a 100-mL loss of TBW causes approximately a 10-mL loss of plasma volume, a 30-mL loss of ECF, and a 60-mL loss of ICF ( 14). Hypertonic dehydration occurs when hypotonic fluid is lost, causing an increase in plasma osmolality, e.g., water restriction or excessive sweating. Moreover, dehydration is a common condition ( 15, 48) and poses a high risk of morbidity and mortality in children, the elderly, and inpatients ( 24, 51). Excessive sweating, diarrhea, diabetes insipidus, diuretic drugs, diabetes mellitus, or age-associated hypodipsia are major causes of dehydration ( 26, 39, 45, 52). Dehydration occurs when water intake and water formation from metabolism does not compensate for obligatory water loss, e.g., urine, sweat, and stool production. Severe dehydration is defined as a loss of water exceeding 5% of body weight and is life threatening due to hyperthermia and hypoperfusion of organs ( 1). Many diseases and drugs can disturb water homeostasis, and, as a result, fluid disorders are one of the most frequent issues in clinical medicine ( 52).ĭehydration is an abnormal decrease in total body water (TBW) of more than 2% of body weight (1.4 L for 70 kg) ( 9). ECF is divided into the interstitial fluid and intravascular fluid, or blood volume, accounting for around 16% and 4% of body weight, respectively. Whereas intracellular fluid (ICF) accounts for ~40% of body weight, extracellular fluid (ECF) accounts for ~20% of body weight. Water is the most abundant component of the body and represents 45−60% of total body weight in an adult, depending on race, age, and sex ( 11). This method allows analysis of kinetic changes to stimuli before investigating with terminal methods and will allow further understanding of fluid disorders. TD-NMR is, therefore, the first method to allow direct measurement of discrete changes in ECF in conscious small animals.
BODY FLUID COMPARTMENTS PERCENTAGE FREE
We showed, for the first time, that mineralocorticoids induced a transient ~15% increase in free fluid in conscious mice.
Finally, we studied the effect of mineralocorticoids that are known to induce a transient increase in ECF but for which no direct measurements have been performed in mice. We determined the effect of 24-h water deprivation on mouse body parameters and detected a sequential and overlapping decrease in free fluid and lean mass during water deprivation. We assessed the feasibility of coupling TD-NMR analysis to a longitudinal metabolic cage study by monitoring mice daily. Moreover, this apparatus enables rapid, noninvasive, and repeated measurements on the same animal. This technique allows differentiation of protons in a liquid environment (free fluid) from protons in soft tissues containing a majority of either small molecules (lean) or large molecules (fat). We examined the feasibility of monitoring mouse ECF by a noninvasive method using time-domain nuclear magnetic resonance (TD-NMR). Water homeostasis studies in small animals require the use of invasive or terminal methods that make intracellular fluid volume and extracellular fluid volume (ECF) monitoring over time stressful and time consuming. Many diseases and drugs affect water balance and plasma osmolality. Maintaining water homeostasis is fundamental for cellular function.
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