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Water is the most abundant constituent in the body, comprising ~50% of body weight in women and 60% in men. Total-body water is distributed in two major compartments: 55–75% is intracellular (intracellular fluid [ICF]), and 25–45% is extracellular (extracellular fluid [ECF]). The ECF is further subdivided into intravascular (plasma water) and extravascular (interstitial) spaces in a ratio of 1:3. Fluid movement between the intravascular and interstitial spaces occurs across the capillary wall and is determined by Starling forces, i.e., capillary hydraulic pressure and colloid osmotic pressure. The transcapillary hydraulic pressure gradient exceeds the corresponding oncotic pressure gradient, thereby favoring the movement of plasma ultrafiltrate into the extravascular space. The return of fluid into the intravascular compartment occurs via lymphatic flow.

The solute or particle concentration of a fluid is known as its osmolality, expressed as milliosmoles per kilogram of water (mOsm/kg). Water easily diffuses across most cell membranes to achieve osmotic equilibrium (ECF osmolality = ICF osmolality). Notably, the extracellular and intracellular solute compositions differ considerably owing to the activity of various transporters, channels, and ATP-driven membrane pumps. The major ECF particles are Na+ and its accompanying anions Cl and HCO3, whereas K+ and organic phosphate esters (ATP, creatine phosphate, and phospholipids) are the predominant ICF osmoles. Solutes that are restricted to the ECF or the ICF determine the “tonicity” or effective osmolality of that compartment. Certain solutes, particularly urea, do not contribute to water shifts across most membranes and are thus known as ineffective osmoles.

Water Balance

Vasopressin secretion, water ingestion, and renal water transport collaborate to maintain human body fluid osmolality between 280 and 295 mOsm/kg. Vasopressin (AVP) is synthesized in magnocellular neurons within the hypothalamus; the distal axons of these neurons project to the posterior pituitary or neurohypophysis, from which AVP is released into the circulation. A network of central “osmoreceptor” neurons, which includes the AVP-expressing magnocellular neurons themselves, sense circulating osmolality via nonselective, stretch-activated cation channels. These osmoreceptor neurons are activated or inhibited by modest increases and decreases in circulating osmolality, respectively; activation leads to AVP release and thirst.

AVP secretion is stimulated as systemic osmolality increases above a threshold level of ~285 mOsm/kg, above which there is a linear relationship between osmolality and circulating AVP (Fig. 49-1). Thirst and thus water ingestion are also activated at ~285 mOsm/kg, beyond which there is an equivalent linear increase in the perceived intensity of thirst as a function of circulating osmolality. Changes in blood volume and blood pressure are also direct stimuli for AVP release and thirst, albeit with a less sensitive response profile. Of perhaps greater clinical relevance to the pathophysiology of water homeostasis, ECF volume strongly modulates the relationship between circulating osmolality and AVP release, such that hypovolemia reduces the osmotic threshold and increases the slope of the response curve to osmolality; ...

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