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Total body water is distributed as follows: two-thirds in the intracellular space and one-third in the extracellular space. Seventy-five percent of the water in the extracellular space is located interstitially, while the remaining 25% is located intravascularly. For the extracellular fluid (ECF) space, sodium is the primary cation, while chloride and bicarbonate are the primary anions. For the intracellular fluid (ICF), potassium is the primary cation, while phosphate is the primary anion.


The tonicity (the measurement of osmotic pressure) of body fluids is tightly regulated within a physiologic range (osmolality of 275–290 mOsm/kg). While the body actually regulates tonicity, labwork measures osmolality (the concentration of solution, in terms of number of solute particles per kilogram). High osmolality (what is measured in a lab) does not always mean high tonicity. For example, urea, ethanol, methanol, and ethylene glycol freely cross cell membranes, so there is no water shift and no change in cell volume. In this case, tonicity is not affected, but osmolality is. Tonicity and osmolality align so closely in most situations, however, that these terms are used interchangeably in this chapter. Sodium concentration is the dominant factor in serum osmolality, as shown by the following estimation:

Osmolality = 2 [Na+] +BUN (mg/dL)/2.8 + glucose (mg/dL)/18


The two principal regulatory factors that maintain osmolality (and indirectly, the sodium concentration) in the normal range are antidiuretic hormone (ADH) and thirst.


Antidiuretic Hormone

ADH is the main determinant of free water excretion. It is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary. Hypertonicity triggers its release, causing resorption of water by the kidney’s collecting tubules. ADH release is also triggered by hypovolemia (via volume receptors in the carotid sinuses), but not as powerfully. Other stimuli for ADH release include CNS disorders, meningitis, postoperative state, malignancies, pneumonia, pain, and stress (resulting in the syndrome of inappropriate antidiuretic hormone [SIADH]). When ADH is present, urine osmolality ranges from 300 to 1200 mOsm/kg, and urine specific gravity is >1.010. When ADH is absent, urine osmolality ranges from 50 to 80 mOsm/kg, and urine specific gravity is <1.005. The urine specific gravity is not as accurate a measure of ADH action as the urine osmolality, because specific gravity reflects the weight of particles in the urine, not just their number. For example, proteinuria may lead to a high urine specific gravity but a low urine osmolality.


A small rise in ECF tonicity stimulates thirst. Consequent decreased water excretion and increased water intake restore body fluid tonicity. High serum sodium and osmolality stimulate thirst and the intake of hypotonic fluids, while ...

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