http://surgerybook.net/

Osmotic Activity of Body Fluids

The concentration of solutes in the fluid compartments depends on the osmotic activity generated by the

ion species contained in each compartment. When two solutions are separated by a semipermeable

membrane, water moves across the membrane to equalize the concentration of osmotically active

particles to which the membrane is impermeable. The maintenance of osmotic equilibrium across a

semipermeable membrane is based primarily on the number of solute particles rather than on the molar

concentration of the solution on each side of the membrane due to the flow of water.

The unit of measurement of osmotically active particles is the osmole (Osm) or milliosmole (mOsm)

rather than the conventional units of solute concentration such as milliequivalents per liter (mEq/L). In

solution, osmolarity (mOsm/L) and osmolality (mOsm/kg water) define the osmotic activity of

particles. When 1 mol of NaCl dissociates in water to Na+ and Cl−, it produces 2 Osm. The same

relationship holds true of dissociating salts of multivalent ions such as calcium and magnesium. One mol

of a nondissociating molecule, such as glucose, produces 1 Osm (1,000 mOsm). The measured

osmolality of a solution may not equal the calculated osmolality if the ions do not totally dissociate.

Body fluids are aqueous solutions composed of water and various solutes within the different body

fluid compartments. Because cells are bounded by a semipermeable membrane, adding free water to the

fluid surrounding a cell causes water to move across the cell membrane to equalize the osmolality

differential between the intracellular and extracellular compartments. On a larger scale, adding free

water to the ECF of the body causes an immediate expansion of the extracellular space, followed by a

redistribution of water into the intracellular compartment (Fig. 11-1A). Conversely, loss of free water

from the extracellular space ultimately leads to a shift of water from the intracellular to the

extracellular space (Fig. 11-1B). An osmotic gradient of just 1 mOsm generates a pressure gradient of

19.3 mm Hg.

Colloid Oncotic Pressure (Colloid Osmotic Pressure)

Plasma proteins are confined primarily to the intravascular space and contribute to the osmotic pressure

developed between the plasma and the interstitial fluid. Normal plasma protein levels of 7 g/dL

contribute approximately 0.8 mOsm/L.

Figure 11-1. A: The equilibration of water from the extracellular to the intracellular space after the addition of free water to the

339

http://surgerybook.net/

extracellular fluid compartment. Osmolality transiently decreases in the extracellular compartment, causing water to move across

the cell membranes into the intracellular space. B: Similar shifts after free water loss from the extracellular compartment. Water

moves from the intracellular space to the extracellular space in response to the osmolal gradient that is established.

Osmoregulation

4 Osmolality of body fluids stays fairly constant at approximately 285 to 295 mOsm/L as the result of

tightly regulated water balance. Osmoreceptor cells in the paraventricular and supraoptic nuclei of the

hypothalamus exert central control over the thirst mechanism and antidiuretic hormone (ADH) secretion

from the posterior pituitary.5 In the presence of excess free water, ECF osmolality falls toward 280

mOsm/kg H2O, thirst is inhibited, and ADH levels decline. In the absence of ADH, the permeability of

renal collecting tubules to water is decreased, causing free water reabsorption to decrease and excretion

to increase. Urine osmolality (Uosm) can decline to 50 mOsm/kg H2O (Fig. 11-2). As excess free water is

eliminated, Posm begins to rise. Conversely, free water depletion causes an increase in Posm. As Posm

approaches 295 mOsm/kg H2O, thirst is stimulated as is ADH secretion. As ADH levels rise to

approximately 5 pg/mL, the renal collecting tubules become maximally permeable to water. Water is

reabsorbed from the collecting ducts in response to the concentration gradient developed in the renal

medullary interstitium. Thus, the final concentration of urine depends on both the permeability of the

collecting ducts (controlled by ADH secretion) and the concentration of the medullary interstitium.5

Maximal Uosm may approach 1,200 mOsm/kg H2O. The net effect of these mechanisms is to promptly

return high or low Posm to normal. The high sensitivity of the osmoreceptors and the responsiveness of

the ADH feedback system ensure that even small changes in Posm result in marked alterations in urine

concentration. This relation can be expressed as follows:

Urine osmolality = 95 × Plasma osmolality

Thus, a 1-mOsm change in Posm results in a 95-fold change in Uosm.

Angiotensin II and neural input from medullary baroreceptors can also influence ADH secretion and

thirst, thus tying water balance to hemodynamic alterations. Relatively small changes in pressure have

little effect on ADH secretion, but large decreases in pressure can cause tremendous increases in ADH

release. Therefore, ADH release as a response to changes in serum osmolality is regulated by a very

sensitive system (only small changes in serum osmolality outside its normal range lead to dramatic

changes in ADH release), while the nonosmotic release of ADH occurs in the setting of profound

hypotension for the purposes of preserving volume homeostasis with the subsequent effect of water

retention regardless of serum osmolality (Fig. 11-3).

Tonicity of Body Fluids

Tonicity refers to the effect of the particles on cell volume. (NB: Osmolality defines the concentration of

osmotically active particles in solution.) Permeable solutes can freely cross cell membranes, whereas

impermeable solutes cannot. Although permeable solutes contribute to the osmolality of a solution, they

have no effect on tonicity because they contribute neither to oncotic gradients across cell membranes

nor to alterations in cell volume. Sodium is an example of an impermeable solute that affects both

osmolality and tonicity. Urea and ethanol are permeable solutes that contribute to osmolality but have

little effect on tonicity because they distribute equally across membranes.

340

http://surgerybook.net/

Figure 11-2. The relation of plasma antidiuretic hormone (arginine vasopressin [AVP]) secretion to plasma (A) and urine (B)

osmolality in healthy adults in varying states of water balance. (Reproduced with permission from Robertson GL, Berl T. Water

metabolism. In: Brenner BM, Rector FC Jr, eds. The Kidney. Philadelphia, PA: WB Saunders; 1986:392.)

Figure 11-3. Effect of acute changes in blood volume or pressure on the osmoregulation of antidiuretic hormone (ADH;

vasopressin). The heavy oblique line in the center represents the relation between plasma ADH and osmolality under

normovolemic, normotensive conditions. The lines to the left and right show the shift in the relation when blood volume or blood

pressure is acutely decreased or increased by the percentage indicated in the circles. (Reproduced with permission from Robertson

GL. Physiology of ADH secretion. Kidney Int 1987;32(Suppl 21):520.)

Both impermeable and permeable solutes can contribute to hyperosmolar and hypoosmolar states.

However, hypoosmolar states are always accompanied by hypotonicity, whereas hyperosmolar states

are not always associated with hypertonicity. There may be marked hyperosmolality without

hypertonicity with elevation of blood urea nitrogen (BUN) levels because urea is a freely permeable

molecule. In contrast, elevated levels of plasma glucose in diabetic patients are associated with

hyperosmolarity and associated hypertonicity. Insulin increases the transport of glucose across cell

membranes, rendering these osmoles ineffective and reducing hypertonicity. Plasma hyperglycemia is

associated with the movement of intracellular water to the extracellular space. This causes expansion of

ECF and plasma volume and a consequent decrease in the concentration of plasma sodium. For every

100 mg/dL elevation in blood glucose, measured serum sodium is calculated to fall 1.5 mEq/L, without

an actual alteration of body sodium content. The osmotic diuresis caused by the elevated glucose level

tends to normalize the serum sodium if adequate hydration is maintained. Some patients with

uncontrolled diabetes also have marked hyperlipidemia. Because of this, the concentration of measured

sodium falls. This condition is termed pseudohyponatremia, an artifactual hyponatremia most commonly

caused by severe hypertriglyceridemia, or by severe hyperproteinemia.

Plasma osmolality (Posm) is an excellent measure of total body osmolality. Osmolality differentials

between fluid compartments are only transient because fluid shifts maintain isosmotic conditions.

Sodium is the predominant extracellular cation; thus, estimates of Posm can be made by simply doubling

the serum sodium concentration (serum [Na+]):

Posm (mOsm/L) = 2 × serum [Na+]

Because glucose and BUN may make significant contributions to Posm in certain disease states, this

formula is modified for glucose and for BUN:

Posm (mOsm/L) = 2 × Serum [Na+] - Glucose/18 − BUN/2.8

Discrepancies of greater than 15 mOsm/L between calculated Posm and Posm measured in the clinical

laboratory may be the result of the presence of other osmotically active particles, such as mannitol,

ethanol, or ethylene glycol, or of a reduced fraction of plasma water secondary to high levels of

myeloma proteins or hypertriglyceridemia.

FLUID BALANCE

Sodium Concentration and Water Balance

Abnormalities in serum sodium are usually indicative of abnormal TBW content. This is due to sodium

being the primary extracellular cation. As potassium is the predominant intracellular cation, the serum

[Na+] approximates the sum of the exchangeable total body sodium (Na+

e) and total body

341

http://surgerybook.net/

exchangeable potassium (K+

e) divided by TBW:

Serum [Na+] = (Na+

e − K+

e)/TBW

Because the sum of total body solute content (Na+

e − K+

e) remains relatively stable over time, changes

in TBW content is, therefore, inversely proportional to changes in the serum [Na+] (Fig. 11-4).

Volume Control

5 Changes in volume (i.e., hypovolemic/nonosmotic stimuli) are detected by both osmoreceptors and

baroreceptors.3 The osmoreceptors are responsible for the day-to-day fine-tuning of volume by

responding to changes in tonicity, whereas the baroreceptors contribute relatively little to the control of

fluid balance under normal conditions. As mentioned previously, large changes in circulating volume

(10% to 20% blood volume loss) can modify the osmoregulation of ADH secretion. Cardiac atrial

baroreceptors control volume by means of sympathetic and parasympathetic neural mechanisms,

whereas ANP released by atrial myocytes in response to atrial wall distention may influence sodiumlinked volume control by inhibition of renal sodium reabsorption.6–8

Figure 11-4. Relation between serum [Na+] and the ratio of (Na+e + K+e) to total body water (TBW). (Reproduced with

permission from Edelman IS, Liebman J, O’Meara MP, et al. Interrelationships between serum sodium concentration, serum

osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest 1958;37:1236.)

Osmoreceptors

Specialized cells in the hypothalamus that respond to changes in extracellular tonicity are known as

osmoreceptors. It is believed that the activity of ion channels in the cell membrane, aquaporins, and

changes in cell volume contribute to the function of these receptors. As the majority of the ECF tonicity

is contributed by sodium, under normal physiologic conditions, these receptors function as “osmosodium” receptors. Osmoreceptors can respond to changes in tonicity as small as a few percent. In

effect, these receptors monitor water balance by monitoring the tonic effect of changes in water

volume. Therefore, ECF [Na+] is an effective monitor of TBW.

Baroreceptor Modulation of Volume Control

Effective circulating volume describes that portion of the extracellular volume that perfuses the organs of

the body and affects the baroreceptors. The effective circulating volume normally corresponds to the

intravascular volume.

Changes in the effective circulating volume are sensed by volume receptors in the intrathoracic

capacitance vessels and atria, pressure receptors of the aortic arch and carotid arteries, intrarenal

baroreceptors, and hepatic and cerebrospinal volume receptors.8,9 These stretch receptors respond to

changes in pressure and circulating volume and, through a complex system of neural and hormonal

actions, alter sodium and water balance in the kidneys. Hormonal effects are mediated by the renin–

angiotensin system, aldosterone, ANP, dopamine, and renal prostaglandins.

Baroreceptor Function

The low-pressure baroreceptors of the intrathoracic vena cava and atria are located in vessels that are

distensible and not affected by sympathetic stimulation; thus, they are ideally situated to detect changes

in venous volume.8 These receptors send continuous signals through vagal afferent nerves to the

cardiovascular control centers of the medulla and hypothalamus, which, in turn, send signals through

parasympathetic and sympathetic fibers to the heart and kidneys. Changes in stretch of these vessels

342