volume - Plasma volume)
From Guyton AC, Hall JE: Human Physiology and Mechanisms of Disease, 6th ed. Philadelphia: WB Saunders, 1997.
From Guyton AC, Hall JE: Human Physiology and Mechanisms of Disease, 6th ed. Philadelphia: WB Saunders, 1997.
principle can be used to calculate total body water (Table 25-3). Another substance that has been used to measure total body water is antipyrine, which is very lipid soluble and can rapidly penetrate cell membranes and distribute itself uniformly throughout the intracel-lular and extracellular compartments.
Measurement of Extracellular Fluid Volume. The volume of extracellular fluid can be estimated using any of several substances that disperse in the plasma and interstitial fluid but do not readily permeate the cell membrane. They include radioactive sodium, radioactive chloride, radioactive iothalamate, thiosulfate ion, and inulin. When any one of these substances is injected into the blood, it usually disperses almost completely throughout the extracellular fluid within 30 to 60 minutes. Some of these substances, however, such as radioactive sodium, may diffuse into the cells in small amounts. Therefore, one frequently speaks of the sodium space or the inulin space, instead of calling the measurement the true extracellular fluid volume.
Calculation of Intracellular Volume. The intracellular volume cannot be measured directly. However, it can be calculated as
Intracellular volume = Total body water - Extracellular volume
Measurement of Plasma Volume. To measure plasma volume, a substance must be used that does not readily penetrate capillary membranes but remains in the vascular system after injection. One of the most commonly used substances for measuring plasma volume is serum albumin labeled with radioactive iodine (125I-albumin). Also, dyes that avidly bind to the plasma proteins, such as Evans blue dye (also called T-1824), can be used to measure plasma volume.
Calculation of Interstitial Fluid Volume. Interstitial fluid volume cannot be measured directly, but it can be calculated as
Interstitial fluid volume = Extracellular fluid volume - Plasma volume
Measurement of Blood Volume. If one measures plasma volume using the methods described earlier, blood
Total blood volume =
Plasma volume 1 - Hematocrit
For example, if plasma volume is 3 liters and hemat-ocrit is 0.40, total blood volume would be calculated as
= 5 liters
Another way to measure blood volume is to inject into the circulation red blood cells that have been labeled with radioactive material. After these mix in the circulation, the radioactivity of a mixed blood sample can be measured, and the total blood volume can be calculated using the dilution principle. A substance frequently used to label the red blood cells is radioactive chromium (51Cr), which binds tightly with the red blood cells.
Regulation of Fluid Exchange and Osmotic Equilibrium Between Intracellular and Extracellular Fluid
A frequent problem in treating seriously ill patients is maintaining adequate fluids in one or both of the intracellular and extracellular compartments. As discussed in Chapter 16 and later in this chapter, the relative amounts of extracellular fluid distributed between the plasma and interstitial spaces are determined mainly by the balance of hydrostatic and colloid osmotic forces across the capillary membranes.
The distribution of fluid between intracellular and extracellular compartments, in contrast, is determined mainly by the osmotic effect of the smaller solutes— especially sodium, chloride, and other electrolytes— acting across the cell membrane. The reason for this is that the cell membranes are highly permeable to water but relatively impermeable to even small ions such as sodium and chloride. Therefore, water moves across the cell membrane rapidly, so that the intracellular fluid remains isotonic with the extracellular fluid.
In the next section, we discuss the interrelations between intracellular and extracellular fluid volumes and the osmotic factors that can cause shifts of fluid between these two compartments.
The basic principles of osmosis and osmotic pressure were presented in Chapter 4. Therefore, we review here only the most important aspects of these principles as they apply to volume regulation.
Osmosis is the net diffusion of water across a selectively permeable membrane from a region of high water concentration to one that has a lower water concentration. When a solute is added to pure water, this reduces the concentration of water in the mixture. Thus, the higher the solute concentration in a solution, the lower the water concentration. Further, water diffuses from a region of low solute concentration (high water concentration) to one with a high solute concentration (low water concentration).
Because cell membranes are relatively impermeable to most solutes but highly permeable to water (i.e., selectively permeable), whenever there is a higher concentration of solute on one side of the cell membrane, water diffuses across the membrane toward the region of higher solute concentration. Thus, if a solute such as sodium chloride is added to the extracellular fluid, water rapidly diffuses from the cells through the cell membranes into the extracellular fluid until the water concentration on both sides of the membrane becomes equal. Conversely, if a solute such as sodium chloride is removed from the extracellular fluid, water diffuses from the extracellular fluid through the cell membranes and into the cells. The rate of diffusion of water is called the rate of osmosis.
Relation Between Moles and Osmoles. Because the water concentration of a solution depends on the number of solute particles in the solution, a concentration term is needed to describe the total concentration of solute particles, regardless of their exact composition. The total number of particles in a solution is measured in osmoles. One osmole (osm) is equal to 1 mole (mol) (6.02 x 1023) of solute particles. Therefore, a solution containing 1 mole of glucose in each liter has a concentration of 1 osm/L. If a molecule dissociates into two ions (giving two particles), such as sodium chloride ionizing to give chloride and sodium ions, then a solution containing 1 mol/L will have an osmolar concentration of 2 osm/L. Likewise, a solution that contains 1 mole of a molecule that dissociates into three ions, such as sodium sulfate (Na2SO4), will contain 3 osm/L. Thus, the term osmole refers to the number of osmotically active particles in a solution rather than to the molar concentration.
In general, the osmole is too large a unit for expressing osmotic activity of solutes in the body fluids. The term milliosmole (mOsm), which equals 1/1000 osmole, is commonly used.
Osmolality and Osmolarity. The osmolal concentration of a solution is called osmolality when the concentration is expressed as osmoles per kilogram of water; it is called osmolarity when it is expressed as osmoles per liter of solution. In dilute solutions such as the body fluids, these two terms can be used almost synonymously because the differences are small. In most cases, it is easier to express body fluid quantities in liters of fluid rather than in kilograms of water. Therefore, most of the calculations used clinically and the calculations expressed in the next several chapters are based on osmolarities rather than osmolalities.
Osmotic Pressure. Osmosis of water molecules across a selectively permeable membrane can be opposed by applying a pressure in the direction opposite that of the osmosis. The precise amount of pressure required to prevent the osmosis is called the osmotic pressure. Osmotic pressure, therefore, is an indirect measurement of the water and solute concentrations of a solution. The higher the osmotic pressure of a solution, the lower the water concentration and the higher the solute concentration of the solution.
Relation Between Osmotic Pressure and Osmolarity. The osmotic pressure of a solution is directly proportional to the concentration of osmotically active particles in that solution. This is true regardless of whether the solute is a large molecule or a small molecule. For example, one molecule of albumin with a molecular weight of 70,000 has the same osmotic effect as one molecule of glucose with a molecular weight of 180. One molecule of sodium chloride, however, has two osmotically active particles, Na+ and Cl-, and therefore has twice the osmotic effect of either an albumin molecule or a glucose molecule. Thus, the osmotic pressure of a solution is proportional to its osmolarity, a measure of the concentration of solute particles.
Expressed mathematically, according to van't Hoff's law, osmotic pressure (p) can be calculated as p = CRT
where C is the concentration of solutes in osmoles per liter, R is the ideal gas constant, and T is the absolute temperature in degrees kelvin (273° + centigrade°). If p is expressed in millimeters of mercury (mm Hg), the unit of pressure commonly used for biological fluids, and T is normal body temperature (273° + 37° = 310° kelvin), the value of p calculates to be about 19,300 mm Hg for a solution having a concentration of 1 osm/L. This means that for a concentration of
1 mOsm/L, p is equal to 19.3 mm Hg. Thus, for each milliosmole concentration gradient across the cell membrane, 19.3 mm Hg osmotic pressure is exerted.
Calculation of the Osmolarity and Osmotic Pressure of a Solution. Using van't Hoff's law, one can calculate the potential osmotic pressure of a solution, assuming that the cell membrane is impermeable to the solute. For example, the osmotic pressure of a 0.9 per cent sodium chloride solution is calculated as follows: A 0.9 per cent solution means that there is 0.9 gram of sodium chloride per 100 milliliters of solution, or 9 g/L. Because the molecular weight of sodium chloride is 58.5 g/mol, the molarity of the solution is 9 g/L divided by 58.5 g/mol, or about 0.154 mol/L. Because each molecule of sodium chloride is equal to
2 osmoles, the osmolarity of the solution is 0.154 x 2, or 0.308 osm/L. Therefore, the osmolarity of this solution is 308 mOsm/L. The potential osmotic pressure of this solution would therefore be 308 mOsm/L x 19.3 mm Hg/mOsm/L, or 5944 mm Hg.
This calculation is only an approximation, because sodium and chloride ions do not behave entirely independently in solution because of interionic attraction between them. One can correct for these deviations from the predictions of van't Hoff's law by using a correction factor called the osmotic coefficient. For sodium chloride, the osmotic coefficient is about 0.93. Therefore, the actual osmolarity of a 0.9 per cent sodium chloride solution is 308 x 0.93, or about 286 mOsm/L. For practical reasons, the osmotic coefficients of different solutes are sometimes neglected in determining the osmolarity and osmotic pressures of physiologic solutions.
Osmolarity of the Body Fluids. Turning back to Table 25-2, note the approximate osmolarity of the various osmot-ically active substances in plasma, interstitial fluid, and intracellular fluid. Note that about 80 per cent of the total osmolarity of the interstitial fluid and plasma is due to sodium and chloride ions, whereas for intracel-lular fluid, almost half the osmolarity is due to potassium ions, and the remainder is divided among many other intracellular substances.
As shown in Table 25-2, the total osmolarity of each of the three compartments is about 300 mOsm/L, with the plasma being about 1 mOsm/L greater than that of the interstitial and intracellular fluids. The slight difference between plasma and interstitial fluid is caused by the osmotic effects of the plasma proteins, which maintain about 20 mm Hg greater pressure in the capillaries than in the surrounding interstitial spaces, as discussed in Chapter 16.
HYPOTONIC Cell swells
HYPOTONIC Cell swells
ISOTONIC No change
HYPERTONIC Cell shrinks
Effects of isotonic (A), hypertonic (B), and hypotonic (C) solutions on cell volume.
Corrected Osmolar Activity of the Body Fluids. At the bottom of Table 25-2 are shown corrected osmolar activities of plasma, interstitial fluid, and intracellular fluid.The reason for these corrections is that molecules and ions in solution exert interionic and intermolecular attraction or repulsion from one solute molecule to the next, and these two effects can cause, respectively, a slight decrease or an increase in the osmotic "activity" of the dissolved substance.
Total Osmotic Pressure Exerted by the Body Fluids. Table 25-2 also shows the total osmotic pressure in millimeters of mercury that would be exerted by each of the different fluids if it were placed on one side of the cell membrane with pure water on the other side. Note that this total pressure averages about 5443 mm Hg for plasma, which is 19.3 times the corrected osmolarity of 282 mOsm/L for plasma.
Osmotic Equilibrium Is Maintained Between Intracellular and Extracellular Fluids
Large osmotic pressures can develop across the cell membrane with relatively small changes in the concentrations of solutes in the extracellular fluid. As discussed earlier, for each milliosmole concentration gradient of an impermeant solute (one that will not permeate the cell membrane), about 19.3 mm Hg osmotic pressure is exerted across the cell membrane. If the cell membrane is exposed to pure water and the osmolarity of intracellular fluid is 282 mOsm/L, the potential osmotic pressure that can develop across the cell membrane is more than 5400 mm Hg. This demonstrates the large force that can move water across the cell membrane when the intracellular and extracellular fluids are not in osmotic equilibrium. As a result of these forces, relatively small changes in the concentration of impermeant solutes in the extracellular fluid can cause large changes in cell volume.
Isotonic, Hypotonic, and Hypertonic Fluids. The effects of different concentrations of impermeant solutes in the extracellular fluid on cell volume are shown in Figure 25-5. If a cell is placed in a solution of impermeant solutes having an osmolarity of 282 mOsm/L, the cells will not shrink or swell because the water concentration in the intracellular and extracellular fluids is equal and the solutes cannot enter or leave the cell. Such a solution is said to be isotonic because it neither shrinks nor swells the cells. Examples of isotonic solutions include a 0.9 per cent solution of sodium chloride or a 5 per cent glucose solution. These solutions are important in clinical medicine because they can be infused into the blood without the danger of upsetting osmotic equilibrium between the intracellular and extracellular fluids.
If a cell is placed into a hypotonic solution that has a lower concentration of impermeant solutes (less than 282 mOsm/L), water will diffuse into the cell, causing it to swell; water will continue to diffuse into the cell, diluting the intracellular fluid while also concentrating the extracellular fluid until both solutions have about the same osmolarity. Solutions of sodium chloride with a concentration of less than 0.9 per cent are hypotonic and cause cells to swell.
If a cell is placed in a hypertonic solution having a higher concentration of impermeant solutes, water will flow out of the cell into the extracellular fluid, concentrating the intracellular fluid and diluting the extracellular fluid. In this case, the cell will shrink until the two concentrations become equal. Sodium chloride solutions of greater than 0.9 per cent are hypertonic.
Isosmotic, Hyperosmotic, and Hypo-osmotic Fluids. The terms isotonic, hypotonic, and hypertonic refer to whether solutions will cause a change in cell volume. The tonicity of solutions depends on the concentration of impermeant solutes. Some solutes, however, can permeate the cell membrane. Solutions with an osmo-larity the same as the cell are called isosmotic, regardless of whether the solute can penetrate the cell membrane.
The terms hyperosmotic and hypo-osmotic refer to solutions that have a higher or lower osmolarity, respectively, compared with the normal extracellular fluid, without regard for whether the solute permeates the cell membrane. Highly permeating substances, such as urea, can cause transient shifts in fluid volume between the intracellular and extracellular fluids, but given enough time, the concentrations of these substances eventually become equal in the two compartments and have little effect on intracellular volume under steady-state conditions.
Osmotic Equilibrium Between Intracellular and Extracellular Fluids Is Rapidly Attained. The transfer of fluid across the cell membrane occurs so rapidly that any differences in osmolarities between these two compartments are usually corrected within seconds or, at the most, minutes. This rapid movement of water across the cell membrane does not mean that complete equilibrium occurs between the intracellular and extracellular compartments throughout the whole body within the same short period. The reason for this is that fluid usually enters the body through the gut and must be transported by the blood to all tissues before complete osmotic equilibrium can occur. It usually takes about 30 minutes to achieve osmotic equilibrium everywhere in the body after drinking water.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.