PHYSIOLOGY OF WATER-ELECTROLYTES BALANCE

PHYSIOLOGY OF WATER-ELECTROLYTES BALANCE

The maintenance of a relatively constant volume and a stable composition of the body ﬂuids is essential for homeostasis. Some of the most common and important problems in clinical medicine arise because of abnormalities in the control systems that maintain this constancy of the body ﬂuids. In this chapter and in the following chapters on the kidneys, we discuss the overall regulation of body ﬂuid volume, constituents of the extracellular ﬂuid, acid-base balance, and control of ﬂuid exchange between extracellular and intracellular compartments.

Fluid Intake and Output Are Balanced During Steady-State Conditions

The relative constancy of the body ﬂuids is remarkable because there is continuous exchange of ﬂuid and solutes with the external environment as well as within the different compartments of the body. For example, there is a highly variable ﬂuid intake that must be carefully matched by equal output from the body to prevent body ﬂuid volumes from increasing or decreasing.

Daily Intake of Water

Water is added to the body by two major sources: (1) it is ingested in the form of liquids or water in the food, which together normally add about 2100 ml/day to the body ﬂuids, and (2) it is synthesized in the body as a result of oxidation of carbohydrates, adding about 200 ml/day. This provides a total water intake of about 2300 ml/day (Table 25–1). Intake of water, however, is highly variable among different people and even within the same person on different days, depending on climate, habits, and level of physical activity.

Daily Loss of Body Water

Insensible Water Loss. Some of the water losses cannot be precisely regulated. For example, there is a continuous loss of water by evaporation from the respiratory tract and diffusion through the skin, which together account for about 700 ml/day of water loss under normal conditions. This is termed insensible water loss because we are not consciously aware of it, even though it occurs continually in all living humans.

The insensible water loss through the skin occurs independently of sweating and is present even in people who are born without sweat glands; the average water loss by diffusion through the skin is about 300 to 400 ml/day. This loss is minimized by the cholesterol-ﬁlled corniﬁed layer of the skin, which provides a barrier against excessive loss by diffusion. When the corniﬁed layer becomes denuded, as occurs with extensive burns, the rate of evaporation can increase as much as 10-fold, to 3 to 5 L/day. For this reason, burn victims must be given large amounts of ﬂuid, usually intravenously, to balance ﬂuid loss.

Insensible water loss through the respiratory tract averages about 300 to 400 ml/day. As air enters the respiratory tract, it becomes saturated with moisture, to a vapor pressure of about 47 mm Hg, before it is expelled. Because the vapor pressure of the inspired air is usually less than 47 mm Hg, water is continuously lost through the lungs with respiration. In cold weather, the atmospheric vapor pressure decreases to nearly 0, causing an even greater loss of water from the lungs as the temperature decreases. This explains the dry feeling in the respiratory passages in cold weather.

Fluid Loss in Sweat. The amount of water lost by sweating is highly variable, depending on physical activity and environmental temperature. The volume of sweat normally is about 100 ml/day, but in very hot weather or during heavy exercise, water loss in sweat occasionally increases to 1 to 2 L/hour. This would rapidly deplete the body ﬂuids if intake were not also increased by activating the thirst mechanism.

Water Loss in Feces. Only a small amount of water (100 ml/day) normally is lost in the feces. This can increase to several liters a day in people with severe diarrhea. For this reason, severe diarrhea can be life threatening if not corrected within a few days.

Water Loss by the Kidneys. The remaining water loss from the body occurs in the urine excreted by the kidneys. There are multiple mechanisms that control the rate of urine excretion. In fact, the most important means by which the body maintains a balance between water intake and output, as well as a balance between intake and output of most electrolytes in the body, is by controlling the rates at which the kidneys excrete these substances. For example, urine volume can be as low as 0.5 L/day in a dehydrated person or as high as 20 L/day in a person who has been drinking tremendous amounts of water.

This variability of intake is also true for most of the electrolytes of the body, such as sodium, chloride, and potassium. In some people, sodium intake may be as low as 20 mEq/day, whereas in others, sodium intake may be as high as 300 to 500 mEq/day. The kidneys are faced with the task of adjusting the excretion rate of water and electrolytes to match precisely the intake of these substances, as well as compensating for excessive losses of ﬂuids and electrolytes that occur in certain disease states. In Chapters 26 through 30, we discuss the mechanisms that allow the kidneys to perform these remarkable tasks.

Body Fluid Compartments

The total body ﬂuid is distributed mainly between two compartments: the extracellular ﬂuid and the intracellular ﬂuid. The extracellular ﬂuid is divided into the interstitial ﬂuid and the blood plasma. There is another small compartment of ﬂuid that is referred to as transcellular ﬂuid. This compartment includes ﬂuid in the synovial, peritoneal, pericardial, and intraocular spaces, as well as the cerebrospinal ﬂuid; it is usually considered to be a specialized type of extracellular ﬂuid, although in some cases, its composition may differ markedly from that of the plasma or interstitial ﬂuid.All the transcellular ﬂuids together constitute about 1 to 2 liters.

In the average 70-kilogram adult human, the total body water is about 60 per cent of the body weight, or about 42 liters.This percentage can change, depending on age, gender, and degree of obesity. As a person grows older, the percentage of total body weight that is ﬂuid gradually decreases. This is due in part to the fact that aging is usually associated with an increased percentage of the body weight being fat, which decreases the percentage of water in the body.Because women normally have more body fat than men, they contain slightly less water than men in proportion to their body weight. Therefore, when discussing the “average” body ﬂuid compartments, we should realize that variations exist, depending on age, gender, and percentage of body fat.

Intracellular Fluid Compartment

About 28 of the 42 liters of ﬂuid in the body are inside the 75 trillion cells and are collectively called the intracellular ﬂuid. Thus, the intracellular ﬂuid constitutes about 40 per cent of the total body weight in an “average” person.

The ﬂuid of each cell contains its individual mixture of different constituents, but the concentrations of these substances are similar from one cell to another. In fact, the composition of cell ﬂuids is remarkably similar even in different animals, ranging from the most primitive microorganisms to humans. For this reason, the intracellular ﬂuid of all the different cells together is considered to be one large ﬂuid compartment.

Extracellular Fluid Compartment

All the ﬂuids outside the cells are collectively called the extracellular ﬂuid.Together these ﬂuids account for about 20 per cent of the body weight, or about 14 liters in a normal 70-kilogram adult. The two largest compartments of the extracellular ﬂuid are the interstitial ﬂuid, which makes up more than three fourths of the extracellular ﬂuid, and the plasma, which makes up almost one fourth of the extracellular ﬂuid, or about 3 liters. The plasma is the noncellular part of the blood; it exchanges substances continuously with the interstitial ﬂuid through the pores of the capillary membranes.These pores are highly permeable to almost all solutes in the extracellular ﬂuid except the proteins.

Therefore, the extracellular ﬂuids are constantly mixing, so that the plasma and interstitial ﬂuids have about the same composition except for proteins, which have a higher concentration in the plasma.

Blood Volume

Blood contains both extracellular ﬂuid (the ﬂuid in plasma) and intracellular ﬂuid (the ﬂuid in the red blood cells).However, blood is considered to be a separate ﬂuid compartment because it is contained in a chamber of its own, the circulatory system. The blood volume is especially important in the control of cardiovascular dynamics.

The average blood volume of adults is about 7 per cent of body weight, or about 5 liters. About 60 per cent of the blood is plasma and 40 per cent is red blood cells, but these percentages can vary considerably in different people, depending on gender, weight, and other factors.

Hematocrit (Packed Red Cell Volume). The hematocrit is the fraction of the blood composed of red blood cells, as determined by centrifuging blood in a “hematocrit tube” until the cells become tightly packed in the bottom of the tube. It is impossible to completely pack the red cells together; therefore, about 3 to 4 per cent of the plasma remains entrapped among the cells, and the true hematocrit is only about 96 per cent of the measured hematocrit.

In men, the measured hematocrit is normally about 0.40, and in women, it is about 0.36. In severe anemia, the hematocrit may fall as low as 0.10, a value that is barely sufﬁcient to sustain life. Conversely, there are some conditions in which there is excessive production of red blood cells, resulting in polycythemia. In these conditions, the hematocrit can rise to 0.65.

Constituents of Extracellular and Intracellular Fluids

Because the plasma and interstitial ﬂuid are separated only by highly permeable capillary membranes, their ionic composition is similar. The most important difference between these two compartments is the higher concentration of protein in the plasma; because the capillaries have a low permeability to the plasma proteins, only small amounts of proteins are leaked into the interstitial spaces in most tissues.

Because of the Donnan effect, the concentration of positively charged ions (cations) is slightly greater (about 2 per cent) in the plasma than in the interstitial ﬂuid. The plasma proteins have a net negative charge and, therefore, tend to bind cations, such as sodium and potassium ions, thus holding extra amounts of these cations in the plasma along with the plasma proteins. Conversely, negatively charged ions (anions) tend to have a slightly higher concentration in the interstitial ﬂuid compared with the plasma, because the negative charges of the plasma proteins repel the negatively charged anions. For practical purposes, however, the concentration of ions in the interstitial ﬂuid and in the plasma is considered to be about equal.

The extracellular ﬂuid, including the plasma and the interstitial ﬂuid, contains large amounts of sodium and chloride ions, reasonably large amounts of bicarbonate ions, but only small quantities of potassium, calcium, magnesium, phosphate, and organic acid ions.

The composition of extracellular ﬂuid is carefully regulated by various mechanisms, but especially by the kidneys, as discussed later. This allows the cells to remain continually bathed in a ﬂuid that contains the proper concentration of electrolytes and nutrients for optimal cell function.

Important Constituents of the Intracellular Fluid

The intracellular ﬂuid is separated from the extracellular ﬂuid by a cell membrane that is highly permeable to water but not to most of the electrolytes in the body. In contrast to the extracellular ﬂuid, the intracellular ﬂuid contains only small quantities of sodium and chloride ions and almost no calcium ions. Instead, it contains large amounts of potassium and phosphate ions plus moderate quantities of magnesium and sulfate ions, all of which have low concentrations in the extracellular ﬂuid.Also, cells contain large amounts of protein, almost four times as much as in the plasma.

The volume of a ﬂuid compartment in the body can be measured by placing an indicator substance in the compartment, allowing it to disperse evenly throughout the compartment’s ﬂuid, and then analyzing the extent to which the substance becomes diluted. This means that the total mass of a substance after dispersion in the ﬂuid compartment will be the same as the total mass injected into the compartment.

A small amount of dye or other substance contained in the syringe is injected into a chamber, and the substance is allowed to disperse throughout the chamber until it becomes mixed in equal concentrations in all areas. Then a sample of ﬂuid containing the dispersed substance is removed and the concentration is analyzed chemically, photoelectrically, or by other means.

Determination of Volumes of Speciﬁc Body Fluid Compartments

Measurement of Total Body Water. Radioactive water (tritium, 3 H2O) or heavy water (deuterium, 2 H2O) can be used to measure total body water. These forms of water mix with the total body water within a few hours after being injected into the blood, and the dilution principle can be used to calculate total body water. 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 intracellular 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 (125 I-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 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.

Basic Principles of Osmosis and Osmotic Pressure

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 ells. 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) 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 osmotically 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 intracellular ﬂuid, almost half the osmolarity is due to potassium ions, and the remainder is divided among many other intracellular substances.

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.

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. 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 osmolarity 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.

Volume and Osmolality of Extracellular and Intracellular Fluids in Abnormal States

Some of the different factors that can cause extracellular and intracellular volumes to change markedly are ingestion of water, dehydration, intravenous infusion of different types of solutions, loss of large amounts of ﬂuid from the gastrointestinal tract, and loss of abnormal amounts of ﬂuid by sweating or through the kidneys.

One can calculate both the changes in intracellular and extracellular ﬂuid volumes and the types of therapy that should be instituted if the following basic principles are kept in mind:

1. Water moves rapidly across cell membranes; therefore, the osmolarities of intracellular and extracellular ﬂuids remain almost exactly equal to each other except for a few minutes after a change in one of the compartments.

2. Cell membranes are almost completely impermeable to many solutes; therefore, the number of osmoles in the extracellular or intracellular ﬂuid generally remains constant unless solutes are added to or lost from the extracellular compartment.

With these basic principles in mind, we can analyze the effects of different abnormal ﬂuid conditions on extracellular and intracellular ﬂuid volumes and osmolarities.

Effect of Adding Saline Solution to the Extracellular Fluid

If an isotonic saline solution is added to the extracellular ﬂuid compartment, the osmolarity of the extracellular ﬂuid does not change; therefore, no osmosis occurs through the cell membranes. The only effect is an increase in extracellular ﬂuid volume.The sodium and chloride largely remain in the extracellular ﬂuid because the cell membrane behaves as though it were virtually impermeable to the sodium chloride.

If a hypertonic solution is added to the extracellular ﬂuid, the extracellular osmolarity increases and causes osmosis of water out of the cells into the extracellular compartment. Again, almost all the added sodium chloride remains in the extracellular compartment, and ﬂuid diffuses from the cells into the extracellular space to achieve osmotic equilibrium. The net effect is an increase in extracellular volume (greater than the volume of ﬂuid added), a decrease in intracellular volume, and a rise in osmolarity in both compartments.

If a hypotonic solution is added to the extracellular ﬂuid, the osmolarity of the extracellular ﬂuid decreases and some of the extracellular water diffuses into the cells until the intracellular and extracellular compartments have the same osmolarity.

Both the intracellular and the extracellular volumes are increased by the addition of hypotonic ﬂuid, although the intracellular volume increases to a greater extent.

Glucose and Other Solutions Administered for Nutritive Purposes

Many types of solutions are administered intravenously to provide nutrition to people who cannot otherwise take adequate amounts of nutrition. Glucose solutions are widely used, and amino acid and homogenized fat solutions are used to a lesser extent.When these solutions are administered, their concentrations of osmotically active substances are usually adjusted nearly to isotonicity, or they are given slowly enough that they do not upset the osmotic equilibrium of the body ﬂuids After the glucose or other nutrients are metabolized, an excess of water often remains, especially if additional ﬂuid is ingested. Ordinarily, the kidneys excrete this in the form of a very dilute urine.The net result, therefore, is the addition of only nutrients to the body.

Clinical Abnormalities of Fluid Volume Regulation: Hyponatremia and Hypernatremia

The primary measurement that is readily available to the clinician for evaluating a patient’s ﬂuid status is the plasma sodium concentration. Plasma osmolarity is not routinely measured, but because sodium and its associated anions (mainly chloride) account for more than 90 per cent of the solute in the extracellular ﬂuid, plasma sodium concentration is a reasonable indicator of plasma osmolarity under many conditions. When plasma sodium concentration is reduced more than a few milliequivalents below normal (about 142 mEq/L), a person is said to have hyponatremia. When plasma sodium concentration is elevated above normal, a person is said to have hypernatremia.

Fluids in the “Potential Spaces” of the Body

Perhaps the best way to describe a “potential space” is to list some examples: pleural cavity, pericardial cavity, peritoneal cavity, and synovial cavities, including both the joint cavities and the bursae. Virtually all these potential spaces have surfaces that almost touch each other, with only a thin layer of ﬂuid in between, and the surfaces slide over each other. To facilitate the sliding, a viscous proteinaceous ﬂuid lubricates the surfaces.

Fluid Is Exchanged Between the Capillaries and the Potential Spaces. The surface membrane of a potential space usually does not offer signiﬁcant resistance to the passage of ﬂuids, electrolytes, or even proteins, which all move back and forth between the space and the interstitial ﬂuid in the surrounding tissue with relative ease. Therefore, each potential space is in reality a large tissue space. Consequently, ﬂuid in the capillaries adjacent to the potential space diffuses not only into the interstitial ﬂuid but also into the potential space.

Lymphatic Vessels Drain Protein from the Potential Spaces. Proteins collect in the potential spaces because of leakage out of the capillaries, similar to the collection of protein in the interstitial spaces throughout the body. The protein must be removed through lymphatics or other channels and returned to the circulation. Each potential space is either directly or indirectly connected with lymph vessels. In some cases, such as the pleural cavity and peritoneal cavity, large lymph vessels arise directly from the cavity itself.

Edema Fluid in the Potential Spaces Is Called “Effusion.” When edema occurs in the subcutaneous tissues adjacent to the potential space, edema ﬂuid usually collects in the potential space as well, and this ﬂuid is called effusion. Thus, lymph blockage or any of the multiple abnormalities that can cause excessive capillary ﬁltration can cause effusion in the same way that interstitial edema is caused.The abdominal cavity is especially prone to collect effusion ﬂuid, and in this instance, the effusion is called ascites. In serious cases, 20 liters or more of ascitic ﬂuid can accumulate.

The other potential spaces, such as the pleural cavity, pericardial cavity, and joint spaces, can become seriously swollen when there is generalized edema. Also, injury or local infection in any one of the cavities often blocks the lymph drainage, causing isolated swelling in the cavity.

The dynamics of ﬂuid exchange in the pleural cavity are mainly representative of all the other potential spaces as well. It is especially interesting that the normal ﬂuid pressure in most or all of the potential spaces in the nonedematous state is negative in the same way that this pressure is negative (subatmospheric) in loose subcutaneous tissue. For instance, the interstitial ﬂuid hydrostatic pressure is normally about –7 to –8 mm Hg in the pleural cavity, –3 to –5 mm Hg in the joint spaces, and –5 to –6 mm Hg in the pericardial cavity.