Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema PDF

CHAPTER 25 UNIT V Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema Th...

CHAPTER 25 UNIT V Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema The maintenance of a relatively constant volume and stable are not consciously aware of it, even though it occurs con- composition of the body fluids is essential for homeosta- tinually in all living people. sis. Some of the most common and important problems Insensible water loss through the skin occurs inde- in clinical medicine arise because of abnormalities in pendently of sweating and is present even in people who the control systems that maintain this relative constancy are born without sweat glands; the average water loss by of the body fluids. In this chapter and in the following diffusion through the skin is about 300 to 400 ml/day. chapters on the kidneys, we discuss overall regulation of This loss is minimized by the cholesterol-­filled, cornified body fluid volume, constituents of the extracellular fluid, layer of the skin, which provides a barrier against exces- acid–base balance, and control of fluid exchange between sive loss by diffusion. When the cornified layer becomes extracellular and intracellular compartments. 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, persons with burns must be given FLUID INTAKE AND OUTPUT ARE large amounts of fluid, usually intravenously, to balance BALANCED DURING STEADY-­STATE fluid loss. CONDITIONS Insensible water loss through the respiratory tract The relative constancy of the body fluids is remarkable, normally averages about 300 to 400 ml/day. As air because there is continuous exchange of fluid and solutes enters the respiratory tract, it becomes saturated with with the external environment, as well as within the dif- moisture to a vapor pressure of about 47 mm Hg before ferent body compartments. For example, fluid added to it is expelled. Because the vapor pressure of the inspired the body is highly variable and must be carefully matched air is usually less than 47 mm Hg, water is continu- by an equal output of water from the body to prevent ously lost through the lungs with respiration. In cold body fluid volumes from increasing or decreasing. weather, the atmospheric vapor pressure decreases to nearly 0, causing an even greater loss of water from DAILY INTAKE OF WATER the lungs as the temperature decreases. This process Water is added to the body by two major sources: (1) it explains the dry feeling in the respiratory passages in is ingested in the form of liquids or water in food, which cold weather. together normally add about 2100 ml/day to the body flu- Fluid Loss in Sweat. The amount of water lost by sweat- ids; and (2) it is synthesized in the body by oxidation of ing is highly variable, depending on physical activity and carbohydrates, adding about 200 ml/day. These mecha- environmental temperature. The volume of sweat normal- nisms provide a total water intake of about 2300 ml/day ly is about 100 ml/day, but in very hot weather or during (Table 25-­1). However, intake of water is highly variable heavy exercise, fluid loss in sweat occasionally increases among different people and even within the same person to 1 to 2 L/hour. This fluid loss would rapidly deplete the on different days, depending on climate, habits, and level body fluids if intake were not also increased by activating of physical activity. the thirst mechanism, as discussed in Chapter 29. Water Loss in Feces. Only a small amount of water DAILY LOSS OF BODY WATER (100 ml/day) normally is lost in the feces. This loss can increase to several liters a day in people with severe diar- Insensible Water Loss. Some water losses cannot be pre- rhea. Therefore, severe diarrhea can be life-­threatening if cisely regulated. For example, humans experience contin- not corrected within a few days. uous water loss by evaporation from the respiratory tract and diffusion through the skin, which together account Water Loss by the Kidneys. The remaining water loss for about 700 ml/day of water loss under normal condi- from the body occurs in the urine excreted by the kidneys. tions. This loss is termed insensible water loss ­because we Multiple mechanisms control the rate of urine excretion. 305 UNIT V The Body Fluids and Kidneys Table 25-­1  Daily Intake and Output of Water (ml/day) OUTPUT INTAKE Kidneys Prolonged Lungs Intake or Output Normal Heavy Exercise Feces Sweat Plasma Intake Skin 3.0 L Lymphatics Fluids ingested 2100 ? Capillary membrane fluid (14.0 L) Extracellular From metabolism 200 200 Total intake 2300 ? Interstitial Output fluid 11.0 L Insensible: skin 350 350 Insensible: lungs 350 650 Cell membrane Sweat 100 5000 Feces 100 100 Urine 1400 500 Total output 2300 6600 Intracellular fluid The most important means whereby the body maintains 28.0 L balance between water intake and output, as well as a bal- ance between intake and output of most electrolytes in the body, is by controlling the rate 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 Figure 25-­1. Summary of body fluid regulation, including the major body fluid compartments and the membranes that separate these 20 L/day in a person who has been drinking tremendous compartments. The values shown are for an average 70-­kg man. amounts of water. This variability of intake is also true for most of the electrolytes of the body, such as sodium, chloride, and the fact that aging is usually associated with an increased potassium. In some people, sodium intake may be as low percentage of the body weight being fat, which decreases as 20 mEq/day, whereas in others, sodium intake may be the percentage of water in the body. as high as 300 to 500 mEq/day. The kidneys have the task Because women normally have a greater percentage of adjusting the excretion rate of water and electrolytes of body fat compared with men, their total body water to match the intake of these substances precisely, as well averages about 50% of the body weight. In premature and as compensating for excessive losses of fluids and elec- newborn babies, the total body water ranges from 70% to trolytes that occur in certain disease states. In Chapters 75% of body weight. Therefore, when discussing average 26 through 32, we discuss the mechanisms that allow the body fluid compartments, we should realize that varia- kidneys to perform these remarkable tasks. tions exist, depending on age, sex, and percentage of body fat. In many other countries, the average body weight (and BODY FLUID COMPARTMENTS fat mass) has increased rapidly during the past 30 years. The total body fluid is distributed mainly between two The average body weight for adult men older than 20 years compartments, the extracellular fluid and the intracellu- in the United States is estimated to be approximately 88.8 lar fluid (Figure 25-­1). The extracellular fluid is divided kg (∼196 pounds), and for adult women it is 77.4 kg (∼170 into the interstitial fluid and the blood plasma. pounds). Therefore, data discussed for an average 70-­kg There is another small compartment of fluid that man in this and other chapters would need to be adjusted is referred to as transcellular fluid. This compartment accordingly when considering body fluid compartments includes fluid in the synovial, peritoneal, pericardial, and in most people. intraocular spaces, as well as the cerebrospinal fluid; it is usually considered to be a specialized type of extracellular INTRACELLULAR FLUID COMPARTMENT fluid, although in some cases its composition may differ About 28 of the 42 liters of fluid in the body are inside the markedly from that of the plasma or interstitial fluid. All trillions of cells and is collectively called the intracellular the transcellular fluids together constitute about 1 to 2 fluid. Thus, the intracellular fluid constitutes about 40% of liters. the total body weight in an “average” person. In a 70-­kg adult man, the total body water is about 60% The fluid of each cell contains its individual mixture of the body weight, or about 42 liters. This percentage of different constituents, but the concentrations of these depends on age, sex, and degree of obesity. As a person substances are similar from one cell to another. In fact, grows older, the percentage of total body weight that is the composition of cell fluids is remarkably similar, even fluid gradually decreases. This decrease is due in part to in different animals, ranging from the most primitive 306  Chapter 25 Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema microorganisms to humans. For this reason, the intracel- Cations Anions 150 lular fluid of all the different cells together is considered to be one large fluid compartment. EXTRACELLULAR 100 EXTRACELLULAR FLUID COMPARTMENT All the fluids outside the cells are collectively called the UNIT V extracellular fluid. Together these fluids account for 50 about 20% of the body weight, or about 14 liters in a 70-­kg HCO3− man. The two largest compartments of the extracellular Na+ Ca2+ Cl− mEq/L fluid are the interstitial fluid, which makes up more than 0 K+ Mg2+ PO–––4 and organic anions Protein three-fourths (11 liters) of the extracellular fluid, and the INTRACELLULAR plasma, which makes up almost one-fourth of the extra- cellular fluid, or about 3 liters. The plasma is the noncellu- 50 lar 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 100 all solutes in the extracellular fluid, except the proteins. Therefore, the extracellular fluids are constantly mixing, so the plasma and interstitial fluids have about the same 150 composition, except for proteins, which have a higher Figure 25-­2. Major cations and anions of the intracellular and ex- concentration in the plasma. tracellular fluids. The concentrations of Ca2+ and Mg2+ represent the sum of these two ions. The concentrations shown represent the total of free ions and complexed ions. BLOOD VOLUME Blood contains extracellular fluid (the fluid in plasma) and intracellular fluid (the fluid in the red blood cells). How- ever, blood is considered to be a separate fluid compart- ment because it is contained in a chamber of its own, the circulatory system. The blood volume is especially impor- Phospholipids: 280 mg/dl tant in the control of cardiovascular dynamics. The average blood volume of adults is about 7% of body weight, or about 5 liters. About 60% of the blood is plasma and 40% is red blood cells, but these percentages can vary considerably in different people, depending on sex, weight, and other factors. Hematocrit (Packed Red Blood Cell Volume). The he- Cholesterol: 150 mg/dl matocrit 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. Because the centrifuge does not Neutral fat: 125 mg/dl completely pack the red blood cells together, about 3% to Glucose: 90 mg/dl 4% of the plasma remains entrapped among the cells, and the true hematocrit is only about 96% of the measured Urea: 14 mg/dl hematocrit. Lactic acid: 10 mg/dl In men, the measured hematocrit is normally about Uric acid: 3 mg/dl 0.40, and in women, it is about 0.36. In persons with Creatinine: 1.0 mg/dl severe anemia, the hematocrit may fall as low as 0.10, a Bilirubin: 0.5 mg/dl value that is barely sufficient to sustain life. Conversely, Bile salts: trace in persons with some conditions, excessive production of Figure 25-­3. Nonelectrolytes of the plasma. red blood cells occurs, resulting in polycythemia. In these persons, the hematocrit can rise to 0.65. intracellular fluid are shown in Figures 25-­2 and 25-­3 and in Table 25-­2. CONSTITUENTS OF EXTRACELLULAR Similar Ionic Composition of Plasma and AND INTRACELLULAR FLUIDS Interstitial Fluid Comparisons of the composition of the extracellular Because the plasma and interstitial fluid are separated fluid, including the plasma and interstitial fluid, and the only by highly permeable capillary membranes, their 307 UNIT V The Body Fluids and Kidneys Table 25-­2 Osmolar Substances in Extracellular and Intracellular Fluids Plasma Interstitial Intracellular (mOsm/L (mOsm/L (mOsm/L Indicator Mass A = Volume A × Concentration A Substance H2O) H2O) H2O) Na+ 142 139 14 Indicator Mass A = Indicator Mass B K+ 4.2 4.0 140 Ca2+ 1.3 1.2 0 Mg2+ 0.8 0.7 20 Cl− 106 108 4 HCO3 − 24 28.3 10 HPO4−, H2PO4− 2 2 11 SO4 − 0.5 0.5 1 Phosphocreatine 45 Carnosine 14 Indicator Mass B = Volume B × Concentration B Volume B = Indicator Mass B/Concentration B Amino acids 2 2 8 Figure 25-­4. Indicator-­dilution method for measuring fluid volumes. Creatine 0.2 0.2 9 Lactate 1.2 1.2 1.5 Adenosine 5 fluid, contains large amounts of sodium and chloride triphosphate ions and reasonably large amounts of bicarbonate ions Hexose 3.7 but only small quantities of potassium, calcium, magne- monophosphate sium, phosphate, and organic acid ions. The composi- Glucose 5.6 5.6 tion of extracellular fluid is carefully regulated by various Protein 1.2 0.2 4 mechanisms, but especially by the kidneys, as discussed Urea 4 4 4 later. This regulation allows the cells to remain continually Others 4.8 3.9 10 bathed in a fluid that contains the proper concentration of Total mOsm/L 299.8 300.8 301.2 electrolytes and nutrients for optimal cell function. Corrected osmolar 282.0 281.0 281.0 activity (mOsm/L) INTRACELLULAR FLUID CONSTITUENTS Total osmotic 5441 5423 5423 The intracellular fluid is separated from the extracellular pressure at 37°C fluid by a cell membrane that is highly permeable to water (98.6°F) (mm Hg) but is not permeable to most electrolytes in the body. In contrast to the extracellular fluid, the intracellular fluid contains only small quantities of sodium and chloride ionic composition is similar. The most important dif- ions and almost no calcium ions. Instead, it contains large ference between these two compartments is the higher amounts of potassium and phosphate ions plus moder- concentration of protein in the plasma; because the capil- ate quantities of magnesium and sulfate ions, all of which laries have a low permeability to the plasma proteins, only have low concentrations in the extracellular fluid. Also, small amounts of proteins are leaked into the interstitial cells contain large amounts of protein—almost four times spaces in most tissues. as much as in the plasma. Because of the Donnan effect, the concentration of positively charged ions (cations) is slightly greater (∼2%) in MEASUREMENT OF BODY FLUID plasma than in interstitial fluid. Plasma proteins have a net COMPARTMENT VOLUMES— negative charge and therefore tend to bind cations such as INDICATOR-­DILUTION PRINCIPLE sodium and potassium ions, thus holding extra amounts of these cations in the plasma, along with the plasma proteins. The volume of a fluid compartment in the body can be Conversely, negatively charged ions (anions) tend to have a measured by placing an indicator substance in the com- slightly higher concentration in interstitial fluid compared partment, allowing it to disperse evenly throughout with plasma because the negative charges of the plasma the compartment’s fluid, and then analyzing the extent proteins repel the negatively charged anions. For practical to which the substance becomes diluted. Figure 25-­4 purposes, however, the concentrations of ions in intersti- shows this indicator-­dilution method of measuring the tial fluid and plasma are considered to be about equal. volume of a fluid compartment. This method is based Referring again to Figure 25-­2, one can see that the on the conservation of mass principle, which means that extracellular fluid, including the plasma and interstitial the total mass of a substance after dispersion in the fluid 308  Chapter 25 Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema compartment will be the same as the total mass injected Table 25-­3  Measurement of Body Fluid Volumes into the compartment. Volume Indicators In the example shown in Figure 25-­4, a small amount 3H O, 2H O, Total body water antipyrine of dye or other substance contained in the syringe is 2 2 Extracellular fluid 22Na, 125I-­iothalamate, thiosulfate, injected into a chamber, and the substance is allowed to inulin disperse throughout the chamber until it becomes mixed UNIT V in equal concentrations in all areas. Then a sample of fluid Intracellular fluid (Calculated as total body water— extracellular fluid volume) containing the dispersed substance is removed, and the Plasma volume 125I-­albumin, Evans blue dye (T-­1824) concentration is analyzed chemically, photoelectrically, 51Cr-­labeled or by other means. If none of the substance leaks out of Blood volume red blood cells, or the compartment, the total mass of substance in the com- calculated as blood volume = plasma volume/(1 − hematocrit) partment (Volume B × Concentration B) will equal the total mass of the substance injected (Volume A × Con- Interstitial fluid Calculated as extracellular fluid volume − plasma volume centration A). By simple rearrangement of the equation, one can calculate the unknown volume of chamber B as follows: Measurement of Extracellular Fluid Volume. The vol- Volume A × Concentration A ume of extracellular fluid can be estimated using any of Volume B = Concentration B several substances that disperse in the plasma and in- terstitial fluid but do not readily permeate the cell mem- For this calculation, one needs to know the following: brane. These include radioactive sodium, radioactive (1) the total amount of substance injected into the cham- chloride, radioactive iothalamate, thiosulfate ion, and ber (the numerator of the equation); and (2) the concen- inulin. When any one of these substances is injected into tration of the fluid in the chamber after the substance has the blood, it usually disperses almost completely through- been dispersed (the denominator). out the extracellular fluid within 30 to 60 minutes. Some For example, if 1 milliliter of a solution containing 10 of these substances, however, such as radioactive sodium, mg/ml of dye is dispersed into chamber B, and the final may diffuse into the cells in small amounts. Therefore, concentration in the chamber is 0.01 mg/ml of fluid, the one frequently speaks of the sodium space or inulin space unknown volume of the chamber can be calculated as instead of calling the measurement the true extracellular follows: fluid volume. 1ml × 10 mg/ml Volume B = = 1000 ml Calculation of Intracellular Volume. The intracellular 0.01mg/ml volume cannot be measured directly. However, it can be This method can be used to measure the volume of calculated as follows: virtually any compartment in the body as long as the fol- Intracellular volume lowing occur: (1) the indicator disperses evenly through- = Today body water −Extracellular volume out the compartment; (2) the indicator disperses only in the compartment that is being measured; and (3) the Measurement of Plasma Volume. Plasma volume can indicator is not metabolized or excreted. If the indicator be measured using a substance that does not readily pen- is metabolized or excreted, correction must be made for etrate capillary membranes but remains in the vascular loss of the indicator from the body. Several substances system after injection. One of the most commonly used can be used to measure the volume of each of the differ- substances for measuring plasma volume is serum albu- ent body fluids. min labeled with radioactive iodine (125I-­albumin) or with a dye that avidly binds to the plasma proteins, such as Ev- ans blue dye (also called T-­1824). DETERMINATION OF VOLUMES OF SPECIFIC BODY FLUID COMPARTMENTS Calculation of Interstitial Fluid Volume. Interstitial fluid volume cannot be measured directly, but it can be calcu- Measurement of Total Body Water. Radioactive water lated as follows: (tritium, 3H2O) or heavy water (deuterium, 2H2O) can be e used to measure total body water. These forms of water − Plasma volume mix with the total body water within a few hours after Measurement of Blood Volume. If one measures the being injected into the blood, and the dilution principle hematocrit (the fraction of the total blood volume com- can be used to calculate total body water (Table 25-­3). posed of cells) and plasma volume using the methods de- Another substance that has been used to measure total scribed earlier, blood volume can also be calculated using body water is antipyrine, which is very lipid-­soluble, rap- the following equation: idly penetrates cell membranes, and distributes uniformly throughout the intracellular and extracellular compart- Plasma volume Total blood volume = ments. 1 – Hematocrit 309 UNIT V The Body Fluids and Kidneys For example, if the plasma volume is 3 liters and hema- into the extracellular fluid until the water concentration on tocrit is 0.40, the total blood volume would be calculated both sides of the membrane becomes equal. Conversely, as follows: if a solute such as sodium chloride is removed from the 3 liters extracellular fluid, water diffuses from the extracellular = 5 liters 1 – 0.4 fluid through the cell membranes and into the cells. Another way to measure blood volume is to inject red Osmolality and Osmolarity. The osmolal concentration blood cells that have been labeled with radioactive mate- of a solution is called osmolality when the concentration rial into the circulation. After these mix in the circulation, is expressed as osmoles per kilogram of water; it is called the radioactivity of a mixed blood sample can be mea- osmolarity when it is expressed as osmoles per liter of solu- sured, and the total blood volume can be calculated using tion. In dilute solutions such as the body fluids, these two the indicator-­dilution principle. One substance that can terms can be used almost synonymously because the dif- used to label the red blood cells is radioactive chromium ferences are small. Most of the calculations used clinically (51Cr), which binds tightly with the red blood cells. and the calculations expressed in the next several chap- ters are based on osmolarities rather than osmolalities. FLUID EXCHANGE AND OSMOTIC Calculation of the Osmolarity and Osmotic Pressure EQUILIBRIUM BETWEEN of a Solution. Using the van’t Hoff law, one can calcu- INTRACELLULAR AND EXTRACELLULAR late the potential osmotic pressure of a solution, assuming FLUID that the cell membrane is impermeable to the solute. For A frequent problem in treating seriously ill patients is example, the osmotic pressure of a 0.9% sodium chloride maintaining adequate fluids in one or both of the intra- solution is calculated as follows. A 0.9% solution means cellular and extracellular compartments. As discussed in that there is 0.9 gram of sodium chloride per 100 millilit- Chapter 16 and later in this chapter, the relative amounts ers of solution, or 9 g/L. Because the molecular weight of of extracellular fluid distributed between the plasma and sodium chloride is 58.5 g/mol, the molarity of the solu- interstitial spaces are determined mainly by the balance of tion is 9 g/L divided by 58.5 g/mol, or about 0.154 mol/L. hydrostatic and colloid osmotic forces across the capillary Because each molecule of sodium chloride is equal to 2 membranes. osmoles, the osmolarity of the solution is 0.154 × 2, or The distribution of fluid between intracellular and 0.308 Osm/L. Therefore, the osmolarity of this solution is extracellular compartments, in contrast, is determined 308 mOsm/L. The potential osmotic pressure of this so- mainly by the osmotic effect of smaller solutes—espe- lution would therefore be 308 mOsm/L × 19.3 mm Hg/ cially sodium, chloride, and other electrolytes—acting mOsm/L, or 5944 mm Hg. across the cell membrane. The reason for this is that the This calculation is an approximation, because sodium cell membranes are highly permeable to water but rela- and chloride ions do not behave entirely independently in tively impermeable to even small ions such as sodium and solution as a result of interionic attraction between them. chloride. Therefore, water moves across the cell mem- One can correct for these deviations from the predictions brane rapidly, and the intracellular fluid remains isotonic of van’t Hoff’s law by using a correction factor called the with the extracellular fluid. osmotic coefficient. For sodium chloride, the osmotic coef- In the next section, we discuss the interrelations ficient is about 0.93. Therefore, the actual osmolarity of a between intracellular and extracellular fluid volumes and 0.9% sodium chloride solution is 308 × 0.93, or about 286 the osmotic factors that can cause shifts of fluid between mOsm/L. For practical reasons, the osmotic coefficients of these two compartments. different solutes are sometimes neglected in determining the osmolarity and osmotic pressures of physiologic solutions. BASIC PRINCIPLES OF OSMOSIS AND Osmolarity of Body Fluids. Referring back to Table 25-­2, OSMOTIC PRESSURE note the approximate osmolarity of the various osmoti- The basic principles of osmosis and osmotic pressure cally active substances in plasma, interstitial fluid, and were presented in Chapter 4. Therefore, we review here intracellular fluid. About 80% of the total osmolarity of only the most important aspects of these principles as the interstitial fluid and plasma is due to sodium and chlo- they apply to volume regulation. ride ions, whereas for intracellular fluid, almost half the Because cell membranes are relatively impermeable to osmolarity is due to potassium ions, and the remainder is most solutes but are highly permeable to water (i.e., they divided among many other intracellular substances. are selectively permeable), whenever there is a higher As shown in Table 25-­2, the total osmolarity of each concentration of solute on one side of the cell membrane, of the three compartments is about 300 mOsm/L, with water diffuses across the membrane toward the region the plasma being about 1 mOsm/L greater than that of of higher solute concentration. Thus, if a solute such as the interstitial and intracellular fluids. The slight differ- sodium chloride is added to the extracellular fluid, water ence between plasma and interstitial fluid is caused by the rapidly diffuses from the cells through the cell membranes osmotic effects of the plasma proteins, which maintain 310  Chapter 25 Regulation of Body Fluid Compartments: Extracellular and Intracellular Fluids; Edema about 20 mm Hg greater pressure in the capillaries than shrink or swell because the water concentration in the in- in the surrounding interstitial spaces, as discussed in tracellular and extracellular fluids is equal, and the solutes ­Chapter 16. cannot enter or leave the cell. Such a solution is said to be isotonic because it neither shrinks nor swells the cells. Corrected Osmolar Activity of Body Fluids. At the bot- Examples of isotonic solutions include a 0.9% solution of tom of Table 25-­2 are shown corrected osmolar activi- sodium chloride or a 5% glucose solution. These solutions UNIT V ties of plasma, interstitial fluid, and intracellular fluid. The are important in clinical medicine because they can be reason for these corrections is that cations and anions ex- infused into the blood without the danger of upsetting the ert interionic attraction, which can cause a slight decrease osmotic equilibrium between the intracellular and extra- in the osmotic activity of the dissolved substances. cellular fluids. Osmotic Equilibrium Between If a cell is placed into a hypotonic solution that has Intracellular and Extracellular Fluids a lower concentration of impermeant solutes (