Homeostasis of Body Fluids

CHAPTER 2 Homeostasis of Body Fluids


Normal cellular function requires that the intracellular composition of ions, small molecules, water, pH, and a host of other substances be maintained within a narrow range. This is accomplished by the transport of many substances and water into and out of the cell with the use of membrane transport proteins as described in Chapter 1. In addition, each day food and water are ingested and waste products are excreted from the body. In a healthy individual this occurs without significant changes in either the volume of body fluids or their composition. Such maintenance of steady-state balance, where the volume and composition of body fluids remain constant despite the addition and elimination of water and solutes from the body, to a large degree reflects the function of epithelial cells. These cells, which constitute the interface between the internal environment of the body and the external world, maintain the volume and composition of the fluid bathing all cells (i.e., the extracellular fluid [ECF]) constant. The ECF, in turn, helps cell maintain a constant intracellular environment.


The ability of the body to maintain constant volume and composition of the intracellular fluid (ICF) and ECF is a complex process that involves all organ systems of the body. Transport by the epithelial cells of the gastrointestinal tract, kidneys, and lungs controls both the intake and excretion of numerous substances and water. The cardiovascular system delivers nutrients to and removes waste products from cells and tissues. Finally, the nervous and endocrine systems provide regulation and integration of these important functions.


To provide background for further study of the organ systems, this chapter presents an overview of the concept of steady-state balance, reviews the normal volume and composition of body fluids, and describes how cells maintain their intracellular composition and volume. Included is a presentation on how cells generate and maintain a membrane potential, which is fundamental to understanding the function of excitable cells (e.g., neurons and muscle cells). Finally, because epithelial cells are so central to the process of regulating the volume and composition of body fluids, the principles of solute and water transport by epithelial cells are reviewed.



CONCEPT OF STEADY-STATE BALANCE


The concept of steady-state balance can be illustrated by considering a river on which a dam is built to create an artificial lake. Each day, water enters the lake from the various streams and rivers that feed it. In addition, water is added by rain and snow. At the same time, water is lost through the spillways of the dam and by the process of evaporation. For the level of the lake to remain constant (i.e., steady-state balance), the rate at which water is added, regardless of the source, must be exactly matched by the amount of water lost, again by whichever route. Because the addition of water and loss by evaporation are not easily controlled, the only way to maintain the level of the lake constant is to regulate the amount that is allowed through the spillways. For such a system to work, there must be a “set point,” or a determination of what the optimal level of water in the lake should be. There must also be some way to measure deviations from the set point, such as a measure of the depth of the lake. Finally, there must be a mechanism, or “effector,” that regulates the amount of water that leaves the lake through the spillway. In this example, the dam operator, who controls the spillways, is that effector.


For virtually every substance in the body, the amount or concentration of which must be maintained within a narrow range, there is a set point and mechanism for monitoring deviations from that set point and effector mechanisms to maintain amounts or concentrations of that substance within the body constant, or in steady-state balance.


In keeping with the dam and lake analogy, consider the maintenance of steady-state water balance in humans (see Chapter 34 for details). Each day various volumes of liquid are ingested, and water is produced through cellular metabolism. Importantly, the amount of water added to the body each day is not constant, although it can be regulated to a degree by the thirst mechanism. In addition, water is lost from the body via respiration, sweating, and feces. The amount of water lost by these routes also varies over time, depending on the respiratory rate, physical activity, ambient temperature, and the presence or absence of diarrhea. The only regulated route for excretion of water from the body is the kidneys. The body maintains steady-state water balance by ensuring that the amount of water added to the body each day is exactly balanced by the amount lost or excreted from the body.


The body monitors the amount of water that it contains through changes in the osmolality of ECF. When excess water is added to the body, the osmolality of ECF decreases. Conversely, when excess water is lost from the body, osmolality increases. Cells within the hypothalamus of the brain monitor changes in ECF osmolality around each person’s genetically determined set point. When deviations from the set point occur, neural and hormonal signals are activated (i.e., effectors). For example, when ECF osmolality is increased, neural signals are sent to another region of the hypothalamus to stimulate the sensation of thirst. At the same time, antidiuretic hormone (ADH) is secreted from the posterior pituitary and acts on the kidneys to reduce the excretion of water. Thus, water intake is increased at the same time that its loss from the body is reduced, and the osmolality of ECF returns to its set point. When the osmolality of ECF is decreased, thirst is inhibited, as is the secretion of ADH. As a result, intake of water is reduced, and its excretion by the kidneys is increased. Again, these actions return the osmolality of ECF to the set point.



OVERVIEW OF THE INTRACELLULAR AND EXTRACELLULAR COMPARTMENTS



Definitions and Volumes of Body Fluid Compartments


Water makes up approximately 60% of the body’s weight, with variability among individuals being a function of the amount of adipose tissue. Because the water content of adipose tissue is lower than that of other tissue, increased amounts of adipose tissue reduce the fraction of total body weight attributable to water. The percentage of body weight attributed to water also varies with age. In newborns it is approximately 75%. This decreases to the adult value of 60% by the age of 1 year.


As illustrated in Figure 2-1, total body water is distributed between two major compartments, which are divided by the cell membrane.* The intracellular fluid compartment is the larger compartment and contains approximately two thirds of total body water. The remaining third is contained in the extracellular fluid compartment. Expressed as percentages of body weight, the volumes of total body water, ICF, and ECF are


image

Figure 2-1 Relationship between volumes of the various body fluid compartments. The actual values shown are for an individual weighing 70 kg.


(Modified from Levy MN, Koeppen BM, Stanton BA: Berne & Levy’s Principles of Physiology, 4th ed. St. Louis, Mosby, 2006.)



image



The ECF compartment is further subdivided into interstitial fluid and plasma, which are separated by the capillary wall. The interstitial fluid surrounds the cells in the various tissues of the body and accounts for three fourths of the ECF volume. ECF includes water contained within bone and dense connective tissue, as well as cerebrospinal fluid. Plasma represents the remaining fourth of ECF. Under some pathological conditions, additional fluid may accumulate in what is referred to as a “third space.” Third-space collections of fluid are part of the ECF and include, for example, the accumulation of fluid in the peritoneal cavity (ascites) of individuals with liver disease.



Composition of Body Fluid Compartments


Table 2-1 summarizes the composition of the ECF and ICF for a number of important ions and molecules. As discussed in detail later, the composition of ICF is maintained by the action of various specific membrane transport proteins. Principal among these transporters is Na+,K+-ATPase, which converts the energy in ATP into ion and electrical gradients, which in turn can be used to drive the transport of other ions and molecules.


Table 2-1 Ionic Composition of a Typical Cell




































  Extracellular Fluid Intracellular Fluid
Na+ (mEq/L) 135-147 10-15
K+ (mEq/L) 3.5-5.0 120-150
Cl− (mEq/L) 95-105 20-30
HCO3− (mEq/L) 22-28 12-16
Ca++ (mmol/L)* 2.1-2.8 (total) ≈10−7 (ionized)
1.1-1.4 (ionized)
Pi (mmol/L)* 1.0-1.4 (total)  
0.5-0.7 (ionized) 0.5-0.7 (ionized)

* Ca++ and Pi (H2PO4−/HPO4−2) are bound to proteins and other organic molecules. In addition, large amounts of Ca++ can be sequestered within cells. Large amounts of Pi are present in cells as part of organic molecules (e.g., ATP).


The composition of the plasma and interstitial fluid compartments of the ECF is similar because they are separated only by the capillary endothelium, a barrier that is freely permeable to ions and small molecules. The major difference between interstitial fluid and plasma is that the latter contains significantly more protein. Although this differential concentration of protein can affect the distribution of cations and anions between these two compartments by the Gibbs-Donnan effect (see later for details), this effect is small, and the ionic composition of interstitial fluid and plasma can be considered to be identical.


Because of its abundance in ECF, Na+ (and its attendant anions, primarily Cl− and HCO3−) is the major determinant of the osmolality of this compartment. Accordingly, a rough estimate of ECF osmolality can be obtained by simply doubling the sodium concentration [Na+]. For example, if a blood sample is obtained from an individual and the [Na+] of plasma is 145 mEq/L, its osmolality can be estimated as



Equation 2-1 image



Because water is in osmotic equilibrium across the capillary endothelium and the plasma membrane of cells, measurement of plasma osmolality also provides a measure of the osmolality of the ECF and ICF.



Fluid Exchange between the ICF and ECF


Water moves freely and often rapidly between the various body fluid compartments. Two forces determine this movement: hydrostatic pressure and osmotic pressure. Hydrostatic pressure from pumping of the heart (and the effect of gravity on the column of blood in the vessel) and osmotic pressure exerted by plasma proteins (oncotic pressure) are important determinants of fluid movement across the capillary wall (see Chapter 17). By contrast, because hydrostatic pressure gradients are not present across the cell membrane, only osmotic pressure differences between ICF and ECF cause movement of fluid into and out of cells.


Osmotic pressure differences between ECF and ICF are responsible for movement of fluid between these compartments. Because the plasma membrane of cells contains water channels (aquaporins), water can easily cross the membrane. Hence, a change in the osmolality of either ICF or ECF results in rapid movement (i.e., minutes) of water between these compartments. Thus, except for transient changes, the ICF and ECF compartments are in osmotic equilibrium.


In contrast to water, the movement of ions across cell membranes is more variable from cell to cell and depends on the presence of specific membrane transport proteins (see later). Consequently, as a first approximation, fluid exchange between the ICF and ECF compartments can be analyzed by assuming that appreciable shifts of ions between the compartments do not occur.


A useful approach to understanding the movement of fluids between the ICF and the ECF is outlined in Figure 2-2. To illustrate this approach, consider what happens when solutions containing various amounts of NaCl are added to the ECF.*


image

Figure 2-2 Principles for analysis of fluid shifts between ECF and ICF.




IN THE CLINIC


In clinical situations a more accurate estimate of plasma osmolality and thus the osmolality of ECF and ICF is obtained by also considering the osmoles contributed by glucose and urea because these are the next most abundant solutes in ECF (the other components of ECF contribute only a few additional milliosmoles). Accordingly, plasma osmolality can be estimated as



image



The glucose and urea concentrations are expressed in units of mg/dL (dividing by 18 for glucose and 2.8 for urea* allows conversion from the units of mg/dL to mmol/L and thus to mOsm/kg H2O). This estimation of plasma osmolality is especially useful when dealing with patients who have an elevated plasma [glucose] secondary to diabetes mellitus and in patients with chronic renal failure, whose plasma [urea] is elevated.



* The [urea] in plasma is measured as the nitrogen in the urea molecule, or blood urea nitrogen (BUN).




IN THE CLINIC


Neurosurgical procedures and cerebrovascular accidents (strokes) often result in the accumulation of interstitial fluid in the brain (i.e., edema) and swelling of neurons. Because the brain is enclosed within the skull, edema can raise intracranial pressure and thereby disrupt neuronal function, eventually leading to coma and death. The blood-brain barrier, which separates the cerebrospinal fluid and brain interstitial fluid from blood, is freely permeable to water but not to most other substances. As a result, excess fluid in brain tissue can be removed by imposing an osmotic gradient across the blood-brain barrier. Mannitol can be used for this purpose. Mannitol is a sugar (molecular weight of 182 g/mol) that does not readily cross the blood-brain barrier and membranes of cells (neurons, as well as other cells in the body). Therefore, mannitol is an effective osmole, and intravenous infusion results in the movement of fluid from brain tissue by osmosis.



Example 1: Addition of Isotonic NaCl to ECF


Addition of an isotonic NaCl solution (e.g., intravenous infusion of 0.9% NaCl, osmolality of ≈290 mOsm/kg H2O)† to ECF increases the volume of this compartment by the volume of fluid administered. Because this fluid has the same osmolality as ECF and therefore also ICF, there will be no driving force for movement of fluid between these compartments, and the volume of ICF will be unchanged. Although Na+ can cross cell membranes, it is effectively restricted to the ECF by the activity of Na+,K+-ATPase, which is present in the plasma membrane of all cells. Therefore, there is no net movement of the infused NaCl into the cells.



Example 2: Addition of Hypotonic NaCl to ECF


Addition of a hypotonic NaCl solution to ECF (e.g., intravenous infusion of 0.45% NaCl, osmolality of ≈145 mOsm/kg H2O) decreases the osmolality of this fluid compartment and results in movement of water into the ICF. After osmotic equilibration, the osmolality of ICF and ECF is equal but lower than before the infusion, and the volume of each compartment is increased. The increase in ECF volume is greater than the increase in ICF volume.



Example 3: Addition of Hypertonic NaCl to ECF


Addition of a hypertonic NaCl solution to ECF (e.g., intravenous infusion of 3% NaCl, osmolality of ≈1000 mOsm/kg H2O) increases the osmolality of this compartment and results in the movement of water out of cells. After osmotic equilibration, the osmolality of ECF and ICF will be equal but higher than before the infusion. The volume of ECF is increased, whereas that of ICF is decreased.




IN THE CLINIC


Fluid and electrolyte disorders are seen commonly in clinical practice (e.g., in patients with vomiting or diarrhea, or both). In most instances these disorders are self-limited, and correction of the disorder occurs without any need for intervention. However, more severe or prolonged disorders may require fluid replacement therapy. Such therapy may be administered orally with special electrolyte solutions, or intravenous fluid may be administered.


Intravenous solutions are available in many formulations. The type of fluid administered to a particular patient is dictated by the patient’s need. For example, if an increase in the patient’s vascular volume is necessary, a solution containing substances that do not readily cross the capillary wall is infused (e.g., 5% protein or dextran solutions). The oncotic pressure generated by the albumin molecules retains fluid in the vascular compartment and thereby expands its volume. Expansion of ECF is accomplished most often by using isotonic saline solutions (e.g., 0.9% NaCl or lactated Ringer’s solution). As already noted, administration of an isotonic NaCl solution does not result in the development of an osmotic pressure gradient across the plasma membrane of cells. Therefore, the entire volume of the infused solution will remain in the ECF. Patients whose body fluids are hyperosmotic need hypotonic solutions. These solutions may be hypotonic NaCl (e.g., 0.45% NaCl or 5% dextrose in water, so-called D5W). Administration of D5W solution is equivalent to the infusion of distilled water because the dextrose is metabolized to CO2 and water. Administration of these fluids increases the volume of both ICF and ECF. Finally, patients whose body fluids are hypotonic need hypertonic solutions. These are typically NaCl-containing solutions (e.g., 3% and 5% NaCl). These solutions expand the volume of ECF but decrease the volume of ICF. Other constituents, such as electrolytes (e.g., K+) or drugs, can be added to intravenous solutions to tailor the therapy to the patient’s fluid, electrolyte, and metabolic needs.



MAINTENANCE OF CELLULAR HOMEOSTASIS


Normal cellular function requires that the composition of ICF be tightly controlled. For example, the activity of some enzymes is dependent on pH. Therefore, intracellular pH must be regulated. The intracellular ionic composition is similarly held within a narrow range. This is necessary for establishment of the membrane potential, a cell property especially important for the normal function of excitable cells (e.g., neurons and muscle cells) and for intracellular signaling (e.g., intracellular [Ca++]–see Chapter 3). Finally, the volume of cells must be maintained because shrinking or swelling of cells can lead to cell damage or death. Regulation of intracellular composition and cell volume is accomplished through the activity of specific transporters in the plasma membrane of cells. This section reviews the mechanisms by which cells maintain their intracellular ionic environment and membrane potential and control their volume.



Ionic Composition of Cells


The intracellular ionic composition of cells varies from tissue to tissue. For example, the intracellular composition of neurons is different from that of muscle cells, which differs from that of blood cells. Nevertheless, there are similar patterns, and these are presented in Table 2-1. When compared with ECF, ICF is characterized by a low [Na+] and a high [K+]. This is the result of the activity of Na+,K+-ATPase, which transports 3 Na+ ions out of the cell and 2 K+ ions into the cell for each molecule of ATP hydrolyzed. As will be discussed, the activity of Na+,K+-ATPase is not only important for establishing the cellular Na+ and K+ gradients but is also involved in indirectly determining the cellular gradients for many other ions and molecules. Because Na+,K+-ATPase transports three cations out of the cell in exchange for two cations, it is electrogenic and thus contributes to the establishment of membrane voltage (cell interior negative). However, Na+,K+-ATPase typically contributes only a few millivolts to the membrane potential. More importantly, it is the leakage of K+ out of the cell through K+-selective channels that is a major determinant of membrane voltage (see later). Thus, Na+,K+-ATPase converts the energy in ATP into ion gradients (i.e., Na+ and K+) and a voltage gradient (i.e., membrane potential) as a result of leakage of K+ out of the cell driven by the K+ concentration gradient across the membrane ([K+]i > [K+]o).


The Na+,K+-ATPase–generated ion and electrical gradients are used to drive the transport of other ions and molecules into or out of the cell (Fig. 2-3). For example, as described in Chapter 1, a number of solute carriers couple the transport of Na+ to that of other ions or molecules. The Na+-glucose and Na+–amino acid symporters use the energy in the Na+ electrochemical gradient, directed to bring Na+ into the cell, to drive the secondary active cellular uptake of glucose and amino acids. Similarly, the inwardly directed Na+ gradient drives the secondary active extrusion of H+ from the cell and thus contributes to the maintenance of intracellular pH. The 3Na+-1Ca++ antiporter, along with plasma membrane Ca++-ATPase, extrudes Ca++ from the cell and thus contributes to maintenance of a low intracellular [Ca++].* Finally, the membrane voltage drives Cl− out of the cell through Cl−-selective channels, thus lowering the intracellular concentration below that of the ECF.


image

Figure 2-3 Cell model depicting how cellular gradients and the membrane potential (Vm) are established. (1) Na+,K+-ATPase decreases intracellular [Na+] and increases intracellular [K+]. Some K+ exits the cell via K+-selective channels and generates the Vm (cell interior negative). (2) The energy in the Na+ electrochemical gradient drives the transport of other ions and molecules via the use of various solute carriers. (3) The Vm drives Cl− out of the cell through Cl−-selective channels. (4) Ca++-H+-ATPase and the 3Na+-1Ca++ antiporter maintain the low intracellular [Ca++].

< div class='tao-gold-member'>

Related posts:

  1. The Autonomic Nervous System and Its Central Control
  2. Smooth Muscle
  3. The Small Intestinal Phase of the Integrated Response to a Meal
  4. Organization of Motor Function

Stay updated, free articles. Join our Telegram channel
Tags:
Jul 4, 2016 | Posted by in PHYSIOLOGY | Comments Off on Homeostasis of Body Fluids

Full access? Get Clinical Tree
Get Clinical Tree app for offline access