Chapter 1 Applied Physiology of Body Fluids in Dogs and Cats
Appropriate treatment of fluid and electrolyte abnormalities requires a basic understanding of the physiology of fluid balance. The purpose of this chapter is to provide an overview of the principles of body fluid homeostasis, beginning with a brief review of body fluid compartments. This is followed by a discussion of measurement of solutes in body fluids and the concepts of anion gap, osmolal gap, and zero balance.
In health, approximately 60% of an adult animal’s body weight is water. Estimates of total body water in adult dogs that are neither very thin nor obese are 534 to 660 mL/kg.26,59 Total body water of adult cats also was determined to be approximately 60%.56 There are some species and individual variations in total body water, likely related to age, sex, and body composition. In humans, total body water decreases with age and is lower in women than in men.13 Neonatal dogs and cats have higher total body water content (80% of body weight) than adults (60% of body weight),30 and an age-related decrease in total body water has been described in puppies and kittens during the first 6 months of life.35 Total body water was approximately 70% of total body weight in racing Greyhounds, likely due to low body fat content.21 Because fat has a lower water content than lean tissue, fluid needs should be estimated on the basis of lean body mass to avoid overhydration, especially in patients with cardiac or renal insufficiency or in those with hypoproteinemia. Formulas for estimating lean body mass are based on the assumptions that (1) in normal small animal patients, approximately 20% of body weight is due to fat, (2) morbid obesity increases body fat to approximately 30% of body weight, and (3) body weight is a reasonable estimate of lean body mass in thin patients:
Water is the major component of all body fluids, which are distributed into several physically distinct compartments. Body fluids in each compartment equilibrate with fluids in other compartments by multiple mechanisms across a wide variety of membranes to maintain homeostasis. The volume of fluid in each of these compartments has been estimated using various isotope or dye dilution techniques and calculating their volumes of distribution. Results are expressed either as a percentage of body weight, which is easy to measure when calculating fluid therapy needs, or as a percentage of total body water, which is a useful conceptualization of body fluid compartments. Studies of body fluid compartments often are performed in experimental animals that have been anesthetized, splenectomized, or nephrectomized. Data from these kinds of studies vary with the protocol used and thus provide only approximations of fluid compartment sizes in healthy awake animals. The second edition of this book contains a more detailed discussion of the techniques involved in determination of total body water and the amount of fluid in the various compartments.
As shown in Figure 1-1, the largest volume of fluid in the body is inside cells. The intracellular fluid (ICF) compartment comprises approximately 40% of body weight (approximately two thirds of total body water). The composition of ICF is very different from extracellular fluid (ECF) (Fig. 1-2). Intracellular homeostasis is maintained by shifts in water, solutes, and numerous other substances across the cell membrane.
Any fluid not contained inside a cell is in the extracellular fluid compartment (approximately one third of total body water). Fluid shifts that occur during changes in hydration can have a marked effect on the ECF, and in most disease states, loss of fluids occurs initially from the ECF. For example, in diarrhea, a large volume of gastrointestinal fluid is lost; in renal failure, a large volume of ECF may be excreted. Fluid losses often are treated using parenteral fluids, which initially enter the ECF. Therefore, it is important to be able to estimate the volume of the ECF compartment and the volume of fluid lost to initiate appropriate fluid replacement and monitor fluid therapy.
Unfortunately, data from dye dilution studies of ECF volume are difficult to interpret because no indicator is truly confined to the ECF space. Estimates of ECF vary dramatically with the indicator used. ECF volumes reported for adult, healthy dogs and cats vary between 15% and 30% of body weight. The wide range in estimates of ECF volume likely results from the variety of techniques used to measure this space and the heterogeneity of ECFs, which include interstitial fluid (ISF), plasma, and transcellular fluids. Dense connective tissue, cartilage, and bone also contain a small amount of ECF. From a physiologic perspective and based on multiple studies using various indicators, the most accurate estimate of the ECF in adult small animals is 27% of lean body weight. However, an easier distribution of body fluids to remember is the 60:40:20 rule: 60% of body weight is water, 40% of body weight is ICF, and 20% of body weight is ECF (see Fig. 1-1). Many clinicians use 20% as an estimate for ECF when calculating fluid therapy needs for their patients.
As mentioned above and as shown in Figure 1-1, ECF is distributed among several different subcompartments. Most ECF (about three fourths) is in spaces surrounding cells and is called interstitial fluid. Although accurate studies of the size of the ISF compartment in dogs and cats have not been reported, estimates derived from measurement of fluids in other compartments indicate that the ISF comprises approximately 15% of body weight (approximately 24% of total body water). About one fourth of the ECF is within blood vessels and is called the intravascular compartment (plasma). Intravascular fluids are approximately 5% of body weight (approximately 8% to 10% of total body water). Most of the intravascular fluid is plasma. Plasma volume estimates range from 42 to 58 mL/kg in adult dogs that are neither very thin nor obese.26 Estimates for plasma volume in cats are 37 to 49 mL/kg.26 Blood volume, which includes erythrocytes, is a function of lean body mass, and estimated blood volume in dogs is 77 to 78 mL/kg (8% to 9% of body weight) and in cats is 62 to 66 mL/kg (6% to 7% of body weight).24 Racing Greyhounds may have higher blood volumes (110 to 114 mL/kg) than other breeds, possibly related to higher lean body mass.21
Fluids produced by specialized cells to form cerebrospinal fluid, gastrointestinal fluid, bile, glandular secretions, respiratory secretions, and synovial fluid are in the transcellular fluid compartment, which is estimated as approximately 1% of body weight (approximately 2% of total body water). Dense connective tissues, bone, and cartilage contain approximately 15% of total body water. However, these tissues exchange fluids slowly with other compartments. Because this fluid usually is not taken into account for routine fluid therapy, this compartment is not shown in Figure 1-1. Thus, a more simplified distribution of total body water often used for fluid therapy is:
Although body fluids traditionally are conceptualized anatomically within these various compartments, water and solutes in these spaces are in dynamic equilibrium across the cell membrane, capillary endothelium, and specialized lining cells. Fluids and electrolytes shift among compartments to maintain homeostasis within each compartment. In health, the concentration of a particular substance may be similar or very different among the various fluid compartments. During disease, fluid volumes and solute concentrations may change dramatically. Loss or gain of fluid or electrolytes from one compartment likely will alter the volume and solute concentrations of other compartments.
In addition to water, body fluids contain various concentrations of solutes. Total body content of solutes may be measured by cadaver analysis (desiccation) or by isotope dilution studies. Every solute has a space or apparent volume of distribution. Dilution studies of body solute content yield variable results, depending on the volume of distribution of the particular tracer used to estimate the solute space. There are limited data in the literature from cadaver and isotope dilution studies of body solute content in small animals, and most of the following discussion is based on data from studies in humans.13,48
Solutes are not distributed homogeneously throughout body fluids. Vascular endothelium and cell membranes have different permeabilities for various solutes. Healthy vascular endothelium is relatively impermeable to the cellular components of blood and to plasma proteins. Consequently, the volume of distribution of cells and proteins is the plasma space itself. However, the vascular endothelium is freely permeable to ionic solutes, and the concentration of these ions is almost the same in ISF as in plasma. Cell membranes maintain intracellular solutes at very different concentrations from those of the ECF. The compositions of solutes in the ECF and ICF are compared in Figure 1-2, and concentrations of solutes in plasma and in ISF and ICF are listed in Table 1-1.
The slightly increased concentration of cations and anions in ISF compared with plasma water occurs primarily because of the presence of negatively charged proteins in plasma. The equilibrium concentrations of permeable anions and cations across the vascular endothelium are determined by the Gibbs-Donnan equilibrium, which occurs because negatively charged, nondiffusible proteins affect the distribution of other small charged solutes. In clinical practice, the difference in concentrations of anions and cations across the vascular endothelium is negligible, and the effects of the Gibbs-Donnan equilibrium are usually ignored. Thus, in clinical practice, plasma concentrations of solutes are considered to reflect solute concentrations throughout the ECF. Average values for plasma concentrations of important solutes in dogs and cats are given in Table 1-2.
Table 1-1 shows that, although the solute compositions of ECF and ICF are quite different, the total numbers of cations and anions in all body fluids are equal to maintain electroneutrality. The most abundant cation in the ECF is sodium (Na+). Most of the body Na+ is in the extracellular space. Approximately 70% of body Na+ in humans is exchangeable, and 30% is fixed as insoluble salts in bone.48 The percentage of exchangeable sodium is important because only exchangeable solutes are osmotically active. Cell membranes are permeable to Na+, which tends to diffuse into cells. In health, however, cell membrane sodium, potassium-adenosinetriphosphatase (Na+, K+-ATPase) actively removes Na+ from cells, thus maintaining a steep extracellular-to-intracellular concentration gradient for Na+. The ECF also contains a small but physiologically important concentration of K+. For example, alterations in ECF K+ concentrations may result in muscle weakness (hypokalemia) or cardiotoxicity (hyperkalemia). The most abundant anions in ECF are chloride (Cl−) and bicarbonate (HCO3−). The volume of distribution of Cl− is primarily the ECF volume. Bicarbonate is present in all body fluids and can be generated from CO2 and H2O in the presence of carbonic anhydrase.
In contrast to ECF, the primary cations in ICF are K+ and magnesium (Mg2+). Most of the body K+ is in the ICF, where K+ is the most abundant cation. Cell membranes are permeable to K+. The K+ concentration gradient between ICF and ECF is maintained by cell membrane Na+, K+-ATPase, which moves K+ into cells against a concentration gradient. The ratio of intracellular to extracellular K+ concentration is important in generating and maintaining the cell membrane potential at approximately −70 mV (see Appendix). Almost 100% of body K+ in humans is exchangeable.48 Unfortunately, a reliable, practical method for measuring the intracellular K+ concentration is not available, and changes in serum K+ concentration may not reflect changes in total body K+ stores (see Chapter 5). The predominant anions in the ICF are organic phosphates and proteins.
ICFs are not homogeneous. Concentrations of solutes vary in different cell types and in different subcellular compartments. From a clinical perspective, these differences usually are ignored. The heterogeneity of solute distribution between ICF and ECF may, however, play an important role in some disease processes.
Transcellular fluids include cerebrospinal fluid, gastrointestinal fluid, bile, glandular secretions, and joint fluid. Transcellular fluids usually are not simply transudates of plasma. Transcellular fluid composition varies according to the cells that form the fluid. Concentrations of solutes in transcellular fluids will be discussed in later chapters, related to alterations in fluid balance involving specific transcellular fluids, such as loss of enteric fluids in diarrhea.
Definitions can be tedious, but familiarity with a few may help with understanding the subsequent sections in this chapter. The definitions are presented in sequence of discussion, not alphabetically.
Most naturally occurring elements consist of one or more isotopes of that element, each of which has a different mass. For example, carbon in the environment consists of approximately 99% 12C and 1% 13C. The atomic mass of an element is an average mass based on the distribution of stable isotopes for that element, and is determined by the weight of that element relative to the weight of the 12C isotope of carbon, which is defined as 12.000. Atomic mass usually is reported with no units or as atomic mass units. The atomic mass is shown in most periodic tables of the elements. The atomic weights of some biologically important elements in body fluids are listed in Table 1-3.
Many elements combine to form physiologically important compounds. The molecular mass of a compound is the sum of the atomic masses of the atoms that form the compound. For example, the molecular mass of water (H2O) is 18 and represents two times the atomic mass of hydrogen (2 × 1) plus the atomic mass of oxygen (16). The molecular weights of important compounds in body fluids are shown in Table 1-3.
Ionic compounds do not really form molecules, and a more appropriate term for the mass of these substances is formula weight. For example, the formula weight of CaCl2 is the atomic mass of Ca2+ (40) plus two times the atomic mass of Cl− (2 × 35.5) = 111.
A mole is defined as 6.023 × 1023 particles. Some physiology texts define a mole as the molecular (or atomic) weight of a substance in grams, but a mole really just describes 6.023 × 1023 (Avogadro’s number) particles. It is defined as the number of atoms in exactly 12 g of 12C. One mole of a substance weighs its molecular weight in grams (see section on Molecular Mass).
The molar mass is the mass in grams of 1 mol of a substance. By definition, 1 mol of carbon has a mass of 12 g. Molar masses are numerically equivalent to atomic or molecular weights but are reported in grams. For example, 1 mol Na+ weighs 23 g. Molar mass and gram molecular weight often are used interchangeably.
Molality refers to the number of moles of solute per kilogram of solvent, whereas molarity refers to the number of moles of solute per liter of solution. The molarity and molality of most biologic solutions are approximately equal because the density of water is 1 kg/L. The slight difference between molarity and molality of a substance in plasma is because of nonaqueous proteins and lipids, which make up about 6% of the total volume. In body fluids, this difference is relatively unimportant, and the terms molality and molarity often are used interchangeably.
Concentration refers to the amount of a substance that is present in a specified volume. The amount of a substance can be expressed as mass (grams or milligrams), moles (or millimoles), or equivalents (or milliequivalents). Volume usually is expressed as liters (L), deciliters (dL), or milliliters (mL). A deciliter is one tenth of a liter (i.e., 100 mL).
Many solutions used for fluid therapy are percent solutions. Percent concentration refers to a number of parts in 100 parts of solution. This may be used to express concentration in terms of weight per unit weight, weight per unit volume, or volume per unit volume. For example, a 0.9% solution of NaCl contains 0.9 g of NaCl per 100 mL of solution, because 100 mL of H2O is equal to 100 g of H2O (0.9 g NaCl/100 g H2O). Because a gram is equal to 1000 mg and a deciliter is equal to 100 mL of solution, a 0.9% solution of NaCl contains 900 mg of NaCl per deciliter (9 g NaCl/L). Similarly, a 10% solution of CaCl2 contains 10 g of CaCl2 per 100 mL of solution, or 10 g of CaCl2 per deciliter (100 g/L), and 5% dextrose contains 5 g of dextrose per deciliter (50 g/L).
Ions in body fluids combine according to ionic charge (valence) rather than weight. The number of cations (positively charged ions) in a solution always equals the number of anions (negatively charged ions) to maintain electroneutrality. A univalent anion has a charge of negative one (e.g., Cl−); a divalent cation has a charge of positive two (Ca2+). One atom of Ca2+ combines with two atoms of Cl− to form CaCl2. It is useful to express concentrations of solutes in body fluids in equivalents per liter (Eq/L) or milliequivalents per liter (mEq/L) to reflect the charge or valence of the solute. The equivalent weight of a substance is the atomic, molecular, or formula weight of a substance divided by the valance.
One equivalent is defined as the weight in grams of an element that combines with or replaces 1 g of hydrogen ion (H+). Because 1 g of H+ is equal to 1 mol of H+ (containing approximately 6.023 × 1023 particles), 1 mol of any univalent anion (charge equals 1−) will combine with this H+ and is equal to 1 equivalent (Eq).
For example, 1 mol (1 equivalent) of Cl− combines with 1 mol of H+; 1 mol (1 equivalent) of Na+ could replace 1 mol of H+; 1 mol (2 equivalents) of Ca2+ combines with 2 mol (2 equivalents) of Cl− to form 1 mol of CaCl2. Therefore, it is useful to express concentrations of solutes in body fluids in equivalents per liter (Eq/L), thus reflecting the charge or valence of the solute.
The equivalent weight of a substance is the atomic, molecular, or formula weight divided by the valence. The milliequivalent (mEq) weight is 10−3 times the equivalent weight. For an element such as sodium, which has a valence of +1, the milliequivalent weight is equal to its atomic weight. Therefore, each millimole of Na+ provides 1 mEq. In contrast, the milliequivalent weight of Ca2+ is one half its atomic weight because its valence is +2. Each millimole of Ca2+ provides 2 mEq (0.5 mmol provides 1 mEq). These relationships may be summarized as:
Phosphate can exist in body fluids in three different ionic forms: H2PO4−, HPO42−, and PO43− (see Chapter 7). At the normal pH of ECF, approximately 80% of phosphate is in the HPO42− form and 20% is in the H2PO4− form. Therefore, the average valence of phosphate in ECF is 0.8 × (−2) + 0.2 × (−1) = −1.8. At a normal plasma phosphate concentration of 4 mg/dL, the phosphate concentration expressed in mEq/L would be:
Regardless of its weight, 1 mol of any substance contains the same number of particles (6.023 × 1023; Avogadro’s law). Solutes exert an osmotic effect in solution that is dependent only on the number of particles in solution, not their chemical formula, weight, size, or valence. One osmole (Osm) is defined as 1 g molecular weight of any nondissociable substance; therefore, each osmole also contains 6.023 × 1023 molecules.
If a substance does not dissociate in solution (e.g., glucose), 1 mol equals 1 Osm. If a substance dissociates in solution, the number of osmoles equals the number of dissociated particles. For example, assuming that NaCl completely dissociates into Na+ and Cl− in solution, each millimole of NaCl provides 2 milliosmoles (mOsm): 1 mOsm of Na+ and 1 mOsm of Cl−. If a compound in solution dissociates into three particles, the number of osmoles in solution is increased three times (e.g., CaCl2). The milliosmolar concentration of a solution may be expressed as the solution’s milliosmolarity or milliosmolality.
Osmolality refers to the number of osmoles per kilogram of solvent. An aqueous solution with an osmolality of 1.0 results when 1 Osm of a solute is added to 1 kg of water. The volume of the resulting solution exceeds 1 L by the relatively small volume of the solute. In clinical veterinary medicine, osmolality is expressed as milliosmoles per kilogram.
Osmolarity refers to the number of osmoles per liter of solution. If 1 Osm of a solute is placed in a beaker and enough water is added to make the total volume 1 L, the osmolarity of the resulting solution is 1. In clinical medicine, osmolarity is expressed as milliosmoles per liter. In biologic fluids, there is a negligible difference between osmolality and osmolarity, and the term osmolality is used in this discussion
In clinical medicine, osmolality is measured in serum, because the addition of anticoagulants for plasma samples would increase solute in the sample. Serum osmolality usually is measured by freezing-point depression, which is more precise and accurate than vapor pressure determinations. One osmole of a solute in 1 kg of water depresses the freezing point of the water by 1.86° C.55 Average values for measured serum osmolality in the dog and cat are 300 and 310 mOsm/kg, respectively.8,17 Measured osmolality may not be the same as calculated osmolality (see later discussion).
In any fluid compartment, the osmotic effect of a solute is in part dependent on the permeability of the solute across the membranes separating the compartment. Consider the two fluid compartments in a rigid box in Figure 1-3. Assume that the membrane dividing the two compartments is freely permeable to urea and water but is impermeable to glucose. When urea is added to the left compartment (top of figure), it moves down its concentration gradient from left to right, and water moves down its concentration gradient from right to left until there are equal concentrations of urea and water on both sides of the membrane. No fluid rises in the column attached to the left fluid compartment because urea is an ineffective osmole and does not generate osmotic pressure. In biologic fluids, urea is a small molecule that freely diffuses across most cell membranes and therefore does not contribute to effective osmolality.
Figure 1-3 Effective and ineffective osmoles. Top, Effect of adding a permeable solute such as urea (small closed circles) to the fluid on one side of a membrane. In this setting, equilibrium is reached by urea equilibration across the membrane rather than water movement into the urea compartment. Consequently, no osmotic pressure is generated. Bottom, Effect of adding an impermeable solute such as glucose (large open circles) to the fluid on one side of a membrane. As water moves into the glucose compartment, hydraulic pressure is generated (measured by the height of the column of water above the glucose compartment), which at equilibrium equals the osmotic pressure of the solution.
When glucose is added to the left compartment (bottom of figure), water moves down its concentration gradient from right to left, but glucose cannot move across the membrane. This movement of water from a solution of lesser solute concentration across a semipermeable membrane to a solution of greater solute concentration is called osmosis. The influx of water into the left compartment resulting from the osmotic effect of glucose causes the solution to rise in the column. The height of fluid in the column is proportional to the osmotic pressure generated by glucose. In this example, glucose is an effective osmole because it generates osmotic pressure by causing a shift of water across the boundary membrane. Glucose is an effective osmole in this setting because the boundary membrane is impermeable to glucose but permeable to water. In biologic fluids, glucose can contribute to osmolality because it is not freely diffusible.
The effective osmolality of a solution is referred to as the tonicity of the solution. A freezing-point depression osmometer measures all osmotically active particles in the solution. Thus, the measured osmolality of a solution includes both effective and ineffective osmoles. The tonicity of a solution may be less than the measured osmolality if both effective and ineffective osmoles are present. Thus, the tonicity and osmolality of a solution are not necessarily equal—a circumstance that often is true in biologic solutions.
The calculated osmolality is an estimate of serum osmolality using various formulas. The formulas include solutes that have a major contribution to total osmolality. Calculated osmolality often is less than measured osmolality because the formulas either exclude some osmotically active particles or estimate their contribution.
|Concentration of 0.9% NaCl:||0.9 g NaCl/100 mL of solution = 900 mg NaCl/dL|
|Convert milligrams to grams and deciliters to liters||900 mg NaCl/100 dL × 1 g/1000 mg × 10 dL/L = 9 g NaCl/L|
|Formula weight of NaCl:|
(use atomic weight from
or periodic table)
|Atomic mass of Na + atomic mass of Cl|
= 23 + 35.5 = 58.5
|Molar mass of NaCl:||58.5 g|
|Convert grams to moles:||9 g NaCl × (1 mol/58.5g) = 0.154 mol NaCl|
|Convert moles to millimoles:||0.154 mol × (1000 mmol/mol) = 154 mmol NaCl|
|Determine millimoles of Na+ and Cl−||NaCl in solution dissociates into Na+ and Cl−, yielding 154 mmol/L of Na+ and 154 mmol/L of Cl−|
|Determine milliequivalents of Na+ and Cl−||millimoles × valence = milliequivalents|
Na+ and Cl− each have a valence of 1
154 mmol ×1 = 154 mEq of Na+
154 mmol ×1 = 154 mEq of Cl−
|Determine milliosmoles of Na+ and Cl−||NaCl in solution dissociates into Na+ and Cl−, so the mOsm/L in 0.9% NaCl is the sum of the mOsm for each component:|
154 mEq/L Na+ + 154 mEq/L Cl−
154 mOsm/L Na+ + 154 mOsm/L Cl−
= 308 mOsm/L
|Concentration of 10% CaCl2:||10 g CaCl2/100 mL of solution = 10 g CaCl2/dL|
|To convert deciliters to liters:||10 g CaCl2/dL × 10 dL/L = 100 g CaCl2/L|
|Formula weight of CaCl2:|
(use atomic weight from
or periodic table)
|Atomic mass of Ca + 2 × (atomic mass of Cl)|
= 40.1 + (2 × 35.5) = 111.1
|Molar mass of CaCl2:||111.1 g|
|Convert grams to moles:||100 g CaCl2 × (1 mol/111.1 g) = 0.9 mol CaCl2|
|Convert moles to millimoles||0.9 mol × (1000 mmol/mol) = 900 mmol CaCl2|
|Determine millimoles of Ca+2 and Cl−:||CaCl2 in solution dissociates into Ca+2 and 2Cl, yielding 900 mmol/L of Ca+2 and 1800 mmol/L of Cl−|
|Determine milliequivalents of Ca+2 and Cl−||millimoles × valence = milliequivalents|
Ca+2 has a valence of 2; Cl− has a valence of 1
900 mmol Ca+2 × 2 = 1800 mEq of Ca+2
1800 mmol Cl− × 1 = 1800 mEq of Cl−
|Determine milliosmoles of Ca+2 and Cl−:||CaCl2 in solution dissociates into Ca+2 + 2Cl−|
mOsm/L in 10% CaCl2 is the sum of the milliosmoles for each component:
1800 mEq/L Ca+2 + 1800 mEq/L Cl−
900 mOsm/L Ca+2 + 1800 mOsm/L Cl−
= 2700 mOsm/L
Colloids are large molecular weight (MW = 30,000) particles present in a solution. The component of the total osmotic pressure in plasma contributed by colloids is called the colloid osmotic pressure (oncotic pressure). Plasma proteins are the major colloids present in normal plasma. Although colloid osmotic pressure is only about 0.5% of the total osmotic pressure, oncotic pressure is extremely important in transcapillary fluid dynamics. Oncotic pressure can be measured using a colloid osmometer (oncometer).