Osmoles, osmolality and osmotic

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1 Copyright econtent Management Pty Ltd. Contemporary Nurse (2008) 29: Osmoles, osmolality and osmotic pressure: Clarifying the puzzle of solution concentration ABSTRACT Key Words solution concentration; osmolarity; osmolality; osmotic pressure; tonicity; nursing Nurses are routinely involved in the collecting and testing of urine and plasma, dialysis, the administration of intravenous fluids and the treatment of osmolar disorders, all of which require an understanding of solution concentration.this article discusses the various ways in which the concentration of solutions are stated, how they differ and why the different ways of expressing concentration are useful in human physiology. It also explains the similarities and differences between the terms used to describe solution concentration: tonicity, percentage concentration, density, specific gravity, molarity, osmolarity, osmolality and osmotic pressure.the terms osmolarity, osmolality and osmotic pressure appear routinely in textbooks used in undergraduate nursing courses but often are used incorrectly as synonyms.the usefulness and the appropriate context to use the different ways of expressing solution concentration is discussed. Osmolality (or osmolarity) should be used instead of osmotic pressure to describe Cthe N movement of water between compartments while the use of osmotic pressure should be reserved for situations where filtration and osmosis are operating together. Received 27 April 2007 Accepted 26 February 2008 MARTIN CAON Senior Lecturer in Biophysical Science School of Nursing and Midwifery Flinders University Adelaide SA, Australia INTRODUCTION Nurses are routinely involved in collecting and testing of urine and plasma, renal dialysis, administration of intravenous fluids and treatment of osmolar disorders, all of which require an understanding of solution concentration.the solutions in the body contain a great diversity of solutes (ions and molecules) which include electrolytes, dissolved gases, nutrients, wastes, proteins, vitamins, enzymes, hormones and other things. A healthy body is characterised by having the concentrations of almost all these solutes lying within narrow, normal ranges.the healthy range for a particular solute varies from one fluid compartment of the body to another. For example, sodium concentration is higher in the extracellular compartment than in the intracellular compartment.water and some of these solutes are able to move between compartments by passing through the intervening cell mem- 92 C N Volume 29, Issue 1, May 2008

2 Osmoles, osmolality and osmotic pressure: Clarifying the puzzle of solution concentration C N branes.these membranes are said to be selectively permeable.that is, some particles such as water and urea can pass through (are permeant) while others (such as sodium and potassium) cannot. In addition, the solutes that are unable to cross a cell s plasma membrane influence the movement of water across the membranes. Osmosis is a term reserved to describe the movement (diffusion) of water through a membrane from the side where there is a higher concentration of water molecules to the side where there is a lower concentration of water molecules is called. Dialysis refers to the diffusion of solute particles through a membrane along their concentration gradient. It is because the concentration of solutes in the body s solutions provide an insight into its state of health that they are of great diagnostic use for nursing assessment and practice.whilst the precise concentrations of these solutes are measured by laboratory tests, the concentration of solutions that are given orally, intravenously, excreted as urine or removed as drainage are of nursing interest. The variety of the body s solutions, the diverse nature of the solutes in those solutions and the purpose for which the value of a solution s concentration is required results in many ways to state the concentration of a solution. SUBTLE DIFFERENCES IN MEANING BETWEEN SIMILAR TERMS The diversity of ways in which solution concentration is stated.the subtle differences between concepts such as density and specific gravity, osmolarity and osmolality, and the use of the word pressure in a term that refers to solution concentration, has resulted in erroneous explanations of tonicity and osmotic pressure appearing in print.the following quotes from nursing textbooks will serve as examples. The statements in Crisp and Taylor (2005: 1102, 1125) The osmotic pressure of a solution is called its osmolarity ; A solution with the same osmolarity as blood plasma is called isotonic ; and isotonic solutions are those that have the same effective osmolality as body fluids imply that osmotic pressure, osmolarity and osmolality are all the same thing. Also implied is that being isotonic is determined by osmolarity alone. Both contentions are misconceptions. Craven and Hirnle (2000: 886) state: Osmotic pressure, the force of attraction for water by undissolved particles, ; and A solution that has the same osmotic pressure or osmolarity as blood plasma is called iso-osmotic or isotonic. The first statement is wrong osmotic pressure is not a force, and dissolved or undissolved particles do not exert such an attraction while the second, without significant qualifications, is in error due to oversimplification. Lewis et al (2004: 333) state that: Osmotic pressure is measured in milliosmoles and may be expressed as either fluid osmolarity or fluid osmolality. Osmolality measures the osmotic force of solute per unit of weight of solvent This statement assigns an incorrect unit to osmotic pressure, again equates osmolarity, osmotic pressure and osmolality, and incorrectly uses force and pressure as synonyms. Nursing texts are not alone in struggling to explain these difficult-to-express concepts. Some anatomy and physiology textbooks also erroneously equate pressure and force in their attempt to explain osmotic pressure. In Martini (2006: 89): osmotic pressure of a solution is a measure of the force with which pure water moves into that solution as a result of its solute concentration. In Jenkins et al (2007: 73), To further complicate matters, the solution with the impermeable solute also exerts a force, called the osmotic pressure. The casual reader may take the Jenkins statement out of context and infer that solutions within the human body exert a force by virtue of their dissolved solutes, but the inference would be wrong. Volume 29, Issue 1, May 2008 C N 93

3 C N Martin Caon The purpose of this article is to focus attention on the incorrect descriptions of the concepts of osmolarity, and osmotic pressure that have appeared in textbooks and to try to correct them. It also discusses the various ways in which the concentration of solutions are stated, how they differ and why the different ways of expressing concentration are useful in human physiology. HYPOTONIC, ISOTONIC AND HYPERTONIC SOLUTIONS An important property of intravenous solutions is their concentration compared to the concentration of the solution within red blood cells. A semi-quantitative descriptor of the concentration of one solution compared to another is tonicity. A solution that is isotonic with plasma is one that will not cause a net movement of water into or out of red blood cells that are placed in the solution.this definition is preferable to one that refers to the concentration of dissolved particles to define an isotonic solution. Some solutes (such as sodium) are unable to passively pass through the cell membrane they are non-permeant and it is this type of particle that determines tonicity. Permeant particles such as urea, cross the membrane as easily as water does.this means that urea molecules will cross the membrane and distribute themselves evenly on both sides of the membrane, rather than causing water molecules to move. A hypotonic solution will cause red blood cells to swell as water moves into the cell.they may burst (haemolyse) if the influx of water is too great. A hypertonic solution will cause a net outflow of water from a red blood cell and the cell membrane will wrinkle (crenate) as the cell volume decreases.the tonicity of a solution is a statement of the physiological effect that the concentration of non-permeant solutes in the solution will have on red blood cells. Movement of water through the plasma membrane will still occur even when a cell is placed in an isotonic solution. However, the amount of water moving into the cell is equal to the amount of water moving out of the cell. Examples of solutions that are isotonic with blood (and with the solution inside red blood cells) are 0.9% sodium chloride and 5% glucose. Note that solutions may be isotonic without being identical. 0.9% sodium chloride (Na + Cl ) contains only sodium ions, chloride ions and water molecules. Blood on the other hand, contains a great many other solutes in addition to sodium and chloride. Further note that if a solute is permeant (as are urea and ethanol) then in addition to water molecules, the permeant solutes will also move through the plasma membrane and this greatly complicates the situation. In addition to tonicity, there are several quantitative measures of solution concentration and these are discussed below. PERCENT CONCENTRATION (GRAMS PER 100 ML) Nurses will routinely handle bags of intravenous fluids that have their concentration stated as a percentage and printed boldly on the bag.when a solution is prepared by dissolving one or a few solutes in water, as are intravenous solutions, the mass of solute that has been dissolved and the volume of the resulting solution are usually both known.this makes it possible to state the solution concentration as a percentage. Percent concentration is a statement about how many grams of solute have been dissolved in each 100 ml of solution percent means literally in the hundred. Thus a 5% (5 gram in 100 ml) glucose solution has 5 g of glucose dissolved in enough water to make 100 ml of solution (and is isotonic). An intravenous solution of 3.3% glucose and 0.3% Na + Cl contains 3.3 g of glucose and 0.3 g of Na + Cl in enough water to make 100 ml of solution (and is isotonic). Note that a 5% solution is not made by adding 5 g of glucose to 100 ml of water because if you start with 100 ml of water and then add 5 g of glucose, the addition will take the combined volume to a little more than 100 ml. 94 C N Volume 29, Issue 1, May 2008

4 Osmoles, osmolality and osmotic pressure: Clarifying the puzzle of solution concentration C N DENSITY (GRAM PER ML) The density of a solution is easily measured and is a useful guide to solution concentration when the masses of solutes are not known.the density of a solution is the number of grams that 1 ml of solution weighs. The density of water is exactly 1.0 g/ml (at 20 C). When a solute is added to water the mass of the solution that results is exactly equal to the mass of solute added plus the mass of water used. However the volume of the resulting solution is not the same as the sum of the volumes of solute and solvent. It is less. A solution will have a greater density than the pure solvent alone and as more solute is added to the solution, the density increases further. Because density increases almost in direct proportion to the concentration of the solution, density may be used as a measure of concentration.this is particularly useful if the solution whose concentration we are interested in is made up of an unknown solute or mixture of solutes. Urine, for example, contains a great many solutes. While the concentration of one solute found in urine may sometimes be measured, it is more common for the total solute concentration to be determined. To do this, density is measured and since there is (nearly) a direct relationship between the density of a solution and its solute concentration, the measurement of urine density provides a substitute for the measurement of urine concentration. In order to determine density, it is necessary to accurately measure both a solution s mass and its volume.this requires a laboratory equipped with calibrated glassware and an accurate balance. In practice, solution density is rarely measured; instead nurses measure a closely related quantity called specific gravity. SPECIFIC GRAVITY (DENSITY WITHOUT THE UNITS) Specific gravity is the ratio of the density of the solution being measured to the density of water. While it may seem a complicated procedure to divide the density of urine by that of water, in practice specific gravity is easily measured using a hydrometer designed for use with urine (a urinometer), a clinical refractometer or a urinalysis reagent strip.the urinometer floats higher in concentrated urine because it is denser (and is indicative of a dehydrated patient) and sinks deeper into more dilute urine.the urinometer has been displaced as a clinical measuring device by the test strip.as the reagents on the test strip provide a chemical test for what is essentially a physical quantity, the result is accurate only to within (Bayer 1992). Specific gravity, being a ratio, has no units and the range of specific gravity values for urine, that is in the range (for very dilute urine) to about It is easy to convert a specific gravity reading into a density value in g/ml as the density of water is 1.0 g/ml.to obtain the density, simply place the units g/ml after the specific gravity value. MOLARITY (MOLES PER LITRE) The standard international unit for amount of substance is the mole. The entities whose amounts are being referred to here are atoms, ions or molecules. While more well-known units for amount of substance such as the dozen and the ream are used for stating a quantity of (say) eggs and sheets of paper, a much larger unit is required when referring to objects the size of molecules dissolved in water. One mole of ions is ions (or in scientific notation ). The mass of substance that contains a mole of particles is obtained from the chemical formula for the substance and the atomic weight of the atoms in the formula. Thus for glucose (C 6 H 12 O 6 ), 180 g is a mole, for sodium chloride a mole has a mass of 58.5 g and for urea (CON 2 H 4 ) 43 g is one mole. The dilute solutions that exist in the body, or are infused into the body, have much less than a mole of substance dissolved per litre, so the quantity of dissolved substance is stated in millimole (thousandths of a mole). The labels printed on bags of intravenous Volume 29, Issue 1, May 2008 C N 95

5 C N Martin Caon solutions state their concentration in percent and also in millimoles per litre (or 500 ml). One litre of 5% glucose has 50 g of glucose dissolved in the litre.this mass of glucose is equal to 278 millimole/l (0.278 moles). One litre of 0.9% Na + Cl has 9 g of Na + Cl dissolved in the litre. This mass of sodium chloride is equal to 154 millimoles of sodium chloride. However, when 9 g of sodium chloride crystals dissolves in water, the ions in the crystals lattice structure separate so that 154 millimoles of Na + ions and 154 millimoles of Cl ions are in the litre of solution.together these two types of ion make the concentration of solute particles in the sodium chloride solution 308 millimole/l. It is because some (covalent) substances separate into molecules when they dissolve while others (ionic substances) disassociate into their constituent ions in solution, that osmolarity another measure of solution concentration is defined. It is not simple to compare the concentrations of solutions that contain different solutes. While it is true that 10% glucose is a more concentrated solution than 5% glucose, a 5% glucose solution is not more concentrated than 0.9% Na + Cl. The latter, somewhat counterintuitive result arises because percent concentration is a statement about the mass of solute dissolved in 100 ml of solution rather than a statement about the number of solute particles per 100 ml. In order to compare the concentrations of solutions where the dissolved particles are molecules and solutions where the solutes are ions, the concept of osmolarity is required. OSMOLARITY (OSMOLES PER LITRE) Almost all pure substances contain more than one type of atom.these substances have either a molecular structure or an ionic structure. When the former type of substance dissolves in water it separates into molecules and these molecules contain all of the atoms in the chemical formula for the substance in the correct ratio and the atoms are bonded to each other in the way that defines that substance. Thus glucose separates into molecules of 24 atoms (C 6 H 12 O 6 ) bonded together in a particular arrangement. On the other hand, substances that are ionic compounds, such as sodium chloride, fall apart when they dissolve so that they become separate ions. That is, they are not held together in an association that reflects the chemical formula of the original substance.thus solute particles may be small portions of the original substance (molecules) or may not (ions). Note that the size of the different particles in a solution is not important for the determination of osmolarity. Thus particles that are single atoms (like Na + ), small molecules like glucose (with 24 atoms) and macromolecules like the plasma protein albumin (with thousands of atoms) all count as one particle for the purposes of calculating osmolarity. As the concentration of particles (rather than the amount of substance) is so important in determining the effect of a solution on cells (and because ionic substances give rise to more than one type of particle), it is useful to have a way of expressing solution concentration in terms of the number of particles rather than the amount of a substance. For this purpose, the osmole is defined. An osmole is the amount of substance which must be dissolved in order to produce particles. For glucose, the number of osmoles is the same as the number of moles. For ionic substances like sodium chloride (which has two ions in its formula), the number of osmoles is two times the number of moles. Thus, in the example used above, if moles of sodium chloride is dissolved in a litre of water, the solution concentration could be stated as 154 millimole/l (of sodium chloride) or as 308 milliosmole/l of dissolved particles. In practice a small proportion of the sodium ions and chloride ions remain associated so that there is somewhat less than 308 milliosmole/l of separate particles. Plasma osmolarity is about 282 mosmol/l (Guyton 2006: 294). 96 C N Volume 29, Issue 1, May 2008

6 Osmoles, osmolality and osmotic pressure: Clarifying the puzzle of solution concentration C N The three ions sodium, chloride and potassium account for about 250 mosmol/l while the plasma proteins account for about 1 mosmol/l. Nevertheless, plasma proteins contribute significantly to osmotic pressure as will be discussed later. Solutions that have the same osmolarity are said to be iso-osmotic. Iso-osmotic is not the same thing as isotonic. For a solution to be isotonic it must have the same osmolarity as plasma ie it must have a particular value of osmolarity. Five percent glucose, 0.9% sodium chloride and 1.25% urea all have an osmolarity that falls within the normal range for plasma and hence are iso-osmotic with plasma. However, glucose, Na + and Cl are non-permeant solutes while urea can pass easily through the plasma membrane of a red blood cell, so the first two solutions are also isotonic while 1.25% urea is hypotonic. In the case of 1.25% urea, urea molecules would enter red blood cells, leaving the surrounding solution less concentrated and the cytoplasm of the cells more concentrated. Consequently there would be a net movement of water into the cell and it would lyse. OSMOLALITY (OSMOLES PER KILOGRAM) Osmolality may look like a mis-spelling of osmolarity but it is not. The latter states the solution concentration in osmoles per litre (ie per volume of solution), while the former states concentration in osmoles per kilogram (ie per mass of solvent). The distinction is necessary because the volume of solution changes with temperature and pressure, but mass does not. Hence osmolarity is difficult to determine very accurately. The mass of a solution does not change with temperature or pressure and so osmolality is a more precise measurement (intravenous liquids have their solution concentration expressed as osmolality, printed on the container). Osmolality is easily determined in a laboratory using a technique known as freezing point depression (the more solute in a solution, the lower will be its freezing point). For the concentrations of solutions found in the human body, the difference between their osmolarity and osmolality is very small. Consequently in human physiology the two terms are used interchangeably (Silverthorn 2007: 156). In fact, bags of intravenous saline and glucose state the osmolality of the contents as being approximate because these solutions have been prepared by dissolving a known mass of the solute in enough water to make one litre.that is, the osmolarity is known but this is deemed to be sufficiently close to the osmolarity for the two measures to be stated as approximately equal. Solutions that have the same concentration of particles per kilogram are said to be isoosmotic, so solutions with the same osmolality are iso-osmotic.the normal extreme limits of plasma osmolality are mosmol/kg (Worthley 1999). OSMOTIC PRESSURE (MILLIMETRES OF MERCURY OR KILOPASCALS) Movement of water and solutes through membranes in the direction of their concentration gradients (osmosis and dialysis respectively) occurs by diffusion. In addition movement through a membrane may be effected by a difference in hydrostatic pressure between the two sides of a membrane.this movement due to a pressure gradient is called filtration and occurs in the capillaries of the systemic circulation and in the glomerular capillaries of the kidney.thus water and solutes can move through membranes because of the solution concentration gradient and because of the hydrostatic blood pressure gradient. Furthermore, these two influences may be in opposite directions. Hence, it is convenient to have a way of summing the two influences.this can be done if the concentration gradient and the pressure gradient are expressed in the same units. Osmotic pressure is a statement of solution concentration expressed as a pressure unit (usually in mm Hg rather than the metric kpa where 1 mm Hg = kpa). Volume 29, Issue 1, May 2008 C N 97

7 C N Martin Caon The osmotic pressure of a solution at 38 C can be calculated approximately from its osmolarity: Osmotic pressure (mm Hg) = 19.3 osmolarity (mmoles/l) (Guyton 1991: 279). Thus a healthy blood osmotic pressure is about 5600 mm Hg (745 kpa) and about 0.5% (28 mm Hg) of this is due to the plasma proteins (ie to colloids). FIGURE 1: (A) SUCROSE SOLUTION SEPARATED FROM WATER BY A SEMI-PERMEABLE MEMBRANE; (B) AFTER OSMOSIS HAS OCCURRED, THERE IS A DIFFERENCE IN HEIGHT H, BETWEEN THE SOLUTION AND WATER. Source: From Caon and Hickman 2003 A value for the osmotic pressure of a solution can be determined by comparing it to pure water. When pure water is separated from a solution (of non-permeant solute such as sucrose) by a semi-permeable membrane, more water will cross the membrane from the pure water side into the solution than will cross in the other direction (see Figure 1).The resulting difference in height (h in Figure 1) is called the head of liquid and exerts a pressure of about h cm H 2 O because of its weight, on the water in the container. If the tube were tall enough and there was sufficient water in the container, the level in the tube would continue to rise until the head of liquid was large enough to exert the pressure required to force as much water back to the water side of the membrane (by filtration) as crossed into the solution side (by osmosis).when this equilibrium situation is reached, the pressure produced by the head of liquid is the osmotic pressure of the original solution (if the solution was plasma, the tube would need to be more than 70 m tall). Apart from colloids, human blood and interstitial fluid have almost identical solutes and solute concentrations, so it is usual to refer only to the osmotic pressure of blood that results from the colloidal proteins.this is called colloid osmotic pressure and is quite small compared to the osmotic pressure of plasma. As an example of the combined use of solution concentration (colloid osmotic pressure) and blood pressure when both are stated in units of mm Hg, to characterise water movement, we will consider the influences that move water into and out of a capillary (see Table 1). As solution concentration and blood pressure are stated in the same units, they may be summed to give their net influence on water movement.water moves out of the capillary at the arterial end due to the 10 mm Hg difference and in at the venous end due to the 8 mm Hg difference. CONCLUSION Eight different ways of expressing the concentration of a solution have been discussed. Some of them are used only in specific contexts. For example, specific gravity is used only for urine concentration, percent concentration is used only when referring to the concentration of laboratory prepared solutions such as intravenous solutions. The terms osmolarity, osmolality and osmotic pressure cause confusion and are sometimes used (erroneously) as if they were synonyms. In fact, the difference between osmolarity and 98 C N Volume 29, Issue 1, May 2008

8 Osmoles, osmolality and osmotic pressure: Clarifying the puzzle of solution concentration C N TABLE 1: INFLUENCES THAT MOVE WATER INTO AND OUT OF CAPILLARIES Influences causing water to move out of the arterial end of a capillary Influences causing water to move out of the venous end of a capillary BP in capillary 35 mm Hg BP in capillary 17 mm Hg Interstitial fluid colloid osmotic pressure 1 mm Hg Interstitial fluid colloid osmotic pressure 1 mm Hg Total outward pressure = 36 mm Hg Total outward pressure = 18 mm Hg Influence causing water to move into of the arterial end of a capillary Influences causing water to move into of the venous end of a capillary Blood colloid osmotic pressure 26 mm Hg Blood colloid osmotic pressure 26 mm Hg The net influence is = 10 mm Hg The net influence is = 8 mm Hg out of the capillary into the capillary Values from Marieb and Hoehn (2007: 740) osmolality for solutions encountered in nursing and existing within the body is so slight that it is acceptable to use them synonymously (although the latter term is more precise). However osmotic pressure is too often used when it would be appropriate to use osmolality.the common meaning of the word pressure along with its appearance in the term osmotic pressure provokes some writers, when describing water movement in the body, to invoke forces and to describe pressures that do not exist in the body. Furthermore, as the value of osmotic pressure for body fluids may be obtained from their osmolality (by multiplying by 19.3), the term osmolality should almost always be used instead of osmotic pressure when describing the movement of water between compartments. Using a pressure unit to describe solution concentration obscures the meaning of solution concentration and should be avoided. The appropriate context in which to use the term osmotic pressure is when water is moving across a membrane as the result of the additive (or competing) influences of a difference in solution concentration and the existence of a trans-membrane pressure (where the pressure in the fluid on one side of a membrane is different to the pressure in the fluid on the other side of the membrane). Such a situation exists when water is moving into and out of blood capillaries and in extra-corporeal haemodialysis. References Bayer Corporation (1992) Multiple reagent strips for urinalysis. Package insert for MULITSTIX 10 SG (#2300) Caon M and Hickman R (2003) Human Science: Matter and Energy in the Human Body, 3rd edn, Crawford House Australia, Adelaide. Craven R and Hirnle C (2000) Fundamentals of Nursing: Human Health and Function, 3rd edn, Lippincott, Philadelphia. Crisp J and Taylor C (2005) Potter and Perry s Fundamentals of Nursing, 2nd edn, Elsevier, Sydney. Guyton A and Hall J (2006) Textbook of Medical Physiology, 11th edn, Elsevier Saunders, Philadelphia. Guyton A (1991)Textbook of Medical Physiology, 7th edn, W.B. Saunders, Philadelphia. Jenkins GW, Kemnitz CP and Tortora GJ (2007) Anatomy and Physiology: From science to life,wiley, Hoboken. Lewis S, Heitkemper M and Dirksen S (2004) Medical Surgical Nursing:Assessment and management of clinical problems, 5th edn, Mosby, St Louis. Marieb E and Hoehn K (2007) Human Anatomy and Physiology, 7th edn, Pearson Benjamin Cummins, San Francisco. Martini FH (2006) Fundamentals of Anatomy and Physiology, 7th edn, Pearson Benjamin Cummins, San Francisco. Silverthorn DU (2007) Human Physiology:An integrated approach, 4th edn, Pearson Benjamin Cummins, San Francisco. Worthley LIG (1999) Osmolar Disorders, Critical Care and Resuscitation 1: 45 54, accessed at /J1999%20(a)%20March/Osmolar%20disorders. pdf on July 19, Volume 29, Issue 1, May 2008 C N 99