Osmolarity vs. Tonicity

Osmolarity vs. Tonicity

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We're learning about osmoregulation in AP Biology and the terms Tonicity and Osmolarity are really confusing me. I watched this video on Khanacademy to try to understand what the difference is, and from my understanding Tonicity refers to strictly two solutions (ex: you can't take a cup with water and salt in it and claim it's hyper, hypo, or iso- tonic because there's nothing to compare it to), whereas Osmolarity refers to the composition of the single solution itself.

But then my Campbell's biology textbook completely confuses me. It has the following picture and text:

… osmosis, a special case of diffusion, is the movement of water across a selectively permeable membrane. It occurs whenever two solutions separated by the membrane differ in osmotic pressure, or osmolarity (total solute concentration expressed as molarity, that is, moles of solute per liter of solution)… If two solutions separated by a selectively permeable membrane have the same osmolarity, they are said to be isoosmatic. Water molecules continually cross the membrane, but under these conditions they do so at equal rates in both directions…

And then as if to clarify, they claim that tonicity refers to "solutions of known solute concentrations"… but how does this differ from osmolarity?

You're correct that tonicity needs two solutions to define.

Osmolarity (or osmotic concentration) is the measure of solute concentration, defined as the number of osmoles of solute per litre (L) of solution (Osm/L).

Tonicity, on the other hand, refers to the relative concentration of two solutions separated by a semipermeable membrane.

The difference is based what is considered for osmosis and tonicity. In case of osmosis, it is the water (or solvent) which moves across the membrane, while tonicity depends on the solutes which cannot move across the membrane. From Wikipedia:

… osmolarity takes into account the total concentration of penetrating solutes and non-penetrating solutes, whereas tonicity takes into account the total concentration of only non-penetrating solutes.

No More Confusion: Osmosis vs. Tonicity

We have all heard the human body is 60% water and we have all heard all the jokes generated from thi s information (1). It’s more than just a joke dosing a drug depends on the amount of water in the body and that amount changes depending on age and gender. Water is able to flow freely through cells and distributes itself until the water concentration is even everywhere. The two terms we use to describe the movement of water are osmosis and tonicity. Osmosis and tonicity are often confused, but I’ll explain them in a way that you will never get them mixed up again.

Osmosis is the movement of water across a semipermeable membrane to compensate for changes in solute concentration (2). Your body needs a certain concentration of certain molecules for the body to function. Sodium, for example, needs to be at 140 millimoles per liter in your plasma (2). Plasma is the water in your blood so for every liter of blood you need 140 millimoles of sodium. Water will flow in and out of your blood vessels so that the concentration of sodium stays within range.

Let’s compare osmosis to the dodgeball. The center line is like the semipermeable membrane. The people can’t cross, but the dodgeballs can, hence semipermeable. The dodgeballs are like the water, they can freely pass into all areas of the court. The people are like sodium they have to stay in their designated area. In order for the game to work, the players need dodgeballs. The more players, the more dodgeballs. Once the game starts, both teams run up to the center line and each team gets an even number of dodgeballs. Equal players, equal dodgeballs or equal sodium, equal water. As the game progresses and one side loses players the dynamics shift. The side with more players needs more balls to throw, they want more dodgeballs. Just like if a solution has more sodium it will need more water to compensate so it will take it from another solution.

The easiest trick to osmosis is to remember that water moves from areas of low concentration to areas of high concentration. [Low] → [High] It’s all about concentration. If you know the concentration of the two solutions, you can figure out which way the water moves then you can compare the two solutions and know which is hyperosmotic and which is hypoosmotic. These terms are used to compare the two solutions. They tell us which solution has more solutes and where the water will flow.

The following diagram, Figure 1, shows the movement of water to compensate for different concentrations of sodium. In Scenario 1, solution A is hypoosmotic to solution B. In Scenario 2 solution A is isosmotic to solution B. In Scenario 3, solution A is hyperosmotic to solution B. The easiest way to remember this is to pay attention to the number of solutes in each solution.

Let’s go back to our dodgeball metaphor. At the beginning of the game, both sides have an equal number of people and usually grab an equal number of dodgeballs. This is an isosmotic solution, equivalent to Scenario 2. Equal players, equal dodgeballs or equal sodium, equal water. As the game progresses, one side has more players than the other side. If Team A has more players than Team B, Team A will want more dodgeballs. More players, more dodgeballs or more sodium, more water. That means that Team A is hyperosmotic to Team B and Team B is hypoosmotic to Team A.

Tonicity describes a solution and how that solution affects the cell volume when that cell is placed in the solution (2). Tonicity tells us if the solution has more solutes, fewer solutes or the same amount of solutes than the cell. For example, if a cell with fewer particles is put into a solution with more particles, the water will flow from the cell into the solution and the cell shrinks. The water wants to balance out the difference in concentrations and the solution is then hypertonic. On the flip side, if a cell with more particles is put into a solution with fewer particles, the water will flow from the solution into the cell and the cell swells. The solution is then hypotonic.

Blood cells are the perfect way to explain tonicity. Blood cells can swell or shrink if the plasma has a different concentration of sodium than the cell. Under normal conditions, plasma is isotonic. There is no net movement between the cell and the plasma. If the plasma is hypotonic, the red blood cells will swell and may explode (3). This can occur with dehydration. If the plasma is hypertonic, the red blood cells will shrivel (3). This can occur with too much salt in the diet or with too many carbonated drinks.

The following diagram shows how water moves for each solution. Solution A is hypotonic. Solution B is isotonic. Solution C is hypertonic. It is helpful to remember that is the solution has fewer solutes than it is hypotonic. The prefix hypo means less than or little. This is the same with hyperosmotic solutions.

Tonicity is the effective osmolality and is equal to the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane.

The key parts are effective and capacity to exert. The implication is that tonicity is less then osmolality. How much less? Its value is less then osmolality by the total concentration of the ineffective solutes it contains. Why are some solutes effective and others ineffective?

Consider this experiment: Imagine a glass U-tube which contains two sodium chloride solutions which are separated from each other by a semipermeable membrane in the middle lowest part of the U-tube (see figure below). The membrane is permeable to water only and not to the solutes (Na + and Cl - ) present. If the total particle concentration (osmolality) of Na + and Cl - on one side of the membrane was higher than the other side, water would move through the membrane from the side of lower solute concentration (or alternatively: higher H2O concentration) to the side of higher solute concentration. Water (the solvent) moves down its concentration gradient.

If the water levels were different in the two limbs of the U-tube at the start of the experiment then:

  • What would be the equilibrium situation as regards particle (ie solute) concentration on the two sides of the membrane?
  • What would the difference (if any) be in the heights of the water levels on the two sides of the membrane?
  • Is the equilibrium condition reached when the particle concentration (ie osmolality) is equal on the two sides of the membrane?

The answer to the last question is no because this neglects the probable difference in the height of the water columns in the two limbs. This height difference is a hydrostatic (or hydraulic) pressure difference and this provides an additional force which must be accounted for in the balancing of forces needed to reach an equilibrium. (An equilibrium is present when there is no net water movement across the membrane.)

The equilibrium would occur when this net hydrostatic pressure is balanced by the remaining difference in osmolality between the two solutions. This osmolality difference results in an osmotic force which tends to move the water in the opposite direction to the hydrostatic pressure gradient. Equilibrium is when these opposing forces are equal.

Now consider what would happen in the above situation if the membrane was changed to one which was freely permeable both to the water and to the ions (sodium & chloride) present. Now none of the particles present has the capacity to exert an osmotic force across the membrane. At equilibrium there is no difference in the fluid levels in the two limbs of the U-tube because the particles present will move across the membrane until the concentration gradients for Na + or Cl - are eliminated. The osmolality is now the same on both sides of the membrane. At equilibrium there will be no hydrostatic gradient either.

The conclusion is that if the membrane allows certain solutes to freely cross it, then these solutes are totally ineffective at exerting an osmotic force across this membrane and this must be corrected for when considering the particle concentrations across the membrane. Tonicity is equal to the osmolality less the concentration of these ineffective solutes and provides the correct value to use.

Osmolality is a property of a particular solution and is independent of any membrane.

Tonicity is a property of a solution in reference to a particular membrane.

It is strictly wrong to say this or that fluid is isotonic with plasma - what should be said is that the particular fluid is isotonic with plasma in reference to the cell membrane (ie the membrane should be specified.) By convention, this specification is not needed in practice as it is understood that the cell membrane is the reference membrane involved.

From a cell's viewpoint, it is net osmolar gradient across the cell membrane at any moment that is important. Tonicity (and not osmolality) is important for predicting the overall final outcome (the equilibrium state) of a change in osmolality because it allows for those solutes which will cross the membrane. All the cells in the body (with a few exceptions eg cells in the hypertonic renal medulla) are in osmotic equilibrium with each other. Movement of water across cell membranes occurs easily and rapidly and continues until intracellular and extracellular tonicities are identical. If water can cross the membrane faster than the ineffective solute can cross then the effect of an abrupt change in extracellular osmolality may be initially and temporarily different from that predicted from the acute tonicity change alone.

If a hyperosmolar solution was administered to a patient, this would tend to cause water to move out of the cell. However if the solute responsible for the hyperosmolality was also able to cross cell membranes it would enter the cell, increase intracellular osmolality and prevent this loss of intracellular fluid. This is the situation with hyperosmolality due to high urea concentrations as urea crosses cell membranes relatively easily.

Hyperglycaemia in untreated diabetics results in ECF which is both hyperosmolar and hypertonic (as compared to the normal situation) as glucose cannot easily enter cells in these circumstances. Water moves out of the cells until the osmolar gradient is abolished.

In some situations, a more operational definition of tonicity is used to explain the term: though not incorrect this explanation is less versatile and rigorous than the one discussed above. This is based on the experiment of immersing red cells in various test solutions and observing the result. If the red cells swell and rupture, the test solution is said to be hypotonic compared to normal plasma. If the red cells shrink and become crenated, the solution is said to be hypertonic.

If the red cells stay the same size, the test solution is said to be isotonic with plasma. The red cell membrane is the reference membrane. Red cells placed in normal saline (ie 0.9% saline) will not swell so normal saline is said to be isotonic. Haemolysis does not occur until the saline solution is less then 0.5%. The point about this definition of tonicity is that it is qualitative and not quantitative. It does imply that permeant solutes will be ineffective because it is essentially a test against a real membrane.

A major physiology text (Ganong 16th ed., 1993) defines tonicity as a term used to describe the osmolality of a solution relative to plasma (as in hypotonic, isotonic or hypertonic). This less rigorous definition is wrong as it does not cover the full sense in which the term tonicity is used. Ganong argues that an infusion of 5% dextrose is initially isotonic but that when the glucose is taken up and metabolised by cells, the overall effect is of infusing a hypotonic solution. This is really a problem with his definition. More correctly, one would say that the 5% dextrose is initially isosmolar with plasma (and this avoids haemolysis). Glucose is a permeant solute in the non-diabetic and can easily enter cells. When infused, the 5% dextrose is very hypotonic (with reference to the cell membrane) despite being isosmolar. Water does not leave the cells initially (and haemolysis does not occur) because there is no osmolar gradient across the cell membrane. The solution is however hypotonic and when the glucose enters cells water does also. If insulin is not present, this movement of glucose does not occur. In this latter case, the solution is isosmolar before infusion and can be considered isotonic after infusion as well.

The particular problem with this definition is that it does not distinguish tonicity from osmolality as it makes no recognition of whether the available solutes are permeant (and thus 'ineffective') or non-permeant (and thus 'effective') with respect to a particular membrane as in the example of the 5% glucose which is isosmolar but hypotonic. The definition really doesn't add much more then could be achieved by the terms hypo- and hyper-osmolality. Of course, the referencing to actual plasma osmolality means this definition is effectively the same as the 'red cell test' definition, while obscuring the fact that tonicity is referenced to the cell membrane.

Note that tonicity is defined in several ways which don't all have exactly the same meaning. This is confusing. The definition based on tonicity as the effective osmolality is best.

  • Effective osmolality - The best definition as it accounts for permeant solutes and is quantitative.
  • The red cell test - A practical qualitative definition that emphasises the requirement that tonicity is defined in reference to a membrane.
  • Comparison with osmolality of plasma - Does not account for permeant solutes, and not quantitative.

A final point here regarding the meaning of the term "osmotic pressure".

Consider again the U-tube experiment but pure water on one side and a test solution of unknown osmolality on the other side of a semipermeable membrane which is permeable only to water. Water will move into the test solution. What would happen if further amounts of the test solution were added before any movement of water had occurred? An equilibrium situation would be reached at which the hydrostatic pressure (ie difference in fluid heights in the two limbs of the U-tube) on the test solution side of the membrane would balance the osmotic tendency for water to move across the membrane into the test solution.

At this equilibrium point, the hydrostatic pressure is a measure of the osmotic tendency in the test solution: indeed the opposing hydrostatic pressure needed to balance the osmotic forces is usually referred to as the osmotic pressure.

There would be practical difficulties in performing this experiment with body fluids as the test solution as the osmotic pressure to be measured is over 7 atmospheres and an extremely long-limbed U-tube would be necessary! Alternatively, the pressure could be supplied from a piston or a compressed gas source rather than a column of fluid.

Osmosis: Osmolarity, Osmotic Pressure and Tonicity

Practice: An undergraduate playing around in lab combines 1 L of pure water, 150 mmols of glucose, and 150 mmols of KCl. Assuming complete dissociation, which of the following is the osmolarity of the resulting solution?

Practice: Filtrate inside of the nephron (part of the kidney) has an osmolarity of 500 mOsM. Fluid outside of the nephron has an osmolarity of 750 mOsM. Which of the following describes the fluid inside of the nephron relative to the fluid outside of the nephron.

Practice: Filtrate inside of the nephron (part of the kidney) has an osmolarity of 500 mOsM. Fluid outside of the nephron has an osmolarity of 750 mOsM. Assume that water can move between the compartments, but solute cannot. Which compartment is hypertonic, and what is going to happen to the volume of that compartment?

Practice: The cytosol of red blood cells is approximately 300 mOsM, mostly from NaCl. You place the RBC in a extracellular solution of 600 mM sucrose. RBC membranes are not permeable to NaCl or sucrose. Circle the answer.

a. Which solution is hyperosmotic? ( Cytosol / Extracellular Solution )

b. Which solution has a higher osmotic pressure? ( Cytosol / Extracellular Solution )

c. Which direction will water move? ( Toward Cytosol / Toward Extracellular Solution )

Isosmotic is not always isotonic: the five-minute version

Address for reprint requests and other correspondence: D. U. Silverthorn, Dept. of Medical Education, Dell Medical School, Univ. of Texas at Austin, 1501 Red River St., Austin, TX 78712 (e-mail: [email protected] ).

what is the difference between osmolarity and tonicity? Recently, I was tasked with explaining this in 5 min at the 2016 annual meeting of the Human Anatomy and Physiology Society (HAPS). The HAPS conference now highlights a new presentation session called Synapse, which is run PechaKucha-style (4) with automatically advancing slides. The theme this year was “You thought you knew X, but really . . .”. As I worked on my talk, I realized that we often try to teach this complicated subject without putting it into a memorable context. So here is the 5-min version explaining why isosmotic is not always isotonic. The PowerPoint slides are available as Supplemental Material on the Advances in Physiology Education web site and appended to this Illuminations article.

Slide 1.

Omolarity is not the same as tonicity. Both terms describe solutions, but the similarity ends there. Osmolarity is concentration expressed in units of solute/volume. It can be measured on a machine called an osmometer, and it has units, usually osmoles or milliosmoles per liter (osmolality is expressed using kilograms of water instead of liters).

Slide 2.

Tonicity is a behavioral term. It describes what a solution would do to a cell's volume at equilibrium if the cell was placed in the solution. A cell placed in a hypotonic solution will gain volume and swell. A cell placed in a hypertonic solution will lose volume and shrink. Tonicity cannot be measured on an osmometer, and it has no units. It tells what effect a solution has on a cell, and it depends both on the osmolarity of the solution and on whether or not solutes in the solution can enter the cell (i.e., are they penetrating?).

Slide 3.

Why do we care about the difference between osmolarity and tonicity? We care because understanding tonicity is the basis for intravenous (iv) fluid therapy, and administering the wrong iv solution to patients can harm or even kill them. Unfortunately, many easily accessed resources attempting to explain osmolarity and tonicity are either wrong or so vague that they create misunderstanding. Let's look at some examples.

Slide 4.

“Tonicity is the relative concentration of solutions that determine the direction and extent of diffusion” (5).

“Tonicity: . . . is related to the number of particles found in solution. Osmolarity is most often used when referring to blood, and tonicity is most often used when referring to iv fluid, but the terms may be used interchangeably” (1).

“Isotonic solution: a solution that has the same salt concentration as cells and blood” (2).

“When two environments are isotonic, the total molar concentration of dissolved solutes is the same in both of them” (3).

Slide 5.

Let's look at the osmolarity and tonicity of two of the most commonly used iv solutions: normal saline (or 0.9% NaCl) and D-5-W [or 5% dextrose (glucose)] in water. If we measure their concentrations on an osmometer, we find that they are both 278 mOsmol/l, so they are isosmotic.

But if we administer them to a person by an iv infusion, we find that normal saline is isotonic because NaCl does not enter cells, whereas D-5-W is hypotonic because glucose goes into cells. Here is an important example of when isosmotic is not isotonic.

Slide 6.

How can you explain this difference in tonicity to students? One way is to have them remember blood glucose homeostasis. If you give someone an iv of glucose solution, such as D-5-W, over time all of the glucose you gave them will go into cells. As glucose enters cells, the movement of solute from the extracellular fluid into the cells causes water to follow by osmosis. The cell gains volume, so the solution is hypotonic.

But the story doesn't stop there. Glucose inside the cell is metabolized by aerobic respiration with the end products of CO2 and water. So the end result of giving a D-5-W solution is the same as if you gave the person pure water.

Slide 7.

The bottom line: isosmotic solutions are not always isotonic. Hyperosmotic solutions are not always hypertonic. But hyposmotic solutions are always hypotonic.

The response to this rapid fire presentation of osmolarity and tonicity was overwhelmingly positive. It also brought a few questions that require additional explanation.

Is the tonicity of a solution always the same? No, it depends what cell you are comparing with the solution. An isosmotic solution of sucrose will be isotonic to a mammalian cell because mammals do not have transporters for sucrose, and sucrose cannot enter the cell. On the other hand, plant cells do have sucrose transporters, so an isosmotic sucrose solution will be hypotonic to the plant cell.

What determines the tonicity of a solution? The tonicity is determined by comparing the concentration of nonpenetrating solutes, those that cannot enter the cell, in the solution to the concentration of the cell. If the solution has a lower concentration of nonpenetrating solutes than the cell does, then there will be net movement of water into the cell at equilibrium and the solution is hypotonic. A solution of 5% dextrose has zero nonpenetrating solutes, and therefore, it is hypotonic.

How can a hyperosmotic solution be hypotonic? Tonicity depends only on the concentration of nonpenetrating solutes, so any solution of pure glucose will be hypotonic, no matter what its osmolarity, and tonicity describes only the change in cell volume at equilibrium. Water crosses cell membranes faster than solutes do, so a cell placed in a hyperosmotic but hypotonic solution of 10% dextrose will initially lose volume as water leaves and then start regaining volume as glucose is transported into the cell and water follows by osmosis. Using the rule of nonpenetrating solutes, at equilibrium the cell will have gained volume, and the 10% dextrose solution is hypotonic.

Using the presentation.

I have not yet tried this PechaKucha style of presentation in my teaching, although I have used many of the slides from the presentation with my classes. The novelty in this approach is tying together the concepts of hypotonic glucose solutions, blood glucose homeostasis, and glucose metabolism. Students do not usually have trouble with the latter two concepts, so it is my hope that by linking them with iv fluids, it will help students expand their understanding of osmolarity and tonicity beyond red blood cells shrinking and swelling.

This fall, I plan to add the presentation to my classroom teaching. I expect my students to read and take a preclass reading quiz prior to coming to class, so it will be easy to check their comprehension using a classroom response system. I am hopeful that their responses will be similar to that of an undergraduate nursing student at the HAPS meeting who told me, “That made it so clear! I never really understood tonicity before.”

Big Mechanisms of Information Flow in Cellular Systems in Response to Environmental Stress Signals via System Identification and Data Mining

Bor-Sen Chen , Cheng-Wei Li , in Big Mechanisms in Systems Biology , 2017

The specific protective mechanism in response to sorbitol osmotic stress signal

At high osmolarity , two branches of the HOG pathway, the SHO1 branch and the SLN1 branch, are observed to sense osmotic changes and rapidly make internal adjustments. In Fig. 6.10 , sorbitol osmotic stress is shown to have many more mutual interactions and feedforward loops in the HOG pathway than hypo-osmotic stress ( Fig. 6.9 ). The connections may make pathways more rapid and more robust (acting against external noise) in response to sorbitol osmotic stress.

According to Table 6.2B , the new found proteins are the 12 proteins (highlighted by gray color) which interact with a significant number (>5) of preselected proteins. The 12 proteins are grouped and will be discussed in the following paragraphs based on the research shown in Table 6.2B .

Two proteins, namely WSC3 and SPA2, are the new found proteins which are known as members of the cell-wall integrity pathway. WSC3 is involved in the maintenance of cell wall integrity [82] , while SPA2 acts as a scaffold protein for MKK1 and MPK1 [64] . In addition, BEM4 is probably involved in the RHO1-mediating signaling pathway [78] . BEM4 is functionally relevant to RHO1 and should play a novel role in the signaling pathway mediated by RHO1. One possible role of BEM4 is to act like chaperone in the stabilizing or folding of RHO1. According to the cell-wall integrity pathway shown in Fig. 6.10 , we suggest that RHO1, PKC1, and SLT2 may play important roles in the inactive cell-wall integrity pathway under sorbitol osmotic stress.

In the pheromone response pathway, four proteins, including GPA1, SST2, FAR1, and GIC2, are the new found proteins as shown in Table 6.2B . GIC2, whose function is still unknown, can interact with CDC42, and therefore GIC2 is grouped with the pheromone response pathway and the SHO1 branch of the HOG pathway [79] . GPA1, a Gα subunit, has been involved in mediating pheromone response pathway [64,80] . SST2 is required to prevent receptor-independent signaling of the pheromone response pathway [81] . Additionally, Far1 is a cell cycle arrest mediator [76] .

In the SLN1 branch of the HOG pathway, SKN7 and NBP2 are new found proteins participating in this important pathway under sorbitol osmotic stress. SLN1-YPD1-SKN7 has been proven to act as a phosphorelay system that turns on the HOG pathway until the yeast suffers from cell shrinking ( Fig. 6.10 ) [37,64] . In addition, SKN7 appears to have different functions, such as acting as a transcription factor or a protein in signaling systems, not only mediating different stresses but also linking the cell-wall integrity pathway to the HOG pathway mediated by interacting directly with RHO1 ( Fig. 6.7 ). During yeast adaptation, NBP2 is predicted to act as an adapter, recruiting PTC1 to the PBS2-HOG1 complex in the PTC1 inactivation of HOG1. We suggest that the activated HOG pathway under sorbitol osmotic stress is due to the unbound NBP2-PBS2 complex which results in HOG1 which cannot be inactivated by PTC1 [75] .

In the SHO1 branch of the HOG pathway, the new found proteins OCH1, SKM1, and RGA1 are probably important in response to high osmolarity. The promoter of OCH1, which encodes a mannosyltransferase, responds to the presence of SLN1, and KSS1 is activated by the mutation of OCH1 [64] . Therefore, we suggest that OCH1 participates in the SHO1 branch of the HOG pathway under sorbitol osmotic stress. SKM1, which is similar to STE20 and CLA4, is probably a downstream effector of CDC42, but the function of SKM1 is still unclear [37] . According to [92] , CDC42 may promote the phosphorylation of GIC2 by recruiting STE20 and SKM1. Therefore, we suggest that SKM1 is a member of the SHO1 branch of the HOG pathway under sorbitol osmotic stress. RGA1 is suggested as a link between CDC42 and pheromone pathway components [83] ( Fig. 6.7 ). Although the 12 new found proteins are probably important in response to sorbitol osmotic stress, most of them, such as BEM4, GIC2, FAR1, OCH1, SKM1, and RGA1, are functionally unclear, and likely even participate in multiple pathways with complicated roles. We can only infer some possible protective mechanisms according to previous studies and these results.

Guide To Intravenous Fluids

This page is dedicated to providing a comprehensive resource that covers the topic of intravenous fluids that are commonly used in medicine. A related but distinct topic is the page dedicated to managing electrolytes.

Having an important guide to covering the topic of IV fluids can be important (source)


Before discussing specific IV fluids, it is important to try and appreciate the different compartments within the body that store fluid. The initial branching point is to discuss intracellular vs. extracellular fluids.

This figure provides a general overview of where the fluid in the body is stored (source)

Intracellular Fluid (ICF):

two thirds) of the total body water is present within cells. The principal ICF cation is potassium (K+).

Extracellular Fluid (ECF):

A significant portion of the body’s fluid is present outside of cells. The principal ECF cation is sodium (Na+). ECF fluid can either be intravascular or interstitial. Oncotic pressure and hydrostatic pressure dictate the movement of fluid between these two ECF spaces.

Interstitial ECF:

80% of the ECF is present in the interstitial spaces of the patient.

Intravascular ECF:

20%of the ECF is intravascular (in the plasma of the patient).

    The veins contain


Often when discussing the topic of IV fluids the terms tonicity, osmolarity, and osmolality can become confusing! They are each defined clearly below:

This term refers to the measure of the solute concentration per unit VOLUME of solvent.

This term refers to the measure of the solute concentration per unit MASS of the solvent.

This term is the measure of the osmotic pressure gradient between two solutions. Unlike osmolarity IT IS ONLY INFLUENCED BY SOLUTES THAT CANNOT CROSS THE SEMIPERMEABLE MEMBRANE BETWEEN THE SOLUTIONS. It is for this reason that you can have two solutions that have the same osmolarity (iso-osmolar) but have different tonicities (they are not isotonic because of the nature of the solutes they contain).

A perfect example of a solute that will not contribute to the tonicity is dextrose because it can so easily penetrate cell walls and move between fluid compartments of the body. It is for this reason that 5% dextrose in water, when infused, is iso-osmolar with body fluid compartments (

300 mOsm/L) but is also hypotonic.

Urea is another example of a solute that does not contribute to tonicity.

A Comparative Study of Osmolarity Vs. Osmolality Vs. Tonicity

There is a lot of confusion between the terms osmolarity, osmolality, and tonicity, which are incorrectly interchanged. This ScienceStruck post explains these terms by telling you the differences between them along with examples, and how to calculate them.

There is a lot of confusion between the terms osmolarity, osmolality, and tonicity, which are incorrectly interchanged. This ScienceStruck post explains these terms by telling you the differences between them along with examples, and how to calculate them.

Did You Know?

The terms osmolarity and osmolality can be freely interchanged when dealing with human physiology. The former deals with 1 liter of solution, while the latter involves 1 kilogram of solvent. In the human body, this ‘solution’ is plasma which, being dilute, is almost similar to water, which is the ‘solvent’. Also, 1 liter of water weighs 1 kilogram.

When two solutions of different concentrations are separated by a semipermeable membrane, then the solvent molecules pass from the dilute solution to the concentrated one across the membrane. This happens until both the solutions are of equal concentrations. This process is called osmosis, and examples of membranes across which it can occur are lipid bilayers, polyamide membranes, and even plasma membranes of human cells.

When it occurs in human cells, osmosis can have important repercussions. It can cause red blood cells to swell and burst, called hemolysis, or in other cases, cause them to shrink and contract. However, the human body is equipped with a range of inbuilt mechanisms to prevent such mishaps, and maintain osmotic stability called homeostasis.

To maintain such stability, the body uses a phenomenon called osmotic pressure. It is the minimum pressure that must be applied to prevent the flow of solvent across a semipermeable membrane. Basically, it means that a solution with high osmotic pressure will attract more solvent towards it. This term can be better explained using the concepts of osmolarity and osmolality, which deal with the number of solute particles, while tonicity helps us to understand the effect of such solutes on cells. The difference between osmolarity, osmolality, and tonicity are further explained below.


Osmolarity is a method used to depict the concentration of an osmotic solution. It is defined as the number of osmoles of a solute in one liter of solution. The term ‘osmoles’ represents the number of particles of solute in the solution. These particles may be molecules or ions, depending on whether the solution dissociates or not.

In general, the formula of osmolarity for a solution with one type of solute is:

Osmolarity = Number of moles in one liter × Number of osmotically active particles per mole

For example, the osmolarity of 1 mole of NaCl is 2 osmoles per liter. This is because NaCl splits up into two ions, Na+ and Cl-, which are its osmoles. The osmolarity of 1 mole of glucose is 1 osmole per liter, because glucose being non-ionic does not split, and thus, 1 mole represents only 1 osmole.

Osmolarity is a colligative property, which means that it depends on the number of particles dissolved in solution, and not their weight. Since the volume occupied by both the solute particles and the solvent in solution changes with change in temperature, the osmolarity can be difficult to determine. Its unit is osmol/L or Osm/L.

Based on their osmolarity, solutions can be divided into:

Hyperosmotic: A solution that has a higher number of osmoles per liter than another is said to be hyperosmotic to it.

Hyposmotic: A solution that has a lower number of osmoles per liter than another is said to be hyposmotic to it.

Isosmotic: Two solutions that have the same number of osmoles per liter are said to be isosmotic to each other.


Osmolality is used to display the concentration of an osmotic solution based on the number of particles, with respect to the weight of the solvent. More specifically, it is the number of osmoles in each kilogram of solvent. Thus, it shows the variation between the solute and solvent in a better fashion.

Since the weight of the solvent does not change with temperature, osmolality is preferred over osmolarity in clinical applications, and also because the patient’s fluid volume is more difficult to determine than his weight.

The unit of osmolality is osmol/kg or Osm/kg. Since human blood plasma contains an excess of sodium ions, its osmolality formula is:

Plasma Osmolality * = 2 × sodium level
* When glucose level is in control.

While calculating osmolality, only the weight of the solvent is considered, while in osmolarity, the volume of both the solute and the solvent are taken into account. This is why the value of the latter is slightly lesser than the former. The body fluids are mostly composed of water, and the weight of one liter of water is roughly equal to one kilogram. Therefore, the terms osmolarity and osmolality are freely interchanged in human physiology. The osmolarity and osmolarity of human body fluids is in the range of 270 to 300 mOsm/L or mOsm/kg, respectively.


Tonicity is the osmolality of a solution with reference to a semipermeable membrane. It is the concentration of those solute particles, which cannot pass through, i.e., are impermeable to a given membrane. Thus, tonicity not only depends on the properties of the solute, but it also depends on the properties of the membrane in question. Tonicity is also defined as the relative concentration of a solution outside a cell with respect to the concentration inside it.

When a solution contains a mixture of permeable and impermeable solutes, then tonicity deals with only those solutes that do not pass through the membrane, while the rest that pass through are not considered. Since impermeable sodium ions are the major osmoles in an extracellular fluid, tonicity is effectively equal to the osmolality of all body cells.

Unlike osmolarity or osmolality, tonicity does not have any units. It is calculated by the formula:

Fluid Tonicity = 2 × sodium level of plasma

Depending on their tonicity, solutions are of three types:

Hypertonic: When the tonicity of the solution outside the membrane is higher than that of the solution inside, the solution is hypertonic. A cell placed in a hypertonic medium will lose water across its plasma membrane and shrink.

Hypotonic: When the tonicity of the solution outside the membrane is lesser than that inside, the solution is hypotonic. A cell placed in a hypotonic medium will gain water across its plasma membrane and swell up, causing it to burst.

Isotonic: When the tonicity of both solutions is equal to each other, the solutions are said to be isotonic. Cells placed in an isotonic medium will not be damaged in any way.

While osmolarity includes both concentrations, i.e., that of the solutes which cross the membrane and those that don’t, tonicity is only restricted to those that don’t. So, if a solution contains only non-penetrating solutes, then a hyperosmotic solution will also be hypertonic, a hyposmotic one will be hypotonic, and an isosmotic one will be isotonic, with regard to a cell. However, this is not true in other cases.

For example, a solution of 150 mM (millimolar) NaCl will be isosmotic to a cell because its osmolarity is 300 mM, equal to that of body fluids. It is also isotonic because Na+ ions are impermeable to cell membranes. However, a solution of 300 mM urea, while being isosmotic, is not isotonic because urea can permeate the cell membrane.

To conclude, it can be said that while osmolarity and osmolality are concentrations of individual solutions, tonicity deals with the interaction between two solutions across a semipermeable membrane. Tonicity helps understand whether a cell exposed to osmotic pressure will swell, shrink, or remain of the same size.

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Using IV Fluid Therapy to Teach the Principles of Osmolarity & Tonicity

There is considerable confusion in parts of the medical community about the differences between osmolarity and tonicity. Many instructional resources, ranging from introductory biology texts to commercial continuing education courses for nurses, confuse osmolarity and tonicity. If health care professionals are to treat fluid balance disorders appropriately, they must understand how intravenous fluid solutions distribute among body compartments and how they may cause transient fluid shifts between compartments on the way to equilibrium. The goal of this resource is to give students a conceptual understanding of the differences between osmolarity and tonicity so that they can make scientifically based decisions about appropriate solutions for intravenous fluid therapy. This is done through the use of an Instructor's Guide and content contained in a Word document. These materials have been used with upper division undergraduate students for more than 10 years. They often report that when they go on to medical school, they are able to teach the concepts to their peers.

Copyright & Permissions

© 2010 Silverthorn. This is an open-access publication distributed under the terms of the Creative Commons Attribution-NonCommercial-Share Alike license.

When the osmotic pressure of the solution outside the blood cells higher than the osmotic pressure inside the red blood cells, the solution is hypertonic. The water inside the blood cells exits the cells in an attempt to equalize the osmotic pressure, causing the cells to shrink or create.

When the osmotic pressure outside the red blood cells is the same as the pressure inside the cells, the solution is isotonic with respect to the cytoplasm. This is the usual condition of red blood cells in plasma.

Watch the video: Tonicity u0026 Osmolarity (July 2022).


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