Tonicity, Osmoticity , Osmolarity , & Osmolality

1. Tonicity, Osmoticity, Osmolarity, & Osmolality

2. How to get an A and grasp this concept! • Know the differences between osmosis and diffusion • Know page 171 in your calculations book, backwards and forward • Instead of “plugging and chugging” actually understand where the equations come from and what they are giving you • Understand why this concept is important. You WILL see it again in other classes whether you realize it or not (i.e. major drug classes revolve around this concept, such as diuretics)

3. How to get an A and grasp this concept! • Understand the difference between hypertonic, hypotonic, and isotonic and how it affects cells • Remember to double check your work. • An eraser costs 10 cents, a mistake can cost you millions and your pharmacy license!

4. Basic Concept: Osmosis and Diffusion

5. Basic Concept: Osmosis and Diffusion • Osmosis is the passage of WATER from an area of high concentration to an area of low concentration through a partially permeable membrane • Diffusion is the passage of molecules from an area of high concentration to an area of lower concentration

6. Basic Concept: Osmosis and Diffusion • In the previous example, osmosis occurs because the membrane is NOT PERMEABLE to the sugar molecules but is permeable to the water. • If there was a completely permeable membrane, the water would move to the left and the sugar molecules would move to the right until EQUAL concentrations of each were on both sides

7. Basic Concept: Osmotic Pressure • The pressure required to prevent solvent from passing through a semipermeable membrane from a region of higher concentration of solute to a region of lower concentration of solute.

8. Osmosis and Diffusion: Application to real life • What does all this have to do with pharmacy? • Believe it or not, all cells are semi-permeable • Thus, they allow some stuff to pass while inhibiting others from passing • This occurs through various processes, such as active diffusion, passive diffusion, etc. • The concept we need to understand is that cells will behave differently based on what solution they are in because water can move by way of osmosis

9. Osmosis and Diffusion: Application to real life • Say we have a human cell that contains 10% (THIS IS A CONCENTRATION) NaCl within its cell membrane. • There are basically 3 different solutions we can place it in • There are solutions that are more concentrated • There are solutions that are less concentrated • There are solutions that are the same concentration

10. Osmosis and Diffusion: Application to real life • If we placed the cell in the previous slide in a solution that contains the same concentration of NaCl then there would be no net movement of water because the cell is at “equlibrium” • When this occurs, the solution is said to be isotonic • Note that even though there is no net movement of water, water still goes back and forth

11. Osmosis and Diffusion: Application to real life • What would happen if we placed a cell with 20% NaCl in a solution that only had 10% NaCl?

12. Osmosis and Diffusion: Application to real life • In this situation, the cell is MORE CONCENTRATED with solute particles than the solution (i.e. the outside of the cell has more WATER per unit volume) • Remember, water moves from an area of high concentration to low concentration • Thus, water will move into the cell • This type of solution is called Hypotonic

13. Osmosis and Diffusion: Application to real life • What if the solution contained a higher concentration of solute (NaCl)?

14. Application to life: One step further • Instead of a regular cell, let’s see what would happen with a red blood cell!

15. Application to life: One step further • When a red blood cell is placed in an isotonic solution nothing happens • When a red blood cell is placed is a hypertonic solution the cell begins to shrink as water goes out of the cell, a process called CRENATION • When a red blood cell is placed in a hypotonic solution the cell begins to swell and burst, a process called lysis (hemolysis)

16. One more step further • Knowing what you know now, explain what would happen in the following situations • Applying 5% NaCleyedrops to the eye given that the “concentration” of the eye is 0.9% • Commercially available as Muro 128 ® eyedrops • Swallowing mannitol which is a nonelectrolyte that behaves like NaCl and is impermeable to the intestines • Hold your pee for a Wii®!!!

17. Important Note • Remember, osmotic pressure that is produced on either side of a membrane is related to the number of particles the solute produces, not just the concentration. • i.e. A cell placed in a 10% solution of KCl will behave differently than a cell placed is a solution of 10% NaCl because of Osmolarity of the different molecules • Explained in detail later

18. Basic Concept: Electrolyte vs. Nonelectrolyte • An electrolyte is a molecule that dissociates into solution and conducts current due to a charge on the molecule • Examples include NaCl, KCl, etc. • When an electrolyte is placed in a solution, it produces 1 Osmol for every particle that dissociates (assuming 1 molecular weight) • NaCl Example • A nonelectrolyte doesn’t dissociate when placed in solution • Examples include Dextrose, Boric Acid, Mannitol • When an electrolyte is placed in a solution, it only produces 1 Osmol (assuming 1 molecular weight) • Dextrose Example

19. Basic Concept: Molecular weight and other measures • The molecular weight and the "electrolyte status” of a molecule gives us a bunch of information • Know that 1 Osmol is the amount of a solute that will provide 1 Avagadro’s Number of particles • Based on this information, we can deduce that if we have a solution of 1 molar dextrose and 1 molar NaCl that the NaCl solution would have more particles because it gives 2 Osmol per mole

20. Understanding the differences between substances • Suppose in the below diagram we had 58.5 g (1 mole) of NaCl on the left side of the semi-permeable membrane and on the right side we had 61.8 g (1 mole) of Boric acid • Which way would the water move? Why?

21. Understanding the differences between substances • With only knowing the fact that NaCl is an electrolyte and Boric Acid is a nonelectrolyte and that we have 1 molecular weight of each we can tell that the NaCl side would have more particles • Thus, water would move into the NaCl compartment

22. Understanding the differences between substances • Suppose in the below diagram we had 10% NaCl on the left side and 10% KCl on the right side (assume equal volume of solution on each side) • Which way would the water move?

23. Understanding the differences between substances • In the example, we have to take into consideration the molecular weights and Osmolarity of the two substances. • The MW of NaCl is 58.5 g which provides 2 Osmol, thus in a 10% solution we would only have 0.1709 moles or 0.3418 Osmol • The MW of KCl is 75 g which provides 2 Osmol, thus in a 10% solution we would only have 0.1333 moles or 0.2666 Osmol • Based on this we can see that there would be more particles on the NaCl side and thus water would move into the NaCl compartment

24. Understanding the differences between substances • Suppose we had 0.1 molar solutions of two different nonelectrolytes, say dextrose and boric acid, in the below diagram • Which way would water move?

25. Understanding the differences between substances • Because there are an equal number of moles of two nonelectrolytes, and thus the same number of particles, the net movement of water will be zero!

26. Homework! • Look up NORMALITY and know how it would come into play in the above scenarios (i.e. 1N NaCl on one side and 1N KCl on one side)

27. A side note on particle number • How many Osmol would 1 mole of CaCl2 provide in solution?

28. What’s the purpose of all this? • The whole idea is to be able to make a solution that will either be isotonic, hypertonic, or hypotonic with body fluids in order to get the effects we want. • For example, if we want to give someone fluid to prevent dehydration we want it to be isotonic with the blood so we won’t hurt the red blood cells. • Or if we want to make someone have a bowel movement we want to make the inside of the intestines Hypertonic so water will come into the intestines and produce a bowel movement

29. Colligative properties • Colligative properties are properties of solutions that depend on the number of molecules in a given volume of solvent and not on the properties (e.g. size or mass) of the molecules • There are 4 colligative properties: Boiling point, Freezing point, Vapor Pressure, and Osmotic Pressure • To understand how each of these behave, let’s talk about salt.

30. Colligative properties continued • Thus, when we add salt to a pot of water 4 things happen: • The vapor pressure goes down • The osmotic pressure goes up • The boiling points goes up • The freezing point goes down • To help you remember this, just keep in mind:

31. Colligative properties continued • Of the properties, we will be using the freezing point for class purposes • When you add exactly 1 mole of a nonelectrolyte to water it brings the freezing point down to -1.86 degrees celcius • What do you think would happen if we added 1 mole of an electrolyte? • Would it bring it down even further (depress it) or raise it further?

32. Colligative properties continued • If we add an electrolyte, it will depress it even further depending on how much the molecule dissociates in solution (i.e. creates more particles) • This brings us to the concept of the “i value” • Is a proportionality constant that relates number of particles to freezing point depression • We determine this value based on the assumption that electrolytes, with a few exceptions, dissociate at 80% in solution

33. Colligative properties continued • How to calculate NaCl Value • How to calculate KCl Value • How to calculate CaCl2 value • Exceptions (Zinc Sulfate)

34. The body’s freezing point • Based on the concentration of different solutes in our blood and bodily fluids, it has been found that we will freeze at -0.52 degrees Celsius • Walt-Disney! • If we know that a 1 molar solution of NaCl freezes at 1.8 * -1.86 degrees Celsius then we can determine what molar solution of NaCl freezes at -0.52 degrees Celsius • Thus, it will be isotonic with body fluids

35. Equation number 1! Mole in gL-1.= - 1.86oC*i XgL-1. - 0.52oC

36. Standard Calculations • Now we are able to calculate what percent solution of different solutes are isotonic with bodily fluids • NaCl • Dextrose • Boric Acid • KNO3

37. Standard Calculations • Note: There is a difference between something that is isotonic and isoosmotic! • Isoosmotic => Same number of Osmoles • Isotonic=> Physiological compatability

38. Standard Calculations • What’s the difference between 1 mole of NaCl and 1 mole of KCl? • What’s the deal with Boric Acid? • IS ISO-OSMOTIC WITH BOTH BLOOD & LACRIMAL FLUID BUT ONLY ISOTONIC WITH LACRIMAL FLUID

39. Standard Calculations • True or False: Everything that is isotonic is isoosmotic. • True or False: Everything that is isoosmotic is isotonic.

40. Methods for making something isotonic • There are three different ways to calculate how to make something isotonic • The “D” Method, or depression method • The “E” Method, or equivalent method • The “V” Method, or volume method

41. The “D” Method • You’re working in a compounding pharmacy when you receive the following prescription from Dr. Saber Samaan: Rx NaphazolineHCl 0.02% [247 ,2] Zinc sulfate 0.25% Purified water qs 30 mL Mft Isotonic solution

42. Freezing Point “D”epressionExplaination • With the D method, you are seeing how much each drug required of the prescription depresses the freezing point towards -0.52 degrees celsius. You will then make up the difference with NaCl or whatever other agent the prescription calls for to make it isotonic!

43. Freezing Point “D”epression • The first step is to calculate how much NaCl would be needed to make the volume of the prescription isotonic! • It’s a simple proportion from the 0.9% reference we already know • If 0.9 grams will make 100 mL isotonic, how many grams will make 30 mL isotonic?

44. FREEZING POINT “D”EPRESSION NaphazolineHCl 247gL-1 = - 1.86oC*1.8 0.2gL-1 - XoC - 0.0027oC

45. FREEZING POINT “D”EPRESSION ZnSO4 288gL-1 = - 1.86oC*1.4 2.5gL-1 - XoC 0.0226 oC

46. Total depression 0.0027oC +0.0226oC 0.0253 oC

47. Subtracte actual solution freezing depresion contribution from the reference isotonic solution. = -0.52-(-0.0253) = 0.4947 oC

48. NaCl needed to fil the 0.4947oC gap. 270 mg 0.52oC Xmg 0.4947oC 256.8 mg NaCl

49. The “E”quivalent Method • The “E” method is a littler different • Here, we are basically seeing how much NaCl produces the same osmotic effect as 1 gram of the drug! • In essence, we are “converting” the drugs in the prescription to its NaCl equivalent • In order to do so we have to take into account the drugs i value and molecular weight

50. The “E”quivalent Method • The first step here is the same as the first step in the D method