Cell Volume Regulation

Hello All,

It appears that my 'speech' about not waiting too long to study worked because there were MANY more questions regarding this lecture.  I greatly appreciate that you are all getting caught up and prepared for the exam on Monday.  Below are your questions and my responses.  Note: Questions are Bolded, Answers are not.  As always, if you have additional questions please feel free to comment below or email me directly.  

For those of you who are looking to meet with me, I will be available tomorrow from 8:30am-1pm, but not available on Friday.  I realize you have a lecture-free day but it is a learning day for faculty and I will be engaged in learning (aside from spending time with you all at CTL: Cognitive Skills).  If these times do not work for you, I apologize but we will need to communicate electronically.  I will be available electronically this weekend, but you should know that if you wait until Sunday afternoon to email me there may be a chance I may not get to your questions in time to optimize your studies.  

Good luck with your studies and Good luck on Monday!

1)  By far the most common question was regarding #10 in the practice problems.  Here are a few of your questions regarding that question:

 10.  As part of an experimental study, a volunteer agrees to have 10g of mannitol injected intravenously.  After sufficient time for equilibration, blood is drawn, and the concentration of mannitol in the plasma is found to be 65 mg/100mL.  Urinalysis reveals that 10% of the mannitol had been excreted into the urine during this time period.  What is the approximate extracellular fluid volume for this volunteer?

            A.  10 L

            B.  15 L

            C.  22 L

            D.  30 L

            E.  42 L

What is the math on this problem?  Is the 10% excreted into urine not relevant?

I am having a pretty hard time with #10.  One thing is that for the equation I would need at least 3 numerical values to figure out the fourth, and there is only 2 here I believe the initial volume is missing.  Also, the second problem would be that Mannitol is used for ECF and the question says the concentration found was in the Plasma, which is only 20% of the ECF.  But I couldn't get through the first part anyways to get there.  Another thing, since 10% was excreted from the Urine would that mean that I would take off 1g from the original 10g of Mannitol? 

 

question number 10 mentioned that urinalysis reveals that 10% mannitol has been excreted. Does this have any effect on the volume of ECF in general? In this question, when I did not take the 10% into account, my answer was 15L. When I took the 10% into account, my answer was 17L which is not a huge difference. Basically, is the 10% influencing the answer to this problem?

As one of your fellow students answered this question better than even I could have I have included their mathamatical work here:

i get 13.85L as my answer, but your answer is 15L. I was wondering if your answer is rounded up. 

I calculated it by knowing that:

m1 = m2

m1 = C x V

m1/C2 = V2

10g/ .65/L = 15.35 (.1) = 13.85 L

As Indicated above, remember that mass = concentration X volume.  In this question you are given one mass (so that math is already completed for you) and the final concentration.  (YES, Mannitol is used for specifically the ECF volume, but remember that the plasma volume is PART of the ECF, so if this indicator is distributed into the whole ECF if you take a portion of the plasma and measure the concentration you will have the concentration for the entire system.)  Therefore, you take the mass injected and divide it by the concentration of the indicator after it is within the system (as shown in the math above) to get your final volume answer.

The 10% indicator loss in the urine can be dealt with by one of two ways.  You need to remove this indicator from the system because it is lost.  Therefore you can initially remove it and assume that the indicator you started with was 9g rather than 10g, or you can remove 10% at the end from the final volume (as demonstrated above).  

Following these math steps, you will come up with an answer closest to 15L (which is the correct answer).  Remember that one of the caveats of multiple choice questions is that you only have a limited choice of answers.  The precise answer you may want (in this case 13.85L or 14L) is not an option, but the answer CLOSEST to that number 15L (answer choice B) is an answer.

2)  I have a few questions regarding today's lecture. You said that TBW = ICF+ECF and that ECF is composed of

1. interstitial fluid

2. transcellular fluid

3. plasma volume

Shouldn't ECF be composed of

1. interstitial fluid

2. transcellular fluid

3. intravascular fluid which is composed of plasma volume and Hct?

I noticed this in the notes section of your lecture and wanted some clarification.  

By definition the hematocrit is actually the volume of the blood that is made up of red blood cells.  Since in this case we are talking specifically about fluids, NO the extracellular FLUID is made up of the plasma volume.  Hematocrit, pertains to the blood volume.  We did not discuss this, but is referenced in the notes, but will be covered for you in more detail during the Heme/Lymph module.

Additionally, the notes say that "transcellular fluid is the water in the space surrounded by epithelial cells" but during lecture i thought i heard you say endothelial cells. I doubt it makes a difference which cell type but wanted to know in case it comes up in a future lecture. 

I apologize if I mistakenly said endothelial cells, you are correct that it IS the water in the space surrounded by epithelial cells.

3)  I needed some clarification for questions 3 and 5. For number 3, I don't understand why Urea and not mannitol would make an RBC swell up. Is it assumed that since answer choices A, B, and C contain Chloride that the membrane is impermeable to Chloride?

For number 5, I guess I have the same question. Is the Chloride the determining factor here?

3.  A red blood cell will swell the most when it is placed in a solution containing which of the following?

  A.  100 mM CaCl2

  B.  150 mM NaCl

  C.  200 mM KCl

  D.  250 mM Urea

  E.  400 mM Mannitol

5.  A red blood cell will shrink the most when its placed in which of the following solutions?

  A.  100 mM calcium chloride

  B.  150 mM sodium chloride

  C.  200 mM potassium chloride

  D.  250 mM urea

  E.  300 mM mannitol

 

 Remember for the volume of the cells to change there must be a difference in the osmolarity between the inside of the cell and the system or solution that the cell is placed in.  For these two questions, therefore, you are being asked which solution has the lowest osmolarity and the highest osmolarity (respectively).  This is due to the fact that if the osmolarity in the solution is much lower than the osmolarity within the cell, then the water will be pulled into the cell causing it to swell.  In contrast, if the osmolarity in the solution is much higher than the osmolarity within the cell then the water will be pulled from the cell into the solution, thereby causing the cell to shrink.  Also remember, the typical cellular osmolarity of ~300 mOsmol/L (290 mOsmol/L precisely).  The answer choices here are given to you in mM (or mMol/L) so need to be converted to mOsmol/L.  Remember that inorganic salts (CaCl2, NaCl, and KCl) will separate into their ionic components.  So, for example, 100 mM CaCl2 would become 300 mOsmol/L in solution.  Urea and Mannitol do not disassociate into components as they are organic substances and therefore 250 mM Urea would be 250 mOsmol/L.  SO, which of the solutions has the lowest osmolarity and would therefore create the cell to swell the most?  The only solution with an osmolarity lower than 300mOsmol/L is Urea at 250 mOsmol/L.  Which of the solutions, therefore, has the highest osmolarity?  200 mM KCl would become 400 mOsmol/L in solution and would therefore cause the cells to shrink the most in solution.

4)  Quick question about problem 2 with Elizabeth. In problem one, we calculated ECFV = 9L and then ICFV= 37... So shouldn't the TBW be 46, not 37? (I think we have 37 as both IFC and TBW in lecture?) just wanted to clarify.

Remember that for the second Elizabeth problem we were ASKED to calculate her ICFV, but the indicator we were given was one that was able to determine her TBW, NOT her ICFV.  To determine her ICFV, we needed to remember that TBW = ECFV + ICFV; therefore we had utilized an indicator to determine her ECFV in the first question at 9L and an indicator in the second question to determine her TBW at 37L an could therefore calculate her ICFV at 28L.

5)  What is the normal extracellular fluid (plasma) and intracellular fluid (red blood cell) osmolarity? 

what is normal range for plasma osmolality?

One point to remember here is that ALL OF THESE SYSTEMS should have the same normal cellular osmolarity.  If that is not the case then water would be moving in order to correct that.  Remember, differences in osmolarity is what makes water move.  The normal cellular osmolarity of ALL cells and volume systems of the body are approximately 300 mOsmol/L (precisely 290 mOsmol/L).  This is a value that you can either choose to remember or it will be printed on your 'Normal Lab Values' document (which includes a bunch of normal human lab values for) that you are given at every exam (RUSM exams AND national licensing exams).

6)  I had a question on the slide where a patient is given Hypertonic Saline. I can't seem to grasp why is it that ICFV increases in osmolarity.  Is it because as the water rushes out of the ICF into the ECF the osmolarity increases due to the molecules left behind in comparison to the molecules of water that remain after the water in the ICF is rushing out?

As I stated above, differences in osmolarity cause water to move.  Therefore, if there is a higher osmolarity within the ECFV (in this case), the ICFV can sense that difference and water will move towards the higher osmolarity (the ECFV in this case).  Therefore, the molecules/particles that are in the ICFV do not typically move (remember that was an initial point of these slides), but the water can...so the left over molecules/particles are now left within a smaller amount of volume thereby increasing the osmolarity.

 

Also for the Hypotonic Saline, I understand how the volume of the ICFV increases due to the rushing of water. But, I don't understand why the ICFV would decrease? Is it because its relative to the amount of water molecules that are going in the ICFV (it dilutes it??) 

The exact opposite of above holds true here:  If you have the same number of molecules now submurged within a larger amount of volume, you now have a lower osmolarity (remember that osmolarity is the number of particles per volume...if either of those factors change, either number of particles OR volume, the osmolarity will change).

7)  1.  A membrane separating two compartments is permeable to urea but not permeable to NaCl (normal physiological conditions).  If compartment 1 contains 200 mmol/L of NaCl and 100 mmol/L of urea, and compartment 2 contains 100 mmol/L of NaCl and 300 mmol/L of urea, which of the following will occur?

            A.  Urea will move from compartment 1 to compartment 2

            B.  NaCl will move from compartment 1 to compartment 2

            C.  Water will move from compartment 1 to compartment 2

            D.  NaCl and Urea will move from compartment 2 to compartment 1

            E.  Water and Urea will move from compartment 2 to compartment 1

If NaCl has 2 osmols and Urea has one...then aren't the solutions iso-osmotic to each other in total particle concentration, so no "net" movement of particles? Additionally if you simply look at the molecules that are not permeable, which is NaCl...1 is hypertonic as compared to 2, so water would flow to 1 with  urea?  In these types of questions how do you know to look at the tonicity vs. the osmoality?

 Yes, exactly you must look at the tonicity AND the osmolarity.  You are correct that initially they are iso-osmotic to each other.  However, the concentration of urea is not the same in both compartments.  Therefore, as the urea has the option to move from one compartment to another, it will.   Once the urea balances between compartments there will then be a difference in osmolarity between compartments and then water will be inspired to move to balance that out.  Therefore, in the end analysis, both water AND urea will move from compartment 2 to compartment 1.

 

8) My question though just so you know what it is about, is it in regards to the osmotic pressure: and because it's function is to 'stop the net movement of water across a selectively permeable membrane', so the less permeable the membrane is for a solute, the higher the osmotic pressure. Does that mean that the osmotic pressure is actually a 'physical' thing where it prevents the water from rushing to the side of the membrane with the solutes in this case? The way that I see it as, is that because because those solutes, take for example NaCl are not permeable they will stay in one side of the membrane and pull the water towards them. But the osmotic pressure will stop the water from rushing into the compartment that contains the NaCl but there will still be movement of water, just not a rush of it. From what I just said, do I make sense? Thank you so much for your help! 

That's a great question.  In fact osmotic pressure CAN be measured as a physical entity and would in fact be the pressure needed within a system to stop the flow of water across a membrane towards solutes.  Therefore it can be thought of in terms of either the 'sucking force' that is pulling water towards solutes or the amount of pressure that would be needed to stop the water movement towards the solutes.