sameeralord said:
Hey thanks Bobze. I appreciate the help
From looking at your answer, it seems I have to go back and check on what is happening to electrolytes in acidosis. I have heard about chloride shift but not potassium shift.
This should be covered with renal physiology stuff. But, its important to remember that the response isn't limited to just cells of the nephron.
sameeralord said:
As you have mentioned earlier, why does resting membrane potential decrease when potassium moves out and H+ moves into the cell. Is the H+ buffered, so you can't consider it as a replacemet cation inside the cell.
There is simply not enough H+ to exert a major influence to balance the RMP back out. Remember the RMP is determined pretty much just by Na, K and Cl.
Also as you suggest, intracellular concentrations of non-bicarbonate buffers are high. ICF protein concentrations are around 40 mEq/L (vs ~5 extraceullarly), so what extra H+ ions are taken up are (as you suggest) buffered.
Think about it from the body's standpoint. The extracellular pH is plummeting (7.4 to 7 is a big difference for the body, alarm bells are ringing), so by taking up H+ in cells (which can be buffered better) the body can slow that decreasing pH. But we can't have our cake and eat it too, to maintain electrical neutrality you have to get rid of something in place of H+--K is the man for the job.
If they would have given you this patient's bicarb levels, they probably would have been around 5 mEq/L.
sameeralord said:
Also does the lack of water in the body, elevate concentrations of all electrolytes especially creatine.
I'm pretty sure that in ketoacidoses, the keto acids interfere with creatinine assays. The elevated creatinine in diabetic ketoacidosis (DKA) is usually exaggerated because of this. You would expect, that it is somewhat higher because of the dehydration, but I don't think most labs test sensitively enough to really tell.
For determining DKA status, you normally look at the anion gap. Which is;
[Na]-[Cl]-[HCO3]
A normal value should be below 12.
sameeralord said:
Also what about sodium potassium pump. I know for sure that insulin increases the activity of sodium potassium pump, bringing K+ into the cells.
Yes that is correct and which is why when she received insulin, the response to lowering K+ would be very fast.
sameeralord said:
Also in acidosis HPO4-2 is filtered. I'm assuming this is formed by phosphate, so as you said phosphate decreases by excretion via buffering of H+, not due to diuresis right as you have written (I think you wrote in a hurry, just to clariy). If osmotic diurisis is involved, is it the reduction in concentration of phosphat in tubular fluid due to osmotic diuresis that causes the lack of absorption.
PO4 is a "2 strikes" kind of thing. Insulin increases cellular permeability to PO4 and the decreasing ECF pH causes a shift of PO4 out of cells. So not only does your cellular concentrations of PO4 start to fall, but those cells can't take it back up as well.
Normally about 85% of PO4 should be reabsorbed in the PCT. Since the patient is acidotic though, her H+ concentration will be higher in the collecting tubules (lower pH). PO4 is a titratable acid.
**Yes I was using PO4 in place of the word phosphates, sorry laziness on my part.
To be more precise for you, you are correct HPO4-- is what is being filtered (the dibasic form) and as the pH approaches 7 in the collecting tubules it will favor the monobasic form, H2PO4-. This is not taken back up by the kidney and gets excreted.
So even though her plasma HPO4-- concentration is high, she's loosing more HPO4-- than she normally would.
This is why clinically, when you treat DKA you have to monitor their phosphate levels because (as with your example problem) they can fall too low causing the patient to become hypophosphatemic
sameeralord said:
Also why does phosphate move out, is it because so much bicarbonate is coming in, is it like choloride shift, can you explain the mechanism.
See above, I'm not sure of the exact mechanism. I gave it a quick look into in a couple of hardcore physiology and pathophysiology books and didn't get much. It might be one of those things we only know from observation and the details of the mechanism aren't all worked out yet.
The one book says "increases permeability of cells to potassium, magnesium and phosphate ions" then goes on to just discuss effects on the Na-K ATPase. The other books do a similar injustice. The mechanism of the shift, is equally unhelpfully explained--Just a mention that the shift of HPO4- out of cells occurs, no mechanism.
sameeralord said:
Does the same thing happen with creatinine, does it move out?
See above. The couple clinical and pathophys books I just looked at all say you can't take a reliable lab for creatinine during ketoacidosis. The Interpreting clinical labs text states this often leads to diabetics undergoing unnecessary evaluation for renal failure even.
sameeralord said:
Also since there is hypovolemia would this cause increased excretion of potassium and hydrogen ions due to aldosterone.
Yes, but not because the hypovolemia really. It can be important for aldo secretion, but you need large reductions to blood volume before aldo responds to changes, compared to very small changes in osmolarity which increase aldo secretion a lot.
Aldo is going to increase Na conservation, that is it's primary goal. It will increase ROMK channels in the collecting duct principle cells, but that isn't going to be able to off set the greater amount of K+ that is being shuffled from ICF space to the ECF space.
Edit to add: You're body's way of getting rid of extra acid (H+) isn't just excreting H+. You have to get rid of it through a titratable acid or ammonia. You are pretty much maxed at titratable acid secretion-Meaning you're kidneys can't concentrate it anymore than what is just coming through. So in this case, it increases because plasma concentrations of it increase and not that the kidney is super concentrating it. Increasing ammonia to get rid of the extra acid, takes a couple of days to get to its maximum level, which is done through RAS-aldo system. Aldo (like you said) acts H+, via the H-ATPase in the intercalated cells in the CD.
sameeralord said:
Also why didn't acetoacetate composition not change much, after treatment compared to b-hydroxybutyrate. I checked some google books, and most have them mentioned what you have said, so you are correct I just want to understand the mechanism behind. Thanks
??Did they give you labs for them? I think it would take a little bit for AA levels to fall off, but BHB can get gobbled up by the brain easy, so if it isn't being produced still by the liver (thanks to the insulin) then the levels should fall off pretty quick. AA on the other hand has to be used by energy for a fewer number of cell types or transferred into BHB and acetone by cells that use KBs.
