RBC Crenellation in High ADH Levels: Mechanisms & Effects

[mtc1973]

Okay - I haven't had time to look this up so any quick response appreciated.

Does a RBC become severely crenallated during its passage through the vasa recta in an individual with high levels of ADH?

The answer must be yes - but what protective mechanisms are there - or does it not matter much? Can't find much in the literature about it atall!

 

[mtc1973]

bump - i still haven't found this discussed in the literature - how odd!

Come on bobz - what happens if you get this in step 1!

 

[nismaratwork]

Huh... I can't find anything either, but... yeah it has to, but I can't find a citation.

Weird.

Moonbear?

 

[bobze]

bump - i still haven't found this discussed in the literature - how odd!

Come on bobz - what happens if you get this in step 1!

Did you mean crenation?

Red cells don't crenate during ADH release. The urine osmolarity goes up (your keeping water) and vasa recta plasma would become more hypotonic--The RBCs gain volume and your Hct goes up I believe.

 

[nismaratwork]

Ooooooohhh... that would make a lot more sense...

 

[mtc1973]

Hmm - crenelated means Luke a battlement, ie spikey appearance - I guess it has the same Latin root as crenated. I've seen both in reference to rbcs.!

No - what I meant was in a dehydrated individual that has the maximum osmolarity gradient possible down through the medulla - so approximately 1200 mosm at the tip of the vasa recta - the blood is in osmotic equilibrium and hence also has an osmolarity to match the medullary interstitial osmolarity. So we have an extremely hypertonic blood at the vasa recta tip. Why don't the rbcs become so crenated/crenelated from water loss?

Bobs - just re read your post...! Hypotonic ?

 

[bobze]

Hmm - crenelated means Luke a battlement, ie spikey appearance - I guess it has the same Latin root as crenated. I've seen both in reference to rbcs.!

No - what I meant was in a dehydrated individual that has the maximum osmolarity gradient possible down through the medulla - so approximately 1200 mosm at the tip of the vasa recta - the blood is in osmotic equilibrium and hence also has an osmolarity to match the medullary interstitial osmolarity. So we have an extremely hypertonic blood at the vasa recta tip. Why don't the rbcs become so crenated/crenelated from water loss?

Bobs - just re read your post...! Hypotonic ?

I thought you were talking about "forcing" an individual to keep taking in more water. I guess I didn't really understand what you were asking. I see what you are asking now.

Basically you're asking why the kidney's don't act as a water "trap" during dehydration. It seems to make sense that water would flow out of the RBCs, to the plasma then to the medullary interstitium. Since the body doesn't do that (loose water to its own kidney) then we know it doesn't happen that way.

I have a reason I suspect it does not, give me a few to confirm it is correct.

 

[mtc1973]

The question is simply - as the rbc goes through the vasa recta - it will experience the most extreme osmolarity shift it can see in the human body - and the RBC volume must deplete severely - (volume exchange will be low though). This must end up with a large reduction in RBC volume - I assumed that this would be detrimental to RBC's - but maybe not - perhaps they can experience huge water losses and rbc cell interior going up to 600 ish mosm.
Well one thing I suspect (Im sure its true though I don't have a ref to hand) is that the RBC is highly permeable to urea - another suspicion I have is that the 1200 mosm books talk about is in reality probably mostly due to other permeable solutes rather than just NaCl (although they would have to be selectively permeable at the nephron lumenal barrier). This would help - since in reality the RBC would not be experiencing a vastly hypertonic solution - even though it were hyperosmotic. I have heard lactate being mentioned as an osmolyte in this respect - I suspect that there are other permeant osmolytes and that the medullary NaCl gradient is no where as high as textbooks suggest. I can't think how to explain the huge osmotic stress RBC's would experience otherwise.

 

[bobze]

The question is simply - as the rbc goes through the vasa recta - it will experience the most extreme osmolarity shift it can see in the human body - and the RBC volume must deplete severely - (volume exchange will be low though). This must end up with a large reduction in RBC volume - I assumed that this would be detrimental to RBC's - but maybe not - perhaps they can experience huge water losses and rbc cell interior going up to 600 ish mosm.
Well one thing I suspect (Im sure its true though I don't have a ref to hand) is that the RBC is highly permeable to urea - another suspicion I have is that the 1200 mosm books talk about is in reality probably mostly due to other permeable solutes rather than just NaCl (although they would have to be selectively permeable at the nephron lumenal barrier). This would help - since in reality the RBC would not be experiencing a vastly hypertonic solution - even though it were hyperosmotic. I have heard lactate being mentioned as an osmolyte in this respect - I suspect that there are other permeant osmolytes and that the medullary NaCl gradient is no where as high as textbooks suggest. I can't think how to explain the huge osmotic stress RBC's would experience otherwise.

That's pretty much what I suspected as well. During dehydration urea clearance decreases, which means the dominant "force" of your gradient is going to be urea and since RBC membranes are permeable to it, I'm not sure the effects will be quite so large.

I wanted to be sure before I said anything though, and emailed the question (and my/our) reasoning to the renal physiologist who taught our renal block. Will let you know what he says.Edit, RE: the gradient. The gradient, in its extreme, is definitely only "half" sodium chloride. That I remember from renal. The other 600ish is urea.

I also suspect, that even when flow rate is "low", like during dehydration, transit time through the maximal gradient is short for the RBC. I suppose then, they may crenate a little then "pop" quickly back up to size as they ascend the VR. I'm betting they don't spend enough time at those gradients to cause functional disruption to the cell (obviously as kidneys seem to work pretty good

 

[mtc1973]

Most sources still say the NaCl gradient is significant though - so maybe RBC's just shrink and swell and have no lasting detrimental effects.
I have asked around a few colleages - and funnily enough none of them had thought about it before!

Its odd how you can take some things for granted just becuase they are in all the textbooks!

 

[nismaratwork]

Most sources still say the NaCl gradient is significant though - so maybe RBC's just shrink and swell and have no lasting detrimental effects.
I have asked around a few colleages - and funnily enough none of them had thought about it before!

Its odd how you can take some things for granted just becuase they are in all the textbooks!

Heh... yeah, funny that... Heh...

*back to redface*

 

[bobze]

Hey MTC, sorry for the late reply--This has been a block from hell!

Anyway, I got a chance to speak with that renal physiologist over the weekend. He basically confirmed what I (we) suspected. That because RBCs are highly permeable to urea the effect of crenation isn't as pronounced as one would expect.

He also said the transit time through the VR, even some being very long, is pretty short and the time spent at the maximum gradient is, obviously, even shorter. He said he didn't know the exact numbers, but transit time is something that has been studied a lot (or so he says) and the numbers should be pretty easy to find.

Interesting note; Human RBCs are highly permeable to urea because their membrane is packed with urea transporters. He noted that not all species have these transporters, so in them it would certainly be interesting of how this affected their RBCs.

He also said, that it has been hypothesized that the cycle of crenation then normalization could affect membrane integrity and play a significant role in the lifespan of RBCs (even in humans, where there isn't as much crenation). He couldn't recall where he read that reference and I haven't had time to look it up.

If you find time, it would be interesting to see what evidence there is about this. I am under the impression that the lifespan of a RBCs is pretty tightly clustered around the 120 day mark, without much deviation for even a large sample of RBCs. I know one reason this is so is due to oxidative damage which changes confirmation of surface glycoproteins--Which tells Big Mac its time to eat! But, I'm not sure all of the reasons are known.

If you look into it, let us know.

 

[mtc1973]

Theoretical effects of UTB urea transporters in the renal medullary microcirculation.
Zhang W, Edwards A.

Department of Chemical and Biological Engineering, Tufts University, 4 Colby St., Medford, MA 02155, USA. wensheng.zhang@tufts.edu

Abstract
A mathematical model of transport in the renal medullary microcirculation was used to investigate the role of the UTB urea transporter expressed in descending vasa recta (DVR) endothelia and red blood cell (RBC) membranes. Our simulations suggest that UTB raises RBC and plasma and interstitial urea concentrations by facilitating radial diffusion of the solute and therefore serves to increase the contribution of urea to the corticomedullary osmolality gradient, assuming no secondary effects on tubular transport. However, by lowering transmural urea concentration gradients, UTB reduces water efflux from DVR through aquaporin-1 (AQP1) water channels, thereby decreasing plasma sodium concentration. The net result of these competing effects on the osmolality gradient depends on the fraction of filtered urea that is reabsorbed by vasa recta. We also found that the contribution of UTB to water transport across DVR and RBCs is negligible, even in the absence of AQP1. Our model predicts that UTB plays a significant role, however, in reducing the shrinking and swelling of RBCs as blood flows along the medulla.

Sounds like this issue really isn't fully studied - we know it must be true because it works! seems to be the best answer. Most studies are also in rat - very rare to find human studies for obvious reasons.

I'll keep looking - but our best guess seems as good as it gets!