Of all the concepts in fluids and electrolytes by far the most difficult is sodium, water and volume regulation. I think the problems stem from multiple angles, one of which is the confusion between total body sodium (reflected in volume status) and sodium concentration (the primary determinant of osmolality). When writing the sodium chapters I kept thinking about that exchange on Dagobah:
Good Afternoon Dr. Topf,
I am a student at OUWB and you ran our TBL this past week. I’ve been struggling with this material and I was previewing for lectures next week. I apologize for emailing over the weekend, but I am confused over a concept that we went over in TBL – that is, the impetus for release/action of the RAAS system and ADH.
From our discussion and our physiology class prior in the week, I am understanding that ADH primarily regulates osmolarity and that aldosterone primarily regulates blood volume. However, it seems that as I go over review books, I’m being told that ADH, “…also responds to low blood volume, which takes precedence over osmolarity,” (First Aid), and from our physiology text book (Costanzo), it indicates that ADH has 3 functions including:
1. increasing H2O permeability of principal cells (which the text indicates is the primary function)
2. increasing activity of the Na+/K+/2Cl- cotransporter
3. increases urea permeability
Upon my own research, a neuroscience text book source (from the University of Texas) indicates that there are angiotensin II receptors located in the subfornical organ which, upon binding of angiotensin II, cause a release of ADH from the posterior pituitary. I feel like I’m getting different information on what ADH’s role is a response to.
In the case of isotonic volume loss (eg. hemorrhage, diarrhea), you would get activation of the RAAS system as a response to low blood volume/BP. My confusion rests in – does ADH get released as a result solely of the volume loss (not in response to a change in osmolarity) via the angiotensin II – subfornical organ – posterior pituitary pathway? (implying its importance and precedence in preserving blood volume over osmolarity?)
OR is the production of aldosterone in this situation which leads to increased Na+ absorption, which in turn increases blood osmolarity leading to ADH release the mechanism for ADH release in relation to preservation of blood volume?
Thank you kindly in advance.
Sources: Physiology 4th ed. Linda S Costanzo pg. 291
First Aid for the USMLE Step-1 2013 Tao Le, Vikas Bhushan pg. 485
http://neuroscience.uth.tmc.edu/s4/chapter02.html Patrick Dougherty, Ph.D
Here was my reply
The goal of medical physiology is to build a model of how the body works so that the student can predict how the body will respond to various inputs. The more advanced the model the more situations the model will accurately predict the outcomes. Of course the down side of the more complex model is it becomes more and more difficult to remember and keep accessible for use.
Every concept in physiology that is taught should be taught as a step in building an accurate model. Any student that tries to memorize the avalanche of physiology facts without fitting them into a model will be lost. Additionally, students that confuse the model for reality will be disappointed because no model can adequately describe the wonderful complexity of the human body. The sweet spot is adopting a model that is accurate enough to describe the clinical scenarios you encounter in medicine without being so complex to confuse the user
This is especially appropriate for renal physiology.
Short answer is you have it right.:
RAAS is for volume (BP and perfusion) regulation and ADH is for osmoregulation.
Additionally the statement that ADH also responds to volume is also correct and essential in understanding why heart failure and volume depletion leads to hyponatremia. In both CHF and hyponatremia the perfusion is compromised so much that ADH is released (not because of high osmolality but because of the low perfusion signal for ADH). This ADH concentrates the urine and lowers urine output. Then even modest amounts of water will exceed intake and sodium is diluted.
The additional statement that it takes precedence over osmolality is critical. When there is simultaneous low osmolality (suppresses ADH) and low blood pressure (stimulates ADH), the volume stimulus wins. In the hierarchy of need, maintaining perfusion takes precedence over osmoregulation.
|a page from the best book I ever wrote|
Regarding Costanzo’s three functions:
- Increase water permeability. Yes this is the primary and most important function of ADH with regard to osmoregulation.
- Increase activity of the NaK2Cl this is likely true because the NaK2Cl is the pump needed to maintain the concentrated medullary interstitium that drives the reabsorption of water in the collecting ducts in response to ADH. Having ADH stimulate this receptor helps maintain that concentrated interstitium so it doesn’t get diluted by the reabsorbed water. However I would recommend you ignore this fact. This complicates the model of osmoregulation and will lead you down false roads.
If you believe this is an important function of ADH you will assume that SIADH, a condition of unregulated over production of ADH will cause sodium accumulation (due to stimulation fo NaK2Cl pump) when in reality the most important aspect of SIADH to understand is that SIADH is a sodium neutral state (sodium in = sodium out) and only causes hyponatremia due to the over reabsorption of water (due to the ADH)
- Increased urea permeability. I have no idea if this is important and why it might be important. It likely is also important in maintaining the concentrated medullary interstitium. That is one of the strangest tissues in the body and ADH induced water reabsorption dilutes it so my guess is that many of the subtler renal affects of ADH are designed to maintain and restore this briny Superfund site in the middle of the kidney. Ignore the italics, that is only to impress other nephrologists that read this far.
In regards to the neuroscience textbook indicting AT2 receptors as a critical signal for ADH release. This is likely the trigger for the volume dependent release of ADH we discussed above. But again this is a fact that can be safely ignored because if you focus on AT2’s role in ADH release you may falsely assume that ACE inhibitors (and angiotensin receptor blockers and renin blockers) will block these receptors, decrease ADH and cause a diabetes insipidus picture. This does not happen. Keep it simple.
Your final question is about isotonic volume loss, the answer is: you are clearly describing a perfusion related release of ADH. Do not use an overly complex Rube Goldberg system of increasing osmolality to release ADH.