Chapter Seven: The Total Body Water and The Plasma Sodium Concentration
Channel Your Enthusiasm
The Underfill Theory for Nephrotic Syndrome
Underfill theory does work in certain circumstances when you have very acute onset of albmnerea. In this over fill mechanism, it's the albunera itself that triggers the sodium retention. Yet, our lob dirotics are pretty goodar still our first line of therapy. We're really goingto hav movement situation at blocking the saloon chamas go ultimate their peltic manoeuvre. Their legs are so big, and you want leaders off. Now, i think it just must be more complicated than that.
Chapter 7
References
Sands JM, Blount MA and Klein JD. Regulation of Renal Urea Transport by Vasopressin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116377/
In this invited piece, Sands and colleagues explain that although urea is permeable across membranes, this is slow, thus urea transporters in the kidney, under control of vasopressin, are needed to facilitate transport and create the medullary gradient.
Text book using 20% of extracellular compartment being in the intravascular compartment. https://courses.lumenlearning.com/ap2/chapter/body-fluids-and-fluid-compartments-no-content/
The chapter I wrote where I went through the math in figure 7-3. It was a major revelation to me: https://docs.google.com/document/d/17BM1xihvlztuQlU8GVNhEDoPLzr6GounHYZAtVUkLvw/edit?usp=sharing
Association Between ICU-Acquired Hypernatremia and In-Hospital Mortality https://journals.lww.com/ccejournal/fulltext/2020/12000/association_between_icu_acquired_hypernatremia_and.26.aspx
Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients https://pubmed.ncbi.nlm.nih.gov/30948456/
Edelman IS, Leibman J, O’Meara MP and Birkenfeld LW. Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. JCI 1958. This classic paper calculates the total body exchangeable sodium and potassium and establishes the relationship between these. Understanding this painstacking work helps understand the effect of supplementing potassium in the setting of hyponatremia.
https://dm5migu4zj3pb.cloudfront.net/manuscripts/103000/103712/cache/103712.1-20201218131357-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Edelman is the Root of Almost All Good in Nephrology https://www.renalfellow.org/2014/11/20/edelman-is-root-of-almost-all-good-in/
Jens Titze and his team published a pair of articles that shocked those interested in salt and water in JCI in 2017.
High Salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation https://www.jci.org/articles/view/88532
Increased salt consumption induces body water conservation and decreases fluid intake https://www.jci.org/articles/view/88530
in this exciting exploration of the basic assumptions that we hold true regarding salt and water (and staring Russian cosmonauts and an incredible controlled simulation of salt and water intake), Titze shows that high sodium intake does not simply drive water consumption (as we usually teach) but instead leads to a complex hormonal and metabolic response (even with diurnal variation!) and results in body water conservation and decreased water consumption.
And accompanying editorial from Mark Zeidel: salt and water, not so simple. https://www.jci.org/articles/view/94004
In addition, Titze and others have done interesting work on sodium deposition in tissues where it may also be a source for systemic inflammation.https://pubmed.ncbi.nlm.nih.gov/28154199/
Jens Titze talking about salt, water, thirsting a TEDx talk. https://www.youtube.com/watch?v=jQQPBmnIuCY
A discussion/debate of the overfill vs. underfill theory of edema in the nephrotic syndrome (hint- overfill theory triumphs) would be incomplete without a reference to congenital analbuminemia. This reference from Frontiers in Genetics explores the diagnosis, phenotype and molecular genetics and reveal that patients tend to have only mild edema but severe hyperlipidemia. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478806/
The finding that proteinuria can directly lead to sodium retention based on a study when puromycin aminoglycoside induced proteinuria of one kidney lead to sodium retention by that kidney which was localized to the distal nephron. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC436841/?page=9
Plasmin may be the culprit at the level of the epithelial sodium channel based on Tom Kleyman’s work: https://jasn.asnjournals.org/content/20/2/233
Amiloride may help! (stay tuned for amiloride in a future episode) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016639/
An old favorite of JC’s from the Kidney International feature which debates the cause of edema in the nephrotic syndrome.
https://www.sciencedirect.com/science/article/pii/S0085253815583075
Under protest, we hobbled through a discussion of the Gibbs Donnan affect even encouraged by one of Amy’s fellows based on this article from QJM: https://academic.oup.com/qjmed/article/101/10/827/1520972 suggesting that our understanding of the role of hyponatremia in fractures might be all wrong- it could be related to hypoalbuminemia.
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