Chapter Seven: The Total Body Water and The Plasma Sodium Concentration
Chapter Seven: The Total Body Water and The Plasma Sodium Concentration
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.
Outline
The Total Body Water and The Plasma Sodium Concentration
Three compartments
Regulation of intracellular volume achieved in part by regulation of plasma osmolality
Plasma volume is sodium balance
Exchange of water between cellular and extracellular fluids
Water moves through cell membranes
All body fluids are in osmotic equilibrium
Intracellular volume is water balance (osmolality)
Brownian motion
Solutes slow movement of particles
Water moves to area of higher osmolality until hydrostatic pressure opposes osmotic pressure
Colligative properties
Ineffective osmole
Primary effective osmole in extrace3llular compartment is sodium
Primary effective osmole of the intracellular compartment is potassium
Footnote about exchangeable sodium and potassium
Figure 7-3 and Table 7-1 Nice demonstration of the effect of adding Na or water to the two compartment model.
Shows why you need to use TBW not extracellular water in calculations about sodium.
Go through all three examples (salt, water, NS)
In each of the examples, the ECC is increased, but the Na increases, decreases and remains the same, emphasizing how [Na] is a concentration not an assessment of volume.
Relation of Plasma Sodium Concentration to Osmolality
NaCl is 75% dissociated
93% of plasma is made of water
Balance is fat and protein
Combine those two and you get osm of Na salts = 1.88 x Na
The remaining 17 mOsm/kg (0.12 x 140) is covered by K, Mg, Ca!
POsm = 2x Na + glucose/18 + BUN/2.8
But urea is ineffective
And glucose only contributes a little bit
So really it is 2xNa
The determinants of plasma sodium
Combining eq 7-4
Effective POsm = 2 x pNa
With eq 7-6
Effect Osm = (2 x Nae + 2 x Ke)/TBW
Gets you eq 7-6
Plasma Na = Nae + Ke/TBW
Talks about diarrhea causing loss of extracellular potassium leading to movement of sodium into the cells in exchange for potassium. No references.
Says osmolality is due to changes in water
Can’t get hypernatremia from gain in potassium because you die of hyperkalemia first.
Exchange of water between plasma and interstitial fluid
Capillaries and post cap venules
Capillary is permeable to sodium and glucose these substances do not behave as effective osmoles.
Only plasma proteins are effective osmoles
Osmotic pressure generated by the plasma proteins is plasma on oncotic pressure
Oncotic pressure balanced by plasma hydraulic pressure
The balance of these pressures, along with the oncotic and hydraulic pressure of the interstitium is expressed as part of Starlings law
After defining the variables rose states, “cap hemodynamics are not uniform, as both open and closed capillaries may be present.” What is an open or closed capillary?
Muscle have lower cap pressure, cap wall is impermeable to proteins, negative interstitial pressure due to lymph drainage.
Net filtration pressure is 0.3 mmHg
Filtration is reversed in the post- capillary venules here venule hydrai\ulic pressure is very low.
Alveoli have lower cap hydraulic pressure, lower trans cap oncotic pressure due to higher permeability of proteins,
Net filtration pressure is 2 mmHg
Low plasma oncotic pressure means this gradient is resistant to changes in albumin
Glomerular
Much higher net filtration from lower pre-cap resistance
Net of 6 mmHg
Cap hydraulic Pressure and autoregulation
Cap hydraulic pressure due to three factors
Arterial pressure
Resistance at the precap sphincter
Autoregulation
Prevents hypertension from causing edema
Postcap resistance in venules and veins
Little control
Plasma oncotic pressure
Hoff’s low states oncotic proessure = solute concentration X gas constant X temp in Kelvin
Since the last two are constants, oncotic pressure changes linearly with solute concentration
However that does not occur!!!!
Oncotic pressure from plasma proteins is greater than predicted due to Gibbs Donnan equilibrium.
Increases plasma oncotic pressure from 0.9 to 1.3 mmosmol/Kg which represents change from 17.4 to 25-26 mmHg
Other poorly understood factors contribute to this discrepancy between predicted and actual values for the oncotic pressure produced by the plasma proteins.
Safety factors
Factors that prevent small changes from causing big filtration
Lymphatic flow
Movement of fluid decreases interstitial oncotic pressure
Increased fluid increases interstitial hydraulic pressure
Talks about under fill and overfill theory of nephrotic syndrome