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Effective circulating volume, a theoretical construct reflecting tissue perfusion, is crucial. The kidneys adjust sodium excretion to maintain this volume. Diuretics initially remove sodium effectively, but their efficacy diminishes over time. Increased sodium intake leads to volume expansion, while reduced intake causes volume decrease.
The kidneys maintain proper electrolyte levels under normal conditions. Abnormalities in sodium, potassium, bicarbonate, or water balance suggest kidney dysfunction. A profound shift in these electrolytes requires underlying renal issues; dietary factors play a limited role in electrolyte imbalances.
Baroreceptors in the aortic arch and carotid sinuses, and the glomerular arterioles sense pressure or stretch, aiding in effective volume control. Piezo channels in the neurons enervating these areas play a crucial role in volume sensing, impacting downstream signaling and maintaining blood pressure.
Environmental stimuli, like neck-deep water immersion, can shift volume within the body. This can activate baroreceptors, influencing sodium and water excretion. Such methods demonstrate the hemodynamic nature of changes in urine output with conditions like cirrhosis.
The body maintains fluid balance through a combination of underfill and overfill states, where conditions like portal hypertension and cirrhosis impact fluid distribution. Immersing individuals in water can alter their intervascular volume, leading to diuresis and highlighting the role of underfill states. Pressure natriuresis, influenced by factors like angiotensin II, plays a crucial role in regulating sodium excretion based on blood pressure changes.
Recent studies like the Paradise-MI trial have called into question the efficacy of albumin infusions in heart failure patients, showing no significant differences in outcomes. The debate over the use of albumin infusions reflects a shift towards personalized treatment approaches and a reconsideration of standard practices in cardiac care.
The kidney's function in regulating fluid balance involves distinguishing between osmoregulation and volume regulation. While osmoregulation controls water excretion and intake based on osmolality, volume regulation involves mechanisms like pressure natriuresis and involves effectors such as angiotensin II. Understanding the intricate balance between these regulatory mechanisms is vital for comprehending conditions like hyponatremia and volume depletion.
References for chapter 8
Robert Schrier proposed a unifying hypothesis to explain the sodium retention seen in edematous states like cirrhosis and heart failure, coining the term effective arterial blood volume (EABV). An open access review in JASN 2007 can be found here: https://jasn.asnjournals.org/content/18/7/2028#ref-3
John P Peters
ASN Annual Award: https://www.asn-online.org/about/awards/award.aspx?awh_key=0ea83199-f86d-4506-9507-d7e4ce688cb4
Short article discussing contributions of Dr. Peters by mentees Dr. Franklin Epstein and Dr. Donald Seldin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588700/ and https://pubmed.ncbi.nlm.nih.gov/12097739/
Epstein FH et al. Studies of the antidiuresis of quiet standing: the importance of changes in plasma volume and glomerular filtration. JCI 1950. In this classic report, investigators studied their own sodium excretion supine, standing and with a variety of maneuvers (saline or albumin infusion) and showed that urinary sodium excretion is limited in the upright position compared to supine position. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC436228/pdf/jcinvest00414-0077.pdf
An interesting review of early concepts on hypertension feature notes on John J Hay and Paul Dudley White. The former was known to say, “The greatest danger to a man with high blood pressure lies in its discovery because then some fool is certain to try and reduce it!” and the latter has been quoted as saying that hypertension might be compensatory but apparently, these quotes are out of context. To find out what they really said, check out: Elias MF and Goodell AL. Setting the record straight for two heroes in hypertension John J Hay and Paul Dudley White. J Clin Hypertens 2019 https://onlinelibrary.wiley.com/doi/epdf/10.1111/jch.13650
VA Cooperative Trial was an important study to establish the hypertension should, in fact, be treated The VA Cooperative Study and the Beginning of Routine Hypertension Screening, 1964-1980
This study was stopped after only 18 months because of an excess of deaths in the untreated group who had a mean diastolic BP of 115 mmHg.
For a long time, only the diastolic BP was felt to be important until the Systolic Hypertension in Elderly Patients (“SHEP study”) clarified that treatment of isolated systolic hypertension is also important
Prevention of Stroke by Antihypertensive Drug Treatment in Older Persons With Isolated Systolic Hypertension
We continued to try to grapple with the work of Jens Titze on sodium which turns many of our assumptions about sodium upside down. His team studied astronauts on a long term high sodium diet and found an unexpected weekly (circaseptan) rhythm seemingly related inversely to aldosterone and directly with cortisol. His work also probes our notion of body sodium content. For a great first hand read, check out Dr TItze’s review in Kidney International 2014 which he aptly dubs, “Spooky Sodium Balence.” https://www.sciencedirect.com/science/article/pii/S0085253815562807
Epstein M. The cardiovascular and renal effects of head-out of water Immersion in Man. Circulation Research 1976 Cardiovascular and renal effects of head-out water immersion in man: application of the model in the assessment of volume homeos
Space flight is an exaggeration of the water immersion experiments. Astronauts on either a low or normal sodium diet had a reset of natriuetic peptides. A Salty Tale: Study Examines Sodium Regulation in Space and Natriuretic Peptide Resetting in Astronauts | Circulation
Baroreceptors feature mechanically activated ion channels called PIEZO1 and PIEZO2. Zeng W, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102061/
We also relearned an unfortunate truth: lots of folks pee in pools. De Laat et al. Water Res. 2011. Concentration levels of urea in swimming pool water and reactivity of chlorine with urea
At the American College of Cardiology meeting in April, investigators shared the news that the combination of an ARB with new class of drugs called angiotensin receptor neprilysin inhibitor (ARNI) was not superior to ACE inhibitors at reduction of heart failure following acute MI. Here’s the press release for the PARADISE-MI trial. Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction
A series of elegant experiments by Alicia McDonald’s team to characterize pressure natriuresis. In these studies, they induce hypertension by constriction of the superior mesenteric artery, the celiac artery and the infrarenal aorta (essentially increasing afterload without directly altering the blood flow to the kidney). With this maneuver, the blood pressure of the experimental animal rises, urinary sodium excretion increases and then they demonstrate a shift in the Na-H ATPase from the apical membrane to intracellular vesicles in the proximal tubule and a shift in NCC from the luminal membrane to the intracellular vesicles in the distal tubules.
Yang L et. al Acute hypertension provokes internalization of proximal tubule NHE3 without inhibition of transport activity. Am J Physiol Renal 2002 https://journals.physiology.org/doi/full/10.1152/ajprenal.00298.2001?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
Lee DH Riquier ADM, Yang LE, Leong PK, Maunsbach and McDonough AA. Acute hypertension provokes acute trafficking of distal tubule NaCl (NCC) to subapical cytoplasmic vesicles. Am J Physiol Renal Physiol. 2009 Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles This review in KI reports is also worth a read McDonough AA. Maintaining Balance under pressure-hypertension and the proximal tubule. 2015 ISN Forefronts Symposium 2015: Maintaining Balance Under Pressure—Hypertension and the Proximal Tubule
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