A chapter by chapter recap of Burton Rose’s classic, The Clinical Physiology of Acid Base and Electrolyte Disorders, a kidney physiology book for nephrologists, fellows, residents and medical students.
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Roger’s Hydrogen to pH table References December 19, 2023 Joel had a patient with severe hypothyroidism and hyponatremia- case report Mel reviewed the endocrine factors that can contribute to hyponatremia in this report (from the 2020 ASN quiz and questionnaire): Pattern Recognition versus Pathogenesis - PMC and amy shared this too: Impact of etiology, age and gender on onset and severity of hyponatremia in patients with hypopituitarism: retrospective analysis in a specialised endocrine unit JC mentioned reports of sodium loss from biliary sodium as a cause of hyponatremia: Severe Persistent H
References This is the famous Edelman equation from JCI in 1958 by Isodore Edelman! Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water (not to be confused by Isildur House of Isildur - Tolkien Gateway Joel mentioned his slide deck on Edelman: https://pbfluids.com/wp-content/uploads/2023/04/QN_III-The-Edelman-Equation-full-lecture-from-2020-07-30.pdf This is an excellent review (with great figures) on Osmotic homeostasis by Danziger and Zeidel in CJASN Joel and JC mentioned the work from Joseph Ver
References Biff Palmer! Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023 Josh what is sensed- pCO2 or pH and some exploration suggests that it is not settled! Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes - PMC and this one with catchy title: Out of thin air: Sensory detection of oxygen and carbon dioxide - PMC If anna does VOG on Haldane- we’ll need references The Response of Extracellular Hydrogen Ion Concentration to Graded Degrees of Chronic Hypercapnia: The Physiologic Limits of the Defense of pH - PMC (this is the correct r
References Chapter 19, Part 3 August 30, 2023Biff Palmer’s Ted Talk-Why not? Biff Palmer at TEDxSMU 2013 Anna mentioned this issue of lactic acidosis in a panic disorder: The Lactic Acid Response to Alkalosis in Panic Disorder | The Journal of Neuropsychiatry and Clinical Neurosciences Reminder of important clinical lesson: Lactate: panicking doctor or panicking patient? - PMC Melanie regaled the group with an excerpt (page 351) Cohen, J. J., Kassirer, J. P. (1982). Acid-base. United States: Little, Brown. Biff Palmer! Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023 Melani
References Chapter 19, Part 3 August 30, 2023 Joel and Roger mentioned the most common cause seems to be Sjögren’s syndrome for an acquired distal RTA. We mentioned this in an earlier episode and referenced this example of an absence of the H+ ATPase, presumably from autoantibodies to this transporter. Here’s a case report: Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosis Joel mentioned this paper in the New England Journal of Medicine in which there were patients who had hyperkalemia with a distal RTA: Hyperkalemic Di
References Chapter 19, Part 12 Metabolic acidosis June 14, 2023 References Chapter 19, Part 2 Roger mentioned MELAS syndrome MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options Josh mentioned this blog on lactate- Understanding lactate in sepsis & Using it to our advantage We discussed the Warburg effect The Warburg Effect: How Does it Benefit Cancer Cells? - PMC and here’s a case from skeleton key- Skeleton Key Group Case #28: Mysterious Acidosis in Cancer - Renal Fellow Network Otto Warburg won the Nobel Prize in Physiology and Medicine in 1931 for describing how ani
References Part 2, March 1, 2023 The alkaline tide phenomenon in studies that measured both the alkaline tide and acid secretion, the bicarbonate accumulation increased in linear fashion with the acid secretion. Melanie thought this was first recognized in the 60’s but later found this manuscript from 1939 in JCI! ALKALINE TIDES - PMC Melanie mentioned this old study that explores the respiratory response of metabolic acidosis and finds it “incomplete” compared to expected. EVALUATION OF RESPIRATORY COMPENSATION IN METABOLIC ALKALOSIS and there’s another image in a review by Michael Emmett Fig
References Chapter 19, Part 1 Metabolic acidosis June 14, 2023 American Society of Nephrology | Medical Students - Kidney TREKS this is the program that Josh mentioned at Mount Desert Island! Effects of pH on Potassium: New Explanations for Old Observations - PMC here’s the review melanie from Peter Aronson that clarifies the fact that there are no H+-K+ antiporters outside the kidney but rather coupled transport- We discussed whether we like “Winter’s formula” Quantitative Displacement of Acid-Base Equilibrium in Metabolic Acidosis | Annals of Internal Medicine Dr. R. W. Winters was charged w
We are a bit slappy at the beginning of the episode since we had just recorded our conversation with the Glaucomfleckens. References Chapter 18 Metabolic alkalosis! Part 1 February 23, 2023 It is chloride depletion alkalosis, not contraction alkalosis classic review by Galla and Luke, the metabolic alkalosis mavens who review the role of chloride. On the mechanism by which chloride corrects metabolic alkalosis in man and this is the study when they induced a metabolic alkalosis and studied the effect of treating with KCl vs NaPhos and found the former (with chloride) reversed the alkalosis but
References I said I used MDCalc but I was mistaken I use MedCalX which is nice but getting dated. We talked about this out of print book that we love: Cohen, J. J., Kassirer, J. P. (1982). Acid-base. United States: Little, Brown. Josh mentioned this article that looked at over 17,000 samples with simultaneous measured and calculated bicarbonate and found a very small difference. Comparison of Measured and Calculated Bicarbonate Values | Clinical Chemistry | Oxford Academic Base deficit or excess- Diagnostic Use of Base Excess in Acid–Base Disorders | NEJM (check out the accompanying letter to
References We talked about winning the 2022 ASN innovation contest and here’s a link to our promo video https://www.dropbox.com/scl/fi/g4osnf0nradsfryyo51fi/ASN-Education-Contest-Channel-Your-Enthusiasm-Podcast.mp4?rlkey=pnso45x07nr3pane9y8cux8yg&e=1&dl=0 We wondered about “permissive hypercreatinemia” and Josh referenced the DOSE trial: Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial - PMC Plus this editorial by Steve Coca: Ptolemy and Copernicus Revisited: The Complex Interplay between the Kidneys and Heart Failur
References Capillary Hemodynamics Insights into Salt Handling and Blood Pressure | NEJM Amy mentioned about the 3 phases of the interstitium Are the precapillary sphincters and metarterioles universal components of the microcirculation? An historical review - PMC Safety factor? Renal Function during Recovery from Minimal Lesions Nephrotic Syndrome - Abstract - Nephron 1987, Vol. 47, No. 3 - Karger Publishers Are diuretics effective for idiopathic lymphedema? : Evidence-Based Practice Rapid diuresis in patients with ascites from chronic liver disease: the importance of peripheral edema for fig
References Proximal Tubule-Specific Deletion of the NHE3 (Na+/H+ Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice Melanie is in love with this paper that shows that sodium retention Bumetanide and furosemide in heart failure everyone agreed that we love this classic paper from Craig Brater on diuretics (and the source of figure 15-6). Lety referenced the Cr x 20 formula, a strategy to multiply the serum creatinine by 20 to estimate the initial furosemide dose. We agreed that this is more appropriate than the House of God formula of age + BUN = dose (wh
Outline Chapter 15 — Clinical Use of Diuretics - Among most commonly used drugs - Block NaCl reabsorption at different sites along the nephron - The ability to induce negative balance has made them useful in multiple diseases - Edematous states - Hypertension - Mechanism of action - Three major classes - Loop - NaK2Cl - Up to 25% of filtered sodium excreted - Thiazide - NCC - Up to 3-5% of filtered sodium excreted - Potassium sparing - ENaC - Up to 1-2% of filtered sodium excreted - Each segment has a unique sodium channel to allow tubular sodium to flow down a concentration gradient into the
Outline Chapter 14 — Treatment - Treatment - Both oral and IV treatment can be used for volume replacement - The goal of therapy are to restore normovolemia - And to correct associated acid-base and electrolyte disorders - Oral Therapy - Usually can be accomplished with increased water and dietary sodium - May use salt tablets - Glucose often added to resuscitation fluids - Provides calories - Promotes intestinal Na reabsorption since there is coupled Na and Glucose similar to that seen in the proximal tubule - Rice based solutions provide more calories and amino acids which also promote sodiu
Outline Chapter 14 - Hypovolemic States - Etiology - True volume depletion occurs when fluid is lost from from the extracellular fluid at a rate exceeding intake - Can come the GI tract - Lungs - Urine - Sequestration in the body in a “third space” that is not in equilibrium with the extracellular fluid. - When losses occur two responses ameliorate them - Our intake of Na and fluid is way above basal needs - This is not the case with anorexia or vomiting - The kidney responds by minimizing further urinary losses - This adaptive response is why diuretics do not cause progressive volume depletio
References JC mentioned that the diagnostic accuracy of 24 hour urine collection increases with more collections! Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis We didn't refer to a particular study on sodium intake and the 24 hour urine but this meta-analysis Comparison of 24‐hour urine and 24‐hour diet recall for estimating dietary sodium intake in populations: A systematic review and meta‐analysis - PMC 24‐hour diet recall underestimated population mean sodium intake. Anna looking up ace i and urinary sodium Effects of ACE inhibition on proximal tubule so
References We considered the complexity of the machinery to excrete ammonium in the context of research on dietary protein and how high protein intake may increase glomerular pressure and contribute to progressive renal disease (many refer to this as the “Brenner hypothesis”). Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease A trial that studied low protein and progression of CKD The Effects of Dietary Protein R
The Channelers went where no nephrology podcasters have gone before, recording in front of a live audience at the National Kidney Foundation Clinical Meeting in Austin. We had all eight Channelers doing a live podcast. We did a Freely Filtered-inspired draft of the best diuretics. The draft order: Leticia Rolon Anna Gaddy Joel Topf Roger Rodby Josh Waitzman Amy Yau JC Velez And Melanie Hoenig References JC Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease Intravenous conivaptan for the treatment of hyponatraemia caused by the syndrome of inappropriate secretion of antidiure
References We considered the effect of a high protein diet and potential metabolic acidosis on kidney function. This review is of interest by Donald Wesson, a champion for addressing this issue and limiting animal protein: Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease Hostetter explored the effect of a high protein diet in the remnant kidney model with 1 ¾ nephrectomy. Rats with reduced dietary acid load (by bicarbonate supplementation) had less tubular damage. Chronic effects of dietary protein in the rat with intact and reduced renal mass Wesson explored tr
References for Chapter 10 We did not mention many references in our discussion today but our listeners may enjoy some of the references below. Effects of pH on Potassium: New Explanations for Old Observations - PMC although the focus of this article is on potassium, this elegant review by Aronson and Giebisch reviews intracellular shifts as it relates to pH and K+. Josh swooned for Figure 10-1 is this right? Which figure was it? which shows the relationship between [H+] and pH. You can find this figure in the original reference from Halperin ML and others, Figure 1 here. Factors That Control t
References for Chapter 9 One of the few papers that Rose wrote as a single author explores electrolyte free water clearance. This seminal paper explores the issue in greater detail than the book. A New approach to disturbances in the plasma sodium concentration Wondering about the volume of sweat? Josh taught us that the volume of “transepidermal volume loss” is not affected by humidity https://www.jidonline.org/article/S0022-202X(15)48145-X/pdf but is greatly affected by temperature: Skin temperature and transepidermal water loss Regarding normal sweat physiology, there is a nice review (with
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/artic
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/ anot
