Podcasts about Aldosterone

What do you do when most trials suggest benefit for an intervention, but then a new trial suggests harm? We thought steroids in pneumonia was a settled question, but REMAP-CAP had other plans!We also review a new RCT for BP targets in patients with hypertension and diabetes, a new aldosterone synthase inhibitor for hypertension, and reduced dose apixaban for cancer-associated thrombosis. Hydrocortisone for Severe CAP (REMAP-CAP)Predicting Benefit of Corticosteroids in PneumoniaIntensive BP Control in Patients with Diabetes (BPROAD)Lorundrostat for Uncontrolled Hypertension (ADVANCE-HTN)Reduced Dose Apixaban for Cancer Associated Thrombosis (API-CAT)Music from Uppbeat (free for Creators!): https://uppbeat.io/t/soundroll/dope License code: NP8HLP5WKGKXFW2R

During this presentation, Donald DiPette, MD, FACP, FAHA, on behalf Robert M. Carey, MD, reviews the role of the RAAS in normal blood pressure and salt and water homeostasis. In addition, Dr. DiPette discusses the role of the RAAS in the pathophysiology of cardiovascular disease, diabetes mellitus, and kidney disease, and he also details the pharmacologic inhibition/blockade of the RAAS.

We sincerely apologize! During the livestream recording, we experienced some technical difficulties between 07:15 to 08:50. Thanks for your patience and understanding.Learn more about becoming an Insider on our website: https://www.benbikman.comDuring The Metabolic Classroom lecture this week, Dr. Bikman dives into the intricate relationship between salt- and water-regulating hormones and metabolic health.Starting with a discussion of the renin-angiotensin-aldosterone system (RAAS), he explains how hormones like angiotensin II, aldosterone, and antidiuretic hormone (ADH) are not only critical for regulating blood pressure but also significantly impact insulin sensitivity and fat cell dynamics. Angiotensin II promotes insulin resistance by increasing ceramide production, which blocks insulin signaling, while also enlarging fat cells and inhibiting their breakdown. Similarly, aldosterone exacerbates insulin resistance by enhancing ceramide levels and promotes both the growth and multiplication of fat cells. ADH complements these effects, particularly by inhibiting fat breakdown through its action on specific receptors.Ben emphasizes the counterintuitive finding that salt restriction, often prescribed to manage hypertension, can worsen insulin resistance, particularly in individuals with metabolic vulnerabilities. Studies highlight that reducing salt intake leads to increased fasting insulin levels, impaired glucose metabolism, and unfavorable lipid changes, such as reduced HDL cholesterol. Additionally, he warns that dehydration, much like salt restriction, activates these same hormonal pathways, compounding their metabolic effects.Dr. Bikman concludes with a reminder that interventions aimed at improving blood pressure should consider their broader metabolic implications, particularly for individuals predisposed to insulin resistance.Show Notes/References:For complete show notes and references referred to in this episode, we invite you to become a Ben Bikman Insider subscriber. As a subscriber, you'll enjoy real-time, livestream Metabolic Classroom access which includes live Q&A with Ben, ad-free Metabolic Classroom Podcast episodes, show notes and references, Ben's Research Reviews Podcast, and a searchable archive that includes all Metabolic Classroom episodes and Research Reviews. Learn more about becoming an Insider on our website: https://www.benbikman.comTimestamps: (approximate)(01:13) Overview of Salt- and Water-Regulating Hormones(02:22) How Angiotensin II Influences Blood Pressure and Insulin Resistance(06:37) The Metabolic Effects of Angiotensin II on Fat Cells(11:22) Aldosterone's Role in Insulin Resistance and Fat Cell Growth(15:57) Metabolic Impacts of Antidiuretic Hormone (ADH)(29:02) The Counterintuitive Effects of Salt Restriction on Metabolic Health(33:13) The Role of Dehydration in Activating Metabolic Hormones(34:51) Conclusion: How Blood Pressure Hormones Influence Metabolic Health#MetabolicHealth #InsulinResistance #Hypertension #SaltAndHealth #BloodPressure #HormonesAndHealth #DrBenBikman #MetabolicSyndrome #LowCarbLife #Type2Diabetes #KetoLife #HealthyLifestyle #NutritionScience #MetabolismMatters #HealthEducation #FatCellBiology #InsulinSensitivity #SaltIntake #Dehydration #HealthTips Hosted on Acast. See acast.com/privacy for more information.

This episode contains short-answer questions on the renin-angiotensin-aldosterone system.Written notes can be found at https://zerotofinals.com/physiology/endocrine/reninangiotensinaldosteronesystem/ or in the Zero to Finals Endocrine System book.You can find short-answer questions, multiple-choice questions, extended-matching questions, digital flashcards, a course on how to learn medicine and the revision tracking tool at members.zerotofinals.com. The audio in the episode was expertly edited by Harry Watchman.

Research Papers: https://www.dryfastingclub.com/studies/ Website: https://dryfastingclub.com Consultation: https://dryfastingclub.com/members Are you curious about the relationship between aldosterone and dry fasting? Aldosterone is a critical hormone responsible for regulating fluid and electrolyte balance in the body, particularly sodium and potassium levels. During dry fasting, the absence of water intake can put stress on the body's ability to maintain hydration, making aldosterone's role even more essential. As aldosterone rises in response to fluid restriction, it helps conserve sodium and water, allowing the body to adapt to the temporary absence of hydration. However, understanding how aldosterone functions during a dry fast is important, especially if you're interested in advanced fasting techniques for health benefits like detoxification and cellular repair. Dry fasting with elevated aldosterone levels can lead to powerful physiological adaptations, but it requires careful attention to ensure safe and effective outcomes. Many individuals report improved electrolyte balance and even better tolerance to fasting with longer-term, gradual practice. By knowing how aldosterone interacts with dry fasting, you can better understand why certain precautions, like sodium and potassium balance, are crucial before and after a fast. This unique hormone-fast connection provides insight into optimizing results, making dry fasting safer and more effective for those exploring its benefits for metabolic health and wellness. Join us on Instagram   / dryfastingclub   Join us on Twitter   / dryfastingclub   The Dry Fasting Club does not provide medical advice. Always seek the advice of your physician or another qualified healthcare provider with any questions you may have regarding a medical condition or treatment before undertaking a new healthcare regimen. If you enjoyed the video, please like, subscribe & share!

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Which MRA to use in which heart failure patient Managing electrical storm Mythbusters: garlic protects from the heart Host: Perry Elliott Guests: Carlos Aguiar, Sana Al-Khatib, Rudolf de Boer Want to watch that episode? Go to: https://esc365.escardio.org/event/1792 Disclaimer ESC TV Today is supported by Bristol Myers Squibb. This scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC. Declarations of interests Stephan Achenbach, Sana Al-Khatib and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, BiAL, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, GSK, Lilly, Novartis, Pfizer, Sanofi, Servier, Takeda, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi Aventis, Novo Nordisk, Terumo. Rudolf de Boer has declared to have potential conflicts of interest to report: direct research funding from European Research Council (ERC), Netherlands Heart Foundation, Fondation leDucq, Netherlands Organization for Scientific Research. Research funding to department or institution: AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, NovoNordisk. Direct fees from Abbott, AstraZeneca, Cardior Pharmaceuticals GmbH, NovoNordisk, Roche Diagnostics. Fees to department or institution: NovoNordisk. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics, AstraZeneca, Forbion. Steffen Petersen has declared to have potential conflicts of interest to report: consultancy for Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada. Emma Svennberg has declared to have potential conflicts of interest to report: Abbott, Astra Zeneca, Bayer, Bristol-Myers, Squibb-Pfizer, Johnson & Johnson.

This episode covers the physiology of the renin-angiotensin-aldosterone system.Written notes can be found at https://zerotofinals.com/physiology/endocrine/reninangiotensinaldosteronesystem/ or in the endocrinology section of the 2nd edition of the Zero to Finals Medicine book.The audio in the episode was expertly edited by Harry Watchman.

What's the deal with statin drugs and “high cholesterol”? Even doctors are starting to raise questions. They say that “high cholesterol” is anything over 200 total, but where does this number come from? Is there evidence that cholesterol over 200 actually leads to heart disease? Why do we need cholesterol, and is it possible for it to get too low? On this episode of Vitality Radio Jared arms you with the information you need to decide what to do, if anything, about your “high” cholesterol.  Pharmaceutical companies often develop drugs that target specific symptoms by interfering with the body's natural processes. These medications can be effective in providing temporary relief from symptoms, but they don't usually address the underlying causes of a condition. This is called suppressive medicine, and such treatments may offer short-term benefits at the cost of long-term health. In this series of episodes on suppressive medicine, Jared aims to help you understand the ways in which these drugs work and what natural alternatives there are that work WITH your body's natural systems to address the root cause and rebalance the body. Products:BerberineAdditional Information:#332: Cholesterol Controversy - Jared's Interview on Inside The Aisle with Niki WolfeVisit the podcast website here: VitalityRadio.comYou can follow @vitalityradio and @vitalitynutritionbountiful on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Please also join us on the Dearly Discarded Podcast with Jared St. Clair.Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

NEJM 2003;348:1309-21.Background In patients with chronic systolic heart failure, aldosterone blockade reduced death and cardiovascular hospitalizations when added to an ACE inhibitor (RALES trial), which will be reviewed in the section involving trials in patients with chronic heart failure. Efficacy of aldosterone blockade in patients with acute myocardial infarction, complicated by LV dysfunction, had not yet been tested. Aldosterone blockade was believed to prevent ventricular remodeling and collagen formation after AMI as well as a number of other important pathophysiological mechanisms. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) was designed to test the hypothesis that the selective aldosterone blocker, eplerenone, would reduce mortality and cardiovascular hospitalizations in patients with AMI complicated by LV dysfunction and heart failure.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Patients were eligible for randomization 3 to 14 days after AMI with LV dysfunction based on an EF of ≤40% and clinical heart failure based on the presence of pulmonary rales, chest X-ray showing pulmonary venous congestion or the presence of a third heart sound. In patients with diabetes, the presence of clinical heart failure was not a requirement. Exclusion criteria included the use of potassium-sparing diuretics, serum creatinine >2.5 mg/dl, or serum potassium >5 mmol/l.Baseline characteristics The average age of patients was 65 years and over 70% were men; 90% were white. Approximately one quarter of patients had a prior MI, more than 30% had diabetes and 60% had hypertension. The average ejection fraction was 34%. Patients were hemodynamically stable with an average blood pressure of 119/72 mmHg. The average time to randomization from AMI was 7 days. Nearly 50% of patients underwent thrombolysis or angioplasty for the primary MI and at the time of randomization 86% of patients were on an ACE inhibitor, 88% on aspirin, 47% on statins, 75% on beta-blockers, and 60% on diuretics.Procedures Patients received either eplerenone 25 mg daily or a matching placebo for 4 weeks and then the dose was increased to 50 mg daily. If at any time during the study the serum potassium was >5.5 mmol/l, the dose of the study drug was reduced or temporarily discontinued until the serum potassium was

Reader feedback, imaging in the cath lab, AF ablation to relieve anxiety, and some possible help in hypertension are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. Reader Feedback Sep 08, 2023 This Week in Cardiology Podcast   https://www.medscape.com/viewarticle/996233 First Clinical Trial of CTO Procedures Fails to Deliver   https://www.medscape.com/viewarticle/877405 -   DanGerShock trial https://pubmed.ncbi.nlm.nih.gov/31176289/ II. Imaging in the Cath Lab Should Intravascular Imaging Be Almost Routine in PCI?    https://www.medscape.com/viewarticle/996375 -   ILUMIEN IV    https://www.nejm.org/doi/full/10.1056/NEJMoa2305861 -   OCTOBER    https://www.nejm.org/doi/full/10.1056/NEJMoa2307770 III. AF Ablation to Relieve Anxiety -   REMEDIAL Trial   https://jamanetwork.com/journals/jama/fullarticle/2809419 -   Sohaib and Francis; Meta analysis of Symptomatic Response Effect of CRT Pacing    https://pubmed.ncbi.nlm.nih.gov/24259043/ IV. HTN 'New Dawn' for Aldosterone as Drug Target in Hypertension?    https://www.medscape.com/viewarticle/996316 -   TARGET HTN -    https://jamanetwork.com/journals/jama/fullarticle/2809625 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

Commentary by Dr Constantine A. Stratakis

PODCAST HIGHLIGHTS: 00:00 Introduction 02:44 Best Time to Take Apple Cider Vinegar 06:48 Do you need more salt? 10:57 Dangers of Low Sodium 12:33 Research studies and U-Shaped Curves 15:58 Orthostatic hypotension 16:39 Functional range of sodium levels 19:31 Salt conscious culture 21:44 Sodium and adrenal fatigue 23:30 Cortisone, Epinephrine, Norepinephrine 23:56 Aldosterone 25:32 Blood...... Continue Reading →

Join experts Drs Matthew Sparks and James Matthew Luther as they discuss how and why they're using mineralocorticoid receptor antagonists to treat patients with diabetic kidney disease in their practice. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/991189). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Chronic Kidney Disease (CKD) https://emedicine.medscape.com/article/238798-overview Physiology, Aldosterone https://www.ncbi.nlm.nih.gov/books/NBK470339/ Angiotensin II https://www.ncbi.nlm.nih.gov/books/NBK499912/ Primary Aldosteronism https://emedicine.medscape.com/article/127080-overview Epithelial Sodium Channel (ENaC) and the Control of Blood Pressure https://pubmed.ncbi.nlm.nih.gov/24721652/ Hypertension Treatment & Management https://emedicine.medscape.com/article/241381-treatment Hypertension Medication https://emedicine.medscape.com/article/241381-medication#2 Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease - Mechanistic and Therapeutic Effects https://pubmed.ncbi.nlm.nih.gov/34675379/ Malignant Hypertension https://emedicine.medscape.com/article/241640-overview Androgenetic Alopecia https://emedicine.medscape.com/article/1070167-overview Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes https://pubmed.ncbi.nlm.nih.gov/33264825/ Cardiovascular Events With Finerenone in Kidney Disease and Type 2 Diabetes https://pubmed.ncbi.nlm.nih.gov/34449181/ Regression to the Mean https://www.britannica.com/topic/regression-to-the-mean Sodium-glucose Transport Protein 2 (SGLT2) Inhibitors https://www.ncbi.nlm.nih.gov/books/NBK576405/ Potassium Binders for Chronic Hyperkalaemia in People With Chronic Kidney Disease https://pubmed.ncbi.nlm.nih.gov/32588430/

The following episode provides part one of sodium physiology examining how the body regulates sodium levels via the renin-angiotensin-aldosterone system.    One of my favorite lectures on this topic: https://www.youtube.com/watch?v=NMWaKdO76NQ    

ReferencesWe 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 diseaseA trial that studied low protein and progression of CKD The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease(and famously provided data for the MDRD eGFR equation A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study GroupWe wondered about dietary recommendations in CKD. of note, this is best done in the DKD guidelines from KDIGO Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment.Joel mentioned this study on red meat and risk of ESKD. Red Meat Intake and Risk of ESRDWe referenced the notion of a plant-based diet. This is an excellent review by Deborah Clegg and Kathleen Hill Gallant. Plant-Based Diets in CKD : Clinical Journal of the American Society of NephrologyHere's the review that Josh mentioned on how the kidney appears to sense pH Molecular mechanisms of acid-base sensing by the kidneyRemarkably, Dr. Dale Dubin put a prize in his ECG book Free Car Prize Hidden in Textbook Read the fine print: Student wins T-birdA review of the role of the kidney in DKA: Diabetic ketoacidosis: Role of the kidney in the acid-base homeostasis re-evaluatedJosh mentioned the effects of infusing large amounts of bicarbonate The effect of prolonged administration of large doses of sodium bicarbonate in man and this study on the respiratory response to a bicarbonate infusion: The Acute Effects In Man Of A Rapid Intravenous Infusion Of Hypertonic Sodium Bicarbonate Solution. Ii. Changes In Respiration And Output Of Carbon DioxideThis is the study of acute respiratory alkalosis in dogs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC293311/?page=1And this is the study of medical students who went to the High Alpine Research Station on the Jungfraujoch in the Swiss Alps https://www.nejm.org/doi/full/10.1056/nejm199105163242003Self explanatory! A group favorite! It Is Chloride Depletion Alkalosis, Not Contraction AlkalosisEffects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosisA review of pendrin's role in volume homeostasis: The role of pendrin in blood pressure regulation | American Journal of Physiology-Renal PhysiologyInfusion of bicarbonate may lead to a decrease in respiratory stimulation but the shift of bicarbonate to the CSF may lag. Check out this review Neural Control of Breathing and CO2 Homeostasis and this classic paper Spinal-Fluid pH and Neurologic Symptoms in Systemic Acidosis.OutlineOutline: Chapter 11- Regulation of Acid-Base Balance- Introduction - Bicarb plus a proton in equilibrium with CO2 and water - Can be rearranged to HH - Importance of regulating pCO2 and HCO3 outside of this equation - Metabolism of carbs and fats results in the production of 15,000 mmol of CO2 per day - Metabolism of protein and other “substances” generates non-carbonic acids and bases - Mostly from sulfur containing methionine and cysteine - And cationic arginine and lysine - Hydrolysis of dietary phosphate that exists and H2PO4– - Source of base/alkali - Metabolism of an ionic amino acids - Glutamate and asparatate - Organic anions going through gluconeogenesis - Glutamate, Citrate and lactate - Net effect on a normal western diet 50-100 mEq of H+ per day - Homeostatic response to these acid-base loads has three stages: - Chemical buffering - Changes in ventilation - Changes in H+ excretion - Example of H2SO4 from oxidation of sulfur containing AA - Drop in bicarb will stimulate renal acid secretion - Nice table of normal cid-base values, arterial and venous- Great 6 bullet points of acid-base on page 328 - Kidneys must excrete 50-100 of non-carbonic acid daily - This occurs by H secretion, but mechanisms change by area of nephron - Not excreted as free H+ due to minimal urine pH being equivalent to 0.05 mmol/L - No H+ can be excreted until virtually all of th filtered bicarb is reabsorbed - Secreted H+ must bind buffers (phosphate, NH3, cr) - PH is main stimulus for H secretion, though K, aldo and volume can affect this.- Renal Hydrogen excretion - Critical to understand that loss of bicarb is like addition of hydrogen to the body - So all bicarb must be reabsorbed before dietary H load can be secreted - GFR of 125 and bicarb of 24 results in 4300 mEq of bicarb to be reabsorbed daily - Reabsorption of bicarb and secretion of H involve H secretion from tubular cells into the lumen. - Thee initial points need to be emphasized - Secreted H+ ion are generated from dissociation of H2O - Also creates OH ion - Which combine with CO2 to form HCO3 with the help of zinc containing intracellular carbonic anhydrase. - This is how the secretion of H+ which creates an OH ultimately produces HCO3 - Different mechanisms for proximal and distal acidification - NET ACID EXCRETION - Free H+ is negligible - So net H+ is TA + NH4 – HCO3 loss - Unusually equal to net H+ load, 50-100 mEq/day - Can bump up to 300 mEq/day if acid production is increased - Net acid excretion can go negative following a bicarb or citrate load - Proximal Acidification - Na-H antiporter (or exchanger) in luminal membrane - Basolateral membrane has a 3 HCO3 Na cotransporter - This is electrogenic with 3 anions going out and only one cation - The Na-H antiporter also works in the thick ascending limb of LOH - How about this, there is also a H-ATPase just like found in the intercalated cells in the proximal tubule and is responsible for about a third of H secretion - And similarly there is also. HCO3 Cl exchanger (pendrin-like) in the proximal tubule - Footnote says the Na- 3HCO3 cotransporter (which moves sodium against chemical gradient NS uses negative charge inside cell to power it) is important for sensing acid-base changes in the cell. - Distal acidification - Occurs in intercalated cells of of cortical and medullary collecting tubule - Three main characteristics - H secretion via active secretory pumps in the luminal membrane - Both H-ATPase and H-K ATPase - H- K ATPase is an exchange pump, k reabsorption - H-K exchange may be more important in hypokalemia rather than in acid-base balance - Whole paragraph on how a Na-H exchanger couldn't work because the gradient that H has to be pumped up is too big. - H-ATPase work like vasopressin with premise H-ATPase sitting on endocarditis vesicles a=which are then inserted into the membrane. Alkalosis causes them to be recycled out of the membrane. - H secretory cells do not transport Na since they have few luminal Na channels, but are assisted by the lumen negative tubule from eNaC. - Minimizes back diffusion of H+ and promotes bicarb resorption - Bicarbonate leaves the cell through HCO3-Cl exchanger which uses the low intracellular Cl concentration to power this process. - Same molecule is found on RBC where it is called band 3 protein - Figure 11-5 is interesting - Bicarbonate resorption - 90% in the first 1-22 mm of the proximal tubule (how long is the proximal tubule?) - Lots of Na-H exchangers and I handed permeability to HCO3 (permeability where?) - Last 10% happens distally mostly TAL LOH via Na-H exchange - And the last little bit int he outer medullary collecting duct. - Carbonic anhydrase and disequilibrium pH - CA plays central role in HCO3 reabsorption - After H is secreted in the proximal tubule it combines with HCO# to form carbonic acid. CA then dehydrates it to CO2 and H2O. (Step 2) - Constantly moving carbonic acid to CO2 and H2O keeps hydrogen combining with HCO3 since the product is rapidly consumed. - This can be demonstrated by the minimal fall in luminal pH - That is important so there is not a luminal gradient for H to overcome in the Na-H exchanger (this is why we need a H-ATPase later) - CA inhibitors that are limited tot he extracellular compartment can impair HCO3 reabsorption by 80%. - CA is found in S1, S2 but not S3 segment. See consequence in figure 11-6. - The disequilibrium comes from areas where there is no CA, the HH formula falls down because one of the assumptions of that formula is that H2CO3 (carbonic acid) is a transient actor, but without CA it is not and can accumulate, so the pKa is not 6.1. - Bicarbonate secretion - Type B intercalated cells - H-ATPase polarity reversed - HCO3 Cl exchanger faces the apical rather than basolateral membrane- Titratable acidity - Weak acids are filtered at the glom and act as buffers in the urine. - HPO4 has PKA of 6.8 making it ideal - Creatinine (pKa 4.97) and uric acid (pKa 5.75) also contribute - Under normal cinditions TA buffers 10-40 mEa of H per day - Does an example of HPO4(2-):H2PO4 (1-) which exists 4:1 at pH of 7.4 (glomerular filtrate) - So for 50 mEq of Phos 40 is HPO4 and 10 is H2PO4 - When pH drops to 6.8 then the ratio is 1:1 so for 50 - So the 50 mEq is 25 and 25, so this buffered an additional 15 mEq of H while the free H+ concentration increased from 40 to 160 nanomol/L so over 99.99% of secreted H was buffered - When pH drops to 4.8 ratio is 1:100 so almost all 50 mEq of phos is H2PO4 and 39.5 mEq of H are buffered. - Acid loading decreases phosphate reabsorption so more is there to act as TA. - Decreases activity of Na-phosphate cotransporter - DKA provides a novel weak acid/buffer beta-hydroxybutyrate (pKa 4.8) which buffers significant amount of acid (50 mEq/d).- Ammonium Excretion - Ability to excrete H+ as ammonium ions adds an important amount of flexibility to renal acid-base regulation - NH3 and NH4 production and excretion can be varied according to physiologic need. - Starts with NH3 production in tubular cells - NH3, since it is neutral then diffuses into the tubule where it is acidified by the low pH to NH4+ - NH4+ is ionized and cannot cross back into the tubule cells(it is trapped in the tubular fluid) - This is important for it acting as an important buffer eve though the pKa is 9.0 - At pH of 6.0 the ratio of NH3 to NH4 is 1:1000 - As the neutral NH3 is converted to NH4 more NH3 from theintracellular compartment flows into the tubular fluid replacing the lost NH3. Rinse wash repeat. - This is an over simplification and that there are threemajor steps - NH4 is produced in early proximal tubular cells - Luminal NH4 is partially reabsorbed in the TAL and theNH3 is then recycled within the renal medulla - The medullary interstitial NH3 reaches highconcentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4 by secreted H+ - NH4 production from Glutamine which converts to NH4 and glutamate - Glutamate is converted to alpha-ketoglutarate - Alpha ketoglutarate is converted to 2 HCO3 ions - HCO3 sent to systemic circulation by Na-3 HCO3 transporter - NH4 then secreted via Na-H exchanger into the lumen - NH4 is then reabsorbed by NaK2Cl transporter in TAL - NH4 substitutes for K - Once reabsorbed the higher intracellular pH causes NH4 to convert to NH3 and the H that is removed is secreted through Na-H exchanger to scavenge the last of the filtered bicarb. - NH3 diffuses out of the tubular cells into the interstitium - NH4 reabsorption in the TAL is suppressed by hyperkalemia and stimulated by chronic metabolic acidosis - NH4 recycling promotes acid clearance - The collecting tubule has a very low NH3 concentration - This promotes diffusion of NH3 into the collecting duct - NH3 that goes there is rapidly converted to NH4 allowing more NH3 to diffuse in. - Response to changes in pH - Increased ammonium excretion with two processes - Increased proximal NH4 production - This is delayed 24 hours to 2-3 days depending on which enzyme you look at - Decreased urine pH increases diffusion of ammonia into the MCD - Occurs with in hours of an acid load - Peak ammonium excretion takes 5-6 days! (Fig 11-10) - Glutamine is picked up from tubular fluid but with acidosis get Na dependent peritublar capillary glutamine scavenging too - Glutamine metabolism is pH dependent with increase with academia and decrease with alkalemia - NH4 excretion can go from 30-40 mEq/day to > 300 with severe metabolic acidosis (38 NaBicarb tabs) - Says each NH4 produces equimolar generation of HCO3 but I thought it was two bicarb for every alpha ketoglutarate?- The importance of urine pH - Though the total amount of hydrogren cleared by urine pH is insignificant, an acidic urine pH is essential for driving the reactions of TA and NH4 forward.- Regulation of renal hydrogen excretion - Net acid excretion vary inverse with extracellular pH - Academia triggers proximal and distal acidification - Proximally this: - Increased Na-H exchange - Increased luminal H-ATPase activity - Increased Na:3HCO3 cotransporter on the basolateral membrane - Increased NH4 production from glutamine - In the collecting tubules - Increased H-ATPase - Reduction of tubular pH promotes diffusion of NH3 which gets converted to NH4…ION TRAPPING - Extracellular pH affects net acid excretion through its affect on intracellular pH - This happens directly with respiratory disorders due to movement of CO2 through the lipid bilayer - In metabolic disorders a low extracellular bicarb with cause bicarb to diffuse out of the cell passively, this lowers intracellular pH - If you manipulate both low pCO2 and low Bicarb to keep pH stable there will be no change in the intracellular pH and there is no change in renal handling of acid. It is intracellular pH dependent - Metabolic acidosis - Ramps up net acid secretion - Starts within 24 hours and peaks after 5-6 days - Increase net secretion comes from NH4 - Phosphate is generally limited by diet - in DKA titratable acid can be ramped up - Metabolic alkalosis - Alkaline extracellular pH - Increased bicarb excretion - Decrease reabsorption - HCO3 secretion (pendrin) in cortical collecting tubule - Occurs in cortical intercalated cells able to insert H-ATPase in basolateral cells (rather than luminal membrane) - Normal subjects are able to secrete 1000 mmol/day of bicarb - Maintenance of metabolic alkalosis requires a defect which forces the renal resorption of bicarb - This can be chloride/volume deficiency - Hypokalemia - Hyperaldosteronism - Respiratory acidosis and alkalosis - PCO2 via its effect on intracellular pH is an important determinant of renal acid handling - Ratios he uses: - 3.5 per 10 for respiratory acidosis - 5 per 10 for respiratory alkalosis - Interesting paragraph contrasting the response to chronic metabolic acidosis vs chronic respiratory acidosis - Less urinary ammonium in respiratory acidosis - Major differences in proximal tubule cell pH - In metabolic acidosis there is decreased bicarb load so less to be reabsorbed proximally - In respiratory acidosis the increased serum bicarb increases the amount of bicarb that must be reabsorbed proximally - The increased activity of Na-H antiporter returns tubular cell pH to normal and prevents it from creating increased urinary ammonium - Mentions that weirdly more mRNA for H-Na antiporter in metabolic acidosis than in respiratory acidosis - Net hydrogen excretion varies with effective circulating volume - Starts with bicarb infusions - Normally Tm at 26 - But if you volume deplete the patient with diuretics first this increases to 35+ - Four factors explain this increased Tm for bicarb with volume deficiency - Reduced GFR - Activation of RAAS - Ang2 stim H-Na antiporter proximally - Ang2 also stimulates Na-3HCO3 cotransporter on basolateral membrane - Aldosterone stimulates H-ATPase in distal nephron - ALdo stimulates Cl HCO3 exchanger on basolateral membrane - Aldo stimulates eNaC producing tubular lumen negative charge to allow H secretion to occur and prevents back diffusion - Hypochloremia - Increases H secretion by both Na-dependent and Na-independent methods - If Na is 140 and Cl is 115, only 115 of Na can be reabsorbed as NaCl, the remainder must be reabsorbed with HCO3 or associated with secretion of K or H to maintained electro neutrality - This is enhanced with hypochloridemia - Concurrent hypokalemia - Changes in K lead to trans cellular shifts that affect inctracellular pH - Hypokalemia causes K out, H in and in the tubular cell the cell acts if there is systemic acidosis and increases H secretion (and bicarbonate resorption) - PTH - Decreases proximal HCO3 resorption - Primary HyperCard as cause of type 2 RTA - Does acidosis stim PTH or does PTH stim net acid excretion

You probably know that the kidneys play an important role in maintaining blood pressure within the normal range. You might also know that they do this by regulating blood volume and the degree of arterial contraction or dilation (the systemic vascular resistance). But do you know how the kidneys do this? The answer is the kidneys accomplish this primarily through a set of hormones and enzymes known together as the renin-angiotensin-aldosterone system (RAAS). In this brick, we will discuss the components, functions, and regulation of the RAAS. Renin is an enzyme released by the kidneys that ultimately causes the formation of the hormone angiotensin II (Ang II) in the body—which in turn stimulates the release of the hormone aldosterone from the adrenal cortex. Ang II and aldosterone act in a number of ways to increase blood volume and blood pressure. RAAS acts to increase sodium reabsorption in the kidney, increase vascular tone, and even stimulate antidiuretic hormone (ADH) to reabsorb more water: all of these defend our extracellular volume and blood pressure. RAAS is therefore a critical system for keeping us upright! After listening to this Audio Brick, you should be able to: Outline the renin-angiotensin-aldosterone system, including sensors, factors that control it, sources of hormone release, and the actions of each hormone. Describe the mechanisms by which the renin-angiotensin-aldosterone system regulates blood pressure. Compare and contrast tubuloglomerular feedback with the renin-angiotensin-aldosterone system. You can also check out the original brick from our Endocrine collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.

ReferencesWe 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 DiseaseHostetter 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 massWesson explored treatment of metabolic acidosis in humans with stage 3 CKD in this study. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rateIn addition to the effect of metabolic acidosis from a diet high in animal protein, this diet also leads to hyperfiltration. This was demonstrated in normal subjects; ingesting a protein diet had a significantly higher creatinine clearance than a comparable group of normal subjects ingesting a vegetarian diet. Renal functional reserve in humans: Effect of protein intake on glomerular filtration rate.This finding has been implicated in Brenner's theory regarding hyperfiltration: The hyperfiltration theory: a paradigm shift in nephrologyOne of multiple publications from Dr. Nimrat Goraya whom Joel mentioned in the voice over: Dietary Protein as Kidney Protection: Quality or Quantity?We wondered about the time course in buffering a high protein meal (and its subsequent acid load on ventilation) and Amy found this report:Effect of Protein Intake on Ventilatory Drive | Anesthesiology | American Society of Anesthesiologists Roger mentioned that the need for acetate to balance the acid from amino acids in parenteral nutrition was identified in pediatrics perhaps because infants may have reduced ability to generate acid. Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition - PMCHe also recommended an excellent review on the complications of parenteral nutrition by Knochel https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2815%2933384-6 which explained that when the infused amino acids disproportionately include cationic amino acids, metabolism led to H+ production. This is typically mitigated by preparing a solution that is balanced by acetate. Amy mentioned this study that explored the effect of protein intake on ventilation: Effect of Protein Intake on Ventilatory Drive | Anesthesiology | American Society of AnesthesiologistsAnna and Amy reminisced about a Skeleton Key Group Case from the renal fellow network Skeleton Key Group: Electrolyte Case #7JC wondered about isolated defects in the proximal tubule and an example is found here: Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalitiesAnna's Voiceover re: Gastric neobladder → metabolic alkalosis and yes, dysuria. The physiology of gastrocystoplasty: once a stomach, always a stomach but not as common as you might think Gastrocystoplasty: long-term complications in 22 patientsSjögren's syndrome has been associated with acquired distal RTA and in some cases, 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 acidosisCan't get enough disequilibrium pH? Check this out- Spontaneous luminal disequilibrium pH in S3 proximal tubules. Role in ammonia and bicarbonate transport.Acetazolamide secretion was studied in this report Concentration-dependent tubular secretion of acetazolamide and its inhibition by salicylic acid in the isolated perfused rat kidney. | Drug Metabolism & DispositionIn this excellent review, David Goldfarb tackles the challenging case of a A Woman with Recurrent Calcium Phosphate Kidney Stones (spoiler alert, many of these patients have incomplete distal RTA and this problem is hard to treat). Molecular mechanisms of renal ammonia transport excellent review from David Winer and Lee Hamm. OutlineOutline: Chapter 11- Regulation of Acid-Base Balance- Introduction - Bicarb plus a proton in equilibrium with CO2 and water - Can be rearranged to HH - Importance of regulating pCO2 and HCO3 outside of this equation - Metabolism of carbs and fats results in the production of 15,000 mmol of CO2 per day - Metabolism of protein and other “substances” generates non-carbonic acids and bases - Mostly from sulfur containing methionine and cysteine - And cationic arginine and lysine - Hydrolysis of dietary phosphate that exists and H2PO4– - Source of base/alkali - Metabolism of an ionic amino acids - Glutamate and asparatate - Organic anions going through gluconeogenesis - Glutamate, Citrate and lactate - Net effect on a normal western diet 50-100 mEq of H+ per day - Homeostatic response to these acid-base loads has three stages: - Chemical buffering - Changes in ventilation - Changes in H+ excretion - Example of H2SO4 from oxidation of sulfur containing AA - Drop in bicarb will stimulate renal acid secretion - Nice table of normal cid-base values, arterial and venous- Great 6 bullet points of acid-base on page 328 - Kidneys must excrete 50-100 of non-carbonic acid daily - This occurs by H secretion, but mechanisms change by area of nephron - Not excreted as free H+ due to minimal urine pH being equivalent to 0.05 mmol/L - No H+ can be excreted until virtually all of th filtered bicarb is reabsorbed - Secreted H+ must bind buffers (phosphate, NH3, cr) - PH is main stimulus for H secretion, though K, aldo and volume can affect this.- Renal Hydrogen excretion - Critical to understand that loss of bicarb is like addition of hydrogen to the body - So all bicarb must be reabsorbed before dietary H load can be secreted - GFR of 125 and bicarb of 24 results in 4300 mEq of bicarb to be reabsorbed daily - Reabsorption of bicarb and secretion of H involve H secretion from tubular cells into the lumen. - Thee initial points need to be emphasized - Secreted H+ ion are generated from dissociation of H2O - Also creates OH ion - Which combine with CO2 to form HCO3 with the help of zinc containing intracellular carbonic anhydrase. - This is how the secretion of H+ which creates an OH ultimately produces HCO3 - Different mechanisms for proximal and distal acidification - NET ACID EXCRETION - Free H+ is negligible - So net H+ is TA + NH4 – HCO3 loss - Unusually equal to net H+ load, 50-100 mEq/day - Can bump up to 300 mEq/day if acid production is increased - Net acid excretion can go negative following a bicarb or citrate load - Proximal Acidification - Na-H antiporter (or exchanger) in luminal membrane - Basolateral membrane has a 3 HCO3 Na cotransporter - This is electrogenic with 3 anions going out and only one cation - The Na-H antiporter also works in the thick ascending limb of LOH - How about this, there is also a H-ATPase just like found in the intercalated cells in the proximal tubule and is responsible for about a third of H secretion - And similarly there is also. HCO3 Cl exchanger (pendrin-like) in the proximal tubule - Footnote says the Na- 3HCO3 cotransporter (which moves sodium against chemical gradient NS uses negative charge inside cell to power it) is important for sensing acid-base changes in the cell. - Distal acidification - Occurs in intercalated cells of of cortical and medullary collecting tubule - Three main characteristics - H secretion via active secretory pumps in the luminal membrane - Both H-ATPase and H-K ATPase - H- K ATPase is an exchange pump, k reabsorption - H-K exchange may be more important in hypokalemia rather than in acid-base balance - Whole paragraph on how a Na-H exchanger couldn't work because the gradient that H has to be pumped up is too big. - H-ATPase work like vasopressin with premise H-ATPase sitting on endocarditis vesicles a=which are then inserted into the membrane. Alkalosis causes them to be recycled out of the membrane. - H secretory cells do not transport Na since they have few luminal Na channels, but are assisted by the lumen negative tubule from eNaC. - Minimizes back diffusion of H+ and promotes bicarb resorption - Bicarbonate leaves the cell through HCO3-Cl exchanger which uses the low intracellular Cl concentration to power this process. - Same molecule is found on RBC where it is called band 3 protein - Figure 11-5 is interesting - Bicarbonate resorption - 90% in the first 1-22 mm of the proximal tubule (how long is the proximal tubule?) - Lots of Na-H exchangers and I handed permeability to HCO3 (permeability where?) - Last 10% happens distally mostly TAL LOH via Na-H exchange - And the last little bit int he outer medullary collecting duct. - Carbonic anhydrase and disequilibrium pH - CA plays central role in HCO3 reabsorption - After H is secreted in the proximal tubule it combines with HCO# to form carbonic acid. CA then dehydrates it to CO2 and H2O. (Step 2) - Constantly moving carbonic acid to CO2 and H2O keeps hydrogen combining with HCO3 since the product is rapidly consumed. - This can be demonstrated by the minimal fall in luminal pH - That is important so there is not a luminal gradient for H to overcome in the Na-H exchanger (this is why we need a H-ATPase later) - CA inhibitors that are limited tot he extracellular compartment can impair HCO3 reabsorption by 80%. - CA is found in S1, S2 but not S3 segment. See consequence in figure 11-6. - The disequilibrium comes from areas where there is no CA, the HH formula falls down because one of the assumptions of that formula is that H2CO3 (carbonic acid) is a transient actor, but without CA it is not and can accumulate, so the pKa is not 6.1. - Bicarbonate secretion - Type B intercalated cells - H-ATPase polarity reversed - HCO3 Cl exchanger faces the apical rather than basolateral membrane- Titratable acidity - Weak acids are filtered at the glom and act as buffers in the urine. - HPO4 has PKA of 6.8 making it ideal - Creatinine (pKa 4.97) and uric acid (pKa 5.75) also contribute - Under normal cinditions TA buffers 10-40 mEa of H per day - Does an example of HPO4(2-):H2PO4 (1-) which exists 4:1 at pH of 7.4 (glomerular filtrate) - So for 50 mEq of Phos 40 is HPO4 and 10 is H2PO4 - When pH drops to 6.8 then the ratio is 1:1 so for 50 - So the 50 mEq is 25 and 25, so this buffered an additional 15 mEq of H while the free H+ concentration increased from 40 to 160 nanomol/L so over 99.99% of secreted H was buffered - When pH drops to 4.8 ratio is 1:100 so almost all 50 mEq of phos is H2PO4 and 39.5 mEq of H are buffered. - Acid loading decreases phosphate reabsorption so more is there to act as TA. - Decreases activity of Na-phosphate cotransporter - DKA provides a novel weak acid/buffer beta-hydroxybutyrate (pKa 4.8) which buffers significant amount of acid (50 mEq/d).- Ammonium Excretion - Ability to excrete H+ as ammonium ions adds an important amount of flexibility to renal acid-base regulation - NH3 and NH4 production and excretion can be varied according to physiologic need. - Starts with NH3 production in tubular cells - NH3, since it is neutral then diffuses into the tubule where it is acidified by the low pH to NH4+ - NH4+ is ionized and cannot cross back into the tubule cells(it is trapped in the tubular fluid) - This is important for it acting as an important buffer eve though the pKa is 9.0 - At pH of 6.0 the ratio of NH3 to NH4 is 1:1000 - As the neutral NH3 is converted to NH4 more NH3 from theintracellular compartment flows into the tubular fluid replacing the lost NH3. Rinse wash repeat. - This is an over simplification and that there are threemajor steps - NH4 is produced in early proximal tubular cells - Luminal NH4 is partially reabsorbed in the TAL and theNH3 is then recycled within the renal medulla - The medullary interstitial NH3 reaches highconcentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4 by secreted H+ - NH4 production from Glutamine which converts to NH4 and glutamate - Glutamate is converted to alpha-ketoglutarate - Alpha ketoglutarate is converted to 2 HCO3 ions - HCO3 sent to systemic circulation by Na-3 HCO3 transporter - NH4 then secreted via Na-H exchanger into the lumen - NH4 is then reabsorbed by NaK2Cl transporter in TAL - NH4 substitutes for K - Once reabsorbed the higher intracellular pH causes NH4 to convert to NH3 and the H that is removed is secreted through Na-H exchanger to scavenge the last of the filtered bicarb. - NH3 diffuses out of the tubular cells into the interstitium - NH4 reabsorption in the TAL is suppressed by hyperkalemia and stimulated by chronic metabolic acidosis - NH4 recycling promotes acid clearance - The collecting tubule has a very low NH3 concentration - This promotes diffusion of NH3 into the collecting duct - NH3 that goes there is rapidly converted to NH4 allowing more NH3 to diffuse in. - Response to changes in pH - Increased ammonium excretion with two processes - Increased proximal NH4 production - This is delayed 24 hours to 2-3 days depending on which enzyme you look at - Decreased urine pH increases diffusion of ammonia into the MCD - Occurs with in hours of an acid load - Peak ammonium excretion takes 5-6 days! (Fig 11-10) - Glutamine is picked up from tubular fluid but with acidosis get Na dependent peritublar capillary glutamine scavenging too - Glutamine metabolism is pH dependent with increase with academia and decrease with alkalemia - NH4 excretion can go from 30-40 mEq/day to > 300 with severe metabolic acidosis (38 NaBicarb tabs) - Says each NH4 produces equimolar generation of HCO3 but I thought it was two bicarb for every alpha ketoglutarate?- The importance of urine pH - Though the total amount of hydrogren cleared by urine pH is insignificant, an acidic urine pH is essential for driving the reactions of TA and NH4 forward.- Regulation of renal hydrogen excretion - Net acid excretion vary inverse with extracellular pH - Academia triggers proximal and distal acidification - Proximally this: - Increased Na-H exchange - Increased luminal H-ATPase activity - Increased Na:3HCO3 cotransporter on the basolateral membrane - Increased NH4 production from glutamine - In the collecting tubules - Increased H-ATPase - Reduction of tubular pH promotes diffusion of NH3 which gets converted to NH4…ION TRAPPING - Extracellular pH affects net acid excretion through its affect on intracellular pH - This happens directly with respiratory disorders due to movement of CO2 through the lipid bilayer - In metabolic disorders a low extracellular bicarb with cause bicarb to diffuse out of the cell passively, this lowers intracellular pH - If you manipulate both low pCO2 and low Bicarb to keep pH stable there will be no change in the intracellular pH and there is no change in renal handling of acid. It is intracellular pH dependent - Metabolic acidosis - Ramps up net acid secretion - Starts within 24 hours and peaks after 5-6 days - Increase net secretion comes from NH4 - Phosphate is generally limited by diet - in DKA titratable acid can be ramped up - Metabolic alkalosis - Alkaline extracellular pH - Increased bicarb excretion - Decrease reabsorption - HCO3 secretion (pendrin) in cortical collecting tubule - Occurs in cortical intercalated cells able to insert H-ATPase in basolateral cells (rather than luminal membrane) - Normal subjects are able to secrete 1000 mmol/day of bicarb - Maintenance of metabolic alkalosis requires a defect which forces the renal resorption of bicarb - This can be chloride/volume deficiency - Hypokalemia - Hyperaldosteronism - Respiratory acidosis and alkalosis - PCO2 via its effect on intracellular pH is an important determinant of renal acid handling - Ratios he uses: - 3.5 per 10 for respiratory acidosis - 5 per 10 for respiratory alkalosis - Interesting paragraph contrasting the response to chronic metabolic acidosis vs chronic respiratory acidosis - Less urinary ammonium in respiratory acidosis - Major differences in proximal tubule cell pH - In metabolic acidosis there is decreased bicarb load so less to be reabsorbed proximally - In respiratory acidosis the increased serum bicarb increases the amount of bicarb that must be reabsorbed proximally - The increased activity of Na-H antiporter returns tubular cell pH to normal and prevents it from creating increased urinary ammonium - Mentions that weirdly more mRNA for H-Na antiporter in metabolic acidosis than in respiratory acidosis - Net hydrogen excretion varies with effective circulating volume - Starts with bicarb infusions - Normally Tm at 26 - But if you volume deplete the patient with diuretics first this increases to 35+ - Four factors explain this increased Tm for bicarb with volume deficiency - Reduced GFR - Activation of RAAS - Ang2 stim H-Na antiporter proximally - Ang2 also stimulates Na-3HCO3 cotransporter on basolateral membrane - Aldosterone stimulates H-ATPase in distal nephron - ALdo stimulates Cl HCO3 exchanger on basolateral membrane - Aldo stimulates eNaC producing tubular lumen negative charge to allow H secretion to occur and prevents back diffusion - Hypochloremia - Increases H secretion by both Na-dependent and Na-independent methods - If Na is 140 and Cl is 115, only 115 of Na can be reabsorbed as NaCl, the remainder must be reabsorbed with HCO3 or associated with secretion of K or H to maintained electro neutrality - This is enhanced with hypochloridemia - Concurrent hypokalemia - Changes in K lead to trans cellular shifts that affect inctracellular pH - Hypokalemia causes K out, H in and in the tubular cell the cell acts if there is systemic acidosis and increases H secretion (and bicarbonate resorption) - PTH - Decreases proximal HCO3 resorption - Primary HyperCard as cause of type 2 RTA - Does acidosis stim PTH or does PTH stim net acid excretion

Today on The Woman's Doctor, we dispel common myths around women's health with Dr.Susanne Bennett. She is an authority on hormonal and gut health with over 30 years of experience as a natural medicine doctor. Dr. Bennett holds specialties in clinical nutrition, environmental medicine, allergies, aging and gut health. She brings a fresh perspective on women's health that inspires hope for a healthy and happy life even into your menopausal years.   Society convinces women that life stops at menopause, treating it like a disease to be avoided and ashamed of. The reality is that menopause is nothing more than the end of your menstrual cycle. By committing to a healthy lifestyle and a diet that feeds healthy mitochondria, you can eliminate anxiety and expect to thrive in the later years of your life.    Hormonal imbalance is just one contributing factor to anxiety and irritability in women. Unhealthy diet and sleep habits influence your ability to deal with stress and lead to uncontrollable anger and chronic illness.Sometimes anxiety can simply be the result of a food allergy. If you truly want to improve the quality of your life, you need to get  to the root cause of your hormonal and gut imbalance.In this episode, Dr. Bennett teaches you everything you need to avoid and habits to adopt to support a healthy mind and body.   Takeaways: [3:48] When the ovaries are unable to ovulate, Menopause begins as the menstrual cycle ends [4:44] Menopause is not a disease it is a natural phase in a woman's life [6:40] Your pituitary gland dictates the function of your thyroid, adrenals and female organs  [7:45] Aldosterone produced by your adrenals, controls your water metabolism in your body [10:58] Unhealthy mitochondria speeds the aging process and contributes to chronic illness [12:00] The luteal phase affects women's mood often causing sleeplessness and irritability  [12:49] Women with low levels of the calming hormone progesterone have trouble sleeping [15:00] Gluten and dairy contain compounds that are considered opiates to the brain [18:30] Fat is our number one source for energy and is essential to mitochondria health   Mentioned in This Episode: DrSusanne.com Book: Mighty Mito Wellness For Life Radio   Twitter: “Your mitochondria has everything to do with the aging process, everything to do with every disease, chronic illnesses  that we deal with from diabetes to heart disease.”[11:10]   “You can get anxiety just from a food allergy!” [16:10]   “Mycotoxins, mold toxins! You're exposed to mold in your environment. You breathe it in and boom! It goes right up through your nose into your brain, that will clearly cause anxiety!”  [16:36]     Podcast Disclaimer:  https://resources.thespadr.com/the-womans-doctor/#disclaimer

Dr. Michelle Gumz is an associate professor at the University of Florida. Her research focuses on the kidney's circadian clock and its relationship to cardiovascular health. In this episode, Dr. Gumz details how the circadian clock provides a mechanism for predictive homeostasis that directly impacts cardiovascular and kidney function. She also explains why normal sleep patterns are critical to long-term health outcomes. Dr. Gumz has a long-time interest in the molecular control of renal function. The Gumz laboratory is investigating the role of the molecular circadian clock in the kidney with the long-term goal of determining how the clock in the kidney contributes to the control of blood pressure and overall cardiovascular health. Aldosterone is a mineralocorticoid hormone that regulates sodium balance and blood pressure. As a graduate student, Dr. Gumz was the first to identify the circadian clock gene Period 1 as an aldosterone target. She has subsequently shown that Period 1 regulates the transcription of alpha ENaC, the aldosterone-regulated and rate-limiting subunit of the epithelial sodium channel. New areas of study include cross-talk between the kidney clock and other tissue clocks and sex differences in the function of Period 1 and Bmal1, another critical core clock gene. Follow Dr. Michelle Gumz on Twitter University of Florida Division of Nephrology, Hypertension & Renal Transplantation Sign up for Erik's weekly newsletter - Adaptation Join the AIM7 Beta Community ABOUT THE BLUEPRINT PODCAST: The BluePrint Podcast is for busy professionals and Household CEOs who care deeply about their families, career, and health. Host Dr. Erik Korem distills cutting edge-science, leadership, and life skills into simple tactics optimized for your busy lifestyle and goals.   Dr. Korem interviews scientists, coaches, elite athletes, entrepreneurs, entertainers, and exceptional people to discuss science and practical skills you can implement to become the most healthy, resilient, and impactful version of yourself.   On a mission to equip people to pursue audacious goals, thrive in uncertainty, and live a healthy and fulfilled life, Dr. Erik Korem is a High Performance pioneer. He introduced sports science and athlete tracking technologies to collegiate and professional (NFL) football over a decade ago. He has worked with the National Football League, Power-5 NCAA programs, gold-medal Olympians, Nike, and the United States Department of Defense.   Erik is an expert in sleep and stress resilience. He is the Founder and CEO of AIM7, a health and fitness app that unlocks the power of wearables by providing you with daily personalized recommendations to enhance your mind, body, and recovery. SUPPORT & CONNECT   Instagram - https://www.instagram.com/erikkorem/ Twitter - https://twitter.com/ErikKorem LinkedIn - https://www.linkedin.com/in/erik-korem-phd-19991734/ Facebook - https://www.facebook.com/erikkorem Website - https://www.erikkorem.com/ Newsletter - https://erikkoremhpcoach.activehosted.com/f/  ______________________________________________________________ QUOTES   “The key is using stress and adapting to it and improving. That's what high performance is to me, the ability to adapt rapidly so you can achieve your potential. There are five key pillars to creating the conditions for adaptability: sleep, exercise, mental resilience, nutrition, and community/relationships.” - Dr. Erik Korem   "Stress is your brain and body preparing you to do something effortful." Dr. Alex Auerbach “I maybe have a different concept on leadership. To me, leading is a verb. If you're leading, you're a leader. If you're swimming, you're a swimmer, if you're driving, you're a driver. If you're leading, you're by definition, a leader. I define leading as being looked to in a particular moment to decide or perform an action based on your unique gifts and abilities. So by that definition, everybody is a leader. All rank and role really describe is how many people are hoping you get it right when it's your turn to wear the weight.” - Clint Bruce "Attention is the currency of performance." - Dr. Peter Haberl “That's what I've discovered in the lives of brilliant, prolific, healthy creatives, is that they have networks of people they leverage in the course of their work. That they learn from, that they were challenged by, that they gave great insight and purview into their own life and work, in such a way that they were able to receive feedback that helped them get better at what they do.” - Todd Henry "Restful and fulfilling sleep enables you to grow, adapt, and thrive. It creates the conditions for adaptation, so you can pursue audacious goals and thrive in uncertainty." - Dr. Erik Korem "Most exercise programs fail, not because the reps and sets are poorly designed, but because the program doesn't adjust for how much stress your body can adapt to that day! That's why Dr. Chris Morris' research and practical application of fluid periodization is the key for unlocking your performance potential." - Dr. Erik KoremSee omnystudio.com/listener for privacy information.

Today we speak with Dr. Ben Bikman, PhD.  Professor of Bioenergetics, Scientific Researcher, and Author of the book "WHY WE GET SICK", an essential manual to understand how to prevent and cure the most prevalent diseases of the XXI century. A revealing interview where we discuss the common denominator, the origin and the cure for conditions such as Diabetes 2, Fatty liver, Cancer, Alzheimer's Disease, and hypertension. In the Laboratory, Dr. Bikman identifies the mechanism of how weight gain is directly related to the risk of disease and what we must do TO NOT GET SICK and to SAY NO TO ANY MEDICAL SENTENCE.TIP: "OFF the record" : To keep your glucose and  insulin at bay,   walk a few minutes after a meal.Episode Guide:02:15 - What is Insulin Resistance04:46 - List of diseases related to insulin resistance07:18 - Does salt impact our blood pressure?08:30 - What is Aldosterone and how is it related to blood pressure10:10 - What causes fatty liver disease12:45 - How the body uses fructose15:13 - Cellular aging and skin disorders18:01 - The key to aging well19:10 - How Insulin Inhibits Autophagy19:30 - Gastric reflux and gastrointestinal imbalances25:10 - What bacteria feed on26:40 - Why we get fat31:40 - How to control hunger35:15 - Recommendations for a good breakfast and the fat burning function39:40 - The best time to eat something sugary41:55 - Ideal time for the last meal of the day48:05 - "Tips" to control "indulgent" meals54:25 - Is Type 2 Diabetes reversible?57:50 - Migraines and recommended diethttps://www.facebook.com/CocoMarchNMDhttps://www.instagram.com/cocomarch.nmd/https://www.youtube.com/channel/UCyT1tdUjfnbA-4Cqrz8BwFghttps://blog.dracocomarch.comhttps://store.dracocomarch.com/es/https://podcast.comocurar.com/

In this extremely HY podcast, I discuss the renin angiotensin aldosterone system in detail and also make lots of integrations that show up as exam questions on all the USMLEs. Definitely worth a listen before you take your test. Audio Download

✅ Why is the recommendation to go on a low-salt diet a scam? In this video, I'll reveal why the science doesn't support this, and how countries that live the longest also eat lots of salt. This is the exact opposite of what our health "experts" recommend. You'll be shocked by the chart I'm going to show you. ✅ Support the Doctor Park Locals.com community. Help me to write my book. https://doctorpark.locals.com/support... ✅ DOWNLOAD TRANSCRIPT https://doctorstevenpark.com/wp-conte... ✅ CHAPTERS: 00:00 Introduction 01:15 Most people don't respond to salt 01:37 The top 3 countries that live the longest also eat very high levels of salt 02:42 Counties that eat more salt live the longest 02:57 Countries that eat less salt die earlier 03:13 Salt intake and U-shaped mortality curve at both extremes ✅ LINKS MENTIONED Salt sensitivity of blood pressure in humans https://www.ahajournals.org/doi/full/... Coronary heart disease age-related death https://www.worldlifeexpectancy.com/c... 11 Countries That Consume the Most Salt https://www.insidermonkey.com/blog/11... Sodium intake, life expectancy, and all-cause mortality https://europepmc.org/backend/ptpmcre... Sodium Intake and Health: What Should We Recommend Based on the Current Evidence? https://www.mdpi.com/2072-6643/13/9/3232 ✅ PRODUCTS & SERVICES How you can sleep great and have more energy and mental clarity. Dr. Park's The 90-Day Sleep Diet. http://the90daysleepdiet.com/ Want to un-stuff your stuffy nose? Read the e-book, How to Un-stuff Your Stuffy Nose: Breathe Better, Lose Weight, Sleep Great (PDF) https://www.unstuffyourstuffynose.com... Your Health Transformation Workbook: Refresh, Restore, & Rejuvenate Your Life (online format) https://doctorpark.samcart.com/produc... Want to have more energy, sleep better, have less pain, and enjoy living again? Reserve a Virtual Coaching session today with Dr. Park https://doctorpark.samcart.com/produc... ✅ CONNECT WITH DR. PARK DoctorStevenPark.com doctorpark@doctorstevenpark.com For inquiries about interviews or presentations, please contact Dr. Park through his website at doctorstevenpark.com. ✅ DISCLAIMER This video is for general educational and informational purposes only. It is not to be taken as a substitute for professional medical advice, diagnosis, or treatment. Please consult with your doctor first before making any changes to your health, exercise, nutrition, or dietary regimen. Certain product links above will take you to Amazon.com. If you then go on to buy the product, Amazon will provide me with a small commission, which will not cost you anything.

The Pickle Jar is all about us SALTY PICKLES in the jar...and I am so happy you are in it with me. Aldosterone is the other LIFE SUSTAINING HORMONE besides cortisol people living the Primary Addison's Disease need to replace it. Aldosterone works with the kidneys to maintain sodium balance in the blood. Sodium together with potassium maintains glucose metabolism and gives us energy. Wasting salt causes INTENSE SALT CRAVES, low blood pressure, light-headedness and muscle cramps. SALT is the electricity of the cells...without it...the LIGHTS are on but no one home!!!!! Please help us build our community. Make this pickle happy and subscribe, review, and share THE PICKLE JAR PODCAST. If you would like to share your journey on THE PICKLE JAR please email me at thepicklejar@rogers.com Follow on Instagram @the_picklejar DISCLAIMER: The information from THE PICKLE JAR represents the experiences of the host Jill Battle and the individual experiences of each guest. No information is intended to provide or replace the medical advice of a medical professional. The host or guests are not liable for any negative consequences from any treatment, action, application or preparation, to any person following the information from the podcast.

  Podcast Highlights: 00:27 Taking Breaks from Adaptogens 04:26– Serum Sodium Ranges 05:40 – U-Shape curves 08:06– Functional Ranges on blood work 09:28 – The Salt Fix 10:50 – Healthy Sodium ranges 12:01– Low Sodium 13:25– Adrenal Fatigue 15:48 – Orthostatic Hypotension 20:36– Table Salt 24:01 - Aldosterone 25:44 - Hypovolemia 28:41 – Mild Hyponatremia...... Continue Reading →

Also asked as mineralocorticoids and glucocorticoids

Podcast Highlights: 01:31:03 – Hypertension and polymorphisms of the Sammi people 10:12:06 – I have a MCV on my blood test of 101, what does that mean? 27:29:18 – What are your thoughts about using mushrooms as an alternative to caffeine or espressos? 30:25:19 – What’s can I put in a protein shakes for my [...]Read More »

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists. I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine. Here's the case: A 6-year-old child with a known h/o craniopharyngioma who has been endocrinologically intact with exception of needing thyroid replacement was admitted to the PICU prior to craniotomy to proceed with further tumor resection as well as the removal of a secondary cyst impacting his brainstem. The patient is receiving Keppra for seizures and per mother, he has recently been significantly more sleepy at school. On POD Op day 5: the PICU the bedside nurse notices increased urine output (6cc/kg/hr to as high as 10cc/kg/hr). Initially, there was an increase in Na to 157mEq/L within 48-72 hours the serum Na dropped to 128mEq/L To summarize key elements from this case, this patient has: Increase UOP Rapidly increasing Na initially followed by a drop All of which brings up a concern for Na abnormality post craniotomy In today's episode, we will be breaking down all things Sodium & the Brain. We will discuss diagnostic & management frameworks related to three pathologies: Central Diabetes Insipidus Syndrome of inappropriate Anti-Diuretic Hormone or SIADH Cerebral Salt Wasting These diagnoses can certainly be seen individually inpatients or as a spectrum of diseases — as we go through each of these diagnoses, pay particular attention to patient characteristics and lab abnormalities. Namely, serum sodium, serum osm, and urine osm. To build the fundamentals, lets first start with classic nephrology saying: Serum Na represents Hydration This takes us into a brief review of normal physiology — talking about three important hormones: ADH Aldosterone Atrial Natriuretic Peptide (ANP) Let's go through a quick multiple-choice question. A patient is recently started on DDAVP for pan-hypopituitarism. The medication acts similarly to a hormone that is physiologically synthesized in which of the following from which are in the body? A. Paraventricular Nucleus of the Hypothalamus B. Supraoptic Nucleus of the Hypothalamus C. Anterior Pituitary D. Vascular Endothelium The correct answer here is B the Supraoptic Nucleus of the Hypothalamus. Remember that ADH is synthesized in the hypothalamus and released from the posterior pituitary. What are the physiologic actions of ADH? ADH Increases H2O permeability by directing the insertion of aquaporin 2 (AQP2) H2O channels in the luminal membrane of the principal cells. Thus, as we will see with Central Diabetes insipidus, in the absence of ADH, the principal cells are virtually impermeable to water. Let's talk about our next hormone, aldosterone. What are the important physiologic considerations? Aldosterone is secreted from the adrenal cortex as a byproduct of the RAAS. Aldosterone increases Na+ reabsorption by the renal distal tubule, thereby increasing extracellular fluid (ECF) volume, blood volume, and arterial pressure. It also helps in secreting K and H. This physiology is applied directly at the bedside when we have patients in the ICU who have a contraction alkalosis secondary to diuretics. The increase in aldosterone as these patients lose free water from their Lasix administration results in hypokalemia and metabolic alkalosis. Alright, what about the third hormone, ANP? Atrial natriuretic peptide (ANP) is released from the atria in response to an increase in blood volume and atrial pressure. ANP causes relaxation of vascular smooth muscle, dilation of arterioles, and decreased TPR. causes increased excretion of Na+ and water by the kidney, which reduces blood volume and attempts to bring arterial pressure down to normal. As ANP causes natriuresis, diuresis, and inhibition of renin, you can consider this hormone as having a complementary & opposite effect to ADH and aldosterone. Alright, now that we...

Heart failure patients are generally multi-morbid and at risk for hyperkalemia, which makes treatment with life-saving therapies like RAASi difficult and leads to compromised medical treatment and in turn poor outcomes. This trials showed that with the use of patiromer, one can simultaneously lower the risk of hyperkalemia and increase optimal medical therapy for heart failure with reduced ejection fraction. In this interview, Javed Butler, MD MPH MBA, Anthony N. DeMaria MD, MACC, with Ioannis Mastoris, MD, MPHcand, discuss the Late Breaker: DIAMOND trial: Patiromer For The Management Of Hyperkalemia In Subjects Receiving Renin-angiotensin-aldosterone System Inhibitor Medications For Heart Failure With Reduced Ejection Fraction.

In this podcast, Dr Murray Epstein, Professor of Medicine Emeritus in the division of Nephrology and Hypertension at the University of Miami, Miller School of Medicine, discusses Aldosterone and Mineralocorticoid Receptor Antagonists in 2021. This podcast is published open access in Diabetes Therapy and is fully citeable. You can access the original published podcast article through the Diabetes Therapy website and by using this link. All conflicts of interest can be found online.   This podcast is intended for medical professionals only.   Open Access This podcast is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The material in this podcast is included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

In this episode, we review the high-yield topic of Renin-Angiotensin-Aldosterone System from the Renal section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbulletsIn this episode --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

Investigating Your Adrenal and Hormones With a DUTCH Test | Podcast #327 Schedule a FREE Consult: http://www.justinhealth.com/free-consultation Recommended products: DUTCH Adrenal Test - https://justinhealth.com/products/dutch-adrenal-test/ DUTCH Complete Hormone Test - https://justinhealth.com/products/dutch-complete-hormone-test/ DUTCH Sex Hormone Metabolites - https://justinhealth.com/products/dutch-sex-hormone- metabolites/ FemmenessencePRO: https://justinhealth.com/products/femmenessence-menopause/ Review us at: http://www.beyondwellnessradio.com/itunes Podcast Transcription: https://justinhealth.com/investigating-your-adrenal-and-hormones-with-a-dutch-test-podcast-327/ Get Show Updates Here: http://justinhealth.com/beyondwellness-newsletter You-tube Podcast Subscribe: http://www.youtube.com/subscription_center?add_user=justinhealth In this podcast, Dr. J and Evan talk about the adrenal glands in our body - to produce certain hormones directly into the bloodstream. These hormones will respond to stress and other necessities to our existence. Also, they are discussing the detailed test needed to identify the root cause of problems and what other materials and hormones are essential to keep our adrenals and body healthy. The adrenal cortex's vital hormones include: (1) Cortisol - controls our sleep/wake cycle. It is released during stress to help your body to boost energy and better handle an emergency. (2) Aldosterone helps regulate the blood pH by controlling the electrolytes' levels in the blood. (3) DHEA and androgenic steroids are precursor hormones that are converted in the testes into male hormones (androgens) and ovaries into female hormones (estrogens). (4) Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline) are often activated in emotionally and physically stressful situations when your body needs additional energy sources to endure unusual strain. To support the body naturally, Dr. J recommends using herbs such as maca and ashwagandha. Progesterone, estrogen, and estriol may be fit for a patient. However, it is essential to know that protocols may be different for every patient since presentations and lab results may differ. ===================================== Subscribe on I-Tunes: http://www.beyondwellnessradio.com/itunes Review us at: http://www.beyondwellnessradio.com/itunes Visit us at: http://www.beyondwellnessradio.com Have a question: http://www.beyondwellnessradio.com/question

On this ID the Future, physician Howard Glicksman and host Eric Anderson dive deeper into the body's exquisite blood pressure control system, cueing off a new discovery described at Science Daily as uncovering “the location of natural blood-pressure barometers inside our bodies that have eluded scientists for more than 60 years.” According to the primary research paper at Circulation Research, “Renin-expressing cells are essential for survival, perfected throughout evolution to maintain blood pressure (BP) and fluid-electrolyte homeostasis.” How did evolution perfect the system? How did it originate the system? The paper never says. The mention of evolution appears to be little more than a de rigueur genuflection before the reigning paradigm of blind evolution. What is bearing actual fruit, according to Glicksman Read More › Source

You probably know that the kidneys play an important role in maintaining blood pressure within the normal range. You might also know that they do this by regulating blood volume and the degree of arterial contraction or dilation (the systemic vascular resistance). But do you know how the kidneys do this? The answer is the kidneys accomplish this primarily through a set of hormones and enzymes known together as the renin-angiotensin-aldosterone system (RAAS). In this brick, we will discuss the components, functions, and regulation of the RAAS. Renin is an enzyme released by the kidneys that ultimately causes the formation of the hormone angiotensin II (Ang II) in the body—which in turn stimulates the release of the hormone aldosterone from the adrenal cortex. Ang II and aldosterone act in a number of ways to increase blood volume and blood pressure. RAAS acts to increase sodium reabsorption in the kidney, increase vascular tone, and even stimulate antidiuretic hormone (ADH) to reabsorb more water: all of these defend our extracellular volume and blood pressure. RAAS is therefore a critical system for keeping us upright! After listening to this Audio Brick, you should be able to: Outline the renin-angiotensin-aldosterone system, including sensors, factors that control it, sources of hormone release, and the actions of each hormone. Describe the mechanisms by which the renin-angiotensin-aldosterone system regulates blood pressure. Compare and contrast tubuloglomerular feedback with the renin-angiotensin-aldosterone system. You can also check out the original brick from our Endocrine collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.

CardioNerd Amit Goyal, Cardio-OB series co-chair and University of Texas Southwestern Cardiology Fellow, Dr. Sonia Shah, and episode lead and Johns Hopkins University Cardiology Fellow, Dr. Anum Minhas, discuss pregnancy and aortic disorders with Dr. Nupoor Narula of Weill Cornell Medical College. Special introduction by Sukrit Narula. In this episode we discuss the presentation and management of aortopathies during pregnancy. We begin by examining the pathophysiology of aortic disease during pregnancy, followed by a review of the heritable aortopathies and their risk of dissection. We then discuss preconception evaluation and antepartum care of women with aortopathies. We end with addressing management at the time of labor and delivery. Claim free CME for enjoying this episode! Abstract • Pearls • Quotables • Notes • References • Guest Profiles • Production Team CardioNerds Cardio-Obstetrics Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Episode Abstract - Pregnancy and Aortic Disorders In this episode we discuss the presentation and management of aortopathies during pregnancy. We begin by examining the pathophysiology of aortic disease during pregnancy, followed by a review of the heritable aortopathies and their risk of dissection. We then discuss preconception evaluation and antepartum care of women with aortopathies. We end with addressing management at the time of labor and delivery. Pearls - Pregnancy and Aortic Disorders 1. Assessment of aortic root and ascending aortic measurements should be performed prior to conception in women with known aortopathies, connective tissue diseases with high risk for aortopathies, bicuspid aortic valve or familial thoracic aortic syndromes. Dimensions should always be verified with multi-modality imaging prior to decision-making. 2. It is important to recognize that the immediate postpartum period is a high risk period for aortic dissection in women with aortopathies. 3. Goal systolic blood pressure is < 120 mmHg and diastolic blood pressure is < 80 mmHg in women with aortopathies. This goal should be discussed with the patient's obstetric provider during pregnancy, however, to ensure a blood pressure target is chosen that is appropriate for optimal maternal and fetal outcomes. Beta-blockers followed by calcium channel blockers should be used for these targets. Aldosterone receptor antagonists are contraindicated during pregnancy. 4. Per the 2018 ESC guidelines, during pregnancy, women with aortic pathology should have an echocardiogram performed every 12 weeks if low risk, and every month (4 weeks) if high risk. 5. Women with type A dissection during pregnancy should be evaluated for urgent Caesarean section and aortic surgery if the fetus is viable. Women with a stable type B dissection may be managed medically if stable. All decisions should be made in a multidisciplinary fashion with consultation with Maternal Fetal Medicine and Cardiothoracic Surgery. Quotables - Pregnancy and Aortic Disorders 1. “First and foremost, we must verify our dimensions. I'll say that again. We must verify our dimensions because nothing could have greater impact.” 2. “You know, our most important role is to provide transparency in pre-pregnancy risk counseling. We have to present the data that are available. We need to present the gaps in literature.  We need to present the possibility that in the right individual, we can proceed through pregnancy safely with close clinical and imaging monitoring and follow up in a multidisciplinary construct. Show notes - Pregnancy and Aortic Disorders What is the risk of aortic dissection during pregnancy in Marfan syndrome?Women who undergo pregnancy with prepartum counseling and close clinical and imaging follow-up usually maintain stability of...

00:00 - Catch-up with Georgi Dinkov, the unraveling COVID narrative 04:53 - Is being around vaccinated people harmful? 14:43 - Stress (cortisol) causes hair loss, hair loss as a marker of circulatory disease, aldosterone, PTH, estrogen, trilostane, progesterone 20:20 - Estrogens cause obesity / PCOS in women, DHT is protective 27:22 - Low DHT can cause hypogonadism symptoms even in eugonadal men 33:00 - Vitamin D (topical) safe and effective for removing scars 36:45 - Vitamin D deficiency impairs muscles by lowering energy production, nitric oxide theory of aging, CRH, prostaglandins 46:23 - Is Georgi doing anything at the moment to prepare for an uncertain future? 50:10 - Ruby Ridge, Waco, Timothy McVeigh 58:53 - Serotonin and oxytocin promote gullibility, trainability, and servility 01:06:51 - What's happening in India? Bogus PCR cycle threshold 01:10:47 - Endotoxin (LPS) may be the cause of fatal lung damage in COVID-19 01:14:37 - Pyrucet for cancer? 01:16:31 - Silica, present in most supplements/food, activates the endotoxin receptor (TLR4), EMF, Danny purchased a Mercola EMF tent

In this episode, we highlighted how the body system balances it's fluid in constancy through the following; 1) hormones ( Aldosterone, Atrial natriuretic peptide-ANP, Angiotensin II and Parathyroid hormone) , 2) Water balance, 3) pH(acid-base) balance. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/oge-osondu/message

In today's podcast, I review the pathophysiology of the Renin Angiotensin Aldosterone System (RAAS). Let's Review!

Have you ever wondered if spot reducing is a real thing? Have you wondered if cutting sodium is a bad idea during peak week? Have you had a binge and wondered what to do next? Are you finding yourself giving into your cravings? In this Q and A IFBB Bikini Professional @chrisnicole_ifbbpro and bikini coach @amyehinger dive into these topics and much much more. Be sure to find us on IG @glamgirlbikini to get registered for the Zoom Posing Seminar on Nov 8th at 1-3pm CST: https://bit.ly/3kPEbkW Apply for coaching: https://www.glamgirlbikini.com/get-started/

Head over to http://buylegion.com/boomboom enter code boom boom at checkout to save 20%, start earning loyalty points, and supplementing with the top supplement company on the market. Apply for our World Renowned Coaching Program, RIGHT HERE. Join The Tailored Trainer (TCM's Membership Site) to gain full access to daily programming and a private coaching forum for guidance. Learn more at: https://tailoredcoachingmethod.com/tailored-trainer/ OR download some free sample programs at: https://tailoredtrainer.securechkout.com/samples  Remember to join our private FB community, RIGHT HERE. ASK BOOM-BOOM YOUR QUESTION HERE ----- Timestamps: 2:46 - I'm a bodybuilder and have been training for nearly 17 years now. I consider myself an advanced trainee and recently had issues with feeling off. Bloodwork showed rock bottom ATCH and Aldosterone. Cortisol and DHEA are normal. I've added more fats and cut back substantially on my volume. That said, how would you periodize strength training for someone recovering from adrenal insufficiency when hypertrophy is the main goal? 11:25 - My original goal these next few months was gonna be to try and put on some size. But with my daughter being here now (2 months old),  and considering all the added stressors that brings, I'm assuming that's not the best idea right? If so, would you suggest just a maintenance in calories for now? 14:58 - The wife and I have agreed to only 3 days of training per week for me for now haha… What do you suggest would be the best way to go about programming with a 3 day split that would still help me keep on as much muscle as possible? 18:40 -What's the youngest client you have worked with professionally? I have a client who has asked me to work with her 14yr old son. I love his desire to get stronger and build muscle but the poor kid has horrible upper and lower body mobility! Any programming tips would be appreciated. 26:27 - Wondering if strength gains necessarily need to equal hypertrophy. I am a rock climber who started listening to your podcast because I found a lot of similarities between physique athlete training and climbing, mostly in terms of the periodization of strength gaining and weight loss phases. As a climber, I'm trying to be as strong as possible without adding extra bulk, so usually take your hypertrophy advice and do the opposite. But can I really be improving strength, say in my legs, without the muscles getting bigger? 31:01 - What exercises can I add on to my current programming to help strengthen pelvic floor muscles? I know this is an area of concern for many women, especially those of us that have had babies. 34:25 - Love your podcast but you guys never introduce yourselves! I know one of you (not sure which one) is Cody McBroom but who is the other guy? 41:50 - What do you feel is the best way to educate your clients about nutrition? Verbal communication, or do you send them reading material? ---- Apply For Coaching: bit.ly/Coaching-App Get Your Free Copy of The Nutrition Hierarchy, HERE Learn How We Coach: Read This Case Study Article Top 4 Episodes: - Nutritional Periodization - Nutrition FAQ - Training FAQ - My Story ---- You can get access to ALL of our content in one place, now: www.tailoredcoachingmethod.com/links/ Check out all of our e-books by visiting www.tailoredcoachingmethod.com/products/ Tailored Coaching Method Coaching Info: www.tailoredcoachingmethod.com/online-coaching/ ---- Social Links: Blog – www.tailoredcoachingmethod.com
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This episode has been highly requested after posting my 5 day Fasting Challenge Results. I've received so many questions about it and hoping to answer most of them in this episode. I'll discuss and compare my two recent 5 day fasts. Topics discussed in this episode: - Who shouldn't fast - Why I decided to compare the 5 day fasts: the only difference between these two fasting challenges was how much I walked. Results were quite astounding and almost double the weight loss. - Benefits of fasting - Why should NOT eat LESS, but Less often - How to prepare for a 5 day fast (soft dry fast vs water/snake juice fast) - Importance of electrolytes on prolonged fasts - How to downregulate hormone Aldosterone and why it is important - What happens in your body during each day of the fast - When to PUSH through your fast & when to STOP your FAST - How to properly break your fast and why this is so IMPORTANT. ______________________ Interview with Dr.Filonov:⠀ ⠀ https://youtu.be/ygVMTAp9JBs⠀ ⠀ More info about Dry Fasting:⠀ ⠀ https://youtu.be/9yqsJXhnae4⠀ _______________________ Connect with Monika: INSTAGRAM: https://www.instagram.com/fit.fat.hotaf/ FACEBOOK PAGE: https://www.facebook.com/FitFatHotAf/ YOUTUBE: https://www.youtube.com/user/monikapl419 Ladies ONLY Private Fasting Facebook Group: https://www.facebook.com/groups/363983234565424/?ref=share --- Support this podcast: https://anchor.fm/monikab/support

Sarah, Callum and Karen jump on Zoom for a salty chat on all things sodium! Join us as we delve into hypOnatraemia, hypERnatraemia, even diabetes insipidus! This ep is peppered with mnemonics!

Episode 22 Salty and Sweet: Hypertension and DiabetesThe sun rises over the San Joaquin Valley, California, today is August 7, 2020.Have you heard any news about COVID-19? You surely have, who hasn’t? But above all the negativity surrounding this disease, including political issues, there is hope for the future. Have you heard of, for example, mRNA 1273?(1) Could this be the vaccine we have been waiting for? We don’t know yet, but there are more than 21 vaccines being tested right now around the world. If an effective vaccine is found, you’ll certainly hear about it in this podcast.Welcome to Rio Bravo qWeek, the podcast of the Rio Bravo Family Medicine Residency Program, recorded weekly from Bakersfield, California, the land where growing is happening everywhere.The Rio Bravo Family Medicine Residency Program trains residents and students to prevent illnesses and bring health and hope to our community. Our mission: To Seek, Teach and Serve. Sponsored by Clinica Sierra Vista, Providing compassionate and affordable care to patients throughout Kern and Fresno counties since 1971. “Everything can be taken from a man but one thing: the last of the human freedoms—to choose one’s attitude in any given set of circumstances, to choose one’s own way.”― Viktor E. Frankl Part I: Primary Aldosteronism with Roberto Velazquez Amador, MD, Rio Bravo Family Medicine Residency Program Who are you?I am Dr Velazquez Amador, I am originally from Jalisco, Mexico where I was born and race. I completed my medical studies at the Universidad of Guadalajara, and now I on the third year of FM residency.What did you learn this week?I learned about a patient whom had an incomplete work up for adrenal insufficiency but still treated. He ended up showing signs of Cushing’s syndrome and resistant hypertension. I want to talk about secondary hypertension and Primary Aldosteronism.Why that knowledge important for you and your patients?It is important because it reminds me that secondary causes of hypertension are often under diagnosed. How did you get that knowledge?Reading upon new cases, specially from the inpatient population, it often leads me to find new differentials and new testing modalities.  Where did that knowledge come from?First line review data place for me is Uptodate now that I am in residency. But the initial knowledge came while on Medical school. Reading physiology and physiopathology books. The book that I like to consult a lot is Kelly’s Essentials for Internal Medicine, this book chapters encompass anatomy, physiology and the pathology aspect beside diagnoses and treatment. It is very complete. While in residency, also my reference is the AAFM articles.  DisorderSuggestive clinical featuresGeneralSevere or resistant hypertension An acute rise in blood pressure over a previously stable value Proven age of onset before puberty Age less than 30 years with no family history of hypertension and no obesity Renovascular diseaseUnexplained creatinine elevation and/or acute and persistent elevation in serum creatinine of at least 50% after administration of ACE inhibitor, ARB, or renin inhibitor Moderate to severe hypertension in a patient with diffuse atherosclerosis, a unilateral small kidney, or asymmetry in kidney size of more than 1.5 cm that cannot be explained by another reason Moderate to severe hypertension in patients with recurrent episodes of flash pulmonary edema Onset of hypertension with blood pressure >160/100 mmHg after age 55 years Systolic or diastolic abdominal bruit (not very sensitive) Primary kidney diseaseElevated serum creatinine concentration Abnormal urinalysis Drug-induced hypertension:  Oral contraceptives Anabolic steroids NSAIDs Chemotherapeutic agents (eg, tyrosine kinase inhibitors/VEGF blockade) Stimulants (eg, cocaine, methylphenidate) Calcineurin inhibitors (eg, cyclosporine) Antidepressants (eg, venlafaxine) New elevation or progression in blood pressure temporally related to exposure PheochromocytomaParoxysmal elevations in blood pressure Triad of headache (usually pounding), palpitations, and sweating Primary aldosteronismUnexplained hypokalemia with urinary potassium wasting; however, more than one-half of patients are normokalemic Cushing's syndromeCushingoid facies, central obesity, proximal muscle weakness, and ecchymoses May have a history of glucocorticoid use Sleep apnea syndromeCommon in patients with resistant hypertension, particularly if overweight or obese Loud snoring or witnessed apneic episodes Daytime somnolence, fatigue, and morning confusion Coarctation of the aortaHypertension in the arms with diminished or delayed femoral pulses and low or unobtainable blood pressures in the legs Left brachial pulse is diminished and equal to the femoral pulse if origin of the left subclavian artery is distal to the coarct HypothyroidismSymptoms of hypothyroidism Elevated serum thyroid stimulating hormone Primary hyperparathyroidismElevated serum calcium  Primary AldosteronismThe evaluation of a patient with hypertension depends upon the likely cause and the degree of difficulty in achieving acceptable blood pressure control since many forms of secondary hypertension lead to "treatment-resistant" hypertension. Because it is not cost effective to perform a complete evaluation for secondary hypertension in every hypertensive patient, it is important to be aware of the clinical clues that suggest secondary hypertension. There are a number of general clinical clues that, in isolation or in combination, are suggestive of secondary hypertension. Primary aldosteronism is  a hormonal disorder that leads to high blood pressure. It occurs when your adrenal glands produce too much of a hormone called aldosterone. The classic presenting signs of primary aldosteronism are hypertension and hypokalemia, but potassium levels are frequently normal in modern-day series of primary aldosteronism. The presence of primary mineralocorticoid excess should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis. However, most patients with primary mineralocorticoid excess are normokalemic and, rarely, some are hypokalemic but normotensive (primarily in young adult females).The most common subtypes of primary aldosteronism are:Aldosterone-producing adenomas (APA)Bilateral idiopathic hyperaldosteronism (IHA; bilateral adrenal hyperplasia)The presence of primary mineralocorticoid excess should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis. In patients diagnosed with primary aldosteronism, treatment of the mineralocorticoid excess results in reversal or improvement of the hypertension and resolution of the increased cardiovascular risk.Who should be tested?Test for primary aldosteronism in the following patients: ●Hypertension and spontaneous or low-dose, diuretic-induced hypokalemiaThe following patients should undergo testing even if they are normokalemic:●Severe hypertension (>150 mmHg systolic or >100 mmHg diastolic) or drug-resistant hypertension (defined as suboptimally controlled hypertension on a three-drug program that includes an adrenergic inhibitor, vasodilator, and diuretic)●Hypertension with adrenal incidentaloma●Hypertension with sleep apnea●Hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (15 ng/dL (416 pmol/L), but may be as low as 10 ng/dL (277 pmol/L).Some clinicians calculate a PAC/PRA ratio as part of the case detection strategy, but we prefer to use the paired random PAC and PRA (or PRC). The mean value for the PAC/PRA ratio in normal subjects and patients with primary hypertension (formerly called "essential" hypertension) is 4 to 10, compared with more than 30 to 50 in most patients with primary aldosteronism In general, a PAC/PRA ratio greater than 20 (depending upon the laboratory normals) is considered suspicious for primary aldosteronism, although others use a cutoff criterion of 30.              Part II: Continuous Glucose Monitoring with Denise Le DeWhitt, MS3, Ross University School of Medicine  What is a CGM?A continuous glucose monitor is a special type of device that allows for continuous measurement of glucose levels from the interstitial fluid rather than the blood. Depending upon the device, glucose levels are measured every 5-15 minutes. CGM allows for a measurement of a trend in a patient’s glucose levels as compared to a measurement of a glucose level at a single point in time, commonly known as traditional finger prick testing. How is it used?A CGM works by placing a small sensor under the patient’s skin, commonly located on the abdomen or under the arm. The glucose readings are sent to a monitor via a transmitter. Depending upon which CGM brand is used, the monitor maybe attached to an insulin pump, which can be easily placed in a patient’s pocket or purse for convenience. Alternatively, some CGM devices may even send the glucose readings directly to a smartphone, or other smart device, if the patient has the app. Why should we prescribe CGM instead of traditional glucometer?Allows patients to take active control of their Diabetes.It gives patients a better idea on how their sugar levels can fluctuate in a day (visually can see hypoglycemic and hyperglycemic level trends).Decreased incidence of having hypoglycemic emergencies.Some devices come with an alarm that can alert the patient when their glucose levels are too high or too low.Reduced finger stick pricks. Most popular brand names, or just focus on Free Style Libre (cheapest)Free Style Libre (APPROVED by Medicare lowest cost and widest inaccuracy in low glucose range)It is a CGM system that automatically measures the blood glucose levels of the person wearing it.Apply the sensor with the provided applicator, and a glucose sensing filament is inserted just below the skin.  The sensor measures glucose in the interstitial fluid.By waving the digital reader above the sensor, it records the amount of glucose in the wearer’s system at the moment and stores the data in the digital reader.It allows for immediate access to glucose levels and to trend hypoglycemia and hyperglycemia. It allows for ease of checking glucose in public discreetly. The system makes it easy for health care providers to have access to the stored glucose logs by connecting the reader to a computer.Dexcom G6: (Medicare approved, costly sensors and transmitters)Senseonics Eversense CGM (NOT approved by Medicare)Medtronic Guardian 3: Impacted by Acetaminophen use, provides real time alerts for highs and lows Medi-Cal and Medicare Coverage Medicare covers therapeutic continuous glucose monitors (CGMs) and related supplies instead of blood sugar monitors for making diabetes treatment decisions, like changes in diet and insulin dosage. For these individuals, coverage of diabetes drugs and technology dramatically increases their chances of living a life free of complications. Despite this, however, continuous glucose monitors (CGM) are not covered by Medi-Cal. CGMs are covered under California Children’s Services (CCS), a state program for children with certain diseases or health problems, this is limited only to children with multiple co-morbidities and children who are disabled.Not currently covered under Medi-cal insurance. How to set up for patient and for our officeFalls under the category of Durable Medical Equipment covered under MedicareIn order to be eligible these are the conditions that must be met:Physician must prescribe the equipment for home use, and it must be medically necessary.Physician prescribing the monitoring system, as well as the supplier, must be enrolled in Medicare and accept Medicare assignment.Medicare recipient must have diabetes and must be using a blood glucose monitor to test levels 4 or more times daily. They must also be taking 3 or more daily insulin injections.With Medicare Part B, Medicare covers 80 percent of the approved amount. Medicare recipients are responsible for paying 20 percent of the final, approved cost, and the Part B deductible will apply.   ______________________________Speaking Medical: Xanthochromiaby Isabelo Bustamante, MS3Have you seen the word xanthochromia in a Cerebrospinal Fluid (CSF) study result? Xanthochromia has a Greek origin combining “yellow” (xantho) and “color” (chromia). Xanthochromia basically meansyellowish-colored CSF that can be seen with the naked eye. CSF is normally crystal clear. Xanthochromia can be found after several hours of bleeding into the subarachnoid space. This is because of the degradation of red blood cells after Subarachnoid Hemorrhage or SAH. Now you know the medical word of the week, xathochromia. Have a nice week.    ____________________________Espanish Por Favor: Azúcarby Dr Claudia CarranzaHi this is Dr Carranza on our section Espanish Por Favor. This week’s word is azúcar.  The word azúcar  was made popular by the famous Cuban singer Celia Cruz; she used it as an expression of happiness and joy “AZÚCAR!” Azúcar is a sweet crystalline substance derived from many plants such as sugar cane and sugar beet. You guessed it! Azúcar means sugar in Spanish. Azúcar is a substance that is part of us as humans and it literally runs through our veins.  Azúcar comes from the Hispanic Arabic assúkkar. Azúcar is a vital word to use when talking to patients with diabetes and obesity. Most people will understand blood glucose if you say just azúcar, but if you see a weird look in your patient you may be more specific with the phrase azúcar en la sangre.  Azúcar alta means high sugar (hyperglycemia), and azúcar baja means low sugar (hypoglycemia).  Now you know the Espanish word of the week, “AZÚCAR”, I hope you have a sweet day full of joy and happiness! Until next time! ____________________________Now we conclude our episode number 22 “Salty and Sweet: Hypertension and Diabetes”. We covered the basics on Primary Aldosteronism with Dr Velazquez, the salty part: sodium and potassium; and Continuous Glucose Monitoring with Denise, the sweet part: sugar. Isabello explained xanthochromia, which is yellowish cerebrospinal fluid, and, to put the cherry on this salty and sweet cake, Dr Carranza taught that sugar in Spanish is azúcar.This is the end of Rio Bravo qWeek. We say good bye from Bakersfield, a special place in the beautiful Central Valley of California, United States, a land where growing is happening everywhere.If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. Our podcast team is Hector Arreaza, Gina Cha, Claudia Carranza, Roberto Velazquez, and the special participation of our medical students Isabelo Lucho Bustamante and Denise Le DeWhitt. Audio edition: Suraj Amrutia. See you soon! _____________________References:mRNA-1273 Approval Status, Reviewed by Judith Stewart, BPharm. Last updated on Jul 27, 2020. https://www.drugs.com/history/mrna-1273.htmlUniversity of Southern California - Health Sciences. “Significantly less addictive opioid may slow progression of osteoarthritis while easing pain.” ScienceDaily, 13 July 2020. www.sciencedaily.com/releases/2020/07/200713120014.htm, accessed on Jul 30, 2020.

This month on Episode 14 of the Discover CircRes podcast, host Cindy St. Hilaire highlights four featured articles from the July 3 and July 17 issues of Circulation Research. This episode also features an in-depth conversation with Dr. Brenda Ogle and Drs. Molly Kupfer and Wei-Han Lin regarding their study, In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.     Article highlights:   Wei, et al. Palmitoylation Cycling and Endothelial Maturity   van Ouwerkerk, et al. Functional Variant Elements in Atrial Fibrillation Models   Ibarrola, et al.  Aldosterone in MVP   Sharma, et al. Atherosclerosis Regression Requires Regulatory T Cells   Cynthia St. Hilaire: Hi, welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr. Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today I'm going to share with you four articles selected from our July issues of Circulation Research, as well as have a discussion with Dr. Brenda Ogle and the first authors, Molly Kupfer and Wei-Han Lin, regarding their study, In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid. So first, the highlights. The first article I want to share with you is titled, "Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease." The first author is Xiaochao Wei, and the corresponding author is Clay Semenkovich from Washington University, St. Louis. Peripheral artery disease, or PAD for short, is a vascular occlusive disease of the lower extremities. It affects more than 2 million individuals globally, and its prevalence is ever increasing as our population ages. While statin therapy can be useful for combating coronary artery disease in peripheral artery disease patients, it does not prevent or reduce PAD patients' rates of lower extremity amputation. So looking to gain insights into the mechanisms underlying PAD, this team focused on the findings that circulating fibronectin and the dietary saturated fatty acid, palmitate, are associated with peripheral artery disease. They found this interesting as lipid modification proteins has been implicated in infections, premature aging, cancer and diabetes. One such protein modification is palmitoylation, which is the formation of a thioester bond between palmitate sand cysteine. Acyl-protein thioesterase 1, or APT1, is a depalmitoylase enzyme, which removes the fatty acid palmitate from protein. Using mouse models with inactivated endothelial APT1, as well as cell systems in arterial samples from humans with end stage peripheral artery disease, they tested whether deficiencies in palmitoylation cycling promotes endothelial instability, which is a hallmark of chronic arterial occlusive diseases. They discovered that as many as 10% of all proteins are palmitoylated. They found deficiency of APT1 in endothelial cells disrupts vascular homeostasis, in part by altering the intracellular trafficking of the small GTPase R-Ras. Impaired R-Ras membrane trafficking was rescued by modifying the palmitoylated R-Ras molecule to promote dissociation from membranes. These observations identify palmitoylation cycling as a potential therapeutic target in the treatment of peripheral vascular disease. The second article I want to highlight is titled, "Identification of Functional Variant Enhancers Associated with Atrial Fibrillation." The first author is Antoinette van Ouwerkerk, and the corresponding authors are Antoine de Vries and Vincent Christoffels, And they're from UMC Amsterdam. As we heard in our podcast last month with our interview with Dr. David McManus, atrial fibrillation, or AFib, is the most common form of arrhythmia, and is a major risk for heart failure, dementia, and stroke, and sudden death. Genome-wide association studies have revealed more than a hundred genetic loci linked to this condition, and many of these loci are found in non-coding regions, which are enriched for transcription factor binding sites and epigenetic modification sites, suggesting that these loci could potentially have gene regulatory roles. To test this idea, they use the method called self-transcribing active regulatory region sequencing, or STARR-seq, which is a method used to identify the sequences that act as transcriptional enhancers in a direct quantitative and genome-wide manner. They use STARR-seq to screen 12 of the strongest AFib linked regions of the genome, which contain more than 1600 individual aphid linked genetic variance, and they did this in cultured rat atrial monocytes. From this screen, they found approximately 400 regulatory elements, of which 24 exhibited variant-specific differences in regulatory activity. For one of these elements, upstream of the gene HCN4, deletion of the orthologous element in mice caused diminished transcriptional activity of the gene. Moreover, these variant-containing mice had brachycardia and sinus node dysfunction, both components of arrhythmia. This proof of principle study confirms that such a regulatory element screen could provide insight into the consequences of variants associated with AFib, or for that matter, many other diseases. The next article I want to share with you is titled, "A New Role for the Aldosterone/Mineralocorticoid Receptor Pathway in the Development of Mitral Valve Prolapse." The first author is Jaime Ibarrola, and the corresponding author is Natalia López-Andrés, and their work was completed at Sanitaria de Navarra in Pamplona, Spain. Mitral valve prolapse is a condition where blood leaks back into the left atrium of the heart, and it is the most common form of heart valve defects. The underlying pathology includes an overabundance of cells in the valve leaflet, so-called valve interstitial cells, or VICs. These activated VICs overproduce extracellular matrix protein, and the combination of increased numbers of VICs and increased amounts of extracellular matrix proteins contributes to the impairment of the structural integrity of the valve leaflet. The increase in VICs is due to excess proliferation, but also transformation of valve endothelial cells, so the cells that line the leaflet, valve endothelial cells, into mesenchymal like VICs. As a driver of endothelial to mesenchymal transition, aldosterone was suspected to play a role. Aldoesterone increased expression of VIC activation markers in cultured valve endothelial cells and increased production of certain extracellular matrix protein components. Spironolactone, an aldosterone inhibitor, prevented these effects, and importantly, prevented valve remodeling in a mouse model of mitral valve prolapse. The team showed that valve tissue from mitral valve prolapse patients taking aldosterone receptor inhibitors displayed less evidence of VIC activation and lower production of disease-regulated extracellular matrix components, than those not taking the drugs. These exciting results suggest aldosterone antagonists, already used for certain patients with heart failure or high blood pressure, may also benefit those with mitral valve prolapse. The last article I want to share before we switch to our interview, is titled, " Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression." The first author is Monika Sharma, and the corresponding author is Kathryn Moore, and they're from New York University. Atherosclerosis is a chronic inflammatory condition characterized by the buildup of fatty deposits in the artery walls, and monocytes and macrophages can infiltrate into these fatty deposits and contribute to the formation of plaque. Cholesterol-lowering drugs, like statins, promote the reduction of low-density lipoproteins in the blood, which can help to slow plaque growth, but they do not reverse disease progression. One possibility for changing the course of the disease is to develop therapies that can reduce plaque inflammation, and therefore, progression. With that goal in mind, this team investigated how the immunosuppressive activity of regulatory T cells, or Tregs, may influence the functions of plaque monocytes and macrophages. Using mouse models in which the disease can be reversed through aggressive lipid lowering, they found that depletion of the Treg population caused an increase in the numbers of monocytes and macrophages in the plaques, and resulted in poorer plaque regression. Indeed, these monocytes and macrophages proliferated more, remained in the plaques longer, and were less likely to adopt an anti-inflammatory pro-plaque resolving M2-like phenotype than plaque macrophages in mice with normal Treg numbers. Together, these results highlight the importance of Tregs for promoting plaque regression, and suggest future therapies aimed at boosting these cells, or indeed, M2 macrophages may enable atherosclerosis remission. Okay, so now we're going to switch over to the interview portion of our podcast. I have with me Dr. Brenda Ogle, who is a professor of biomedical engineering, and first authors Molly Kupfer and Wei-Han Lin, and they're from the University of Minnesota. And today we're going to be discussing their manuscript titled, "In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid." So thank you all for joining me today.   Brenda Ogle: Thank you. Molly Kupfer: Thanks for having us. Wei-Han Lin: Thank you. Cynthia St. Hilaire: Great. I'm glad we can all do this remotely and nice and safe for COVID. So Dr. Ogle, you're the PI of the group, but Molly and Wei-Han, what stages of career are you at? Molly Kupfer: I just recently completed my PhD, so this work is sort of the culmination of that. Cynthia St. Hilaire: Oh, congratulations! Molly Kupfer: Yeah. Thank you. Cynthia St. Hilaire: Well done. Circ Research is a great thesis publication. Congratulations. Molly Kupfer: Thank you. Cynthia St. Hilaire: Wei-Han, how about you? Wei-Han Lin: So I'm a BME PhD student at the University of Minnesota. And I got my master degree in chemical engineering, but in Taiwan, and now I'm working with professor Brenda Ogle on cardiac tissue engineering stuff. Cynthia St. Hilaire: Excellent. So this is a beautiful paper. It's stunning. It has all sorts of wonderful parts, biological, biomechanical, great imaging, and essentially you created a 3D bio-ink that can be used to print and make a living pump, kind of a heart in a dish. And it's something that you're calling this human chambered muscle pump, or ChaMP, which I think is a great name. Can you please describe exactly what that is and why did you want to go about trying to make it? Molly Kupfer: Yeah, it might help if I give a little bit of context to this. So since the beginning, one of the central questions that the lab has been exploring is how do the cells of the heart interact with their environment, or the extracellular matrix, as we call it? We know that these interactions that occur at the cellular level are absolutely critical for cardiac function, both at the tissue and the organ level. And based on years of research studying how the extracellular environment modulates cellular function, we have now sought to apply what we've learned in order to engineer functional human cardiac tissues by recapitulating those very critical interactions in vitro. And actually, back in 2017, we published another study in Circulation Research, where we generated these contractile patches of cardiac tissue using a form of light-based 3D printing that allowed us to fabricate scaffolds with really high resolution micron-level features that were distributed in a way that mimics the native extracellular environment. And what we found is that by organizing the extracellular matrix in that way, we enabled the cells to organize themselves in the scaffold and form connections with each other and with the scaffold itself. And this was critical to achieving synchronous electromechanical function of the tissue as a whole. But these were very small millimeter scale tissues, and so for this new study, we sought to create something on a larger scale where you could incorporate some new geometric features such as chambers and the capacity for perfusion. And as you mentioned, using our knowledge of the interactions between cells and the extracellular matrix, we developed this unique bio-ink that could be used as a vehicle to 3D print these centimeter scale chambered tissue structures that are based on the geometry of the human heart. And so the tissues that resulted from this, the human chambered muscle pumps, or hChaMPs, exhibit thick, contiguous muscularization. They demonstrate electrical connectivity and pump function. And notably, this is the first time that this level of function and muscularization has been achieved in an engineered cardiac tissue of this level of geometric complexity. Cynthia St. Hilaire: So can you maybe talk a little bit about what do you mean by an ink, exactly? Is it actually printed? Is this like a printer that I could buy on Amazon? Obviously there's a huge biological component, but what are the actual technical things that you had to develop to make this chamber happen?  Molly Kupfer: Yes. So we did use an extrusion-based 3D printing, which is similar to probably what people normally think about with 3D printing. Traditionally, it's been with plastics. In this case, we're printing with a bio-ink, which is essentially a formulation of proteins and other materials that we encapsulate the cells in, and then after that, we extrude it from a nozzle in a specific formulation or shape in order to create the structure. Cynthia St. Hilaire: So that's interesting. So in this mix, the cells are already in there as opposed to, I guess, some other things that people tend to call scaffolds where you kind of print that and then seed it?  Molly Kupfer: Mm-hmm (affirmative). And in the example of the paper I discussed from 2017, that was an example where we printed a scaffold and put the cells in. But in this case, for such a large and complex structure, we actually mix the cells in prior to printing, and then we create the structure. Cynthia St. Hilaire: Wow. What's the timeframe of that? Like the cells, you got to digest them and mix things up and then print it. The cells, are they happy?  Molly Kupfer: Yeah, that's a good question. So the actual printing process is quite fast, maybe a couple of minutes for this particular scale. We have to prepare, culture, the cells in advance and we're working with human-induced, pluripotent stem cells, so it takes time to grow them up, and then yes, we do detach them and singularize them, and we then mix them with the components. But overall, the actual printing process is relatively quick. Then it's a matter of maintaining the structure and culturing it and doing the differentiation as we did. And that takes weeks to do over time. But the actual process of making it, initially, is quite quick. Brenda Ogle: Challenging thing about this project was the fact that mature cardiac muscle does not transfer well. Meaning when you move it from a dish to an ink and then print it and ask it to start beating again, it doesn't typically happen. And that is because cardiomyocytes don't proliferate well, or make more of each other, and they also don't move well, or migrate. And so the premise on which most of this paper relies is on printing the stem cells first, letting them expand, sort of like they do with development, and then encouraging them to specify into cardiac cell types. Cynthia St. Hilaire: What's the bigger good that can come out of this? Why do we want to be able to do this in vitro, or even ex vivo heart in a dish? Brenda Ogle: The value is pretty tremendous because, suddenly we have a human model system in which we can perfuse volume, so volume can go in and come out, in which the cells experience those volume metric and fluid-induced forces that we haven't been able to study human cells in this way ever before. In the context of human disease, this is the first time we'll be able to look at onset of a particular disease, what was happening with onset, and then progression. And I think that is what is going to transform this field. Cynthia St. Hilaire: So what was the first one like? I'm thinking back to my graduate school and also my postdoc where I was involved in some disease discovery and I have a very vivid memory of the Western blot that proved the mutation that we found. And I literally ran down the hall holding the film. I'm imagining, maybe I'm projecting too much, but what was seeing that first one beat like? Molly Kupfer: You're not projecting. I feel like that well describes my experience. We had some early experiences where we would start to see beating areas under the microscope, but I think the moment, for me, was, I think there was one night I was working in the lab and I had some plates out, I was looking at stuff under the microscope going through just the mundane lab tasks, and I think I sort of saw it at the corner of my eye in the dish, something was moving. And that was the first time. Like I had watched parts of these things beat under a microscope all the time. I spent years looking at cardiomyocytes under a microscope, but that was the first time, for these hChaMPs, where I could actually see it moving just by my eye. Cynthia St. Hilaire: Wow. Molly Kupfer: And that was a really cool moment. Wei-Han Lin: Yeah. I was mostly working on the printing side, so the first time I realized the heart started beating, it's more like a shock to me, because I'm always printing the models or just the mold. But then really seeing those cells, or the whole structure, start to beat, was quite amazing.   Cynthia St. Hilaire: Could you please tell me a bit about the 3D printing aspect of it? Is it like a shell like the outside of a balloon, or does it have an interior structure that helps dictates where the cell go? Can you explain what the printing is? Wei-Han Lin: So the structure we are printing is derived from MRI image stacks on a real human heart. And the image stack was segmented and reduce the size by 10 times, and then we convert the stack into the STL file, which is the standard operating format. And then we modify the model a little bit to make it into two chambers and with two vessels, and two connected chambers with two openings. And this is the heart we are using for the study. Cynthia St. Hilaire: Got it. So it's got kind of the big picture items of the heart. It's got two tubes going in and it's got two chambers and the fluid can flow between all of those aspects in a specific flow pattern. Wei-Han Lin: Exactly. Cynthia St. Hilaire: You said you have to differentiate them in a dish and you're adding different factors to do that. Do the cells like being in that scaffold, or do they want to seep out of that structure or is there something about the bio-ink that they're happy there? Molly Kupfer: You know, I think this bio-ink was, to a certain extent, optimized or designed such that the cells would be able to continue to attach and grow and remodel. So basically, for the most part, these components are biological materials. Some of them are just proteins. Some of them are proteins that have been modified with photo cross-linkable elements, but they still have these moieties that the cells can attach to. And over time we do see some remodeling and some extracellular matrix gets degraded and some gets deposited. Cynthia St. Hilaire: So have you gone to the next steps of something like single cell seq and trying to see what kind of cells you're getting in this? Or even maybe inputting different, the scaffold is getting one differentiation protocol, but are you possibly able to prime IPS cells such that they're maybe halfway to a vascular cell, or halfway to a cardiomyocyte cell, and then put them in the bio-ink? Brenda Ogle: That's a really interesting idea. I'm going to take that one. Cynthia St. Hilaire: Give me an acknowledgment. Brenda Ogle: So we've been thinking about that, the context of if expansion of IPS cells is the best way, for many cell types, how do we get multiple cell types and organize them? And you can imagine even just printing in specific areas, different cell types. Cynthia St. Hilaire: Oh, sure. Brenda Ogle: But the other thing we've thought about is delivering differentiation factor spatially. So almost printing a cell, but then printing that. depot of a factor, in the area that we wanted or in an arrangement that we want, and then releasing it when we want. And it's challenging for stem cell differentiation, because you really need no release, and then basically zero order release for two or three days, and then no release again. Cynthia St. Hilaire: Right. Brenda Ogle: So it's a challenging drug delivery problem, but we've been thinking a lot about it. Now priming the cells beforehand is another interesting approach. Cynthia St. Hilaire: Well, that's wonderful. I just want to congratulate you all again. Brenda Ogle: Thank you so much for having us. Cynthia St. Hilaire: Yeah, thank you so much. Wei-Han Lin: Thank you so much. Cynthia St. Hilaire:  That's it for our highlights from the July issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and on Instagram with the handle @CircRes and #discovercircres. Thank you to our guests, Dr. Brenda Ogle, Dr. Molly Kupfer and Wei-Han Lin. This podcast is produced by Rebecca McTavish and Ishara Ratnayake, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy texts for highlighted articles was provided by Ruth Williams. I'm your host Dr. Cindy St. Hilaire, and this is Discover CircRes, you're on the go source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

Welcome To The MedFlashGo Podcast. This Is Your Daily 4 Minutes Or Less Rapid Review for medical students. Topics are based on medical board examinations including USMLE, COMLEX, And Shelf Exams. We release a new episode every weekday! In this question of the day, Sean asks students to identify the correct function of aldosterone. These questions are powered by MedFlashGo The First Voice-based interactive medical question bank currently available on Alexa. This tool allows medical students to study medical topics and be interactively tested without the use of a screen. You can study on your couch, in your car, and on the move without the use of a screen. To get access to the free audio-interactive question bank, click here or go to your Alexa application and search medflashgo In the skills section. To learn more details go to medflashgo.com and check out our frequently asked questions section. Please know that these questions were creatively designed by medical students and physicians for the purpose of education and do not replace health information given from your health professionals. We have tried our best to make sure the information is accurate please, so please let us know if you find any errors and we will be sure to correct them. --- Send in a voice message: https://anchor.fm/medflashgo/message

In this podcast, Dr. Kimberlee Thielen, an internal medicine physician and nephrologist with Kidney Specialists of Minnesota, discusses hyponatremia, more specifically a water balance issue. Enjoy the podcast! Objectives:     Upon completion of this podcast, participants should be able to: Define how sodium effects the body. Identify signs and symptoms of hyponatremia. Explain the 4 goals for hospitalized patients with hyponatremia. Select proper treatment modalities for individuals with identified hyponatremia.  CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within approximately 2 weeks.  You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit: CME Evaluation: "Hyponatremia: You Ain't Worth The SALT in my Tears" (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.” FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. SHOW NOTES: CHAPTER 1: When we are talking about hyponatremia we are not talking about Na+ problems but rather a water balance issue. The normal amount of Na+ in the plasma water is usually 136-142 meq/L. The body's Na+ balance is important for volume regulation which is controlled by renin angiotensin/Aldosterone system. This is different than the body's water balance which is maintained by antidiuretic hormone (ADH). Normal physiology of water balance requires ADH which involves the hypothalamus-post pituitary and the kidneys. To understand hyponatremia you need to first understand the physiology of water balance and where ADH is produced. ADH is produced in post pituitary and released by 2 physiologic stimulators: (1) elevated serum osmolality, (2) decrease circulating volume. The majority of serum osms are made up of sodium. When your Na+ is high there are osmoreceptors in your hypothalamus that sense increased extracellular serum Na+ which synthesizes ADH which is released once again from the post-pituitary. The posterior pituitary can also synthesize ADH 2nd low volume status regardless of serum osmolality. Parasympathetic response from left atrium, aortic arch & carotids sense the low volume status or volume contraction with decrease arterial blood flow thereby stimulating a vagus nerve response which leads to the posterior pituitary releasing ADH. ADH once released acts at the renal collecting tubule via cyclic AMP which inserts water channels called aquaporins in the collecting tubules flowing via the medullary interstitial osmotic gradient. Next water moves from the intratubular space to the medullary interstitial space thereby concentrating the osmolality. So the further you travel through the kidney more water is removed from intratubular space to medullary interstitium concentrating the urine. A normal healthy person can concentrate their urine upwards of 1200 milli osms and dilute it to around 60 milli osms, which narrows as we age, likely to nephron drop. We all tend to lose some GFR as we age. Nephron Drop Out attrition of nephron units that scar up generally due to athrescleortic disease. ADH- insert aquaporins into collecting tubules - based on osmolality of urine and interstitial water will flow down the osmotic gradient through the aquaporins. Collecting tubules as they go deeper into the kidney the medullary interstitial osmotic gradient increases. The water that is reclaimed is through a complex peritubular capillary network returning to the venous system. CHAPTER 2: Hyponatremia in most patients is going to be hypo-osmolar hyponatremia. When talking about hyponatremia we are generally talking about a serum Na+ less than 135 mew which once again is a water balance issue. Most cases of hyperosmolar hyponatremia are clinical relevant and usually caused by hyperglycemia, prostate or uterine surgery, glycine, sorbitol, mannitol, IVIG. You get an increased osmolar state in the blood which pulls water from intracellular space leads to hyponatremia. Pseudohyponatremia are iso-osmolar and generally a laboratory artifact. Can have your lab run serum Na+ via direct ion selective electrode measurement to obtain true Na+ level. What is hypo-osmolar hyponatremia? Causes are divided into 3 categories: (1) water intoxication, (2) SIADH, (3) volume stimulated ADH. You can differentiate by 2 urine tests: Test #1- Urine Osmolality which we would expect to be low or max dilute.  Test #2 is Urine Sodium. Water Intox - The urine Osms are maximally dilute. SIADH and Volume stimulate ADH urine osms not max dilute. Urine sodium is low in volume stimulated ADH and generally >40 meq per/L in SIADH. Which is due to the kidney seeing itself as euvolemic. So this will cause the release of sodium into the urine. In volume stimulated ADH the kidney perceives itself ischemic or underperfused. So the urine Na+

Contributor: Nick Tsipis, MD Educational Pearls: Congenital adrenal hyperplasia (CAH) is a group of enzyme deficiencies in the adrenals leading to a deficiency of hormones normally synthesized by the adrenals (mineralocorticoids, glucocorticoids, androgens) 21-hydroxylase is most commonly the deficient enzyme. 21-hydroxylase is needed to produce aldosterone and cortisol, and those with chronic cortisol deficiencies need daily steroid replacement Aldosterone, made in the kidney as part of the renin-angiotensin-aldosterone system (RAAS), increases blood pressure via salt and water retention to maintain adequate organ perfusion Adrenal crisis results in a loss of cortisol leading to hypoglycemia and potential CNS depression with hypotension, hypoglycemia, and hyponatremia Patients in adrenal crisis need salt, volume, and glucose replacement References Martin-Grace, J., et al. Adrenal insufficiency: physiology, clinical presentation and diagnostic challenges. Clin Chim Acta. 2020 Feb 6.  Dineen, R., Thompson, C.J., Sherlock, M. Adrenal crisis: prevention and management in adult patients. Ther Adv Endocrinol Metab. 2019 Jun 13;10:2042018819848218. El-Maouche, D., Arlt, W., Merke, D.P. Congenital Adrenal Hyperplasia. Lancet. 2017 Nov 11;390(10108):2194-2210.   Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

There's been a growing amount of hype around the "Deca only cycle". While it is most commonly referred to as the Deca only cycle, it is actually based on the compound Nandrolone being used on its own. The decanoate ester being abbreviated as "Deca" has just become synonymous nowadays in the bodybuilding community with Nandrolone itself. Seeing the potential merits of Nandrolone as a makeshift hormone replacement therapy alternative to Testosterone, I stopped using Testosterone and instead started using Nandrolone on its own with exogenous Estradiol for 3 months and paid over $1000 for an elaborate blood panel to assess how it affected my health markers. https://youtu.be/kLScNddgkks How Nandrolone Could Potentially Be A Superior HRT Alternative To Testosterone The primitive thought process is that Nandrolone used in conjunction with Testosterone will lead to horrible side effects, but Nandrolone used on its own will just result in all of the benefits of steroids with a near absence of the androgenic or estrogenic side effects associated with Testosterone use. In reality, it's a lot more nuanced than that. The reason why I found this experiment worth pursuing is the lack of androgenicity of Nandrolone in the body. Nandrolone 5α-reduces in tissues that express 5α-reductase to the much less androgenic metabolite Dihydronandrolone (DHN). Nandrolone is basically the only anabolic steroid that is going to maintain 100% anabolic activity of the Nandrolone in muscle tissue where you want it, but also be converted into a much less androgenic metabolite with a lower binding affinity in certain areas of the body where you wouldn't want Nandrolone to bind. The two areas of concern for most individuals being hair follicles and skin. By converting to DHN in these areas, Nandrolone (and by extension DHN) causes less hair loss and acne than Testosterone (and by extension DHT). In addition, some men are genetically predisposed to high levels of aromatization and estrogen receptor expression and can't even use TRT doses of Testosterone without experiencing estrogenic side effects. Nandrolone is not a potent substrate for aromatase, and mainly converts to a weaker estrogen called Estrone (Estradiol is about 10-fold more potent than Estrone). Nandrolone is also mildly estrogenic on its own via its ability to act as an estrogen receptor alpha (ERα) agonist [R]. Overall, Nandrolone is much less androgenic and estrogenic than Testosterone, and may provide symptom relief in those seeking a viable hormone replacement therapy alternative. In this context, Nandrolone may also have great potential as an efficacious alternative to Testosterone as an anabolic agent for some individuals who are prone to androgenic and/or estrogenic side effects. The Neurotoxicity And Cardiotoxicity Of Nandrolone Based on the limited data available, Nandrolone has shown to be more deleterious to cardiovascular and neurological health than testosterone. https://www.youtube.com/watch?v=Gv_v0mJy6Bg By extrapolating the data, we start to get a clearer picture as to why this likely is. Nandrolone is mildly estrogenic on its own, and it does not aromatize nearly enough to create as much Estradiol as Testosterone does. Comparing the effect of testosterone with that of 19-nortestosterone (Nandrolone) and Stanozolol (Winstrol) on neurotoxicity we can clearly see that Estrogen is what protects neurons in the brain, not Testosterone itself. In this study, a physiologic dosage of Testosterone was neuroprotective [R]. Testosterone only amplified neurotoxicity at supraphysiological dosages. The neuroprotective effect of a physiologic dosage of Testosterone was completely eliminated when the aromatase inhibitor Anastrozole (Arimidex) was co-administered, suggesting that the intrinsic toxicity of Testosterone as an androgen is only counterbalanced by its aromatization into 17β-estradiol. As opposed to testosterone, Nandrolone does not appear to aromatize sufficiently into estrogen. As you would expect, Nandrolone was neurotoxic at every single dose evaluated regardless of Arimidex being co-administered or not. If Nandrolone was inherently able to provide enough estrogen receptor alpha (ERα) activation to balance out its androgenicity without even requiring aromatization (it acts as an estrogen on its own to some extent), we would see a neuroprotective effect at equivalent dosages to a physiologic concentration of Testosterone when no AI is used, but that does not appear to be the case either. The anti-androgen flutamide attenuated the neurotoxicity of all three androgens, thus further reinforcing that physiologic dosages of androgens without a sufficient amount of opposing estrogens, or supraphysiological dosages of androgens may facilitate neuronal death. I suspect that the same applies for the inherent cardiotoxicity of Nandrolone as well. Just because you can get your Estradiol levels up to 15 pg/mL with a gram of Deca only, that ratio of androgens to estrogen in the body is way off of what would otherwise be optimal for health based on what I've seen. This is reinforced by the fact that Flutamide (an anti-androgen) was able to attenuate the neurotoxicity of Nandrolone. By preventing Nandrolone from binding to androgen receptors, it is no longer able to transcribe its effects in tissues. Hair loss and acne are one thing, cardiotoxicity and neurotoxicity are another thing and should ultimately take precedence obviously. However, just because Nandrolone monotherapy cannot produce a sufficient ratio of androgens to estrogens, that doesn't mean that there isn't a potential loophole. That loophole is exogenous Estradiol administration. Exogenous Estradiol Use With Nandrolone Only Cycles As we've seen, Estrogen produced via aromatase is what provides neuroprotection from the androgenicity of Testosterone, not the Testosterone itself. We also know that Nandrolone is not able to produce enough estrogenic activity in the body to facilitate this same level of neuroprotection. I theorize that Nandrolone in conjunction with exogenous Estradiol to replace this otherwise missing component could attenuate a significant amount of the deleterious impact Nandrolone has on the heart and brain. In addition, by providing a sufficient amount of exogenous estrogen, libido, muscle growth, fat loss, and several other aspects of health and performance should be more optimized. It isn't a coincidence that cardiovascular disease rates skyrocket once women hit menopause and stop producing Estrogen properly. The same negative effects will apply in men with low Estrogen levels. The lack of sufficient Estrogen is often addressed in Deca only cycles by adding an adjunct anabolic steroid that aromatizes into Estrogen or Estrogen analogs. Obviously for those seeking to minimize androgenic side effects, the ideal way to go about achieving sufficient Estrogen receptor activation is probably not going to be by adding more steroids to their protocol. This is where exogenous Estradiol comes into play, and I believe the majority of Deca only cycles would be more sustainable from a health perspective, and successful in a bodybuilding context as well with its inclusion. I have yet to see one person on a Deca only cycle achieve a sufficient Estradiol level relative to their Nandrolone dosage via a sensitive assay Estradiol blood test. The following blood test result was submitted by an individual on over 1000 mg per week of Deca only. Over a gram of androgens relative to a 19.2 pg/mL Estradiol level is far from ideal in my opinion. I had a good conversation with Vigorous Steve as well about his Deca only cycle experience. He told me that his Estradiol was 12 pg/mL on 1000 mg of Deca per week after 4 weeks, and he ended up adding 25 mg DHEA per day just to bring it up to 25 pg/mL. When it comes to Nandrolone use on its own, most would benefit from more Estrogen in my opinion. My Weekly Nandrolone And Estradiol Dosage For "HRT" Most guys doing Deca only cycles are evaluating Nandrolone at dosages of 600 mg or higher per week for short blasts. My experiment was based on its potential as an alternative long term HRT option for those prone to androgenic side effects. Or alternatively, its potential as a compound to swap to periodically throughout the year from TRT to reverse some of the androgenic side effects of Testosterone and DHT while still maintaining the same amount of muscle mass. Every blood test I've seen of Deca only cycle users was on high doses of Nandrolone without a sufficient amount of Estrogen. I wanted to see how Nandrolone on its own at a "therapeutic dose" would affect my blood work if I had a sufficient amount of Estrogen provided through exogenous Estradiol. Long-term, the only way Nandrolone monotherapy could be even relatively safe in a cardiovascular context would be with exogenous Estradiol supplementation from what I've seen. And even then, I'm sure it has major drawbacks that will likely accumulate over the years. With that being said, it is still something I wanted to explore nonetheless, as it is one of the few compounds that can actually support supraphysiological muscle growth with a relatively minimal impact on androgenic alopecia. Oral micronized Estradiol tablets have quite a few drawbacks. A few of the most notable drawbacks are that oral Estrogen pills can be somewhat liver toxic, they spike SHBG through the roof, and they result in the production of clotting factors in the blood that do not develop with forms of administration that skip the first pass. The two most viable methods of administration that skip the first pass are transdermal topical application, or injection. I chose to topically apply transdermal Estradiol gel (Estrogel) for this experiment. I used 100 mg of Nandrolone phenylpropionate (NPP) per week split into daily injections using an insulin pin rotating between my glutes and ventroglutes. I also applied 2.5 grams of transdermal Estrogel (delivering 1.5 mg Estradiol) to my inner thighs every day for over 3 months straight. Blood Pressure Changes On Nandrolone One of the first things I noticed was that it was a struggle to keep my blood pressure in check on NPP, even at the mild dose I was using. What that was caused by exactly, I'm not sure. I assumed it was Aldosterone prior to this blood work. When I'm on Testosterone, even when I was using TRT as high as 200 mg per week, I could keep my blood pressure at 110/70 with ease. Even if I ate terribly, I could still hold 115/75 without even trying on Testosterone. Within the first week of switching to NPP it became way harder to control my systolic blood pressure. My diastolic blood pressure was fine for the entire 3 months, but my systolic blood pressure would consistently be around 125-128. That is not normal for me, and is borderline stage 1 hypertension. The fact that I even had to try to lower my blood pressure showed to me that Nandrolone is a lot harder to manage in this regard. This is consistent with almost every single person I know who has blasted high doses of Deca. They all had significant issues with blood pressure. Most of the guys who thought they had normal blood pressure were actually stage 1 hypertensive and didn't even realize that their results were indicative of cardiovascular stress. My 125-128 systolic occurred without being in a calorie surplus, without any weight changes, and on what I would consider a very low dose of NPP. The exact same diet, weight, lifestyle, etc. would have me at 110/70 on TRT. Muscle Growth And Strength On Nandrolone I maintained my muscle and do not feel that there was a substantial difference between the anabolic potency of Nandrolone compared to Testosterone. At the very least, the anabolic activity of Nandrolone is comparable to Testosterone, but the androgenic activity is far less than that of Testosterone. In certain contexts for certain individuals, Nandrolone will be the desirable alternative because of this. Reduced Libido On Nandrolone - Deca Dick? My libido was extremely subdued on NPP. That's one of the most obvious things I noticed during my experiment. I had a libido and would still want to have sex, but my libido was much lower than it is on regular TRT. On TRT I can barely go one day without sex before it starts to consume my mind.  On Nandrolone only, I can easily go a couple days barely even thinking about it. However, when it came time to get the job done, I could still get the job done and stay hard the entire time without any issues in erection quality. It was a bit harder to reach orgasm though. On top of the lack of androgenicity causing a reduction in libido, Nandrolone also has progestogenic activity and binds to the Progesterone receptor. Excessive Progesterone is notorious for killing libido and causing erectile dysfunction, and it seems that Nandrolone has similar effects in many individuals via this pathway in conjunction with its 5α-reduction into DHN. My drive was also lower, and I felt less aggressive overall. In many individuals Testosterone and DHT levels will strongly influence libido, drive, aggression, motivation and productivity. Personally, even if I have that support via DHT or DHT derivatives, the increased motivation and drive is actually more counterproductive in a work productivity context because my libido gets way too high. Even when I had high testosterone levels and 0 DHT in my body I still had sex on my mind far more than I would like. When that happens, I can barely get anything done, and then I end up depleting myself of energy for the day through excessive sex. The subdued and normalized libido on Nandrolone is welcomed for me because of this. I don't think this is necessarily just because I'm a good responder to Nandrolone, I think it has more so to do with the fact that I was using exogenous Estrogen during this experiment with the Nandrolone. Despite androgens driving aggression and drive, libido and erection quality is largely dictated by adequate Estrogen levels. With all that being said, DHT (with sufficient Estrogen via Testosterone aromatization) is blatantly better for sexual support than Nandrolone, and testosterone itself, even if you completely inhibited 5α-reductase and nuked DHT, still provides better libido and erection quality than Nandrolone does at equivalent "therapeutic" doses for the majority of people. My Blood Work Results On A Deca Only Cycle For HRT I don't like taking shots in the dark when it comes to something that I see potential in. There is a lot of theory thrown back and forth in the community on Deca only cycles, and I needed to see for myself how Nandrolone in conjunction with exogenous Estradiol would impact my personal blood work. I wanted to check markers of oxidative stress, inflammation, kidney function, Aldosterone, Prolactin, hormone levels via sensitive assay testing, and an array of other health markers that are often debated about but very infrequently actually tested for to reinforce statements made. Expectedly, high dose Deca only cycle blasts will almost always result in low HDL levels, subpar Estradiol levels, and an array of other out of range values that are less common and are more individual dependent. To date I have yet to see someone get their blood work checked with exogenous Estradiol being used in conjunction with Nandrolone at a "therapeutic" dose. This is what I wanted to evaluate. Complete Blood Count with Differential/Platelets I was actually expecting far worse from my blood test results. At a "therapeutic" dose, it doesn't seem like my hematology was negatively affected at all. Comprehensive Metabolic Panel In my metabolic panel, nothing was really off to the point that would cause concern. My BUN being high is likely just the result of being muscular and having a high protein diet. Lipid Panel Going into the lipid panel, we can see the number one most common blood test result among steroid users. My HDL is low. LDL is also borderline high, but not overly concerning when I can see that my Triglycerides are pretty low. The reason why my HDL was too low was that my Estrogen levels were too low. Again, this just reinforces the fact that Nandrolone does not sufficiently aromatize into Estrogen. I will get into my Estrogen level and why it was still too low even with Estrogel administration later once we get to that part of the blood test results, but my HDL could have been in range if my Estrogen level was in check. If I didn't use the Estrogel my HDL likely would have been in the single digits. I know I can get my HDL into the reference range if my estradiol levels were doubled, which I have the leeway to do. Iron And Total Iron Binding Capacity Getting into Iron and TIBC we can see that everything looks pretty normal here. Total Testosterone And Free Testosterone Expectedly, by assessing my Total Testosterone level via liquid chromatography with tandem mass spectrometry (LC/MS-MS) and my Free Testosterone level via equilibrium ultrafiltration, we can see that my Testosterone levels were crashed. Both the total and the free were lower than a healthy female. This is what you should see in your blood work if you’re on just Nandrolone. The only Testosterone being produced in my body was indirectly via the trace amounts of androgens produced in my adrenal cortex, which is why the value wasn't completely bottomed out at 0. I've mentioned many times the importance of getting high sensitivity testing done for hormone levels and how Nandrolone will register as Testosterone in primitive garbage blood tests. This is another great example of this. In addition to high sensitivity testing, I had the same blood tested using electrochemiluminescence immunoassay (ECLIA) for my Total Testosterone level, and direct analog enzyme immunoassay (EIA) for my Free Testosterone level. These were the test results using the exact same blood sample with the terrible default assays that doctors will use to determine how to treat you, and that labs will give you in the majority of your blood work panels. According to ECLIA and EIA, I have a normal Total Testosterone and Free Testosterone level. Hilarious. This just one example of why getting accurate hormone testing is critical. My Testosterone levels are actually in the gutter, but the stupid primitive tests that doctors and labs give out as defaults for people is so f*cking stupid that it can't even tell the difference between Testosterone and 19-nortestosterone in my blood. Renin Activity and Aldosterone My renin activity and Aldosterone appeared to be normal. This is one of the main things I wanted to check because there's a lot of speculation around the effect Nandrolone is going to have on Aldosterone levels. When it comes to the Deca only cycle, there's something going on that throws off homeostatic mechanisms that regulate blood pressure that does not appear to be Estrogen related or Aldosterone related. At least based on my blood work, my Aldosterone was definitely not at a level that could imply any kind of negative effect on blood pressure. My Aldosterone level was low if anything. Granted, some markers in the serum can be relatively worthless when compared to actual tissue concentrations, but at least based on my blood work, Aldosterone does not appear to be the culprit. The first thing many jump to when explaining blood pressure regulation is the effect Nandrolone supposedly has on spiking Aldosterone through the roof, but it just doesn't appear to be the case in my experience as you can see yourself here. Vitamin B12 and Folate My B12 and Folate levels were normal. Pregnenolone Pregnenolone appeared to be normal and within the reference range for men which is notable, as many assume that Nandrolone will shut down the production of precursor steroids. That does not appear to be the case either. I assumed precursor hormone levels like Pregnenolone would be less affected than many seem to think as most circulating Pregnenolone is derived from the adrenal cortex. Dihydrotestosterone (DHT) Expectedly, my DHT was very low. This is because I have almost no Testosterone being produced to 5α-reduce into DHT. If my Testosterone is low, my DHT will be low as well. DHT Backdoor Pathway Contrary to popular belief, there is a backdoor pathway via Pregnenolone that can create DHT as well, which contributes to the chunk of DHT I have in my blood. Hemoglobin A1c Hemoglobin A1c appeared to be normal at 5.1%. Thyroxine (T4) My Free T4 was 1.28 ng/dL, which is acceptable. DHEA-Sulfate My DHEA was in range and actually on the high end of normal. Being on exogenous Nandrolone or Testosterone does not shut down DHEA production. Cortisol Cortisol was "normal" apparently, although it looks a bit high to me. I believe this result was mostly sleep hygiene related rather than entirely Nandrolone related. Thyroid Stimulating Hormone (TSH) My TSH is too high. I've never had a TSH this high before. I have had a TSH in the 2's before, this isn't the first time, but never this high. However, based on my resting heart rate and my morning waking temperature and my mid-day temperature, my metabolic rate seems to be the same as it usually is on TRT, and I have had no standout hypothyroidism symptoms. Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Expectedly, LH and FSH were undetectable. Prolactin My Prolactin was on the low end of normal. This was another interesting health marker to see on Nandrolone, as many will often jump to assuming that Nandrolone spikes Prolactin levels through the roof. That does not appear to be the case though. Prostate-Apecific Antigen (PSA) My PSA level was normal, and did not change from my previous blood work on Testosterone for TRT. D-Dimer My D-Dimer was normal. A friend of mine had a very high D-Dimer level on a Deca only cycle and he wanted me to check mine to see if there was a pattern. It looks like the elevated D-Dimer was case-specific for him and was probably caused by something completely unrelated, as my D-Dimer is normal. C-Reactive Protein C-Reactive Protein is one of the primary markers we have for assessing inflammation in the body. A C-Reactive Protein level of 0.34 mg/L is not overly concerning, although I would like to see it below 0.3 mg/L. I had undetectable C-Reactive Protein levels in the past on TRT, and on Nandrolone it jumped up to 0.34, which is notable. Estradiol, Sensitive My Estradiol (E2) level determined via LC/MS-MS was only 15.4 pg/mL, despite administering 2.5 grams of Estrogel per day. This was disappointing, as I would have liked to see my E2 at least around 30 pg/mL based on the amount of Estrogel I was applying daily. Evidently, my inner thigh was not absorbing the Estrogel very well. This is one of the recommended areas of application, but my results were not even close to in line with the average blood levels found in the Estrogel pharmacokinetics studies. With daily administration of 2.5 g or 5 g Estrogel (corresponding to 1.5 mg or 3 mg estradiol, respectively), mean serum estradiol concentrations of approximately 80 pg/ml (294 pmol/L) and 150 pg/ml (551 pmol/L), respectively, are maintained. Administration of Estrogel also results in increased serum estrone concentrations, producing a physiological estradiol/estrone ratio of approximately one. Therefore, serum concentrations of both estradiol and estrone and the serum estradiol/estrone ratio provided by ESTROGEL® are consistent with physiological levels observed during the follicular phase of the normal menstrual cycle. My inner thigh isn't very hairy at all as I manscape fairly regularly, so I expected at least a 40 pg/mL E2 based on the amount of Estrogel I was applying. I was overly generous with my dose based on the off chance that I would encounter an absorption issue, and my E2 was still way below where I expected it to be. Based on the pharmacokinetics outlined by Merck, 80 pg/mL is the average E2 level for someone applying 2.5 grams of Estrogel per day. There's no way I could have predicted that I would have an absorption issue so problematic that it would result in five times lower absorption than the average. If my E2 was closer to 30 pg/mL, I expect that my HDL would have been pushed into the reference range, and all Estradiol driven physiologic functions likely would have been more optimized. To me, this just reinforced further that Nandrolone is a subpar source of Estradiol as I was using a high dose of transdermal E2 and still could barely reach a satisfactory E2 level. To increase my E2 levels for similar future experiments I will either have to find a better application area, add some DMSO to my Estrogel to increase absorption, or consider Estradiol injections instead. Homocysteine My Homocysteine level was higher than I would like. Normally my Homocysteine is closer to 8-8.5 umol/L. Earlier in the year when I did a shorter Nandrolone experiment for a month using 200 mg per week (double the dose I used for this experiment) I had a Homocysteine level around 8.5, so I doubt this spike was Nandrolone related. This is one of the main markers I always have my eye on because I am homozygous for the C667T polymorphism. Gamma-Glutamyl Transferase (GGT) My GGT looked good. I was worried that this would be cranked through the roof as it is a marker of oxidative stress. Magnesium My magnesium level looked okay. Copper and Zinc My zinc level looked okay. My copper level may be a bit low, which I am now addressing by eating an ounce of beef liver every day. Progesterone My Progesterone was normal, which is notable as it is another precursor hormone that many assume drops to zero when exogenous anabolic steroids are present in the body. Insulin My insulin level was good. Estrone Expectedly, my Estrone was a bit high. This can be a major problem with exogenous Estradiol and Nandrolone unfortunately. Estrone Level Increase From Exogenous Estradiol The ratio of Estrone-to-Estradiol is skewed with massive elevations in Estrone with oral Estrogen administration. Fortunately, this unhealthy ratio can be avoided for the most part with transdermal Estradiol administration. High levels of serum Estrone sulfate (E1S) were found after long-term oral estrogen treatment of commonly prescribed dosages, whereas there was a small increase in E1S levels after transdermal Estradiol (E2) therapy. The mean maximum E1S levels were more than 20-fold higher with oral estradiol (E2) when compared with the 0.05 mg/day transdermal estradiol patch. This is consistent with the 20-fold higher dose of E2 when compared with the transdermal dose [R]. Estrone Level Increase From Nandrolone Nandrolone also significantly elevates concentrations of Estrone in plasma [R]. During a pilot study evaluating the possible beneficial effect of Nandrolone Decanoate (ND) on bone metabolism in patients with rheumatoid arthritis there was a significant increase in the serum levels of Estrone [R]. Despite the fact that Estrone can convert to Estradiol, we can clearly see that the amount this actually happens in the body is minimal based on the consistently skewed ratios of androgens to Estradiol in the blood test results of Deca only users (or Nandrolone in general). Ferritin My Ferritin level is too low. This is likely the result of phlebotomizing too frequently in 2019. Estriol My Estriol level was undetectable, which was expected. Triiodothyronine (T3) My Free T3 level was 2.7 pg/mL. It's not low enough for me to be overly concerned, however, it is suboptimal and should be in the low 3's at least. This is something I will need to address moving forward. With that being said, I like to look at my resting heart rate as well as my body temperature for a more accurate assessment of my metabolism, and both are where I want them to be. My waking temperature has consistently been 98 degrees Fahrenheit, and my midday temperature has consistently been 98.6 degrees Fahrenheit. Sex Hormone-Binding Globulin Expectedly, my sex hormone-binding globulin (SHBG) was low. While this isn't as relevant for a Nandrolone only user as Nandrolone has a very low affinity for SHBG, this is a value I would still like to see in the reference range, especially if I was on TRT. If I had the Estradiol level I was shooting for, I'm confident that my SHBG would have been in the reference range. My Overall Experience On Nandrolone And Exogenous Estrogen For HRT I was expecting to see a bunch of red flags in my blood work, but nothing really stood out as a major concern to me except for the spike in systolic blood pressure, and the high Estrone level. A before and after echocardiogram and calcium scoring would have been nice to see, but unfortunately I can only afford to do so much in these experiments, and the blood work was expensive enough as is. I felt good throughout the entire experiment, I maintained my physique, my libido and penis were functional, and my blood work looked pretty good considering that each issue was something more so related to my Estradiol administration than the Nandrolone itself. Estrone being out of range is a concern, as I would need to use even more exogenous Estradiol to achieve what I would consider a more therapeutic E2 level, which would likely push my Estrone up even higher. The difficulty in controlling the blood pressure spike is also a huge concern and could be a deal breaker. If I gave this experiment more time, it is entirely possible that certain things would have become problematic that appeared to be fine during my three month assessment, like my libido or sense of well-being. It is also possible that despite maintaining a healthy Estrogen level, the same neurological and cardiovascular issues we see in a significant amount of the Nandrolone data could still accumulate over time. In addition, healthy looking serum levels of Estradiol may not necessarily reflect adequate localized Estrogen receptor activation in each tissue. With Testosterone, there is a regulated amount of aromatization occurring in each tissue to satisfy however much Estrogen receptor (ER) activation we need. In the context of Deca only cycles, or Nandrolone monotherapy, there's nothing else I can refer to other than serum levels, my libido, sense of well-being, other cardiovascular health markers, etc. In other words, just because you feel good and your Estrogen levels look good on paper, that doesn't mean that an exogenously administered source of Estrogen is providing the same therapeutic ER activation in all tissues like it would if it were regulated via aromatase. With that being said, you could also argue the opposite as adequate receptor activation via exogenous hormone therapy is essentially all HRT boils down to to begin with in the context of any hormone. More than 95% of our endogenous Testosterone is produced in the testes. Testosterone is supplied to target tissues in the blood, just like most other hormones in the body. If you inject exogenous Testosterone, it then goes into the blood and is supplied to target tissues. If you inject anything it goes into the blood and then is carried to the areas that it is needed. Estrogen replacement has been deemed satisfactory for fulfilling the same functions as endogenously produced Estrogen in women for years, and synthetic Estrogen analogs are handed out like candy to millions of young girls (including teenagers). Is it healthy? Estrogen analogs like Ethinyl Estradiol probably aren't ideal for regulating Estrogen dependent functions, and they definitely aren't ideal for developing women who haven't fully matured. However, there is tons of data to support the fact that exogenous Estradiol is well-tolerated, has a strong safety profile, and can still fulfill physiologic functions sufficiently. In an ideal world, this would be a regulated process in the body in each tissue (aromatization). My experiments do not necessarily reflect what I believe are best practice with these hormones, which should be noted. This was an experiment, and not something that I would recommend someone else do. Using an exogenous progestogen with estrogel certainly isn't what I would consider an optimal HRT protocol, or what is indicative of an ideal means of providing androgenic and estrogenic support in tissues. With that being said, I don't see a better way to go about utilizing Nandrolone on its own for HRT. Should it even be considered as an HRT alternative though? That's the question, and I believe it is largely going to be individual dependent, with a significant amount of users having poor outcomes in one aspect or another. I do believe there are a minority of individuals who are very prone to androgenic and/or estrogenic side effects from exogenous Testosterone use that may benefit from exploring Nandrolone though, and it should not be discarded as a potentially viable alternative simply because it is not the primary bioidentical hormone that men produce.

ENAC| K-wasting vs K-Sparing diuretics | Spironolactone | Aldosterone | Lumen Electropositivity --- Support this podcast: https://anchor.fm/kamesa-anota/support

High plasma aldosterone is an independent risk factor for cardiac mortality, but what is known about the underlying mechanisms linking high levels of aldosterone to cardiac ischemic events? Listen as Consulting Editor Donal O’Leary (Wayne State University) interviews lead author Shawn Bender (University of Missouri & Truman VA) and expert Judy Muller-Delp (Florida State University) about the work led by motivated undergraduate Maloree Khan, which tested the hypothesis that increased plasma aldosterone impairs adenosine-mediated coronary vasodilation. Bender and co-authors found that high plasma aldosterone levels impaired adenosine A2A receptor-mediated dilation, but not adenosine A2B receptor-mediated vasodilation. Using a dose of aldosterone that does not significantly elevate blood pressure, Khan et al observed aldosterone-mediated changes in coronary dilation to adenosine via downregulation of calcium-activated potassium channels. Listen as these experts discuss the role of aldosterone and the mineralocorticoid receptor in ion channel expression in the vasculature, as well as future next steps related to sex differences and cell-specific knockout models.   Maloree Khan, Alex I. Meuth, Scott M. Brown, Bysani Chandrasekar, Douglas K. Bowles, and Shawn B. Bender Aldosterone impairs coronary adenosine-mediated vasodilation via reduced functional expression of Ca2+-activated K+ channels  Am J Physiol Heart Circ Physiol, published June 14, 2019. DOI: doi.org/10.1152/ajpheart.00081.2019

In this episode I cover the pathophysiology, causes, investigations and management of hyperaldosteronism.If you want to follow along with written notes on hyperaldosteronism go to zerotofinals.com/hyperaldosteronism or find the endocrinology section in the Zero to Finals medicine book.This episode covers the pathophysiology, causes, investigations and management of hyperaldosteronism. We specifically look at the renin-angiotensin-aldosterone system, renal artery stenosis and aldosterone antagonists. 

On today's episode, I discuss spironolactone and eplerenone.  We cover the mechanism of action, monitoring parameters, adverse effects, and of course notable drug interactions.  Enjoy the show and please take advantage of our FREE giveaway by following the podcast via email!

Worn out. Unmotivated. Achy. So tired. Depressed. These are just some of the words people use to describe adrenal fatigue. Others are wired, anxious, and overstimulated. The most frustrating part is that those with adrenal fatigue are often ambitious, driven, and hard-working. Yet, exhaustion makes it difficult to function. Don't be surprised if you have all the symptoms, but your doctor hesitates in making an adrenal fatigue diagnosis. Many conventional doctors don't recognize the term adrenal fatigue. However, most understand the concept and see numerous patients with its symptoms. Had I not seen the effects of adrenal fatigue first hand in my wife, I might not comprehend how debilitating it can be. What is adrenal fatigue? Your adrenal glands act in concert with the hypothalamus and pituitary glands. This relationship is called the hypothalamic–pituitary–adrenal (HPA) axis.  Many practitioners prefer the term HPA Axis Dysfunction instead of adrenal fatigue when discussing a patient's symptoms. Your adrenal glands produce and secrete four stress-related adrenal hormones: CortisolAldosteroneNoradrenalineEpinephrine The pituitary and hypothalamus produce additional hormones, too. However, cortisol plays the most significant role in adrenal fatigue. Your adrenal glands secrete cortisol according to circadian rhythm and in response to mental or physical stress. Normal Cortisol Rhythm Naturally, cortisol peaks in the morning to wake you up. The rise in cortisol provides a jolt of energy to get you up and out of bed so you don't feel the need to hit the snooze button repeatedly. From the time you wake up until around noon, cortisol levels drop significantly. As the afternoon and evening progress, the remaining cortisol continues to decline, reaching a low point around bedtime. The low level of cortisol and peak in melatonin helps you get to sleep and stay asleep. Cortisol and Stress Stress stimulates the release of cortisol, noradrenaline, adrenaline, and aldosterone.  Cortisol, noradrenaline, and adrenaline increase heart rate, blood flow, energy, and mental acuity, and enhance your reflexes. Aldosterone increases fluid retention, raising blood pressure. These effects are helpful when dealing with a threat. Once the threat is neutralized or avoided, the hormones and their metabolic effects return to normal. However, issues arise when stress is chronic, and you don't have sufficient time to recover from it. Stress and Recovery Stress is part of life. It is necessary for growth, learning, and physical and mental adaptation. The stress of intimate relationships makes you adapt and develop empathy. Without it, you'd remain a selfish person who thinks the rest of the world should believe what you do. Your business or career's stress causes you to think differently, develop new strategies, and communicate your ideas differently, so others listen. Without that stress and the adaptation to it, your career or business would flatline. The stress of weight training causes your bones to get denser, your muscles get stronger, and your nervous system becomes more coordinated. Without the stress of weight training and the adaptation that follows, you'd be more likely to develop diabetes, osteoporosis, and multiple other diseases. As good as these stressors may be, their benefit only comes to fruition through the recovery that follows the stress. Without the ability to recover, your body can become overloaded by stress, leading to adrenal fatigue. Adrenal fatigue is a state of diminished resilience. Adrenal fatigue is a state of diminished resilience, not necessarily an excess of stress. The solution isn't to escape from stress, but it is to rebuild your resilience. With the combination of constant stress and insufficient time or ability to recover, your cortisol rhythm changes, leaving you feeling like one of the three descriptions below.

In this Episode we hear from senior author Hervé Lefebvre discuss his recent paper 'Mast cell hyperplasia is associated with aldosterone hypersecretion in a subset of aldosterone-producing adenomas.'

Welcome to The Nutritional Pearls Podcast! Focusing on topics that include digestion, adrenal fatigue, leaky gut, supplementation, electrolytes, stomach acid, and so much more, “The Nutritional Pearls Podcast” features Christine Moore, NTP and is hosted by Jimmy Moore, host of the longest running nutritional podcast on the Internet.  Sharing nuggets of wisdom from Christine's training as a Nutritional Therapy Practitioner and Jimmy's years of podcasting and authoring international bestselling health and nutrition books, they will feature a new topic of interest and fascination in the world of nutritional health each Monday. Listen in today as Christine and Jimmy welcome special guest Carole St. Laurent, NTP, a “real food” nutritionist. Carole uses local, properly prepared and nutrient dense foods to restore balance and support wellness, with bio-individual strategies aimed for success. Listen in as they talk all about minerals in Episode 7. Here's what Christine, Jimmy, and Carole talked about in Episode 7: Minerals 1. Roles of minerals A. Maintains proper pH balance in the body B. helps transport nutrients across cell membranes C. Maintains proper nerve conduction D. Helps contract and relax muscles E. regulates tissue growth 2. Breakdown of Macro and Micro Minerals A. Macro Minerals-magnesium, Phosphorus, Calcium, Potassium, chlorine, sodium, and sulfur B. Microminerals-Iron, zinc, copper, chromium, selenium, iodine, boron, manganese, molybdenum, lithium (used to treat bipolar disorder), rubidium (required in smaller amounts in the body) 3. Uses/benefits of minerals A. Electrolytes 1. Salt, for most people is not an issue so don't be afraid of salt. It takes 7.5 grams of salt to raise a normal systolic blood pressure reading 5 or 6 points (140 is considered high). Salt is not good or bad. It's whether it's out of balance with potassium. (New York Times Article and JAMA study (11/23/11 by Gina Kolata “Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events” B. Calcium-Bone remodeling 1. Cofactors needed for calcium a. Systemic pH: normal blood pH should be between 7.35 and 7.45 1. When blood pH rises or becomes more alkaline, calcium is deposited into the bone. 2. When blood pH falls or becomes more acidic, calcium is deposited into the blood. b. Hydration-electrolytes and water c. Hormones-parathyroid in particular d. Other Minerals (Magnesium, Potassium, Phosphorus, Manganese, Boron, Copper, and Zinc e. Vitamins (A, D, E, K)-D needed with the Parathyroid to increase levels of calcium in the blood f. Essential Fatty Acids)-necessary to transport calcium across the cell membrane g. Digestion (proper stomach pH (Between 1.5 and 3) 2. K2 (Activator X) –K2 needed to help get calcium where it needs to go C. Zinc-healthy immunity, better wound healing, aids in stomach acid (HCl) production, DNA synthesis D. Magnesium-helps calcium do what it's supposed to do 4. Endocrine system and minerals-each endocrine gland has a mineral on which it particularly depends. 1. Pituitary Gland: Manganese 2. Thyroid: Iodine 3. Pancreas: Chromium 4. Gonads: Selenium 5. Adrenals: Copper-if adrenals aren't functioning right, they can't produce Aldosterone. If Aldosterone levels are low, your body will dump salt through urination which will lead to an electrolyte imbalance. 6. Prostate: Zinc 5. Signs of mineral deficiency A. magnesium-heart palpitations, nausea, vomiting, loss of appetite B. electrolyte imbalances: fatigue, headache, muscle cramps C. Zinc-Depressed immune system, low HCl production, slow wound healing D. Calcium-numbness in extremities E. Iron-anemia, feeling weak or tired F. Potassium-muscle cramping, weakness, constipation, bloating or abdominal pain, irregular heartbeat 6. Sources of minerals-our body can't make minerals so we have to get them from our diet. A. Calcium-milk, cheese, yogurt, broccoli, kale, Chinese cabbage B. Zinc-oysters, beef, turkey, cheese, swiss chard, pumpkin seeds C. Iron-meat, poultry, or fish, beef liver, clams, spinach, mussels, spirulina (seaweed), oysters, ginger D. Magnesium-Almonds, cashews, seeds, green leafy vegetables (spinach) E. Potassium-avocado, dark leafy greens, beets, cantaloupe, sardines Nutritional Pearls for Episode 7: 1. DON'T BE AFRAID OF SALT! 2. Our body can't make minerals so we have to get them from our diet. 3. Calcium is very important for multiple functions in the body BECOME A NUTRITIONAL THERAPY PRACTITIONER Sign up for the 9-month program NOTICE OF DISCLOSURE: Paid sponsorship GET A $39 BOTTLE OF OLIVE OIL FOR JUST A BUCK GET YOUR $39 BOTTLE FOR JUST $1 NOTICE OF DISCLOSURE: Paid sponsorship YOUR NEW KETO DIET ALLY NOTICE OF DISCLOSURE: Paid sponsorship LINKS MENTIONED IN EPISODE 7 – SUPPORT OUR SPONSOR: Complete nutriton for nutritional ketosis (COUPON CODE LLVLC FOR 10% OFF YOUR FIRST ORDER) – SUPPORT OUR SPONSOR: Become A Nutritional Therapy Practitioner – SUPPORT OUR SPONSOR: The world's freshest and most flavorful artisanal olive oils. Get your $39 bottle for just $1 – JIMMY'S KETO LIVING SUPPLEMENT LINE: Try the KetoEssentials Multivitamin and Berberine Plus ketogenic-enhancing supplements

Did you know that our kidneys control our blood pressure? It does this so it can continually create 180 litres of filtered blood every day to keep us healthy! The system that the kidneys use to control blood pressure is called the renin angiotensin aldosterone system (RAAS) - it's a big name but easy to learn! Many patients with hypertension manage their blood pressure by taking medications that act upon this system! Join Dr. Matt & Dr. Mike in this episode to explore this clinically important system! 

Update your management of heart failure (HF) with expert tips from Cardiologist Dr. Eric Adler, Associate Professor of Medicine and Director of Cardiac Transplant and Mechanical Circulatory Support at UC San Diego. We cover how to use BNP, a simple way to examine jugular venous distention, medical therapy for heart failure, the PARADIGM-HF trial, and how to use sacubitril/valsartan (Entresto). Full show notes available at http://thecurbsiders.com/podcast Join our newsletter mailing list. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Time Stamps 00:00 Intro 04:25 Rapid fire questions 06:00 Palliative care and heart failure 08:40 Book recommendation 10:20 Advice for teachers and learners 12:27 Clinical case of HF 13:38 Classification and staging of HF 17:07 Discussion of BNP 19:35 How to perform neck vein exam for JVD 21:20 BNP for prognosis 23:00 BNP at hospital discharge 26:36 Factors that affect BNP 27:25 Initial patient counseling 32:35 Exercise in HF 34:00 Additional testing at time of diagnosis 36:28 Initial medical therapy 38:30 Discussion of diuretics and dosing 42:50 Aldosterone antagonists 44:30 PARADIGM-HF and entresto 51:27 Medications to avoid in HF 54:14 Digoxin 57:30 Dr. Adler’s take home points 59:11 Stuart questions dosing conventions 60:48 Outro Tags: arni, assistant, care, diuretics, doctor, education, failure, family, foam, foamed, health, heart, hospitalist, hospital, internal, internist, neprilysin, nurse, management, medicine, medical, physician, practitioner, primary, resident, sacubitril, student

Commentary by Dr. Valentin Fuster

The thyroid-adrenal-pancreas axis is one of the most important connections in understanding and healing your thyroid.  In addition to gastrointestinal and blood sugar disorders, adrenal gland dysfunction is one of the most commonly seen imbalance in today’s society.  Adrenal gland imbalances are also one of the major factors that cause thyroid hormone imbalance.  Stress from work, relationships, electronics, poor diet choices such as consumption of refined carbohydrates and trans fats, infections, and environmental toxins all contribute to adrenal disorders.  Let's discuss the thyroid-adrenal-pancreas axis in detail so you can understand this complex connection The Adrenal Glands The adrenal glands are about the size of a walnut and lie on top of the kidneys.  The outer adrenal cortex comprises eighty percent of the gland and produces many hormones including cortisol and DHEA from cholesterol.  Ninety percent of the cholesterol in the body is made by the liver and only ten percent comes from the diet. Cholesterol converts into the hormone pregnenolone in the adrenal cortex which then converts to cortisol, the stress hormone, or DHEA, the sex hormone source, immune enhancer and anabolic.  Cortisol is our “fight or flight” stress hormone.  Cortisol slows down digestion, suppresses immune function and raises blood sugar as a survival mechanism when we are under stress.  The problem arises when this becomes chronic and over time, elevated cortisol will tear down your body. Cortisol is secreted on a circadian rhythm with highest production in the morning that slowly tapers off as the day progresses.  Sleep is when our bodies repair and rejuvenate but high cortisol during sleep will prevent this from happening. Hormones Secreted by the Adrenal Glands DHEA DHEA (dehydroepiandrosterone) is a precursor to estrogens, progesterone and testosterone.  DHEA is extremely important for immune system function and anabolic (building up) processes in the body.  DHEA levels begin to decline after age thirty-five but cortisol can remain elevated during continuing periods of stress.  Low DHEA levels are also found in diseases such as multiple sclerosis, cancer, fibromyalgia, lupus, rheumatoid arthritis, Crohn’s, ulcerative colitis and of course, thyroid disorders. Healthy adrenal glands are required for the conversion of inactive T4 into active T3.  When the adrenals have reached a state of fatigue, they are no longer producing sufficient cortisol or DHEA.  This leaves individuals more susceptible to chronic diseases from an inability to compensate for the stresses they encounter on a daily basis.  It is very important to treat the adrenal glands before commencing treatment of the thyroid.  Increasing thyroid hormone production while the adrenals are in fatigue can overwhelm the adrenals and lead to further exhaustion.  I have found that once the adrenal glands are healthy and the other related system/factors associated with thyroid imbalance are optimized, there is no need to treat the thyroid directly. The inner medulla produces adrenalin and noradrenalin also known as norepinephrine and epinephrine.  The cortex is under the control of hormones produced in the brain and the medulla is under the control of the nervous system. Healthy adrenal glands are vital for women who are peri- and post-menopausal.  The adrenal glands are responsible for producing the majority of sex hormones in a menopausal woman once the ovaries stop functioning.  If the adrenal glands are fatigued and not ready for menopause, there will be an exaggeration of menopausal symptoms such as hot flashes, weight gain, sleep problems, bone loss, mood swings, depression, anxiety, loss of sex drive and vaginal dryness.  Healthy adrenals ensure an easy transition into menopause and beyond.  A vast majority of the women I see in practice approach menopause with adrenal fatigue leading to severe menopausal symptoms and hormone dysfunction. Aldosterone

Commentary by Dr. Valentin Fuster

Editor's Audio Summary by Edward Livingston, MD, Deputy Editor, the Journal of the American Medical Association, for the September 1, 2015 issue

Aldosterone is a hormone secreted in dogs that helps manager potassium and is related to managing blood pressure.  Click on the arrow for Dr. Anne Chauvet‘s audio explanation! The post Aldosterone appeared first on Sarasota Dog.

Recent evidence has shown the increased incidence of PA in approximately 15% of the hypertensive population, making a non-invasive and simple screening method for the measurement of aldosterone levels necessary. The use of saliva for determination of steroid hormones is now widely used and accepted and salivary aldosterone concentrations have previously been reported at around 30% of those seen in plasma. Furthermore, there is a current lack of longitudinal and systematic studies addressing the involvement of aldosterone in the regulation of the RAAS in rodents due to sample volume restrictions and the lack of sensitivity to detect the very low aldosterone concentrations in commercially available assays. We developed a non-isotopic, competitive immunoassay for the determination of aldosterone levels in saliva, as well as in human and mouse plasma samples. The assay employs an aldosterone-biotin conjugate as the tracer and end-point determination through time-resolved fluorescence (TR-FIA) with Streptavidin-Europium as the detectable label. No pretreatment or purification of saliva is necessary while a simple extraction step is incorporated for the assessment of plasma levels. A polyclonal antibody was used for the development of the saliva assay giving a lower limit of detection of 19 pg/ml for each 50µl sample. Similarly, a highly specific monoclonal antibody against aldosterone, exhibiting a more sensitive linear working range starting from 8 pg/ml is used to detect aldosterone in 50µl of plasma. The monoclonal antibody could potentially also be used for the determination of salivary aldosterone levels, however this was not sufficiently evaluated in the studies shown here and further investigation of the exact assay conditions is needed. Inter- and intra-assay coefficients of variation, mean recoveries, accuracy and linearity were validated for both assays and the assay results correlated significantly with a commercially available radioimmunoassay for plasma in both settings. Overall, salivary aldosterone was found to correspond to approximately 28% of the concentrations seen in plasma and reflected the changes seen with posture and ACTH stimulation accurately. The assay presents the additional possibility of using salivary aldosterone levels, in combination with salivary cortisol, as a diagnostic tool in a clinical setting to screen suspected cases of PA and exclude healthy subjects. The salivary aldosterone to cortisol ratio remains elevated in PA persons due to autonomous hypersecretion of aldosterone throughout the day, alongside decreasing levels of cortisol, and can be clearly distinguished from healthy persons above a cut-off level of 0.1. Furthermore, as aldosterone concentrations are acutely affected by ACTH it was determined that sampling for this test should be carried out in the evening to avoid stress factors as well as diurnal fluctuations. In addition, as basal aldosterone values and those after suppression and stimulation under different conditions were found within the linear range of the assay, it is proposed that the assay could be especially useful to monitor adrenocortical function in pharmacological and dietary intervention studies in rodent models where repeated sampling and volumes collected are limited and measurement of multiple blood parameters is desirable.

Nongenomic in vitro effects of aldosterone on the sodium-proton antiport and intracellular second messengers have been described in human mononuclear leukocytes, vascular smooth muscle cells, and endothelial cells. To test the potential physiological relevance of these effects, an in vivo 31P magnetic resonance spectroscopy study on the human calf at rest and during exercise was performed in 10 healthy volunteers receiving either 1 mg aldosterone or placebo iv in a double blind, randomized, cross-over trial. Spectra were analyzed for phosphocreatine, ATP, phosphomonoesters, inorganic intracellular phosphate, and intracellular pH. Resting values remained unchanged by aldosterone. After isometric contraction of the calf (50% body weight for 3 min), phosphocreatine recovered to significantly higher levels after application of aldosterone compared with placebo. Other parameters were not significantly changed by aldosterone. Effects appeared immediately after isometric contraction and, thus, occurred within 8 min of aldosterone administration. They are, therefore, likely to represent the first contemporary evidence of nongenomic in vivo effects of aldosterone in man. These findings also point to an involvement of aldosteron in the acute stress adaptation of cellular oxidative metabolism in human muscle physiology.

Patients with glucocorticoid-remediable aldosteronism (GRA) possess a chimeric gene resulting from fusion of the genes encoding steroid aldosterone synthase and 11 beta-hydroxylase. In the adrenal zona fasciculata, this may lead to ectopic expression under ACTH control of aldosterone synthase activity and increased formation of cortisol C18 oxidation products. We assessed mineralocorticoid and glucocorticoid pathways in three patients with GRA. Baseline plasma progesterone, 17 alpha-hydroxyprogesterone, corticosterone, and cortisol were normal in all patients, whereas 11-deoxycorticosterone, aldosterone, and 11-deoxycortisol were above normal. The ratios of both corticosterone/11-deoxycorticosterone and cortisol/11-deoxycortisol were abnormally low, and decreased further 60 min after administration of ACTH-(1-24) (250 micrograms) as an i.v. bolus. A low corticosterone/11-deoxycorticosterone ratio is consistent with an increased aldosterone synthase activity forming aldosterone by corticosterone. Similarly, a decreased cortisol/11-deoxycortisol ratio could reflect enhanced cortisol C18 oxidation. Our findings are in agreement with a hyperfunction of the 11 beta-hydroxylase/aldosterone synthase complex in the adrenal zona fasciculata of GRA induced by the new chimeric gene.

There is increasing evidence for rapid steroid action on electrolyte transport in human mononuclear leukocytes (HML). In HML, aldosterone stimulates the Na+/H+ antiporter within a few minutes. Because a variety of hormones and growth factors activate the Na+/H+ antiporter via protein kinase C and inositol phospholipids, a possible involvement of inositol-1,4,5-trisphosphate (IP3) in the rapid effects of aldosterone in HML was investigated. The stimulation of IP3 generation was started by the addition of aldosterone, concanavalin A, or other steroids. A significant increase in IP3 levels by aldosterone (1 nmol/L, P < 0.05) was found after 1 min, similar to that found after concanavalin A (25 micrograms/mL). Aldosterone caused a concentration-dependent elevation of IP3 levels, with an apparent EC50 of approximately 0.1 nmol/L. Fludrocortisone stimulated IP3 generation at similar concentrations, whereas a weaker IP3 stimulation by glucocorticoids (hydrocortisone, dexamethasone) occurred at micromolar concentrations only. Canrenone, a potent inhibitor of classical aldosterone action, was not effective up to a concentration of 100 nmol/L. These findings show kinetic and pharmacological similarities with both the functional data on Na+/H+ antiport stimulation by aldosterone and the studies of 125I-aldosterone binding to plasma membranes of HML. Thus, these data are the first to indicate an involvement of the phosphoinositide pathway in the rapid membrane effects of aldosterone.

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p

Fri, 1 Jan 1988 12:00:00 +0100 https://epub.ub.uni-muenchen.de/5769/1/5769.pdf Wernze, H.; Paumgartner, Gustav; Jüngst, Dieter; Schnizer, W.; Gerzer, R.; Arendt, Rainer M.; Gerbes, Alexander L.