Channel Your Enthusiasm

• Chapter Nineteen, Part 1: Metabolic Acidosis, The Show

  ReferencesChapter 19, Part 1 Metabolic acidosis June 14, 2023American Society of Nephrology | Medical Students - Kidney TREKS this is the program that Josh mentioned at Mount Desert Island! Effects of pH on Potassium: New Explanations for Old Observations - PMC here’s the review melanie from Peter Aronson that clarifies the fact that there are no H+-K+ antiporters outside the kidney but rather coupled transport-We discussed whether we like “Winter’s formula” Quantitative Displacement of Acid-Base Equilibrium in Metabolic Acidosis | Annals of Internal Medicine Dr. R. W. Winters was charged with larceny https://www.nytimes.com/1982/05/16/nyregion/ex-columbia-u-doctor-charged-with-larceny.htmlJCI - The Maladaptive Renal Response to Secondary Hypocapnia during Chronic HCl Acidosis in the Dog this was a classic experiment exploring the respiratory response to an infusion of HCl but the animals were maintained in a high pCO2 milieu (not generalizable to humans!)Here’s the thoughtful Pulmcrit post (by Josh Farkas) that Josh mentioned regarding correction of anion gap for hypoalbuminemia: Mythbusting: Correcting the anion gap for albumin is not helpfulJC mentioned that the anion gap does change in cirrhosis when the albumin is very low but using the correction factor may not change the clinical findings Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunctionDiagnostic Importance of an Increased Serum Anion Gap | NEJM Melanie mentioned the work of Patricia Gabow on the anion gap. In this review, she refers to work that she had done to try to identify all the organic anions in the anion gap but it falls short. Also, check out this critical look at the delta/delta: The Δ Anion Gap/Δ Bicarbonate Ratio in Lactic Acidosis: Time for a New Baseline?Roger mentioned near drowning in the Dead Sea and the unusual electrolytes in that instance. Near-Drowning in the Dead Sea: A Retrospective Observational Analysis of 69 PatientsWe discussed this classic NEJM article by Daniel Batlle The Use of the Urinary Anion Gap in the Diagnosis of Hyperchloremic Metabolic AcidosisAmy mentioned this review from Uribarri and Oh in JASN on the urine anion gap: The Urine Anion Gap: Common MisconceptionsJoel has a great blog post on the urine osmolar gap. urine osmolar gap – Precious Bodily Fluids Anna’s VoG on the bicarb deficit: Kurtz, I Acid-Base Case Studies, 2nd Edition. Trafford Publishing 2004. And the Fernandez paper that derived a better equationReference for Josh’s VoG: Key enzyme in charge of ketone reabsorption of renal tubular SMCT1 may be a new target in diabetic kidney diseaseSevere anion gap acidosis associated with intravenous sodium thiosulfate administrationUnexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathySodium Thiosulfate Induced Severe Anion Gap Metabolic AcidosisSodium Thiosulfate and the Anion Gap in Patients Treated by HemodialysisOutline: Chapter 19 Metabolic AcidosisOverviewLow arterial pHReduced HCO3Compensatory hyperventilation (↓ pCO2)Bicarb < 10 strongly suggests metabolic acidosis (renal compensation for respiratory alkalosis does not go that low)PathophysiologyH+ + HCO3- <=> H2CO3 <=> CO2 + H2OAcidosis results from H+ addition or HCO3 lossResponse to Acid LoadExtracellular bufferingExample: Add 12 mmol H+/L → HCO3 falls from 24 → 12 → pH drops to 7.1 (40 to 80 nmol/L)Intracellular and bone buffering55–60% buffered intracellularly and in bone12 mEq/L acid load only reduces serum HCO3 by ~5 mEq/LH+ into cells → K+ out (hyperkalemia)Notably in diarrhea or renal failureLess effect with organic acidosis (e.g., DKA, lactic acidosis)Respiratory compensationStimulates chemoreceptors → ↑ tidal volume (more than RR)Decreases pCO2, increases pHBegins within 1–2 hours; peaks at 12–24 hoursWinters formula alternative: for every 1 mEq ↓ HCO3, pCO2 ↓ by 1.2Chronic: respiratory compensation is blunted by renal adaptationRenal hydrogen excretion50–100 mEq/day acid generated from diet90% filtered HCO3 reabsorbed in PTAcid secreted:10–40 mEq via titratable acid (TA)30–60 mEq via NH3/NH4 (can ↑ to 250 mEq in acidosis)TA: phosphate (DKA → ketones act as TA)Max excretion up to 500 mEq/day in severe acidosisGeneration of Metabolic AcidosisMechanismsInability to excrete H+ (slow)Addition of H+ or loss of HCO3 (rapid)Anion Gap (AG)Normal: 5–11 (falling due to rising Cl-)Mostly due to negatively charged proteins (albumin)Adjust for albumin: AG ↓ 2.5 per 1 g/dL albumin ↓Revised: AG = unmeasured anions - unmeasured cations↑ AG = addition of unmeasured anions (e.g., lactate, ketones)Hyperchloremic acidosis: ↓ HCO3 replaced by ↑ Cl (normal AG)Delta–Delta AnalysisAdjust AG for albuminNormal ΔAG:ΔHCO3 = 1.6:1 (early 1:1)<1 → high + normal AG acidosisOther causes of AG variationHigh AG without acidosis: hemoconcentration, alkalosisLow AG: hypoalbuminemia, ↑ unmeasured cations (lithium, IgG, lab artifact)Urine Anion Gap (UAG)Normal = ~0; should be very negative (< -20) in acidosisType 1 & 4 RTA → UAG positive or near zeroInvalid in ketoacidosis or volume depletion (Na retention → ↓ distal acidification)Urine Osmolal GapEstimate NH4+ via osmolar gapRequires urine Na, K, glucose, ureaEtiologies and DiagnosisLactic AcidosisPyruvate → lactate (LDH; NADH → NAD+)Normal production: 15–20 mmol/kg/dayMetabolized in liver/kidney → pyruvate → glucose or TCANormal lactate: 0.5–1.5 mmol/L; acidosis if > 4–5 mmol/LCauses:↑ production: hypoxia, redox imbalance, seizures, exercise↓ utilization: shock, hepatic hypoperfusionMalignancy, alcoholism, antiretroviralsD-lactic acidosisShort bowel/jejunal bypassGlucose → D-lactate (not metabolized by LDH)Symptoms: confusion, ataxia, slurred speechSpecial assay neededTx: bicarb, oral antibioticsTreatmentUnderlying causeBicarb controversial: may worsen intracellular acidosis, overshoot alkalosis, ↑ lactateTarget pH > 7.1; prefer mixed venous pH/pCO2Ketoacidosis (Chapter 25 elaborates)FFA → TG, CO2, H2O, ketones (acetoacetate, BHB)Requires:↑ lipolysis (↓ insulin)Hepatic preference for ketogenesisCauses:DKA (glucose > 400)Fasting ketosis (mild)Alcoholic ketoacidosisPoor intake + EtOH → ↓ gluconeogenesis, ↑ lipolysisMixed acid-base (vomiting, hepatic failure, NAGMA)Congenital organic acidemias, salicylatesDiagnosis:AG, osmolar gap (acetone, glycerol)Ketones: nitroprusside only detects acetone/acetoacetateBHB can be 90% of total (false negative)Captopril → false positiveTreatment:Insulin +/- glucoseRenal Failure↓ excretion of daily acid loadGFR < 40–50 → ↓ ammonium/TA excretionBone buffering stabilizes HCO3 at 12–20 mEq/LSecondary hyperparathyroidism helps with phosphate bufferingAlkali therapy controversial in adultsIngestionsSalicylatesSymptoms at >40–50 mg/dLEarly: respiratory alkalosis → Later: metabolic acidosisTreatment: bicarb, dialysis (>80 mg/dL or coma)MethanolMetabolized to formic acid → retinal toxicityOsmolar gap elevatedTx: bicarb, ethanol/fomepizole, dialysisEthylene glycol→ glycolic/oxalic acid → renal failureSame treatment + thiamine/pyridoxineOtherToluene, sulfur, chlorine gas, hyperalimentation (arginine, lysine)GI Bicarbonate LossDiarrhea, bile/pancreatic drainage → loss of alkaline fluidsUreterosigmoidostomy → Cl-/HCO3- exchange in colonCholestyramine → Cl- for HCO3-Renal Tubular Acidosis (RTA)Type 1 (Distal)↓ H+ secretion in collecting duct → urine pH > 5.3Etiologies: Sjögren, RA, amphotericinFeatures: nephrocalcinosis, stones, hypokalemiaDiagnosis: NAGMA, persistent ↑ urine pHTreatment: alkali (1–2 mEq/kg/d adults; 4–14 kids), K+ if neededType 2 (Proximal)↓ HCO3 reabsorptionBicarb threshold reduced → self-limitedCauses: multiple myeloma, Fanconi, ifosfamideFeatures: rickets/osteomalacia, no stones, pH variableDiagnosis: NAGMA, pH < 5.3, high FE HCO3 when HCO3 loadedTreatment: alkali (10–15 mEq/kg/d), thiazidesType 4Aldo deficiency/resistance → hyperkalemia + mild acidosisK+ inhibits NH4 generationTx: correct K+, consider loop diureticsSymptomsHyperventilation (dyspnea)pH < 7.0–7.1 → arrhythmias, ↓ contractilityNeurologic: lethargy → coma (CSF pH driven)Skeletal growth issues in childrenTreatment PrinciplesNo alkali needed for keto/lactic acidosis unless pH < 7.2Bicarbonate DeficitDeficit = HCO3 space * (desired - actual HCO3)HCO3 space: 50–70% of body weightWatch for:K+ shifts: beware hypokalemia when correcting acidosisNa+ load in CHFDialysis if necessary

  --------  

  1:45:11
• Chapter Eighteen, part 1

  We are a bit slappy at the beginning of the episode since we had just recorded our conversation with the Glaucomfleckens. ReferencesChapter 18 Metabolic alkalosis! Part 1 February 23, 2023It is chloride depletion alkalosis, not contraction alkalosis classic review by Galla and Luke, the metabolic alkalosis mavens who review the role of chloride.On the mechanism by which chloride corrects metabolic alkalosis in man and this is the study when they induced a metabolic alkalosis and studied the effect of treating with KCl vs NaPhos and found the former (with chloride) reversed the alkalosis but not the sodium containing protocol. Some elegant reports on the increased proximal reabsorption of bicarbonate above normal stimulated by Ang II. Tubular transport responses to angiotensin | American Journal of Physiology-Renal PhysiologyCrosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption - Pontes - 2015 - Experimental Physiology - Wiley Online LibraryTHE RENAL REGULATION OF ACID-BASE BALANCE IN MAN. III. THE REABSORPTION AND EXCRETION OF BICARBONATE 1949 this is the correct figure for 11.14 and shows what happens when filtered bicarb exceeds normal threshold in normal human (men) and appears in the urine. Masterful review Symposium on acid-base homeostasis. The generation and maintenance of metabolic alkalosis by Seldin and Rector And a modern review from Michael Emmet! Metabolic Alkalosis - PMC (so many favorite reviews on this exciting topic!) and this one from Soleimani Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022 both of these elaborate on pendrin’s role. The effect of prolonged administration of large doses of sodium bicarbonate in man (Clin Sci. 1954 Aug;13(3):383-401)Kidney v Renal: KDIGO versus Don’tPlus: We got a little off topic and discussed the Kidney Failure Risk Equation: https://kidneyfailurerisk.com/Outline: Chapter 18Metabolic AlkalosisElevation of arterial pH, increased plasma HCO3, and compensatory hypoventilationHigh HCO3 may be compensatory for respiratory acidosisHCO3 > 40 indicates metabolic alkalosisPathophysiology: Two Key QuestionsHow do patients become alkalotic?Why do they remain alkalotic?Generation of Metabolic AlkalosisLoss of H+ ionsGI loss: vomiting, GI suction, antacidsRenal loss: diuretics, mineralocorticoid excess, hypercalcemia, post-hypercapniaAdministration of bicarbonateTranscellular shiftK+ loss → H+ shifts intracellularlyIntracellular acidosisRefeeding syndromeContraction alkalosisSame HCO3, smaller extracellular volume → increased [HCO3]Seen in CF (sweating), illustrated in Fig 18-1Common theme: hypochloremia is essential for maintenanceMaintenance of Metabolic AlkalosisKidneys normally excrete excess HCO3Example: Normal subjects excrete 1000 mEq NaHCO3/day with minor pH changeImpaired HCO3 excretion required for maintenanceTable 18-2Mechanisms of MaintenanceDecreased GFR (less important)Increased tubular reabsorptionProximal tubule (PT): reabsorbs 90% of filtered HCO3TALH and distal nephron manage the restContributing factors:Effective circulating volume depletionEnhances HCO3 reabsorptionAng II increases Na-H exchangeIncreased tubular [HCO3] enables more H+ secretionDistal nephron HCO3 reabsorptionStimulated by aldosterone (↑ H-ATPase, ↑ Na reabsorption)Negative luminal charge impedes H+ back-diffusionChloride depletionReduces NaK2Cl activity → ↑ renin → ↑ aldosteroneLuminal H-ATPase co-secretes Cl → low Cl increases H+ secretionCl-HCO3 exchanger needs Cl gradient → low Cl impairs HCO3 secretionKey conclusion: Cl depletion > volume depletion in perpetuating alkalosisAlbumin corrects volume but not alkalosisNon-N Cl salts correct alkalosis without fixing volumeHypokalemiaStimulates H+ secretion and HCO3 reabsorptionTranscellular shift (H/K exchange) → intracellular acidosisH-K ATPase reabsorbs K and secretes HSevere hypokalemia reduces Cl reabsorption → ↑ H+ secretionImportant with mineralocorticoid excessRespiratory CompensationHypoventilation: 0.7 mmHg PCO2 ↑ per 1 mEq/L HCO3 ↑PCO2 can exceed 60Rise in PCO2 increases acid excretion (limited effect on pH)EpidemiologyGI Hydrogen LossGastric juice: high HCl, low KClStomach H+ generation → blood HCO3Normally recombine in duodenumVomiting/antacids prevent recombination → alkalosisAntacids (e.g., MgOH)Mg binds fats, leaves HCO3 unbound → alkalosisRenal failure impairs excretionCation exchange resins (SPS, MgCO3) → same effectCongenital chloridorrheaHigh fecal Cl-, low pH → metabolic alkalosisPPI may help by reducing gastric Cl loadRenal Hydrogen LossMineralocorticoid excess & hypokalemiaAldosterone → H+ ATPase stimulation, Na+ reabsorption → negative lumen → ↑ H+ secretionDiuretics (loop/thiazide)Volume contractionSecondary hyperaldosteronismIncreased distal flow and H+ lossPosthypercapnic alkalosisChronic respiratory acidosis → ↑ HCO3Rapid correction (ventilation) → unopposed HCO3 → alkalosisGradual CO2 correction neededMaintenance: hypoxemia, Cl lossLow chloride intake (infants)Na+ reabsorption must exchange with H+/K+H+ co-secretion with Cl impaired if Cl is lowHigh dose carbenicillinHigh Na+ load without ClNonresorbable anion → hypokalemia, alkalosisHypercalcemia↑ Renal H+ secretion & HCO3 reabsorptionCan contribute to milk-alkali syndromeRarely causes acidosis via reduced proximal HCO3 reabsorptionIntracellular H+ ShiftHypokalemiaCommon cause and effect of metabolic alkalosisH+/K+ exchange → intracellular acidosis → ↑ H+ excretionRefeeding SyndromeRapid carb reintroduction → cellular shiftNo volume contraction or acid excretion increaseRetention of BicarbonateRequires impaired excretion to become significantOrganic anions (lactate, acetate, citrate, ketoacids)Metabolism → CO2 + H2O + HCO3Citrate in blood transfusion (16.8 mEq/500 mL)8 units → alkalosis riskCRRT + citrate anticoagulantSodium bicarbonate therapyRebound alkalosis possible with acid reversal (e.g., ketoacidosis)Extreme cases: pH up to 7.9, HCO3 up to 70Contraction AlkalosisNaCl and water loss without HCO3Seen in vomiting, diuretics, CF sweatMild losses neutralized by intracellular buffersSymptomsOften asymptomaticFrom volume depletion: dizziness, weakness, crampsFrom hypokalemia: polyuria, polydipsia, weaknessFrom alkalosis (rare): paresthesias, carpopedal spasm, lightheadednessMore common in respiratory alkalosis due to rapid pH shift across BBBPhysical exam not usually helpfulClues: signs of vomitingDiagnosisHistory is keyIf unclear, suspect:Surreptitious vomitingCFSecret diuretic useMineralocorticoid excessUse urine chlorideTable 18-3: urine Na is misleading in alkalosisTable 18-4: urine chemistry changes with complete HCO3 reabsorptionVomiting: low urine Na, K, Cl + acidic urineSufficient NaCl intake prevents this stageExceptions to low urine Cl:Severe hypokalemiaTubular defectsCKDDistinguishing from respiratory acidosisUse pH as guideCaution with typo (duplicate pCO2)A-a gradient might helpTreatmentCorrect K+ and Cl− deficiency → kidneys self-correctUpper GI losses: add H2 blockersSaline-responsive alkalosisTreat with NaClMechanisms:Reverse contraction componentReduce Na+ retention → promote NaHCO3 excretion↑ distal Cl delivery → enable HCO3 secretion via pendrinMonitor urine pH: from 5.5 → 7–8 with therapyGive K+ with Cl, not phosphate, acetate, or bicarbonateSaline-resistant alkalosisSeen in edematous states or K+ depletionEdema (CHF, cirrhosis): use acetazolamide, HCl, dialysisAcetazolamide: may ↑ CO2 via RBC carbonic anhydrase inhibitionMineralocorticoid excess: K+ + K-sparing diuretic (use caution)Severe hypokalemia:eNaC Na+ reabsorption must be countered by H+ if no K+Corrects rapidly with K+ replacementRestores saline responsivenessRenal failure: requires dialysis

  --------  

  1:05:53
• Chapter Seventeen

  ReferencesI said I used MDCalc but I was mistaken I use MedCalX which is nice but getting dated. We talked about this out of print book that we love: Cohen, J. J., Kassirer, J. P. (1982). Acid-base. United States: Little, Brown.Josh mentioned this article that looked at over 17,000 samples with simultaneous measured and calculated bicarbonate and found a very small difference. Comparison of Measured and Calculated Bicarbonate Values | Clinical Chemistry | Oxford AcademicBase deficit or excess- Diagnostic Use of Base Excess in Acid–Base Disorders | NEJM (check out the accompanying letter to the editor from Melanie challenging this article! Along with colleagues Lecker and Zeidel Diagnostic Use of Base Excess in Acid-Base Disorders )Melanie loves this paper which shows a nice correlation between arterial and venous pH but the rest of the comparisons are disappointing - Comparison of arterial and venous pH, bicarbonate, Pco2 and Po2 in initial emergency department assessment - PMCA nomogram for the interpretation of acid-base data is figure 17-1 in the book, this manuscript with the ! in the conclusion creates the acid-base map. We debated about whether we like Winter’s formula: Quantitative displacement of acid-base equilibrium in metabolic acidosis (melanie does b/c it used real patients). Amy’s Voice of God on Dietary Acid LoadReview of dietary acid load: https://pubmed.ncbi.nlm.nih.gov/23439373/, https://pubmed.ncbi.nlm.nih.gov/38282081/, https://pubmed.ncbi.nlm.nih.gov/33075387/Survey data from kidney stone formers regarding sources of dietary acid load: https://pubmed.ncbi.nlm.nih.gov/35752401/Urine profile for vegans and omnivories (urine pH and cations/anions): https://pubmed.ncbi.nlm.nih.gov/36364731/SWAP-MEAT pilot trial: https://pubmed.ncbi.nlm.nih.gov/39514692/ looked at urine profile on plant based meat diet (Beyond Meat) versus animal based meat dietNot all plant meat substitutes are the same in terms of net acid load: https://pubmed.ncbi.nlm.nih.gov/38504022/Frassetto paper showing that the dietary acid load effect is mostly from sodium chloride: https://pubmed.ncbi.nlm.nih.gov/17522265/Healthy eating is probably more important than plant based diet for CKD: https://pubmed.ncbi.nlm.nih.gov/37648119/, https://pubmed.ncbi.nlm.nih.gov/32268544/KDIGO 2024 guidelines: https://kdigo.org/guidelines/ckd-evaluation-and-management/Association (or lack thereof) of a pro-vegetarian diet and sarcopenia/protein energy wasting in CKD: https://pubmed.ncbi.nlm.nih.gov/39085942/Outline Chapter 17 Introduction to simple and mixed acid-base disordersIntroduction to Simple and Mixed Acid-Base DisordersDisturbances of acid-base homeostasis are common clinical problemsDiscussed in Chapters 18-21This chapter reviews:Basic principles of acid-base physiologyMechanisms of abnormalitiesEvaluation of simple and mixed acid-base disordersAcid-Base PhysiologyFree hydrogen is maintained at a very low concentration40 nanoEq/L1 millionth the concentration of Na, K, Cl, HCO3H+ is highly reactive and must be kept at low concentrationsCompatible H concentration: 16 to 160 nanoEq/LpH range: 7.8 to 6.8Buffers prevent excessive variation in H concentrationMost important buffer: HCO3Reaction: H+ + HCO3 <=> H2CO3 <=> H2O + CO2H2CO3 exists at low concentration compared to its productsHenderson-Hasselbalch Equation (HH Equation)Understanding acid-base can use both H+ concentration and pHMeasurement of pHMust be measured anaerobically to prevent CO2 lossMeasurement methods:pH: Electrode permeable to H+PCO2: CO2 electrodeHCO3: Calculated using HH EquationAlternative: Add strong acid, measure CO2 releasedPCO2 * 0.03 gives mEq of CO2Measured vs. Calculated HCO3pKa of 6.1 and PCO2 coefficient (0.03) varyMeasurement of CO2 prone to errorDebate remains unresolvedDifferences affect anion gap calculationsArterial vs. Venous Blood Gas (ABG vs. VBG)Venous pH is lower due to CO2 retentionVenous blood may be as accurate as arterial for pH if well perfusedPitfalls in pH MeasurementMust cool ABG quickly to prevent glycolysisAir bubbles affect gas readingsHeparin contamination lowers pHArterial pH may not reflect tissue pHReduced pulmonary blood flow skews resultsEnd tidal CO2 > 1.5% indicates adequate venous returnRegulation of Hydrogen ConcentrationHCO3/CO2 as the Principal BufferHigh HCO3 concentrationIndependent regulation of HCO3 (renal) and PCO2 (lungs)Renal Regulation of HCO3H secretion reabsorbs filtered bicarbonateLoss of HCO3 in urine equates to H retentionH combines with NH3 or HPO4, forming new HCO3Pulmonary Regulation of CO2CO2 is not an acid but forms H2CO3Lungs excrete 15,000 mmol of CO2 dailyKidneys excrete 50-100 mmol of H dailyH = 24 * (PCO2 / HCO3)pH compensation via respiratory and renal adjustmentsAcid-Base DisordersDefinitionsAcidemia: Decreased blood pHAlkalemia: Increased blood pHAcidosis: Process lowering pHAlkalosis: Process raising pHPrimary PCO2 abnormalities: Respiratory disordersPrimary HCO3 abnormalities: Metabolic disordersCompensation moves in the same direction as the primary disorderDiagnosis requires extracellular pH measurementMetabolic AcidosisLow HCO3 and low pHCauses:HCO3 loss (e.g., diarrhea)Buffering of non-carbonic acid (e.g., lactic acid, sulfuric acid in renal failure)Compensation: Increased ventilation lowers PCO2Renal excretion of acid restores pH over daysMetabolic AlkalosisHigh HCO3 and high pHCauses:HCO3 administrationH loss (e.g., vomiting, diuretics)Compensation: HypoventilationRenal HCO3 excretion corrects pH unless volume or chloride depletedRespiratory AcidosisDue to decreased alveolar ventilation, increasing PCO2Compensation: Increased renal H excretion raises HCO3Acute phase: Large pH drop, small HCO3 increaseChronic phase: Small pH drop, large HCO3 increaseRespiratory AlkalosisDue to hyperventilation, reducing CO2 and raising pHCompensation: Decreased renal H secretion, leading to bicarbonaturiaTime-dependent compensation (acute vs. chronic phases)Mixed Acid-Base DisordersMultiple primary disorders can coexistExample:Low arterial pH with:Low HCO3 → Metabolic acidosisHigh PCO2 → Respiratory acidosisCombination indicates mixed disorderExtent of renal and respiratory compensation clarifies diagnosisCompensation does not fully restore pHExample: pH 7.4, PCO2 60, HCO3 36 → Combined respiratory acidosis & metabolic alkalosisAcid-Base Map illustrates normal responses to disturbancesClinical Use of Hydrogen ConcentrationH+ vs. pH RelationshipH = 24 * (PCO2 / HCO3)Normal HCO3 cancels out 24, so H = 40 nMol/LpH to H conversion:Increase pH by 0.1 → Multiply H by 0.8Decrease pH by 0.1 → Multiply H by 1.25Example: Salicylate Toxicity7.32 / 30 / xx / 15Goal: Alkalinize urine to pH 7.45 (H+ = 35 nMol/L)Bicarb needs to reach 20 for compensationPotassium Balance in Acid-Base DisordersMetabolic AcidosisH+ buffered in cells, causing K+ to move extracellularlyK+ rises ~0.6 mEq/L per 0.1 pH dropLess predictable in lactic or ketoacidosisDKA-associated hyperkalemia due to insulin deficiencyHyperkalemia can induce mild metabolic acidosisRespiratory Acid-Base DisordersMinimal effect on potassium levels

  --------  

  1:31:49
• Chapter Sixteen, part 2

  ReferencesWe talked about winning the 2022 ASN innovation contest and here’s a link to our promo video https://www.dropbox.com/scl/fi/g4osnf0nradsfryyo51fi/ASN-Education-Contest-Channel-Your-Enthusiasm-Podcast.mp4?rlkey=pnso45x07nr3pane9y8cux8yg&e=1&dl=0We wondered about “permissive hypercreatinemia” and Josh referenced the DOSE trial: Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial - PMCPlus this editorial by Steve Coca: Ptolemy and Copernicus Revisited: The Complex Interplay between the Kidneys and Heart FailureWe refer to the Frank-Starling curve and reference an image from this paper by Jay Cohen: Blood pressure and cardiac performance - ScienceDirectWe felt that this chapter is dated with respect to heart failure. Check out this 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice GuidelinesUnderfilling versus overflow in hepatic ascites an editorial by Frank Epstein Effect of Head-Out Water Immersion on Hepatorenal Syndrome - American Journal of Kidney Diseases studies done by Schrier which Roger mentionedThe fading concept: https://www.tandfonline.com/doi/abs/10.3109/00365528309182102?journalCode=igas2Historical Aspects of Ascites and the Hepatorenal Syndrome - Wong - 2021 - Clinical Liver Disease - Wiley Online LibraryHere’s a great paper from Andrew Allegretti on HRS prognosis: Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT - PubMedJoel mentions landmark paper in NEJM for treating SBP Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis | New England Journal of MedicineAlbumin infusion in patients undergoing large‐volume paracentesis: A meta‐analysis of randomized trials - Bernardi - 2012 - Hepatology - Wiley Online LibraryJoel wondered about the lore that minoxidil could lead to renal recovery: Minoxidil treatment of malignant hypertension. Recovery of renal functionRoger recalled an agent diazoxide: Hyperstat - Side Effects, Uses, Dosage, Overdose, Pregnancy, Alcohol | RxWikiHere’s an entertaining review on whether insulin leads to sodium retention: Invited Review: Sodium-retaining effect of insulin in diabetes - PMCInvasive monitoring for hemodynamicsFACTT: https://www.nejm.org/doi/full/10.1056/NEJMoa062200ESCAPE: https://pubmed.ncbi.nlm.nih.gov/16204662/PACMAN: https://pubmed.ncbi.nlm.nih.gov/16084255/EVEREST trial and use of tolvaptan in HFrEFEVEREST: https://pubmed.ncbi.nlm.nih.gov/17384437/Post-hoc analysis of hyponatremic patients of EVEREST: https://pubmed.ncbi.nlm.nih.gov/23743487/Outline Chapter 16 — Edematous States part 2Symptoms and diagnosisThree factors important in the mechanism of edemaThe pattern of distribution of edema which reflects those capillaries with altered hemodynamic forcesThe central venous pressurePresence or absence of pulmonary edemaPulmonary edemaShortness of breath and orthopneaTachypnic, diaphoretic, wet rales, gallops, murmursCheck a chest x-rayCardiac disease is most commonBut differential includes primary renal Na retention and ARDSWedge pressure will exceed 18-20 mmHg with heart or primary Na retention, but is relatively normal with ARDSUncomplicated cirrhosis does not cause pulmonary edemaIncreased capillary pressure in this disorder is only seen below the hepatic veinNormal or reduced blood volume in the cardiopulmonary circulationPeripheral edema and ascitesPeripheral edema is cosmetically undesireable but produces less serious symptomsSymptoms: swollen legs, difficulty walking, increased abdominal girth, shortness of breath due to pressure on the diaphragm.Pitting edema found in dependent areasAscites found in abdomenNephrotic syndrome low tissue pressure areas like eye orbitsHeart Failure (right sided) peripheral edema, abdominal wall, SOB is due to concomitant pulmonary disease. Right sided heart failure increases venous pressureCirrhosis develop cirrhosis and lower extremity edema, pressure above the hepatic vein is normal or low.Tense ascites can increase the pressure above the diaphragm but is relieved with a tapPortal pressure > 12 mmHg required for fluid retentionLove the case history 16-1Primary renal sodium retentionPulmonary and peripheral edemaJugular venous pressure is elevatedNephrotic SyndromePeriorbital and peripheral edema, rarely ascitesCVP normal to highIdiopathic edemaBehaves as volume depleted (especially with diuretics)Etiology and treatmentGeneral principles of treatmentWhen must edema be treatedWhat are the consequences of the removal of fluidHow rapidly should fluid be removedWhenPulmonary edema is the only form of generalized edema that is life threatening and demands immediate treatmentImportant for note: laryngeal edema and angioedema. Cerebral edemaWhat are the consequencesIf the edema fluid is compensatory (heart failure, cirrhosis, capillary leak syndromes) then removal of fluid with diuretics will diminish effective circulating volume.Despite this drop in effective circulating volume, most patients benefit from the appropriate use of diuretics.Cardiac output falls 20% with diuresis of pulmonary congestion but exercise tolerance increasesSays to be careful in diuresis leads to increases in CrHow rapidly should edema fluid be removedRemoving vascular fluid changes starling forces (reduced venous pressure) so fluid rapidly mobilized from interstitium. 2-3 liters per 24 hours can often be removed without difficultyAn exception is cirrhosis and ascites without peripheral edema. Mobilizing ascites is limited to 500-750 ml/dayHeart failureEdema is due to increase in venous pressure raising capillary hydrostatic pressureIschemic and hypertensive CM impairs left ventricular function causing pulmonary but little peripheral edemaIn acute pulmonary edema the LV disease results in increased LVEDP and increased left atrial pressure which transmit back to the pulmonary veinWhen wedge exceeds 18-20 (normal is 5-12) get pulmonary edemaCor pulmonale due to pure right heart failure prominent edema in the lower extremitiesCardiomyopathies tend to affect right and left ventricles leading to simultaneous onset of pulmonary and peripheral edema.Discusses forward hypothesis in which reduction in cardiac output triggers decreased tissue perfusion activation of SNS and RAAS.Catecholamines increase cardiac outputRAAS increase Sodium retentionEdema is absent and patients can be compensated at the expense of increased LVEDP see Figure 16-6Figure 16-6 A to B to C with compensationEventually the increased sodium retention and increased intracranial pressure are enough to cause edema.He then brings up multiple important points (in bullets none the less)Dual effects of fluid retention:Increased cardiac outputPotential harmful elevation in venous pressureBenefit is found with increase in LVEDP from 12 to 15, after that it seems mostly deleteriousVascular congestion (elevated LVEDP) and a low cardiac output do not have to occur together. See points B and C on 16-6.Frank-Starling relationship varies with exercise.Patients with moderate heart disease may be okay at rest but fail with mild exertion. This leads to more neurohormonal activation. This can worsen sodium retention and ischemia. Rest here can help augment diuretic effect. Doubling diuretic response. 40% increase in GFR.Mild to mod heart disease may have no edema with dietary Na restriction. Na intake will initially increase preload and improve cardiac output and allow the Na to be excreted but as the Frank Starling curves flatten then excess sodium cannot be excreted.Diastolic vs Systolic dysfunctionDecreased compliance in diastolic dysfunction can lead to flash pulmonary edemaMore common with hypertensionLook to the ejection fractionNeurohormonal adaptationInitial benefit long term adverse effectsNorepi, renin, ADH all are vasoconstrictorsThey raise cardiac outputRaise BP which is maladaptive in the long termTreatment of cardiogenic pulmonary edemaMorphineOxygenLoop diureticNTG/nitroprussideIf patient remains in pulmonary edema and has systolic dysfunction consider inotropic agentTreatment of chronic heart failureFeels datedMentions dig and loop diureticBut also ACEi/BB and AADeep diveLoop diureticsACEiCor PolminaleEdema here comes with increased CO2Associated with increased HCO3 which means increasedHCO3 reabsorption int he proximal tubule which leads to more sodium retentionHypoxemia can increase Na retentionCirrhosis and AscitesBoth lymphatic obstruction and increased capillary permeability contributeSinusoidal obstruction leads to increased hydraulic pressure in the sinusoids.Portal hypertension is necessary for ascites> 12 mmHgThe low albumin is often present but is not contributory to edemaSinusoids are freely permeable to albumin so no oncotic pressure from albumin hereMechanism of ascitesRenal sodium conservation is an early finding and some evidence for primary sodium retention but…Mostly underfill is thought to drive Na retentionSplanchnic vasodilation starts this ofNO drives thisEndotoxin absorption stimulates NoNormally endotoxin is detoxed in liver but portosystemic shunting allows endotoxin to escape the liver.Hepatorenal syndromeProgressive hemodynamically mediated fall in GFRInduced by intense renal vasocontstrictionWhere are the PGE and KininsFall in GFR is masked by decreased muscle mass and decreased BUN productionHyponatremia is a grave prognostic sign, as it is in heart failure, Indicates increased activation of vasopressinTreatmentLow Na intakeLow water intakeCare with diuretics, can only mobilize 300-500 ml of ascetic fluid a dayAvoid hypokalemiaStimulates NH3 productionTalks about the mechanism in proximal tubuleAlso discusses pKA of NH3->NH4 reaction and if the pH rises, this will shift the Eq to produce NH3Important aspect in NH3 is lipid soluble and NH is notSays that Spiro is diuretic of choiceStates it is more effective than furosemide in this conditionEffectiveness related to slower rate of drug excretionin urine (compromises furosemide but not spiro) competition with bile saltsRecommends 40 furosemide and 100 of spiroResistant ascitesOptionsparacentesisTIPSComplicated by higher mortalityPeritoneovenous shuntLargely abandoned,Primary renal sodium retentionCKD or AKI where low GFR linits excretion of Water and NaAcute GN or nephrotic syndromeBroken glom with intact tubules, mean the tubules see less Na so they think “underperfused” and then they increase renal retention of NADrugsDirect vasodilators like minoxidilRequire super high furosemide doses to counterOther antihypertensives either block sympathetic NS, Na retention directly or block RAAS explains why they don’t cause Na retentionNSAIDSFludrocortisonePregnancyNormal pregnancy is associated with retention of 900 to 1000 mEq of NaAnd! 6-8 liters of waterRefeeding edemaInsulin stimulate Na retention

  --------  

  1:27:48
• Chapter Sixteen, part 1

  ReferencesCapillary Hemodynamics Insights into Salt Handling and Blood Pressure | NEJMAmy mentioned about the 3 phases of the interstitiumAre the precapillary sphincters and metarterioles universal components of the microcirculation? An historical review - PMCSafety factor?Renal Function during Recovery from Minimal Lesions Nephrotic Syndrome - Abstract - Nephron 1987, Vol. 47, No. 3 - Karger PublishersAre diuretics effective for idiopathic lymphedema? : Evidence-Based PracticeRapid diuresis in patients with ascites from chronic liver disease: the importance of peripheral edema for fig 16-7Activation and Inhibition of Sodium-Hydrogen Exchanger Is a Mechanism That Links the Pathophysiology and Treatment of Diabetes Mellitus With That of Heart FailureAdditional notes from our chat (might be overlap with Amy’s notes belowNew insights into the pathophysiology of edema in nephrotic syndrome by Helbert RondonThe hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosityPlasmin in Nephrotic Urine Activates the Epithelial Sodium ChannelLipoprotein metabolism in experimental nephrosisViscosity regulates apolipoprotein A-1 gene expression in experimental models of secondary hyperlipidemia and in cultured hepatocytesAmiloride in Nephrotic Syndrome | Clinical Research Trial Listing ( oedema | EdemaHypoalbuminemia and proteinuria contribute separately to reduced lipoprotein catabolism in the nephrotic syndromeOrigin of hypercholesterolemia in chronic experimental nephrotic syndromeExtrahepatic lipogenesis contributes to hyperlipidemia in the analbuminemic ratApolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritisAmy’s NotesJosh “Blessed are the days” https://link.springer.com/article/10.1007/s00467-013-2435-6Amy mentions mels’ article Capillary Hemodynamics Insights into Salt Handling and Blood Pressure | NEJM, the 3 phases of the interstitiumJosh mentions a re: management of idiopathic edema (from up to date: https://www.uptodate.com/contents/idiopathic-edema)Amy stemmer sign: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635205/, https://pubmed.ncbi.nlm.nih.gov/31281100/Anna in chat talking about amiloride, ENaC re: edema: https://www.researchgate.net/publication/50989884_New_insights_into_the_pathophysiology_of_edema_in_nephrotic_syndromeOutline Chapter 16 — Edematous StatesEdema is a palpable swelling produced by expansion of the interstitial fluid volumeConditions associated with this Heart failure Cirrhosis Nephrotic syndromePathophysiology of edema formationTwo steps Alteration of capillary hemodynamics that favors movement of fluid out of the capillary Dietary sodium and water are retained by the kidneyEdema does not become clinically apparent until interstitial volume has increased 2.5 to 3 liters If this fluid came the plasma would have hemoconcentration and shock Instead as fluid moves from vascular space to interstitium you get decreased tissue perfusion leading to kidney Na and water retention Net result is expansion of total extracellular volume with maintenance of plasma volume at close to normal levels This means that the kidney is responding appropriately.Important because therapy with diuretics will break this response and may diminish tissue perfusion. There are other situations where primary abnormality is inappropriate renal fluid retention. Here both the plasma and interstitial volumes are expanded and there is no consequences from diuretic therapy. This is over filling. Seen in cirrhosis, primary renal disease. Certain drugs Capillary hemodynamics Exchange of fluids at teh capillary is determined by the hydraulic and oncotic pressures in each compartment This can be expressed by Starlings law Net filtration = LpS (delta hydraulic pressure - delta oncotic pressure) Lp is the unit permeability or porosity of the capillary wall. S is the surface area. Sigma is the reflection coefficient ranging from zero for completely permeable to 1 for for impermeable Difficult to measure these values in humans and animals 16-1 is a table of starling force values. No reflection coefficient though Figure 16-2 shows values in subcutaneous tissues. PCap 17.3 Oncotic pressure in cap is 28. Says mean net gradient is 0.3 mmHg favoring filtration out of the vascular space. This excess net is returned to the systemic circulation by lymphatics. In the liver the values are different. The hepatic sinusoids are highly permeable to protein so oncotic pressure is neutralized by zero reflection coefficient. SO hydraulic pressure favoring filtration is unopposed. Cap hydraulic pressure is lower since two thirds of hepatic blood flow is from low pressure portal vein. Still large pressure gradient favoring filtrationAlveolar capillaries are similar to the liver Low cap hydraulic pressure, more permeable to proteins so no transcapillary oncotic pressure. Edema formation requires alteration of one or more starling forces to favor net filtrationIncreased capillary hydraulic pressure would do it Increased interstitial oncotic pressure tooReduction in plasma oncotic pressureLymphatic obstruction too Increased capillary hydraulic pressureCapillary hydraulic pressure is insensitive to alteration in arterial pressure due to autoregulation in the pre-capillary sphincterConstricts in response to increases in arterial pressureNo sphincter at venous end, so changes in venous pressure are transmitted to capillary bed. Blood volume expanded increases pressure in enough system Heart failure Renal disease Venous obstruction Cirrhosis DVT Decreased plasma oncotic pressure Hypo albuminuria May be less common than previously suspected Increased capillary permeability Promotes edema directly and by permitting albumin to move into interstitium, decreasing the oncotic pressure gradient Burns both histamine and oxygen free radicals cause microvascular injury Therapy with IL-2 increases capillary permeability Episodic idiopathic capillary leak syndromes by IL-2 receptors on mononuclear cells or increased generations of kinins. Patients often with monoclonal gammopathy and during episodes have a massive leak of proteins and fluids, hematocrit rises 70-80%. Aminophylline and terbutaline may prevent. episodes ARDS Ischemia or sepsis induced release of cytokines such as IL-1, IL-8 or TNF may have role in creasing pulmonary capillary permeability DM also increases capillary permeability and may have a role in the edema which is primarily generated by other factors, heart failure or NS Lymphatic obstruction Most often with nodal enlargement due to malignancyCalled lymphedema Hypothyroidism marked increase in interstitial accumulation of albumin and other proteins. Low lymphatic flow in hypothyroidema, myxedema. Resistant to diuretics which will put patient at risk of hypovolemia. Safety factors Needs to be 15 mmHg increase in the gradient favoring filtration before edema is seen Three factors explain this protective response Increased lymphatic flow can remove excess filtrate Fluid entry into interstitium lowers the oncotic pressure by dilution and lymphatic mediated removal of proteins Increased fluid entry to interstitium increases interstitial hydraulic pressure Talks about hypoalbuminemia and edema This is a lot of underfill vs overfill theory. Nice bullet points at bottom of 487 how heterogeneity of etiology of edema with MCD. Talks about pulmonary edema and how high interstitial protein provides large safety factor, interstitial albumin has a long way to fall to prevent pulmonary edema. Mentions kwashiorkor and how it may not be low albumin that causes this. Renal sodium retention Can be due to primary renal disease causing sodium retention NS, GN More commonly is renal salt retention is an appropriate compensatory response to decreased effective circulating volume States that decreased effective circulating volume can become compensated and renin falls back to normal.Had interesting figure 16-5 “The Compensated State”Symptoms and diagnosisThree factors important in the mechanism of edemaThe pattern of distribution of edema which reflects those capillaries with altered hemodynamic forcesThe central venous pressurePresence or absence of pulmonary edemaPulmonary edemaShortness of breath and orthopneaTachypnic, diaphoretic, wet rales, gallops, murmurs Check a chest x-rayCardiac disease is most commonBut differential includes primary renal Na retention and ARDSWedge pressure will exceed 18-20 mmHg with heart or primary Na retention, but is relatively normal with ARDSUncomplicated cirrhosis does not cause pulmonary edemaIncreased capillary pressure in this disorder is only seen below the hepatic veinNormal or reduced blood volume in the cardiopulmonary circulationPeripheral edema and ascitesPeripheral edema is cosmetically undesireable but produces less serious symptomsSymptoms: swollen legs, difficulty walking, increased abdominal girth, shortness of breath due to pressure on the diaphragm.Pitting edema found in dependent areasAscites found in abdomenNephrotic syndrome low tissue pressure areas like eye orbitsHeart Failure (right sided) peripheral edema, abdominal wall, SOB is due to concomitant pulmonary disease. Right sided heart failure increases venous pressureCirrhosis develop cirrhosis and lower extremity edema, pressure above the hepatic vein is normal or low.Tense ascites can increase the pressure above the diaphragm but is relieved with a tapPortal pressure > 12 mmHg required for fluid retentionLove the case history 16-1Primary renal sodium retentionPulmonary and peripheral edemaJugular venous pressure is elevatedNephrotic SyndromePeriorbital and peripheral edema, rarely ascitesCVP normal to highIdiopathic edemaBehaves as volume depleted (especially with diuretics)Etiology and treatmentGeneral principles of treatmentWhen must edema be treatedWhat are the consequences of the removal of fluidHow rapidly should fluid be removedWhenPulmonary edema is the only form of generalized edema that is life threatening and demands immediate treatmentImportant for note: laryngeal edema and angioedema. Cerebral edemaWhat are the consequencesIf the edema fluid is compensatory (heart failure, cirrhosis, capillary leak syndromes) then removal of fluid with diuretics will diminish effective circulating volume. Despite this drop in effective circulating volume, most patients benefit from the appropriate use of diuretics.Cardiac output falls 20% with diuresis of pulmonary congestion but exercise tolerance increasesSays to be careful in diuresis leads to increases in CrHow rapidly should edema fluid be removedRemoving vascular fluid changes starling forces (reduced venous pressure) so fluid rapidly mobilized from interstitium. 2-3 liters per 24 hours can often be removed without difficultyAn exception is cirrhosis and ascites without peripheral edema. Mobilizing ascites is limited to 500-750 ml/dayHeart failureEdema is due to increase in venous pressure raising capillary hydrostatic pressureIschemic and hypertensive CM impairs left ventricular function causing pulmonary but little peripheral edemaIn acute pulmonary edema the LV disease results in increased LVEDP and increased left atrial pressure which transmit back to the pulmonary vein When wedge exceeds 18-20 (normal is 5-12) get pulmonary edema Cor pulmonale due to pure right heart failure prominent edema in the lower extremitiesCardiomyopathies tend to affect right and left ventricles leading to simultaneous onset of pulmonary and peripheral edema.Discusses forward hypothesis in which reduction in cardiac output triggers decreased tissue perfusion activation of SNS and RAAS.Catecholamines increase cardiac output RAAS increase Sodium retentionEdema is absent and patients can be compensated at the expense of increased LVEDP see Figure 16-6Figure 16-6 A to B to C with compensationEventually the increased sodium retention and increased intracranial pressure are enough to cause edema.He then brings up multiple important points (in bullets none the less)Dual effects of fluid retention:Increased cardiac outputPotential harmful elevation in venous pressureBenefit is found with increase in LVEDP from 12 to 15, after that it seems mostly deleterious Vascular congestion (elevated LVEDP) and a low cardiac output do not have to occur together. See points B and C on 16-6.Frank-Starling relationship varies with exercise.Patients with moderate heart disease may be okay at rest but fail with mild exertion. This leads to more neurohormonal activation. This can worsen sodium retention and ischemia. Rest here can help augment diuretic effect. Doubling diuretic response. 40% increase in GFR.Mild to mod heart disease may have no edema with dietary Na restriction. Na intake will initially increase preload and improve cardiac output and allow the Na to be excreted but as the Frank Starling curves flatten then excess sodium cannot be excreted. Diastolic vs Systolic dysfunctionDecreased compliance in diastolic dysfunction can lead to flash pulmonary edema More common with hypertensionLook to the ejection fractionNeurohormonal adaptation Initial benefit long term adverse effectsNorepi, renin, ADH all are vasoconstrictors They raise cardiac outputRaise BP which is maladaptive in the long termTreatment of cardiogenic pulmonary edemaMorphineOxygenLoop diureticNTG/nitroprussideIf patient remains in pulmonary edema and has systolic dysfunction consider inotropic agentTreatment of chronic heart failure Feels datedMentions dig and loop diureticBut also ACEi/BB and AADeep diveLoop diureticsACEiCor Polminale Edema here comes with increased CO2Associated with increased HCO3 which means increasedHCO3 reabsorption int he proximal tubule which leads to more sodium retentionHypoxemia can increase Na retentionCirrhosis and AscitesBoth lymphatic obstruction and increased capillary permeability contributeSinusoidal obstruction leads to increased hydraulic pressure in the sinusoids. Portal hypertension is necessary for ascites> 12 mmHgThe low albumin is often present but is not contributory to edemaSinusoids are freely permeable to albumin so no oncotic pressure from albumin hereMechanism of ascitesRenal sodium conservation is an early finding and some evidence for primary sodium retention but…Mostly underfill is thought to drive Na retentionSplanchnic vasodilation starts this ofNO drives thisEndotoxin absorption stimulates NoNormally endotoxin is detoxed in liver but portosystemic shunting allows endotoxin to escape the liver.Hepatorenal syndromeProgressive hemodynamically mediated fall in GFRInduced by intense renal vasocontstrictionWhere are the PGE and KininsFall in GFR is masked by decreased muscle mass and decreased BUN productionHyponatremia is a grave prognostic sign, as it is in heart failure, Indicates increased activation of vasopressinTreatmentLow Na intakeLow water intakeCare with diuretics, can only mobilize 300-500 ml of ascetic fluid a dayAvoid hypokalemia Stimulates NH3 productionTalks about the mechanism in proximal tubuleAlso discusses pKA of NH3->NH4 reaction and if the pH rises, this will shift the Eq to produce NH3Important aspect in NH3 is lipid soluble and NH is not Says that Spiro is diuretic of choiceStates it is more effective than furosemide in this conditionEffectiveness related to slower rate of drug excretionin urine (compromises furosemide but not spiro) competition with bile saltsRecommends 40 furosemide and 100 of spiroResistant ascitesOptionsparacentesisTIPSComplicated by higher mortality Peritoneovenous shunt Largely abandoned,Primary renal sodium retentionCKD or AKI where low GFR linits excretion of Water and NaAcute GN or nephrotic syndrome Broken glom with intact tubules, mean the tubules see less Na so they think “underperfused” and then they increase renal retention of NADrugsDirect vasodilators like minoxidilRequire super high furosemide doses to counterOther antihypertensives either block sympathetic NS, Na retention directly or block RAAS explains why they don’t cause Na retentionNSAIDSFludrocortisonePregnancyNormal pregnancy is associated with retention of 900 to 1000 mEq of NaAnd! 6-8 liters of waterRefeeding edemaInsulin stimulate Na retention

  --------  

  1:18:54

Mais podcasts de Saúde e fitness

Podcasts em tendência em Saúde e fitness

Sobre Channel Your Enthusiasm