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