Chapter Twenty-Two: Introduction to Disorders of Osmolality

ReferencesThis is the famous Edelman equation from JCI in 1958 by Isodore Edelman! Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water (not to be confused by Isildur House of Isildur - Tolkien GatewayJoel mentioned his slide deck on Edelman: https://pbfluids.com/wp-content/uploads/2023/04/QN_III-The-Edelman-Equation-full-lecture-from-2020-07-30.pdfThis is an excellent review (with great figures) on Osmotic homeostasis by Danziger and Zeidel in CJASN Joel and JC mentioned the work from Joseph Verbalis on hyponatremia- this is an excellent review that includes population data from NHANES plus striking images of the osteopenic bones in hyponatremic rats! Check this out! Hyponatremia‐induced osteoporosis - Verbalis - 2010 - Journal of Bone and Mineral Research - Wiley Online LibraryJoel and JC mentioned “reference 2” from the chapter by Kleeman and others on diuretic induced hyponatremia which invoked hypokalemia as an important player: Diuretic-Induced Hyponatremia | Annals of Internal MedicineWe couldn't help flirting with diarrhea a little Secretory diarrhoea: mechanisms and emerging therapies - PMCWe talked about cravings for those with salt losses and here’s one example Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings - PMCPBFluids classic: Saltiest Sodium. Dumbest DudeVolume Depletion versus Dehydration: How Understanding the Difference Can Guide Therapy here’s one of many articles that argues for choosing language wisely. Amy’s VOG references:PMC304149442321668418463004219516633374011 PMC3041494PMC128849993102222 42060832 41201721 32401639 Link to Goljian Physiology Spotify! Episode 2 is Fluid and Hemodynamics: https://open.spotify.com/show/1uD6090Kkg01b4zr2ouNiM?si=e7f609e0d9634840Outline: Chapter 22Introduction to Disorders of OsmolalityHyponatremia and hypernatremia are common clinical problemsReflect abnormalities of water balance that may or may not be accompanied by changes in Na balanceWater Distribution and Osmotic PressureTBW makes up 60% of lean body weight in men50% of lean body weight in women60% intracellular40% extracellularOne-fifth of extracellular water is in the intravascular spaceBreakdown70 kg manTBW = 42 L25 L intracellular17 L extracellular3 L of the 17 L is intravascularOsmotic forces determine the distribution of waterEach compartment has one major solute that holds water within the compartmentNa → extracellular compartmentK → intracellular compartmentPlasma proteins → plasma spaceUrea is an ineffective osmolePhysiologic Effects of Changes in Plasma OsmolalityFigure 22-1Na pulls water from the intracellular compartmentIncreases extracellular volumeDecreases intracellular volumeEven though Na is locked in the extracellular compartmentAdministering Na increases osmolality everywhere by changing water distributionIncreases extracellular volumeDecreases intracellular volumeExampleAdding 210 mEq Na to 17 L ECF would mathematically increase concentration by 12.5 mEq/L (210/17)Actually only raises serum Na by ~5Water moves from cellsNa remains trapped in ECFUltimately diluted in TBW210/42 L = 5 mEq/LAdding waterExpands both compartmentsDilutes osmolality in both compartmentsGiving isotonic salineExpands extracellular compartment onlyDoes not change intracellular volumeChanges in osmolality and intracellular volumeResponsible for symptoms of hypo- and hypernatremiaIn these examplesExtracellular volume is increasedSodium concentration may be high, low, or normalMeaning of Plasma Sodium ConcentrationNa, glucose, and urea are the primary extracellular osmolesGives osmolality calculationUnder normal conditionsGlucose and BUN contribute <10 mOsm/LThereforePlasma osmolality ≈ 2 × plasma NaHypernatremia represents hyperosmolalityHyponatremia usually reflects hypo-osmolalityException: hyperglycemiaPlasma Sodium Concentration and Total Body OsmolalityIf plasma Na reflects plasma osmolalityAnd plasma osmolality is in equilibrium with total body osmolalityThen plasma Na reflects total body osmolalitySinceTotal body osmolality = (ECF solutes + ICF solutes) / TBWAndNa and K (plus accompanying anions) are the major extracellular and intracellular solutesThenPlasma Na ≈ (Na + K) / TBWFigure 22-2Key Edelman figureLoss of potassiumK moves out of cellsTo maintain electroneutralityNa enters cellsLowers serum NaOr Cl leaves with KLowers intracellular osmolalityWater moves from cells to ECFDilutes serum NaOr extracellular H dissociates from buffers and enters cellsCombines with intracellular buffersNo net movement of soluteWater still leaves cellsSerum Na dilutedSuggests K loss is responsible for much diuretic-induced hyponatremia (Ref 2)DKA example0.45% NS with 40 mEq KCl is insufficient to correct hyperosmolalityHyponatremia and HypernatremiaCan result from alterations inNaKWaterUsually due to water abnormalitiesExceptionThiazidesLoss of both Na and K contributesToxicity of K prevents excess K from producing hypernatremiaDiarrheaIsosmotic to plasmaIonic composition variesSecretory diarrhea (cholera)Na + K approximately equals plasma NaCauses volume depletionDoes not cause hypernatremiaOsmotic diarrheaFecal Na + K between 30 and 110Nonreabsorbed solutes account for remainderCauses hypernatremiaDiarrheal illnessOften causes feverIncreases insensible lossesAlso stimulates ADH and thirstUsually water balance remains near normalInfants commonly become hypernatremicRegulation of Plasma OsmolalityDaily variation in water intake and loss alters plasma osmolalityWater intakeDrinkingWater content of foodWater of oxidationCarbohydrates metabolized to CO2 and H2OWater retention lowers plasma osmolalityWater lossUrineFecesSkinRespiratory tractWater loss raises plasma osmolalityWater intake and excretion are tightly regulatedOsmoreceptors in hypothalamusAfter water loadPlasma osmolality fallsADH release inhibitedUrinary water loss increasesHyperosmolalityStimulates thirstStimulates ADHIncreases water intakeDecreases water lossRegulation disrupted byNeurologic disordersHypothalamusPosterior pituitaryRenal disordersImpaired concentrating or diluting abilityNonosmotic stimuliVolume depletionOsmoregulation versus Volume RegulationTable 22-2Plasma osmolalityRatio of solute to waterExtracellular volumeDetermined by absolute amount of Na and waterTwo examplesExercising on a hot dayLoss of dilute sweat↑ Plasma osmolality (Na)↓ Extracellular volumeSIADH↓ Plasma osmolality (Na)↑ Extracellular volumeNice exercise at bottom of page 691Isotonic salineDoes not change osmolalityHypothalamus not activatedIncreased volume suppresses reninIncreases ANPWater loadInhibits ADHProduces dilute urineRapid restoration of volumeOnly transient volume expansionLittle effect on renin or ANPNaCl without waterExpands extracellular volumeStimulates renal NaCl lossAlso stimulates thirst and ADHProduces small volume of concentrated urineSimilar to intakeVolume Depletion versus DehydrationThey are not synonymsUrine Osmolality and Specific GravityRelation Between Intake and OutputSimply comparing ins and outs is inadequateComposition of fluids may differ markedlyReplacing urinary losses with free waterProduces hyponatremia