3 Total Body Water We will start with some basic concepts. 0.6 x weight1/3 ECF(Intravascular)¼ Plasma¾ Interstitial Fluid2/3 ICFWe will start with some basic concepts.Water is distributed between 2 main components: inside the cells and outside the cellsECF space is about 20% of body’s weightInterstitial fluid surrounds the cells and has the same components of plasma, but with less proteinDifference between plasma and interstitial fluid is oncotic pressure- the oncotic pressure (proteins) maintains intravascular volumePlasma UF can accumulate in a “third” space and result in edema, ascites, or pleural effusions.
4 Composition of Electrolytes: ICF and ECF Intracellular (mEq/L)Extracellular (mEq/L)Na20K1503-5Cl____98-110HCO₃1020-25PO₄5Protein75Electrolytes inside the cell and outside the cell are different.Sodium and chloride are the predominant ECF electrolytes and are responsible for maintaining ECF volume as opposed to potassiumPotassium and phosphate are principal components of ICF- potassium is primarily intracellular so it is very difficult to estimate total body potassium.
6 CaseA 12 year old boy with chronic renal insufficiency secondary to obstructive uropathy is admitted for pancreatitis. He cannot tolerate enteral feeds and is on TPN. He complains of his legs feeling weak. Labs show
7 Case What do you do first? EKG EKG shows peaked T waves What do you do next?Give calcium gluconateStop his TPN, which has K in it!
8 CaseIn addition to this treatment, which one of the following would be the most effective therapy for his hyperkalemia?Subcutaneous insulin and slow infusion of glucoseIntravenous beta – 2 agonistIntravenous insulinIntravenous sodium bicarbonateOral sodium polystyrene sulfonate
9 Potassium Growing child requires 1-2 mEq/kg/day Avoid potassium deficiencyCellular growthSerum potassium concentration does not reflect total body potassium contentEx: Diabetic ketoacidosisDisturbance in serum K⁺ can affect cell membrane resting potentialMuscle paralysisVentricular arrhythmiasDifference between intracellular and extracellular potassium concentrations determines the resting membrane potential of a cell
10 Hyperkalemia Serum K >5 mmol/L (5 meq/L) Kidney failure is the leading causeCan be life-threatening due to risk of ventricular arrhythmiasNormal renal response to hyperkalemiaStimulate aldosterone secretion which then stimulates urinary potassium excretion
12 Hyperkalemia Decreased renal excretion Common Drugs Increased intake Reduced GFRReduced tubular secretionIncreased intakeTranscellular shiftsMetabolic acidosisTumor Lysis SyndromeRhabdomyolysisAldosterone deficiency or resistanceCommon DrugsAmilorideSpironolactoneCyclosporine/TacrolimusHeparinACE inhibitors/ARBsPentamidineTrimethoprim-SulfamethoxazoleRare in individuals with normal renal functionReduced GFR: Acute/Chronic renal failureReduced tubular secretion: Addison’s disease, hypoaldosteronism, potassium sparing diuretics, ACE Inhib, Trimethoprim, Renal tubular acidosisIncreased intake: transfusions, KCl supplementation, sports beverages, IVFs and TPNTranscellular shifts: Cell destruction-trauma, burns, rhabdomyolysis, hemolysis, tumor lysis, catabolismMetabolic acidosis- H shifts inside of cell, K shifts out of cellsAldosterone deficiency: CAH
13 Cells 3 Na 2 K ECF ICF Na= 10 mmol/L K=140 mmol/L Na= 150 mmol/L
14 Hyperkalemia Reason for K to have shifted outside the cells? K shift to outside the cell after the blood was collected?HemolysisTissue hypoxia distal to tourniquetHeel stickAre the kidneys excreting K appropriately?GFRDrugsAldosteroneExcessive dietary K intake contributing to the problem?IVFs and TPN!!!High potassium foodsFigs, molasses, seaweed, dried fruit, nuts, avacodoes, lima beans, spinach, tomatoes, broccoli, carrots, potatoes, cauliflower, bananas, canteloupe, kiwi, oranges, mangoes, ground beef, steak, pork, veal, lamb
15 Treatment Repeat serum K EKG stat If EKG shows changes, start treatment immediatelyProgression of changesPeaked T waves-Prolonged PR interval-ST depression-Widened QRS-Ventricular fibrillation
16 Hyperkalemia EKG Changes Peaked T wavesLoss of P waveWidening of QRSST depressionProlonged PR intervalVentricular dysrhythmiasCardiac arrestAssociated with weakness, parasthesias, tetanyOrder of progression although not always dependent on potassium level
17 Treatment 1. Stop K intake 2. Protect myocardium (any EKG changes) IVFs, TPN2. Protect myocardium (any EKG changes)10 % Calcium gluconate infusion1 ml/kg/dose3. Shift K into the cells (K>7)Insulin 0.1 unit/kg/hr with D25W 1-2 mL/kg/hr (15 min)High dose inhaled beta agonists (albuterol) (30 min)Na Bicarbonate 1-2 meq/kg IV over 5-10 min (3-4hour)
18 Hyperkalemia Treatment Eliminate source of potassium intake or offending drugsK⁺ < 6 mEq/LLow potassium dietDiureticsK⁺ > 6 mEq/LCation exchange resin: SPSTPN and IVFKayexalate- exchange resin that binds K in gutOral is superior to rectal- takes several hours to workDose 1 gram/kg q 4-6 hours
19 Hyperkalemia Treatment EKG changes = EMERGENCYStabilize myocardiumIV calcium chloride or calcium gluconate (10%)Shift potassium into cellsBeta agonists, insulin/glucose, sodium bicarbonateRemove excess potassium from the bodySodium polystyrene sulfonate (SPS)FurosemideHemodialysisRegardless of potassium valueEKG changes occur individually and cannot be correlated with serum K levelLoop diuretics (only work if good renal function)Kayexalate- exchange resin that binds K in gutOral is superior to rectal- takes several hours to workDose 1 gram/kg q 4-6 hours
21 Hypokalemia Weakness or paralysis Ileus Cardiac dysrhythmias Delayed depolarizationFlat/absent T wavesU waves
22 Hypokalemia U waves BMP Renin Aldosterone Cortisol Hypernatremia AlkalosisBartter’sReninAldosteroneCortisolHypernatremia-suggests endocrine cause (increased aldosterone)Alkalosis-consistent with primary alkalosis or tubular disorder (Bartter’s)TTKG- Urine/serum potassium divided by urine/serum osmolalityValues range from 1-15<5: suggestive of low urine losses-not likely the cause of the hypokalemia>9: suggestive of high urine losses-consistent with a renal origin
23 Hypokalemia Treatment If > 2.0 mEq/L and no EKG changes, treat orally with KCl, minimum 2 mEq/kg/dayIf < 2.0 and/or EKG changes, treat intravenously, with KCl 40 mEq/L into IV fluids“Potassium runs”: not recommended unless cardiac/ICU patientMonitor potassium values until normal value is established
25 CaseA 7 yo male with cystic fibrosis and obstructive lung disease is admitted for a 2 week h/o progressive lethargy. He is obtunded.Labs: Na=105, K=4, Cl=72, HCO3=21Plasma osmolality= 222mOsm/kg H20Urine osmolality= 604 mOsm/kg H20Urine Na= 78 mEq/L
26 Case What is the most likely diagnosis? PseudohyponatremiaSIADHPsychogenic polydipsiaHypoaldosteronismHow would you raise the plasma sodium concentration?
27 Osmolality of Body Fluids Normal= mOsm/kgOsmotic equilibrium tightly regulated between ECF and ICF compartmentsWater moves between compartments in response to alterations in osmolality of either compartment2 [Na⁺] + [BUN] + [Glucose]Osmolality is a measure of solute concentrationKidney produces concentrated or dilute urine in response to changes in osmolalityEstimate plasma osmolality from this equation: 2 times Na represents Na + Cl90% of your serum osmolality is determined by sodium and chloride2.818
28 Serum osmolality is tightly regulated SodiumSerum osmolality is tightly regulatedSodium is the major determinant of serum osmolalitySodium balance is regulated by the kidneySerum sodium does not reflect total body sodium contentNa requirements in growing child2-3 mEq/kg/daySince sodium is the main cation of ECF and primary determinant of osmolality, changes in sodium are linked to changes in ECF volume and associated with disorders of water balanceKidneys defend against changes in ECF volume by modulating sodium reabsportion.In neonates and growing child, need a positive sodium balance. Otherwise sodium intake equals sodium excretion in a normal kidney at steady state.Na requirements in growing child with normal renal function- required for growth- more in infants
29 Factitious Hyponatremia Drawn from an indwelling catheterHyperlipidemiaNormal plasma OsmHyperglycemiaDrives water into extracellular space, diluting the Na concentrationPlasma osm will be highNa decreases 1.6 mEq/L for each 100 mg/dL rise in glucose“Dilutional” effect of glucose: Hyperglycemia increases extracellular osmolality and provides an osmotic force for water to leave the intracellular space for the extracellular space. This results in a decrease in the serum sodium concentration.
30 Hyponatremia Serum Na < 130 mEq/L Loss of sodium Gain of water Most common cause is intravascular volume depletion from gastroenteritisAfter volume expansion, will be able to regulate free water excretionLoss of sodium in excess of waterGain of water in excess of sodiumIVVD from dehydration/AGE or decreased effective circulating volumeCause a decrease in GFR, Proximal tubule increase Na and water reabsorptionDiminished fluid delivery to distal portion of diluting segment and decreased free water excretionMost common electrolyte disturbance in children
31 Hyponatremia Loss of Sodium Lose more salt relative to water but still hypovolemicHyponatremic dehydrationGI losses (prolonged AGE/hypotonic intake)Renal lossesChronic diuretic therapySalt wasting nephropathyAdrenal insufficiencySkin lossesCystic fibrosis (hyponatremic/hypochloremic)Relative water excessHypovolemia= loss of salt AND water from ECF
32 Hyponatremia Gain of Water HypervolemiaFluid overloadCongestive heart failureWater intoxicationDiluted formulaHypotonic fluidsSIADHVolume overload- dilutional hyponatremiaHyponatremia in majority of cases is a reflection of relative water excessVolume overload and dilutional hyponatremiaWater intoxication: radio contest winner in a water drinking contest who died of cerebral edema
33 Hyponatremia Evaluation History and PhysicalDetermine volume statusEstimate sodium intake and outputIf hypovolemic:Renal or Extrarenal losses?Urine Na⁺Does kidney respond appropriately to hypovolemia?Urine specific gravityUrine osmolalityPhysical exam is critical – first step is to determine volume status- hyper or hypovolemicUrine Na <20mEq/L , <40 in neonate: Extrarenal lossesUrine Na >20 mEq/L, >40 in neonate: Renal lossesHigh urine sodium: Renal losses: Salt wasting nephropathy, diuretics, adrenal insufficiencyHave to check urine Na NOT on diureticsIf the problem is with the kidney (Na losing nephritis, diuretics, adrenal insufficiency) then the kidney does NOT respond approp to the hypovolemia and instead of a concentrated urine with high SG and osm, it is INAPPROPRIATELY LOW.
34 Treatment Correct underlying cause Hyponatremic dehydrationSIADHFluid restriction (insensible water losses) until Na levels normalizeRate of correction depends on how quickly it developedAcute hyponatremia is more dangerousIncreased risk of herniation or apnea from increased ICP from rapid, unbalanced water movement into brain cellsIn general, correction with hypertonic saline in unnecessary unless there are neurological manifestations of hyponatremia
35 Treatment Symptomatic Actively seizing or impending resp failure CNS manifestations, encephalopathicUse 3% NaCl (513 mEq/L) via infusion pump1 mL/kg/hr of 3%NaCl will raise serum Na by 1 mEq/L/hrContinue until patient is alert and seizure freeNa has increased by 20 meq/L or to mEq/LActively seizing or impending resp failureIncrease t0 4-8 mL/kg/hr
36 Hyponatremic Dehydration Sodium deficit (mEq) = Fluid deficit (L) X0.6 X [Na⁺] in ECF (mEq/L) PLUSExcess sodium deficit =(Desired Na⁺ - Actual Na⁺) X (0.6 L/kg) X Wt (kg)Desired Na⁺ is 135 mEq/LMaintenance and ongoing lossesReplace over 24 hours0.6 L/kg= distribution factor as a fraction of body weightGive one-half replacement over first 8 hours and second half over next 16 hours
37 HyponatremiaAs sOsm falls, water moves into cells, and risk of cerebral edemaIf severe (<120 mEq/L), may observe seizures, altered mental status, vomitingFor Na⁺ < 120 mEq/L, raise Na⁺ to 125 mEq/L by giving 3% salineRapid correction of hyponatremia : central pontine myelinolysisThink osmolality- think sodiumTreatment of symptomatic hyponatremia with 2cc/kg bolus of 3% saline over 10 min. Max 100 cc. Repeat 1-2 times as needs until symptoms improveRapid correction of hyponatremia- central pontine myelinolysis (rehydration leads to brain dehydration)
38 Hyponatremic Encephalopathy EarlyADVANCEDHeadacheNausea and vomitingLethargyWeaknessConfusionAltered consciousnessAgitationGait disturbancesSeizuresComaApneaPulmonary edemaDecorticate posturingDilated pupilsAnisocoriaPapilledemaCardiac arrhythmiasCentral diabetes insipidusMore than 50% of children with serum Na <125 mEq/L will develop hyponatremic encephalopathy due to children’s larger brain to intracranial volume ratio. Children has less room available in their rigid skulls for brain expansion and are likely to develop brain herniation at higher sNa concentration than adults
39 Hyponatremic Encephalopathy 2 ml/kg bolus of 3% NaCl, max 100 ml over 10 minRepeat 1-2 times until symptoms improveGoal of correction is 5-6 mEq/L in first 1-2 hoursRecheck sNa q 2 hoursMoritz et al. Pediatr Nephrol (2010) 25:Stop further therapy when awake, alert, responding to commands, resolution of headache and nausea or acute rise in Na of 10 mEq/L if in first 5 hoursCorrection in first 48 hours should not excees mEq/L and should avoid normo- or hypernatremia
42 QuestionA 9 yr old boy who has cerebral palsy is admitted to CHNOLA following 4 days of diarrhea. His initial serum Na level is 174mEq/L. Once circulatory volume is restored, the primary focus of the fluid management must be to provide appropriate amounts of:ChlorideFree waterGlucosePhosphatePotassium
43 Hypernatremia Serum sodium >150 mEq/L Always abnormal and should be evaluatedFree water deficitIncreased sodium intake/retentionIncreased serum OsmDoes not imply total body sodium overloadAs opposed to hyponatremia which can sometimes be normal in certain physiologic states
44 Hypernatremia Rarely develops in those who have access to free water Most often from inability to access free waterAt riskIneffective breastfeedingCritically ill patientsInfantsNeurologically impairedBody has two defenses to protect against developing hyperNa: ability to prod a concentrated urine (ADH release) and powerful thirst mechanismHyperosmolar-induced thirst sensation kicks in and people drink! Returns sOsm to normal
45 QuestionChildren who have hypernatremic dehydration often appear minimally dehydrated on exam. This is due to maintenance of:Extracellular fluid volumeIntracellular fluid volumeTotal body glucoseTotal body sodium concentrationTotal body water balance
46 Hypernatremia Water Deficit Renal loss Extrarenal loss Diuretic use Nephropathy with renal concentrating defectDiabetes insipidusExtrarenal lossVomiting/DiarrheaSkin lossesWater deficit=hypernatremic dehydrationDiuresis: osmotic, diuretics, post-obstructive, diuretic phase of ATNNephropathy: inability to concentrate the urine in renal dysplasia, obst uropathy, interstitial disease- leads to excess free water lossGI losses, skin losses
48 Hypernatremia Evaluation Determine volume statusBlood pressureRenal water lossKidney does not appropriately respond to hypovolemiaLow urine s.g and osmolalityHigh urine Na⁺Extrarenal water lossKidney responds appropriately to hypovolemiaHigh urine s.g.Low urine Na⁺Compare urine volume with fluid intakeWeight loss: diarrheaWeight gain: Increased Na retention- hyperaldosteronismHTN- HyperaldosteronismCNS- lethargy, weakness, irritability, seizures, anxietyRemember skin turgor is well preserved bc it is intracellular water lossIf hypovolemic and most often will be:Identify cause of water deficit and asses kidney’s response by eval renal conc abilityUrine Osm <800 mOsm/kg in hyperNa is a sign of concentrating defect
49 Hypernatremia Treatment Treat causeCorrect volume disturbance if presentReplace free water deficit4mL/kg x (desired change in serum Na (mEq/L))Risk of cerebral edema from rapid correctionReplace urine volume with hypotonic fluids in addition to deficitNormal saline first if signs of circulatory collapseMeasure electrolytes q 2 hours until neurologically stableOral therapy has less risk of seizures and can tolerate a more rapid rate of correctionCorrection rate not to exceed 1mEq/h unless encephalopathicDo not correct >15mEq/24hr
51 CaseA 19yo female with renal failure in in the ER. She c/o polyuria x 6 months and HA and constipation x 6 weeks. She is on HCTZ for HTN. BP is 140/92, P 86BUN/Cr=61/3Na=140Ca=13.8, Ph=3.9, Mg=1.9, Alb=4.2What do you do next?CalcitoninIV salineLoop diureticsSurgical consultBisphosphonates
54 Treatment Most hypercalcemic patients are also volume depleted Hydration to increase UOP and Ca excretionNS with potassium at 2-3x maintenance if renal function and BP allowForced diuresisFurosemideCalcitoninBisphosphonatesDialysis
55 HypermagnesemiaA 18 month old with ESRD secondary to renal dysplasia on chronic peritoneal dialysis has a serum Mg of He is asymptomatic. All other values are normal except his BUN/Cr.What is your next step in management?Change to hemodialysisIncrease phosphate bindersIncrease vitamin DContinue peritoneal dialysis
56 Hypermagnesemia Etiologies Renal failure Common in CKD due to decreased excretionLevels in AKI parallel potassium and are derived from the intracellular poolRapid cell lysisExcessive administration
57 Hypermagnesemia Symptoms Rarely of clinical significance Treatment Decreased DTRs, lethargy, confusionHypocalcemia (hypermagnesemia suppresses PTH)Rarely of clinical significanceTreatmentStop supplemental MgDiuresisDialysis
59 CaseYou are called to the floor at 2 am to see a 16 yo orthopedic post-op patient because his BP is 160/100What do you do?A 5 yo boy is brought to the ER because of new-onset generalized seizure which has subsided by the time he arrives. He is postictal with BP of 160/100.Is this HTN urgency or emergency?
60 Hypertensive Emergency HTN Emergency is elevated SBP and DBP with acute end-organ damageStroke (ischemic/hemorrhagic)Pulmonary edemaHTN encephalopathyHTN urgency does not have end organ damage.HA, Nausea, Blurred vision
61 Hypertensive Emergency In children, 75% of cases of HTN emergency will be secondary to renal or renovascular causesWhat do you need to do before treatment?Rule out increased ICP as etiology of HTNGet plasma renin activity levelIf the patient is bleeding or coagulopathic, treat the elevated BP urgentlyWorry about hemorrhagic stroke
62 Treatment of HTN Emergency ICUDon’t lower BP too rapidlyLower no more than 20-25% in 1st 8 hoursPreserve cerebral perfusionAcute goal is a mildly elevated BP
63 CaseA 5 yo boy is brought to the ER because of new-onset generalized seizure which has subsided by the time he arrives. He is postictal with BP of 160/100.What would you start?What would be your immediate BP goal?Goal around 130/85 (20% reduction)
64 Treatment of HTN Emergency NitroprussideArterial and venous vasodilatorVery short-actingEasily titratedCyanide toxicityDon’t use in renal or liver failureIV Calcium channel blockersNicardipineCan cause increased ICP
65 HTN Emergency IV Labetalol IV Enalapril (Enalaprilat) IV hydralazine Alpha and beta blocker: decreases peripheral vascular resistanceContinuous or intermittent dosingDo not use in asthmatics, lung disease, CHF, diabeticsIV Enalapril (Enalaprilat)IV hydralazinePotent arterial vasodilatorInfants
66 On callYou are called to the floor for a 8 yo child with PIGN who is seizing. His BP is 155/98What do you do for immediate treatment?IV labetalol bolus doseTransfer to PICU for nicardipine or labetalol infusionGoal is to decrease his BP by 20-25% in first 8 hoursWhat other therapy might be helpful?Lasix- PIGN is assoc with volume overload
67 HTN Urgency Severe asymptomatic HTN May have headacheMost commonly due to non-adherence or ingestion of large amounts of saltReduce BP over several hours to daysOral medications
68 HTN Urgency Oral medications Nifedipine Isradipine Labetalol Short-acting- see effects in min0.25 mg/kg initial dose10 mg capsulesIsradipineShort-acting: effects within one hourmg/kg/doseLabetalolHeart rate is dose limiting factor