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2. Potassium test: 3.7 to 5.2 mEq/L Serum sodium: 136 to 144 mEq/L Total bilirubin: 0.2 to 1.9 mg/dL Total cholesterol: 100 to 240 mg/dL Total protein: 6.3 to 7.9 g/dL Uric acid: 4.1 to 8.8 mg/dL**Note: Normal or healthy values for creatinine can vary with age. Normal value ranges for all tests may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.Key to abbreviations: IU = international unit L = liter dL = deciliter = 0.1 liter g/dL = gram per deciliter mg = milligram mmol = millimole mEq = milliequivalentsWhat Abnormal Results MeanAbnormal results can be due to a variety of different medical conditions, including kidney failure, breathing problems, and diabetes-related complications. See the individual tests listed in the normal values section for detailed information.RisksThere is very little risk involved with having your blood taken. Veins and arteries vary in size from one patient to another and from one side of the body to the other. Taking blood from some people may be more difficult than from others.Other risks associated with having blood drawn are slight but may include: Excessive bleeding Fainting or feeling light-headed Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken)Alternative NamesMetabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20Update Date: 2/23/2009Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is anindependent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinctionfor online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a foundingmember of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch). The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. Copyright 1997-2009, A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited. 3. Skip navigationOther encyclopedia articles: A B C D E F G H I J K L M N O P Q RS T U V W X Y Z 0-9 BUNBUN stands for blood urea nitrogen. Urea nitrogen is what forms when protein breaks MedlinePlus Topics down. Kidney Diseases A test can be done to measure the amount of urea nitrogen in the blood. Read MoreHow the Test is Performed Acute bilateral obstructive uropathy Acute kidney failure Acute tubular necrosis Blood is typically drawn from a vein, usually from the inside of the elbow or the back of Amino acids the hand. The site is cleaned with germ-killing medicine (antiseptic). The health careAmmonium ion provider wraps an elastic band around the upper arm to apply pressure to the area and Gastrointestinal bleeding make the vein swell with blood. Glomerulonephritis Heart attack Next, the health care provider gently inserts a needle into the vein. The blood collectsHeart failure into an airtight vial or tube attached to the needle. The elastic band is removed from your Hypovolemic shock arm.Kidney disease Metabolism Once the blood has been collected, the needle is removed, and the puncture site isRenal covered to stop any bleeding. ShockIn infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed. The blood collects into a small glass tube called a pipette, or onto a slide or test strip. A bandage may be placed over the area if there is any bleeding.How to Prepare for the TestMany drugs affect BUN levels. Before having this test, make sure the health care provider knows which medications you are taking.Drugs that can increase BUN measurements include: Allopurinol Aminoglycosides Amphotericin B Aspirin (high doses) Bacitracin Carbamazepine Cephalosporins Chloral hydrate Cisplatin Colistin Furosemide Gentamicin Guanethidine Indomethacin Methicillin Methotrexate Methyldopa 4. Neomycin Penicillamine Polymyxin B Probenecid Propranolol Rifampin Spironolactone Tetracyclines Thiazide diuretics Triamterene VancomycinDrugs that can decrease BUN measurements include: Chloramphenicol StreptomycinHow the Test Will FeelWhen the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.Why the Test is PerformedThe BUN test is often done to check kidney function.Normal Results7 - 20 mg/dL. Note that normal values may vary among different laboratories.What Abnormal Results MeanHigher-than-normal levels may be due to: Congestive heart failure Excessive protein levels in the gastrointestinal tract Gastrointestinal bleeding Hypovolemia Heart attack Kidney disease, including glomerulonephritis, pyelonephritis, and acute tubularnecrosis Kidney failure Shock Urinary tract obstructionLower-than-normal levels may be due to: Liver failure Low protein diet Malnutrition Over-hydrationAdditional conditions under which the test may be done include: Acute nephritic syndrome Alport syndrome Atheroembolic kidney disease Dementia due to metabolic causes 5. Diabetic nephropathy/sclerosis Digitalis toxicity Epilepsy Generalized tonic-clonic seizure Goodpasture syndrome Hemolytic-uremic syndrome (HUS) Hepatokidney syndrome Interstitial nephritis Lupus nephritis Malignant hypertension (arteriolar nephrosclerosis) Medullary cystic kidney disease Membranoproliferative GN I Membranoproliferative GN II Type 2 diabetes Prerenal azotemia Primary amyloidosis Secondary systemic amyloidosis Wilms' tumorRisksVeins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.Other risks are slight but may include: Excessive bleeding Fainting or feeling light-headed Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken)ConsiderationsFor people with liver disease, the BUN level may be low even if the kidneys are normal.Alternative NamesBlood urea nitrogenReferencesMolitoris BA. Acute kidney injury. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 121.Update Date: 5/13/2009Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Jatin M. Vyas, MD, PhD, Assistant Professor in Medicine, Harvard Medical School, Assistant in Medicine, Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding 6. 07.Creatinine Primaryfunctionofkidney:excreteunwantedmaterials,retainthosechemicalsnecessaryforproperfunction1.passiveexcretion(glomerularfiltration)2.reabsorptionfromthetubulebackintothecirculation3.secretionfromthecirculationintothetubuleExcretioncapacitykidneyfunction.Excretion (bloodstream>administeredsubstance)renalclearance.skeletalmuscle creatinephosphate-------->creatinine+H2PO4- +H+ creatine-------->creatinine+H2O(plasmaconstantrelease) -------->glomerularfiltrate(tubularreabsorption)glomerularfiltrationrate(GFR)excretionserum.----->renalglomerularfunction.creatinineoutput totalbodymassmusclemass1)AssaymethodJaffereaction OH -(0.1MNaOH) creatinine+picrate------------------>redcoloredcomplex(A520nm)i)sample protein(proteinpicrate)ii)constantTemp.:30C,compoundpicrateiii)timeisasignificancefactor:incubationtimenonspecificcoloredproductsinterferenceenzymemethodcreatinineiminohydrolaseammoniumioncolorimetryion-selectiveelectrode.specimen:serum,plasma,urine(1:200dilution)2)Clinicalsignificance*serumcreatinine:renaldamage 7. creatinine:nosignificance0.9-1.5mg/dL(men)>0.7-1.3mg/dL(women)serumcreatinineCreatinineclearance:renalfunctionassaysensitive. glomerularfiltrationrate(GFR) 24hrurinebloodsampleUV1.73 creatinineclearance(ml/min)=----- X----- PS U:urinarycreatinine(mg/L)V:volumeofurine(ml/min)P:plasmacreatinine(mg/L)S:surfaceareaofpatient1.73:standard70kgsurfacearea1.73 Referencerange:95-140ml/min(man),90-130ml/min(woman) creatinineclearance:nosignificancecreatinineclearance:glomerularfiltrationrate 8. Bloodsugar FromWikipedia,thefreeencyclopediaBloodsugarconcentration,orglucoselevel,referstothe amountofglucosepresentinthebloodofahumanor animal.Normally,inmammalsthebloodglucoselevelis maintainedatareferencerangebetweenabout3.6and5.8 mM(mmol/l).Itistightlyregulatedasapartofmetabolic homeostasis.Meannormalbloodglucoselevelsinhumansareabout 90mg/dl,equivalentto5mM(mmol/l)(sincethemolecular weightofglucose,C6H12O6,isabout180g/mol).Thetotal amountofglucosenormallyincirculatinghumanbloodis thereforeabout3.3to7g(assuminganordinaryadultblood volumeof5litres,plausibleforanaverageadultmale). Glucoselevelsriseaftermealsforanhourortwobyafew gramsandareusuallylowestinthemorning,beforethe firstmealoftheday.Transportedviathebloodstreamfrom theintestinesorlivertobodycells,glucoseistheprimary sourceofenergyforbody'scells,fatsandoils(ie,lipids) Thefluctuationofbloodsugar(red)andthesugar-loweringhormone beingprimarilyacompactenergystore. insulin(blue)inhumansduringthecourseofadaywiththreemeals. Oneoftheeffectsofasugar-richvsastarch-richmealishighlighted. Failuretomaintainbloodglucoseinthenormalrangeleads toconditionsofpersistentlyhigh(hyperglycemia)orlow(hypoglycemia)bloodsugar.Diabetesmellitus,characterizedby persistenthyperglycemiafromanyofseveralcauses,isthemostprominentdiseaserelatedtofailureofbloodsugarregulation.Contents 1 Normalvalues 2 Regulation 3 Glucosemeasurement 3.1 Sampletype 3.2 Measurementtechniques 3.3 Bloodglucoselaboratorytests 3.4 Clinicalcorrelation 4 Healtheffects 5 Lowbloodsugar 6 Convertingglucoseunits 7 Comparativecontent 8 Etymologyanduseofterm 9 Bloodglucoseinbirdsandreptiles 10 References 11 SeealsoNormalvalues Despitewidelyvariableintervalsbetweenmealsortheoccasionalconsumptionofmealswithasubstantialcarbohydrateload, humanbloodglucoselevelsnormallyremainwithinaremarkablynarrowrange.Inmosthumansthisvariesfromabout 82mg/dltoperhaps110mg/dl(4.4to6.1mmol/l)exceptshortlyaftereatingwhenthebloodglucoselevelrisestemporarilyup tomaybe140mg/dl(7.8mmol/l)orabitmoreinnon-diabetics.TheAmericanDiabetesAssociationrecommendsapost-meal glucoselevellessthan180mg/dl(10mmol/l)andapre-mealplasmaglucoseof90-130mg/dl(5to7.2mmol/l).[1]Itisusuallyasurprisetorealizehowlittleglucoseisactuallymaintainedinthebloodandbodyfluids.Thecontrolmechanism worksonverysmallquantities.Inahealthyadultmaleof75kg(165lb)withabloodvolumeof5litres(1.3gal),ablood 9. glucoselevelof100mg/dlor5.5mmol/lcorrespondstoabout5g(0.2ozor0.002gal,1/500ofthetotal)ofglucoseinthe bloodandapproximately45g(1ounces)inthetotalbodywater(whichobviouslyincludesmorethanmerelybloodandwill beusuallyabout60%ofthetotalbodyweightinmen).Amorefamiliarcomparisonmayhelp 5gramsofglucoseisabout equivalenttoasmallsugarpacketasprovidedinmanyrestaurantswith coffeeortea,withpeopleusingtypically1to3packets percup.RegulationMain article: Blood sugar regulationThehomeostaticmechanismwhichkeepsthebloodvalueofglucoseinaremarkablynarrowrangeiscomposedofseveral interactingsystems,ofwhichhormoneregulationisthemostimportant.Therearetwotypesofmutuallyantagonisticmetabolichormonesaffectingbloodglucoselevels: catabolichormones(suchasglucagon,growthhormone,cortisolandcatecholamines)whichincreasebloodglucose;andoneanabolichormone(insulin),whichdecreasesbloodglucose.GlucosemeasurementMain article: Blood glucose monitoringSampletypeGlucosecanbemeasuredinwholebloodorserum(ie,plasma).Historically,bloodglucosevaluesweregivenintermsof wholeblood,butmostlaboratoriesnowmeasureandreportthe serumglucoselevels.Becauseredbloodcells(erythrocytes) haveahigherconcentrationofprotein(eg,hemoglobin)thanserum,serumhasahigherwatercontentandconsequentlymore dissolvedglucosethandoeswholeblood.Toconvertfromwhole-bloodglucose,multiplicationby1.15hasbeenshownto generallygivetheserum/plasmalevel.Collectionofbloodinclottubesforserumchemistryanalysispermitsthemetabolismofglucoseinthesamplebybloodcells untilseparatedbycentrifugation.Redbloodcells,forinstance,donotrequireinsulintointakeglucosefromtheblood.Higher thannormalamountsofwhiteorredbloodcellcountscanleadtoexcessiveglycolysisinthesamplewithsubstantialreduction ofglucoselevelifthesampleisnotprocessedquickly.Ambienttemperatureatwhichthebloodsampleiskeptpriorto centrifugingandseparationofplasma/serumalsoaffectsglucoselevels.Atrefrigeratortemperatures,glucoseremains relativelystableforseveralhoursinabloodsample.Atroomtemperature(25C),alossof1to2%oftotalglucoseperhour shouldbeexpectedinwholebloodsamples.LossofglucoseundertheseconditionscanbepreventedbyusingFluoridetubes (ie,gray-top)sincefluorideinhibitsglycolysis.However,theseshouldonlybeusedwhenbloodwillbetransportedfromone hospitallaboratorytoanotherforglucosemeasurement.Red-topserumseparatortubesalsopreserveglucoseinsamplesafter beingcentrifugedisolatingtheserumfromcells.Particularcareshouldbegiventodrawingbloodsamplesfromthearmoppositetheoneinwhichanintravenouslineis inserted,topreventcontaminationofthesamplewithintravenousfluids.Alternatively,bloodcanbedrawnfromthesamearm withanIVlineaftertheIVhasbeenturnedoffforatleast5minutes,andthearmelevatedtodraininfusedfluidsawayfrom thevein.Inattentioncanleadtolargeerrors,sinceaslittleas10%contaminationwith5%dextrose(D5W)willelevateglucose inasampleby500mg/dlormore.Rememberthattheactualconcentrationofglucoseinbloodisverylow,eveninthe hyperglycemic.Arterial,capillaryandvenousbloodhavecomparableglucoselevelsinafastingindividual.Aftermealsvenouslevelsare somewhatlowerthancapillaryorarterialblood;acommonestimateisabout10%.MeasurementtechniquesTwomajormethodshavebeenusedtomeasureglucose.Thefirst,stillinuseinsomeplaces,isachemicalmethodexploiting the nonspecific reducingpropertyofglucoseinareactionwithanindicatorsubstancethatchangescolorwhenreduced.Since otherbloodcompoundsalsohavereducingproperties(e.g.,urea,whichcanbeabnormallyhighinuremicpatients),this techniquecanproduceerroneousreadingsinsomesituations(5to15mg/dlhasbeenreported).Themorerecenttechnique, usingenzymesspecifictoglucose,arelesssusceptibletothiskindoferror.Thetwomostcommonemployedenzymesare 10. glucoseoxidaseandhexokinase.Ineithercase,thechemicalsystemiscommonlycontainedonateststrip,towhichabloodsampleisapplied,andwhichis theninsertedintothemeterforreading.Teststripshapesandtheirexactchemicalcompositionvarybetweenmetersystems andcannotbeinterchanged.Formerly,someteststripswereread(aftertimingandwipingawaythebloodsample)byvisual comparisonagainstacolorchartprintedontheviallabel.Stripsofthistypearestillusedforurineglucosereadings,butfor bloodglucoselevelstheyareobsolete.Theirerrorrateswere,inanycase,muchhigher.Urineglucosereadings,howevertaken,aremuchlessuseful.Inproperlyfunctioningkidneys,glucosedoesnotappearinurine untiltherenalthresholdforglucosehasbeenexceeded.Thisissubstantiallyaboveanynormalglucoselevel,andsois evidenceofanexistingseverehyperglycemiccondition.However,urineisstoredinthebladderandsoanyglucoseinitmight havebeenproducedatanytimesincethelasttimethebladderwasemptied.Sincemetabolicconditionschangerapidly,asa resultofanyofseveralfactors,thisisdelayednewsandgivesnowarningofadevelopingcondition.Bloodglucosemonitoring isfarpreferable,bothclinicallyandforhomemonitoringbypatients.I.CHEMICALMETHODS A.Oxidation-ReductionReaction 1.AlkalineCopperReduction FolinWuBlueend-Methodproduct Benedict's ModificationofFolinwuforQualitativeUrineGlucosemethodNelsonSomoygiBlueend-Methodproduct Yellow- Neocuproine*orangecolor Method NeocuproineShaeffer UtilizestheprincipleofIodinereactionwithCuprousbyproduct. Hartmann ExcessI2isthentitratedwiththiosulfate.Somygi2.AlkalineFerricyanideReductionColorlessendproduct;other HagedornreducingJensen substancesinterferewithreaction B.Condensation UtilizesaromaticaminesandhotaceticacidOrtho-toluidine FormsGlycosylamineandSchiff'sbasewhichisemeraldgreenincolor Method Thisisthemostspecificmethod,butthereagentusedistoxic Anthrone (Phenols) FormshydroxymethylfurfuralinhotaceticacidMethod II.ENZYMATICMETHODS A.GlucoseOxidase Inhibitedby 11. reducing substancesSaifer likeBUA, Gernstenfield Bilirubin, MethodGlutathione, Ascorbic Acid uses4-aminophenazoneoxidativelycoupledwithPhenol TrinderMethod SubjecttolessinterferencebyincreasesserumlevelsofCreatinine,UricAcidorHemoglobin InhibitedbyCatalase ADryChemistryMethodKodak UsesReflectanceSpectrophotometrytomeasuretheintensityofcolorthroughalowertransparent Ektachemfilm HomemonitoringbloodglucoseassaymethodGlucometer UsesastripimpregnatedwithaGlucoseOxidasereagent B.Hexokinase NADPascofactor NADPH(reducedproduct)ismeasuredin340nm MorespecificthanGlucoseOxidasemethodduetoG-6PO_4,whichinhibitsinterferingsubstancesexceptwhen sampleishemolyzedBloodglucoselaboratorytests1.fastingbloodsugar(ie,glucose)test(FBS) 2.urineglucosetest 3.two-hrpostprandialbloodsugartest(2-hPPBS) 4.oralglucosetolerancetest(OGTT) 5.intravenousglucosetolerancetest(IVGTT) 6.glycosylatedhemoglobin(HbA1C) 7.self-monitoringofglucoselevelviapatienttestingClinicalcorrelationThefastingbloodglucose(FBG)levelisthemostcommonlyusedindicationofoverallglucosehomeostasis,largelybecause disturbingeventssuchasfoodintakeareavoided.Conditionsaffectingglucoselevelsareshowninthetablebelow. Abnormalitiesinthesetestresultsareduetoproblemsinthemultiplecontrolmechanismofglucoseregulation.Themetabolicresponsetoacarbohydratechallengeisconvenientlyassessedbyapostprandialglucoseleveldrawn2hours afteramealoraglucoseload.Inaddition,theglucosetolerancetest,consistingofseveraltimedmeasurementsaftera standardizedamountoforalglucoseintake,isusedtoaidinthediagnosisofdiabetes.Itisregardedasthegoldstandardof clinicaltestsoftheinsulin/glucosecontrolsystem,butisdifficulttoadminister,requiringmuchtimeandrepeatedbloodtests. Notethatfoodcommonlyincludescarbohydrateswhichdon'tparticipateinthemetaboliccontrolsystem;simplesugarssuch asfructose,manyofthedisaccarhides(whicheithercontainsimplesugarsotherthanglucoseorcannotbedigestedbyhumans) andthemorecomplexsugarswhichalsocannotbedigestedbyhumans.Andtherearecarbohydrateswhicharenotdigested evenwiththeassistanceofgutbacteria;severalofthefibres(solubleorinsoluble)arechemicallycarbohydrates.Foodalso commonlycontainscomponentswhichaffectglucose(andothersugar's)digestion;fat,forexampleslowsdowndigestive processing,evenforsucheasilyhandledfoodconstituentsasstarch.Avoidingtheeffectsoffoodonbloodglucose measurementisimportantforreliableresultssincethoseeffectsaresovariable. 12. Errorratesforbloodglucosemeasurementssystemsvary,dependingonlaboratories,andonthemethodsused.Colorimetry techniquescanbebiasedbycolorchangesinteststrips(fromairborneorfingerbornecontamination,perhaps)orinterference (eg,tintingcontaminants)withlightsourceorthelightsensor.Electricaltechniquesarelesssusceptibletotheseerrors,though nottoothers.Inhomeuse,themostimportantissueisnotaccuracy,buttrend.Thusifyourmeter/teststripsystemis consistentlywrongby10%,therewillbelittleconsequence,aslongaschanges(eg,duetoexerciseormedicationadjustments) areproperlytracked.IntheUS,homeusebloodtestmetersmustbeapprovedbytheFederalFoodandDrugAdministration beforetheycanbesold.Similarsupervisionisimposedinotherjurisdictions.Finally,thereareseveralinfluencesonbloodglucoselevelasidefromfoodintake.Infection,forinstance,tendstochange bloodglucoselevels,asdoesstresseitherphysicalorpsychological.Exercise,especiallyifprolongedorlongafterthemost recentmeal,willhaveaneffectaswell.Inthenormalperson,maintenanceofbloodglucoseatnearconstantlevelswill neverthelessbequiteeffective. CausesofAbnormalGlucoseLevels PersistentHyperglycemiaTransientHyperglycemiaPersistentHypoglycemia TransientHypoglycemia ReferenceRange,FBG:70-110mg/dlDiabetesMellitusPheochromocytoma Insulinoma AcuteAlcoholIngestion AdrenalcorticalhyperactivityAdrenalcorticalinsufficiency Drugs:salicylates,SevereLiverDisease Cushing'sSyndromeAddison'sDiseaseantituberculosisagentsHyperthyroidism AcutestressreactionHypopituitarism SevereLiverdisease SeveralGlycogenstorage Acromegaly ShockGalactosemia diseasesEctopicInsulinproduction Hereditaryfructose Obesity Convulsions fromtumors intoleranceHealtheffects Ifbloodsugarlevelsdroptoolow,apotentiallyfatalconditioncalledhypoglycemiadevelops.Symptomsmayinclude lethargy,impairedmentalfunctioning,irritability,shaking,weaknessinarmandlegmuscles,sweattingandlossof consciousness.Braindamageisevenpossible.Iflevelsremaintoohigh,appetiteissuppressedovertheshortterm.Long-termhyperglycemiacausesmanyofthelong-term healthproblemsassociatedwithdiabetes,includingeye,kidney,heartdiseaseandnervedamage.Lowbloodsugar Somepeoplereportdrowsinessorimpairedcognitivefunctionseveralhoursaftermeals,whichtheybelieveisrelatedtoadrop inbloodsugar,or"lowbloodsugar".Formoreinformation,see: idiopathicpostprandialsyndrome hypoglycemiaMechanismswhichrestoresatisfactorybloodglucoselevelsafterhypoglycemiamustbequickandeffective,becauseofthe immediatelyseriousconsequencesofinsufficientglucose;intheextreme,coma,butalsolessimmediatelydangerous, confusionorunsteadiness,amongstmanyothersymptoms.Thisisbecause,atleastintheshortterm,itisfarmoredangerous tohavetoolittleglucoseinthebloodthantoomuch.Inhealthyindividualsthesemechanismsaregenerallyquiteeffective,and symptomatichypoglycemiaisgenerallyonlyfoundindiabeticsusinginsulinorotherpharmacologicaltreatment.Such hypoglycemicepisodesvarygreatlybetweenpersonsandfromtimetotime,bothinseverityandswiftnessofonset.Forsevere cases,promptmedicalassistanceisessential,asdamage(tobrainandothertissues)andevendeathwillresultfromsufficiently lowbloodglucoselevels.Convertingglucoseunits Inmostcountries,bloodglucoseisreportedintermsofmolarity,measuredinmmol/L(ormillimolar,abbreviatedmM).Inthe 13. UnitedStates,andtoalesserextentelsewhere, massconcentration,measuredinmg/dL,istypicallyused.Toconvertbloodglucosereadingsbetweenthetwounits: Divideamg/dLfigureby18(ormultiplyby0.055)togetmmol/L. Multiplyammol/Lfigureby18(ordivideby0.055)togetmg/dL.Comparativecontent Referencerangesforbloodtests,comparingbloodcontentofglucose(shownindarkergreen) withotherconstituents. Etymologyanduseofterm Theterm'bloodsugar'hascolloquialorigins.Inaphysiologicalcontext,thetermisamisnomerbecauseitreferstoglucose, yetothersugarsbesidesglucosearealwayspresent.Foodcontainsseveraldifferenttypes(eg,fructose(largelyfrom fruits/tablesugar/industrialsweeteners).galactose(milkanddairyproducts),aswellasseveralfoodadditivessuchassorbitol, xylose,maltose,...).Butbecausetheseothersugarsarelargelyinertwithregardtothemetaboliccontrolsystem(ie,that controlledbyinsulinsecretion),sinceglucoseisthedominantcontrollingsignalformetabolicregulation,thetermhasgained currency,andisusedbymedicalstaffandlayfolkalike.Thetableabovereflectssomeofthemoretechnicalandclosely definedtermsusedinthemedicalfield.Bloodglucoseinbirdsandreptiles Inbirdsandreptilestheprocessingofsugarsisdonedifferently,thepancreasisslightlymorewelldevelopedinbirdsthanin mammals,perhapsasapartialcompensationforthelackofsalivaandchewing.Itproducescarbohydrate,fatandprotein digestingenzymeswhicharesecretedintothesmallintestine.Theliverhastwodistinctlobeseachwithitsownductleading intothesmallintestine.Theliver,asinmammals,housesthebile,whichinbirdshoweverisacidicandnotalkalineasitisin mammals.Manybirdsdonothaveagallbladdertoholdthebile,anditissecreteddirectlyintothepancreaticducts.References 1. ^AmericanDiabetesAssociation.January2006DiabetesCare."StandardsofMedicalCare-Table6andTable7,CorrelationbetweenA1ClevelandMeanPlasmaGlucoseLevelsonMultipleTestingover2-3months."Vol.29Supplement1Pages51-580. JohnBernardHenry,M.D.:ClinicaldiagnosisandManagementbyLaboratoryMethods20thedition,Saunders,Philadelphia,PA,2001. RonaldA.SacherandRichardA.McPherson:Widmann'sClinicalInterpretationofLaboratoryTests11thedition,F.A.DavisCompany,2001.Seealso Currentresearch- Boronicacidsinsupramolecularchemistry:Sacchariderecognition Bloodglucosemonitoring Retrievedfrom"http://en.wikipedia.org/wiki/Blood_sugar" Categories:Humanhomeostasis|Bloodtests|Diabetes Thispagewaslastmodifiedon7December2009at16:52. TextisavailableundertheCreativeCommonsAttribution-ShareAlikeLicense;additionaltermsmayapply.SeeTermsofUsefordetails. 14. WikipediaisaregisteredtrademarkoftheWikimediaFoundation,Inc.,anon-profitorganization. Contactus 15. Web Images Videos ShoppingNews MapsMore MSNHotmailSign in | United States | Preferences Blood sugarBlood sugarMake Bing your decision engineBing Normal valuesReference ranges for blood tests Regulation overviewoutline images locations Glucose measurement ALL RESULTSREFERENCE WIKIPEDIA ARTICLES Submit Query Sample type Search this article highlighter Reference Measurement techniques Blood sugar Blood glucose laboratory testsClinical correlation For the song by Pendulum, see Blood Sugar / Axle Grinder. Health effectsBlood sugar concentration, or glucose level, refers to Low blood sugarthe amount of glucose present in the blood of a human or Converting glucose units animal. Normally, in mammals the blood glucose level is Comparative contentmaintained at a reference range between about 3.6 and Etymology and use of term 5.8 mM (mmol/l). It is tightly regulated as a part of Blood glucose in birds and metabolic homeostasis. reptilesMean normal blood glucose levels in humans are about 90 Referencesmg/dl, equivalent to 5mM (mmol/l) (since the molecular See also weight of glucose, C6H12O6, is about 180 g/mol). The totalamount of glucose normally in circulating human blood is1 therefore about 3.3 to 7g (assuming an ordinary adult ...Locations v... blood volume of 5 litres, plausible for an average adultmale). Glucose levels rise after meals for an hour or twoby a few grams and are usually lowest in the morning,before the first meal of the day. Transported via thebloodstream from the intestines or liver to body cells,glucose is the primary source of energy for body's cells, The fluctuation of blood sugar (red) and the sugar-lowering hormonefats and oils (ie, lipids) being primarily a compact energy insulin (blue) in humans during the course of a day with three meals.One of the effects of a sugar-rich vs a starch-rich meal is highlighted.store. Failure to maintain blood glucose in the normal range leads to conditions of persistently high (hyperglycemia) or low (hypoglycemia) ImagesVideosblood sugar. Diabetes mellitus, characterized by persistent hyperglycemia from any of several causes, is the most prominent diseaserelated to failure of blood sugar regulation. Normal values view all 24view all 15 Despite widely variable intervals between meals or the occasional consumption of meals with a substantial carbohydrate load,human blood glucose levels normally remain within a remarkably narrow range. In most humans this varies from about 80 mg/dl toperhaps 110 mg/dl (4.4 to 6.1 mmol/l) except shortly after eating when the blood glucose level rises temporarily up to maybe 140mg/dl (7.8 mmol/l) or a bit more in non-diabetics. The American Diabetes Association recommends a post-meal glucose level lessthan 180 mg/dl (10 mmol/l) and a pre-meal plasma glucose of 90-130 mg/dl (5 to 7.2 mmol/l). [1] It is usually a surprise to realize how little glucose is actually maintained in the blood and body fluids. The control mechanism workson very small quantities. In a healthy adult male of 75 kg (165 lb) with a blood volume of 5 litres (1.3 gal), a blood glucose level of100 mg/dl or 5.5 mmol/l corresponds to about 5 g (0.2 oz or 0.002 gal, 1/500 of the total) of glucose in the blood and approximately45 g (1 ounces) in the total body water (which obviously includes more than merely blood and will be usually about 60% of the totalbody weight in men). A more familiar comparison may help 5 grams of glucose is about equivalent to a small sugar packet asprovided in many restaurants with coffee or tea, with people using typically 1 to 3 packets per cup. RegulationMain article: Blood sugar regulationThe homeostatic mechanism which keeps the blood value of glucose in a remarkably narrow range is composed of severalinteracting systems, of which hormone regulation is the most important. There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels: catabolic hormones (such as glucagon, growth hormone, cortisol and catecholamines) which increase blood glucose; and one anabolic hormone (insulin), which decreases blood glucose. Glucose measurementMain article: Blood glucose monitoring Sample typeGlucose can be measured in whole blood, serum (ie, plasma). Historically, blood glucose values were given in terms of whole blood,but most laboratories now measure and report the serum glucose levels. Because red blood cells (erythrocytes) have a higherconcentration of protein (eg, hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucosethan does whole blood. To convert from whole-blood glucose, multiplication by 1.15 has been shown to generally give theserum/plasma level. Collection of blood in clot tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells untilseparated by centrifugation. Red blood cells, for instance, do not require insulin to intake glucose from the blood. Higher than normalamounts of white or red blood cell counts can lead to excessive glycolysis in the sample with substantial reduction of glucose level ifthe sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifuging and separation ofplasma/serum also affects glucose levels. At refrigerator temperatures, glucose remains relatively stable for several hours in a bloodsample. At room temperature (25 C), a loss of 1 to 2% of total glucose per hour should be expected in whole blood samples. Loss ofglucose under these conditions can be prevented by using Fluoride tubes (ie, gray-top) since fluoride inhibits glycolysis. However,these should only be used when blood will be transported from one hospital laboratory to another for glucose measurement. Red-topserum separator tubes also preserve glucose in samples after being centrifuged isolating the serum from cells. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted, toprevent contamination of the sample with intravenous fluids. Alternatively, blood can be drawn from the same arm with an IV lineafter the IV has been turned off for at least 5 minutes, and the arm elevated to drain infused fluids away from the vein. Inattention canlead to large errors, since as little as 10% contamination with 5% dextrose (D5W) will elevate glucose in a sample by 500 mg/dl ormore. Remember that the actual concentration of glucose in blood is very low, even in the hyperglycemic. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual. After meals venous levels are somewhatlower than capillary or arterial blood; a common estimate is about 10%. Measurement techniquesTwo major methods have been used to measure glucose. The first, still in use in some places, is a chemical method exploiting the 16. Blood sugar Normal values Regulation overviewoutline images locations Glucose measurement Sample type highlighterMeasurement techniquesBlood glucose laboratory testsClinical correlationHealth effects Low blood sugar Converting glucose units Comparative content Etymology and use of term Blood glucose in birds and reptiles References See also 1 Locations ... ... v... allImages Videosview all 24view all 15 17. Blood sugar Normal values Regulation overviewoutline images locations Glucose measurement Sample type highlighterMeasurement techniquesBlood glucose laboratory testsClinical correlationHealth effects Low blood sugar Converting glucose units Comparative content Etymology and use of term Blood glucose in birds and reptiles References See also 1 Locations ... ... v... allImages Videosview all 24view all 15 18. Blood sugar Normal values Regulation overviewoutline images locations Glucose measurement Sample type highlighterMeasurement techniquesBlood glucose laboratory testsClinical correlationHealth effects Low blood sugar Converting glucose units Comparative content Etymology and use of term Blood glucose in birds and reptiles References See also 1 Locations ... ... v... allImages Videosview all 24view all 15 19. Oliguria Acardinalsignofrenalandurinarytractdisorders,oliguriaisclinicallydefinedasurineoutputoflessthan400ml/24hours.Typically,thissignoccursabruptlyandmayherald seriouspossiblylife-threateninghemodynamicinstability.Itscausescanbeclassifiedasprerenal(decreasedrenalbloodflow),intrarenal(intrinsicrenaldamage),or postrenal(urinarytractobstruction);thepathophysiologydiffersforeachclassification.(SeeHowoliguriadevelops,pages442and443.)Oliguriaassociatedwithaprerenalor postrenalcauseisusuallypromptlyreversiblewithtreatment,althoughitmayleadtointrarenaldamageifuntreated.However,oliguriaassociatedwithanintrarenalcauseis usuallymorepersistentandmaybeirreversible. History and physical examination Beginbyaskingthepatientabouthisusualdailyvoidingpattern,includingfrequencyandamount.Whendidhefirstnoticechangesinthispatternandinthecolor,odor,or consistencyofhisurine?Askaboutpainorburningonurination.Hasthepatienthadafever?Notehisnormaldailyfluidintake.Hasherecentlybeendrinkingmoreorlessthan usual?Hashisintakeofcaffeineoralcoholchangeddrastically?Hashehadrecentepisodesofdiarrheaorvomitingthatmightcausefluidloss?Next,exploreassociated complaints,especiallyfatigue,lossofappetite,thirst,dyspnea,chestpain,orrecentweightgainorloss(indehydration). Checkforahistoryofrenal,urinarytract,orcardiovasculardisorders.Noterecenttraumaticinjuryorsurgeryassociatedwithsignificantbloodlossaswellasrecentblood transfusions.Wasthepatientexposedtonephrotoxicagents,suchasheavymetals,organicsolvents,anesthetics,orradiographiccontrastmedia?Next,obtainadrughistory. Beginthephysicalexaminationbytakingthepatient'svitalsignsandweighinghim.Assesshisoverallappearanceforedema.Palpatebothkidneysfortendernessand enlargement,andpercussforcostovertebralangle(CVA)tenderness.Also,inspecttheflankareaforedemaorerythema.Auscultatetheheartandlungsforabnormalsounds andtheflankareaforrenalarterybruits.Assessthepatientforedemaorsignsofdehydrationsuchasdrymucousmembranes. Obtainaurinespecimenandinspectitforabnormalcolor,odor,orsediment.Usereagentstripstotestforglucose,protein,andblood.Also,useaurinometertomeasure specificgravity. Medical causes Acute tubular necrosis (ATN).AnearlysignofATN,oliguriamayoccurabruptly(inshock)orgradually(innephrotoxicity).Usually,itpersistsforabout2weeks,followedby polyuria.Relatedfeaturesincludesignsofhyperkalemia(muscleweaknessandcardiacarrhythmias),uremia(anorexia,confusion,lethargy,twitching,seizures,pruritus,and Kussmaul'srespirations),andheartfailure(edema,jugularveindistention,crackles,anddyspnea). Calculi.Oliguriaoranuriamayresultfromcalculilodginginthekidneys,ureters,bladderoutlet,orurethra.Associatedsignsandsymptomsincludeurinaryfrequencyand urgency,dysuria,andhematuriaorpyuria.Usually,thepatientexperiencesrenalcolicexcruciatingpainthatradiatesfromtheCVAtotheflank,thesuprapubicregion,andthe externalgenitalia.Thispainmaybeaccompaniedbynausea,vomiting,hypoactivebowelsounds,abdominaldistentionand,occasionally,feverandchills. Cholera.Withcholera,severewaterandelectrolytelossleadtooliguria,thirst,weakness,musclecramps,decreasedskinturgor,tachycardia,hypotension,andabruptwatery diarrheaandvomiting.Deathmayoccurinhourswithouttreatment. Glomerulonephritis (acute).Acuteglomerulonephritisproducesoliguriaoranuria.Otherfeaturesareamildfever,fatigue,grosshematuria,proteinuria,generalizededema, elevatedbloodpressure,headache,nauseaandvomiting,flankandabdominalpain,andsignsofpulmonarycongestion(dyspneaandaproductivecough). Heart failure.Oliguriamayoccurwithleft-sidedheartfailureasaresultoflowcardiacoutputanddecreasedrenalperfusion.Accompanyingsignsandsymptomsinclude dyspnea,fatigue,weakness,peripheraledema,jugularveindistention,tachycardia,tachypnea,crackles,andadryorproductivecough.Withadvancedorchronicheartfailure, thepatientmayalsodeveloporthopnea,cyanosis,clubbing,aventriculargallop,diastolichypertension,cardiomegaly,andhemoptysis. Hypovolemia.Anydisorderthatdecreasescirculatingfluidvolumecanproduceoliguria.Associatedfindingsincludeorthostatichypotension,apathy,lethargy,fatigue,gross muscleweakness,anorexia,nausea,profoundthirst,dizziness,sunkeneyeballs,poorskinturgor,anddrymucousmembranes. Pyelonephritis (acute).Accompanyingthesuddenonsetofoliguriawithacutepyelonephritisareahighfeverwithchills,fatigue,flankpain,CVAtenderness,weakness, nocturia,dysuria,hematuria,urinaryfrequencyandurgency,andtenesmus.Theurinemayappearcloudy.Occasionally,thepatientalsoexperiencesanorexia,diarrhea,and nauseaandvomiting. Renal failure (chronic).Oliguriaisamajorsignofend-stagechronicrenalfailure.Associatedfindingsreflectprogressiveuremiaandincludefatigue,weakness,irritability, uremicfetor,ecchymosesandpetechiae,peripheraledema,elevatedbloodpressure,confusion,emotionallability,drowsiness,coarsemuscletwitching,musclecramps, peripheralneuropathies,anorexia,ametallictasteinthemouth,nauseaandvomiting,constipationordiarrhea,stomatitis,pruritus,pallor,andyellow- orbronze-tingedskin. Eventually,seizures,coma,anduremicfrostmaydevelop. Renal vein occlusion (bilateral).Bilateralrenalveinocclusionoccasionallycausesoliguriaaccompaniedbyacutelowbackandflankpain,CVAtenderness,fever,pallor, hematuria,enlargedandpalpablekidneys,edemaand,possibly,signsofuremia. Toxemia of pregnancy.Withseverepreeclampsia,oliguriamaybeaccompaniedbyelevatedbloodpressure,dizziness,diplopia,blurredvision,epigastricpain,nauseaand 20. vomiting,irritability,andaseverefrontalheadache.Typically,oliguriaisprecededbygeneralizededemaandsuddenweightgainofmorethan3lb(1.4kg)perweekduringthe secondtrimester,ormorethan1lb(0.45kg)perweekduringthethirdtrimester.Ifpreeclampsiaprogressestoeclampsia,thepatientdevelopsseizuresandmayslipintocoma. Urethral stricture.Urethralstrictureproducesoliguriaaccompaniedbychronicurethraldischarge,urinaryfrequencyandurgency,dysuria,pyuria,andadiminishedurinestream. Astheobstructionworsens,urineextravasationmayleadtoformationofurinomasandurosepsis. Other causes Diagnostic studies.Radiographicstudiesthatusecontrastmediamaycausenephrotoxicityandoliguria. Drugs.Oliguriamayresultfromdrugsthatcausedecreasedrenalperfusion(diuretics),nephrotoxicity(mostnotably,aminoglycosidesandchemotherapeuticdrugs),urine retention(adrenergicsandanticholinergics),orurinaryobstructionassociatedwithprecipitationofurinarycrystals(sulfonamidesandacyclovir). Nursing considerations Monitorthepatient'svitalsigns,intakeandoutput,anddailyweight. Dependingonthecauseofoliguria,restrictfluidstobetween0.6and1Lmorethanthepatient'surineoutputforthepreviousday. Provideadietlowinsodium,potassium,andprotein. Preparethepatientfordiagnostictests,suchaslaboratorytests(includingserumbloodureanitrogenandcreatininelevels,ureaandcreatinineclearance,urinesodiumlevels, andurineosmolality),abdominalX-rays,ultrasonography,acomputedtomographyscan,cystography,andarenalscan. Preparethepatientfordialysis. Patient teaching Explainanyfluidanddietaryrestrictions. Explaintheunderlyingdisorderandthetreatmentplan. Pictures 21. Book Source Details Book Title:Nursing:InterpretingSignsandSymptoms Author(s):Springhouse Year of Publication:2007 Copyright Details:Nursing:InterpretingSignsandSymptoms,Copyright2007LippincottWilliams&Wilkins.Other Book Chapters Related to Urinary symptoms ReadexcerptsfromtheseotherbookchaptersrelatedtoUrinarysymptoms: Medical Books ExcerptsDYSURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003)ENURESIS"Algorithmic Diagnosis of Symptoms and Signs" (2003)NOCTURIA"Algorithmic Diagnosis of Symptoms and Signs" (2003)POLYURIA"Algorithmic Diagnosis of Symptoms and Signs" (2003)PROTEINURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003)PYURIA"Algorithmic Diagnosis of Symptoms and Signs" (2003)DIFFICULTY URINATING"Algorithmic Diagnosis of Symptoms and Signs" (2003)FREQUENCY OF URINATION"Algorithmic Diagnosis of Symptoms and Signs" (2003)INCONTINENCE OF URINE "Algorithmic Diagnosis of Symptoms and Signs" (2003)URINE COLOR CHANGES "Algorithmic Diagnosis of Symptoms and Signs" (2003)ANURIA OR OLIGURIA"Algorithmic Diagnosis of Symptoms and Signs" (2003)Dysuria "In a Page: Signs and Symptoms" (2004)Polyuria"In a Page: Signs and Symptoms" (2004)Urinary Stream (Decreased)"In a Page: Signs and Symptoms" (2004)Dysuria "In A Page: Pediatric Signs and Symptoms" (2007)Enuresis"In A Page: Pediatric Signs and Symptoms" (2007) 22. More About Causes of Urinary symptomsBack to symptom: Urinarysymptoms:Introduction(review1071causes)Next Book Extract About Urinary symptoms:Polyuria(Nursing:InterpretingSignsandSymptoms)All Book Extracts: AllOnlineBookExtractsforUrinarysymptoms More About This Book: Title:Nursing:InterpretingSignsandSymptomsAuthors:Springhouse Publisher:LippincottWilliams&Wilkins Copyright:2007 ISBN:1-58255-668-7 Nextpage:Polyuria(Nursing:InterpretingSignsandSymptoms) Rate This Website Whatdoyouthinkaboutthefeaturesofthiswebsite?Takeourusersurveyandhaveyoursay:WebsiteUserSurvey Medical Tools & Articles:Next articles:Polyuria(Nursing:InterpretingSignsandSymptoms)Urinaryfrequency(Nursing:InterpretingSignsandSymptoms)Urinaryhesitancy(Nursing:InterpretingSignsandSymptoms)Urinaryincontinence(Nursing:InterpretingSignsandSymptoms)Urinaryurgency(Nursing:InterpretingSignsandSymptoms) Tools & Services:BookmarkthispageTakeasurveyrelatingtoUrinarysymptomsSymptomSearchSymptomCheckerMedicalDictionaryGiveyourfeedback Medical Articles:Disease&TreatmentsSearchMisdiagnosisCenterFulllistofinterestingarticlesForums & Message BoardsAskoransweraquestionattheBoards: Icannotgetadiagnosis.Pleasehelp.Tellusyourmedicalstory.Shareyourmisdiagnosisstory.Whatisthebesttreatmentformycondition?SeealltheBoards. 23. Section VI . The Kidneys And The Body Fluids This section was written following fruitful discussions with my colleagues Peter Bie, Niels-Henrik Holstein- Rathlou, Paul Leyssac, Finn Michael Karlsen, and medical students Margrethe Lynggaard and Mads Dalsgaard. The concept flux is net-transport of substance per time unit across an area unit. Flux is equal to concentration multiplied by flow or mol per time unit across a barrier area Frequently used abbreviations in this section are Chapter 24 Chapter 24. Body Fluids and RegulationBody Fluids And Regulation Study Objectives Principles Definitions Study Objectives Essentials To define the concepts: Dehydration, hyponatraemia, intracellular fluid volume (ICV), Pathophysiology Equations extracellular fluid volume (ECV), interstitial fluid (ISF), overhydration, oxidation water, Self-Assessment radioactivity, specific activity, and total body water. Answers Highlights To describe the daily water balance, the K+ - and Na+ -balance, sweat secretion, the Further Reading ionic composition in blood plasma, the water content of fat- and muscle- tissue and the Fig. 24-1 daily water transfer across the gastro-intestinal mucosa. To describe the osmotic pressure Fig. 24-2 Fig. 24-3 in the body fluids, the measurement of fluid compartments by indicator dilution, the Fig. 24-4 measurement of total body-K+ and -Na+ and the related dynamic pools. Fig. 24-5 Fig. 24-6 To draw models of the body fluid compartments. Fig. 24-7 Fig. 24-8 To explain the influence of age, sex and weight on the size of the total body water and Fig. 24-9 Fig. 24-10its phases. To explain disorders with increased or reduced extracellular fluid volume and shock. Return to chapter 24 Return to Content To apply and use the above concepts in problem solving and in case histories.Principles The law of conservation of matter states that mass or energy can neither be created nor destroyed (the principle of mass balance). The principle is here used to measure physiological fluid compartments and the body content of ions. DefinitionsConcentration: The concentration of a solute is the amount of solute in a given fluidvolume. Dehydration is a clinical condition with an abnormal reduction of one or more of the major fluid compartments (ie, total body water with shrinkage of blood volume or ISF). Dextrans are polysaccharides of high molecular weight. Intracellular fluid volume (ICV) refers to the volume of fluid inside all cells. This volume normally contains 26-28 litre (l) out of the total 42 l of water in a 70-kg person. - One litre of water equals one kg of water. Extracellular fluid volume (ECV) refers to the interstitial and the plasma volume. The ECV contains the remaining water (14-16 kg) with most of the water in tissue fluid (ISF) and about 3 kg of water in plasma. - Interstitial fluid (ISF) is the tissue fluid between the cells in the extravascular space. Hyperkalaemia refers to a clinical condition with plasma-[K+ ] above 5 mM (mmol/l of plasma).+ 24. Hypokalaemia refers to a clinical condition with plasma-[K ] below 3.5 mM. Hypernatraemia refers to a clinical condition with plasma-[Na+ ] above 145 mM. Hyponatraemia refers to a clinical condition with plasma-[Na+ ] below 135 mM. Oedema refers to a clinical condition with an abnormal accumulation of tissue fluid or interstitial fluid. Osmolality is a measure of the osmotic active particles in one kg of water. Plasma- osmolality is given in Osmol per kg of water. Water occupies 93-94% of plasma in healthy persons. Plasma osmolality is normally maintained constant by the antidiuretic hormone feedback system. Overhydration refers to a clinical condition with an abnormal increase in total body water resulting in an increased ECV and thus salt accumulation. Oxidation water or metabolic water (oxidative phosphorylation) refers to the daily water production by combustion of food - normally 300-400 g of water daily in an adult. Radioactivity is measured as the number of radioactive disintegrations per s (in Becquerel or Bq per l). One disintegration per s equals one Bq. Total body water is destributed between two compartments separated by the cell membrane: The intracellular and the extracellular fluid.Essentials This paragraph deals with 1. The three major fluid compartments, 2. Water balance, 3. Body potassium, 4. Body sodium, 5. The indicator dilution principle, 6. The renin- angiotensin-aldosterone cascade, 7. Output contol, 8. Regulation of renal water excretion, and 9. Regulation of renal sodium excretion. Read first about the nephron (paragraph 1 of Chapter 25). 1. The three major fluid compartments The three major body fluid compartments are the intracellular fluid volume (ICV), the interstitial fluid volume (ISV) and the vascular space (Chapter 1, Fig.1-4). Water permeable membranes separate the three compartments, so that they contain almost the same number of osmotically active particles per kg. The three compartments have the same concentration expressed as mOsmol per kg of water or the same freeze-point depression. They are said to be isosmolal, because they have the same osmolality. The so-called lean body mass, which means a body stripped of fat, contains 0.69 parts of water (69%) of the total body weight in all persons. - Such high values are observed in the newborn and in extremely fit athletes with minimal body fat. Babies have a tenfold higher water turnover per kg of body weight than adults do. As an average females have a low body water percentage compared to males. Such differences show sex dependency, but the important factor is the relative content of body fat, since fat tissue contains significantly less water (only 10%) than muscle and other tissues (70%). This is why the relative water content depends upon the relative fat content. The average for most healthy persons is 60% of the body weight. Sedentary, overweight persons contain only 50-55 % water dependent on the body fat content. The relative content of body fat rises with increasing age and body weight, and the relative mass of muscle tissue becomes less. Consequently, the body water fraction falls with increasing body weight and age. Aging implies loss of cells, but the ECV is remarkably 25. constant through life and under disease conditions. Each body (weight 70 kg) contains 4 mol of both sodium and potassium (ie, the total ion pool). A minor fraction of the potassium is radioactive. The calcium and magnesium content is 25 and 1 mol, respectively. In the renal tubule cells the epithelium is a single layer of cells, joined by junctional complexes near their luminal border (Fig. 25-7). Solutes can traverse the epithelium through transcellular or paracellular pathways. Virtually every cell membrane in the body contains the Na+ - K+ -pump, which maintains the low intracellular Na+ -concentration and develops the negative, intracellular voltage. In the renal tubule cells the Na+ - K+ -pump, is located in the basolateral membrane. Read more about the nephron in Chapter 25 and about hormonal control later in paragraph 8 and 11 of this Chapter. Unfortunately, the simple laws of dilute solutions are unprecise at physiological concentrations. Rough estimates are based on the assumptions that extracellular sodium is associated with monovalent anions and that deviations in osmolality are twice the deviation in plasma sodium concentration.ICV: The dominating intracellular solute is potassium (K+ ), balanced by phosphate and anionic protein, whilst the dominating extracellular solute is NaCl. All compartments have almost the same osmolality 300 mOsmol* kg-1 of water. The thin cell membrane - or the endothelial barrier between ISF and plasma in the vascular phase - cannot carry any important hydrostatic gradient. Water passes freely between the extra- and intra-cellular compartment, as osmotic forces govern its distribution and the membranes are water permeable. Fig. 24-1: The daily water transfer across the gastrointestinal barrier in a healthy standard person. The ICV comprises 26-28 kg out of the total 42-kg of water in a 70-kg person (Fig. 1-4). ECV: The ECV compartment comprises the remaining water (14-16 kg) with most of the water in tissue fluid (interstitial fluid or ISF) and 3 kg of water in plasma (Chapter 1, Fig. 1-4). The size of the ECV compartment is proportional to the total body Na+ . Changes in plasma osmolality indicate problems in water balance. A [Na+ ] in ECV of 150 mmol per kg of plasma water corresponds to a total osmolality of 300 mOsmol per kg. Alterations in plasma-[Na+ ] (osmolality) will be followed by similar changes of the ECV osmolality, because the permeability of of the capillary barrier for Na+ and water is almost equal. The daily water transfer across the gastrointestinal tract amounts to approximately 9 l in each direction (Fig. 24-1). 2. Water balance A healthy person on a mixed diet in a temperate climate receives 1000 ml with the food and drinks 1200 ml daily. Balance is maintained as long as the water loss is the same (Fig. 24-2). Fig. 24-2: The daily water balance in a 70-kg healthy person on a mixed diet. The apparent imbalance between input (2200 ml) and output (2500 ml) is covered by 300 ml of metabolic water. Water is lost in the urine (1500 ml), in the stools (100 ml), in sweat and evaporation from the respiratory tract (900 ml) as a typical example. The total loss of water is 2500 ml, and this corresponds perfectly to the intake plus a normal production of 300 ml of metabolic water per 24 hours (Fig. 24-2). 26. 3. Body potassium The daily dietary intake of potassium varies with the amount of fruit and vegetables consumed (75-150 mmol K+ daily). More than 90% of the body potassium is located intracellularly. Only a few percent of the K+ in the body pool are found outside the cells and subject to control (Fig. 24-3). The main renal K+ -reabsorption is passive and paracellular through tight junctions of the proximal tubules. Moreover K+ -excretion can vary over a wide range from almost complete reabsorption of filtered K+ to urinary excretion rates in excess of filtered load (ie, net secretion of K+ ).The Na+ -K+ -pump located in the cell membrane, maintains the high intracellular [K+ ] and the low intracellular [Na+ ]. The energy of the terminal phosphate bond of ATP is used to actively extrude Na+ and pump K+ into the cell. The membrane also contains many K+ - and Cl - -channels, through which the two ions leak out of the cell.In myocardial cells, as in skeletal muscle and nerve cells, K+ plays a major role in determining the resting membrane potential (RMP), and K+ is important for optimal operation of enzymatic processes. Under normal conditions, the RMP of the myocardial cell is determined by the dynamic balance between the membrane conductance to K+ and to Na+ . As [K+ ] out is reduced during hypokalaemia, the membrane depolarises causing voltage-dependent inactivation of K+ -channels and activation of Na+ -channels, allowing Na+ to make a proportionally larger contribution to the RMP.Fig. 24-3: The total body K + -pool in a healthy person comprises 4000 mmol with more than 90% intracellularly. The normal ECG and the ECG of a patient with hyperkalaemia is shown to the right.The K+ -permeability is around 50 times larger than the Na+ -permeability, so the RMP of normal myocardial cells (typically: -90 mV) almost equals the equilibrium potential for K +(-94 mV).The excretion of K+ by overload is almost entirely determined by the extent of distal tubular secretion in the principal cells. Any rise in serum [K+ ] immediately results in a marked rise in K+ -secretion. This transport mechanism is controlled by aldosterone and by K+ . Aldosterone stimulates the secretion of K+ and H+ by the principal cells of the renal distal tubules and collecting ducts (Fig. 25-11). This is why chronic acidosis decreases and chronic alkalosis increases K+ -secretion. Actually, acute acidosis may reduce K+ - secretion. Of the consumed K+ , 75-150 mmol is daily absorbed in the intestine. Since 90% is excreted renally in a healthy person, there must be a minimum in a typical volume of 1500 ml of daily urine with a concentration of (75/1.5) = 50 mM. Normal urinary [K+ ] is at least 30 mM. A high urinary [K+ ] is indicative of a high total body K+ or a high intake of K+ .The normal excretion fraction (Chapter 25) for K+ is 0.10 (10% or 90 mmol of the 900 mmol in the daily filtrate) corresponding to the daily intake (Fig. 24-4). A K+ -poor diet leads to hypokalaemia with less than 20 mmol K+ in the daily urine. A K+ -rich diet triggers a large secretion and a high excretion in the urine (Box 25-1). A low urinary [K+ ] 27. is indicative of a low total body K+ or of extracellular acidosis with transfer of K + from the cells in exchange of H+ . A low [K+ ] in the distal tubule cells reduces the K+ -excretion.The normal plasma-[K+] level is dependent upon the exchange with the cells, the renal excretion rate, and the extrarenal losses through the gastrointestinal tract or through sweat. Measurement of total and exchangeable body potassium Our natural body potassium is 39K, but we also contain traces of naturally occurring radioactivity (0.00012 or 0.012% is 40K with a half-life of 1.3109 years). When using this natural tracer, injection of radioactive tracer is avoided. The person to be examined is placed in a sensitive whole body counter, and the total activity of the tracer 40K in the body (S Bq) is measured. Specific activity (SA) is the concentration of radioactive tracer in a fluid volume divided by the concentration of naturally occurring, non-radioactive mother-substance. The concentration of mother-substance is traditionally measured in mmol per l (mM). SA is equal to radioactivity (A) per non-radioactive mass unit, m (ie, A/m in Bq/mol). Following even distribution, the SA for a certain substance must be the same all over the body. SA is preferably measured in plasma (with scintillation counters or similar equipment). Specific activity (SA) is here the number of Bq 40K per mol of mother substance ( 39K) in the whole body. We can calculate all 39K or total body potassium: S/SA mol per whole body - when SA is known to be 0.012% or a fraction of 0.00012. The total body potassium of a healthy person is 4000 mmol. The SA of 40K implies a 40K/39K ratio of 0.48 mmol/4000 mmol (=0.00012). An exchangeable ion pool in our body is the dynamic part of the total specific ion content. The remaining content is fixed as insoluble salts in the bones. The dynamic character implies the use of a dilution principle to measure such a pool. In order to measure the exchangeable body potassium pool, a radioactive tracer is injected, such as 42K with a physical half-life of 12 hours (12.4 hours) and urine is collected. The first urine sample is from the first 12 hours, and the second sample is covering 12 - 24 hours. The total tracer dose given must be adjusted for by the loss of tracer in the urine and by the radioactive decay during the first 12 hours mixing period. The two urine samples obtained are examined for tracer and for natural potassium. The tracer is assumed to distribute just as natural potassium after 12 - 24 hours. When the tracer is distributed evenly in the exchangeable body potassium, its SA must be the same in urine, plasma or elsewhere in the body. The exchangeable body potassium is calculated by Eq. 24-2 . The specific activity for the tracer (SA Bq per mol) is known from the plasma measurements. In this way we measure the exchangeable body potassium. The normal values are 41 mmol 39K per kg body weight for females, and 46 mmol per kg for males. 4. Body sodium ( 23Na) The exchangeable body sodium is easy to measure using the dilution principle and a minimum of equipment. Our natural non-radioactive body sodium is 23Na. We administer the radioactive tracer, 24Na, with a physical half-life of 15 hours. We have to use a total period of 30 hours to secure even distribution in the ECV. The total tracer dose given, must be adjusted for by the loss of tracer in the urine, and the radioactive decay of 24Na (see the decay law in Chapter 1). The exchangeable body sodium is calculated by Eq. 24-2. We know the specific activity for the tracer (SA Bq/mol) from the plasma measurements;23 28. therefore calculation of the exchangeable bodyNa is easy. The normal value for exchangeable body sodium is 40 mmol/kg of body weight. In a patient with a body weight of 75 kg the exchangeable sodium is (75 40) = 3000 mmol. The non-exchangeable sodium is fixed in the bones. The total body sodium is measured following discrete radiation with a method called neutron activation analysis. The whole body of the patient is exposed to radiation with neutrons. A small fraction of the natural 23Na now becomes radioactive sodium ( 24Na) by uptake of an extra neutron. A sensitive whole body counter records the radiation from 24Na. Now we can calculate the total body sodium. Normally, the total body sodium is 1000 mmol larger than the exchangeable sodium due to the fixed sodium content of the bones (1000 + 3000 mmol = 4000 mmol 23Na). Fig. 24-4: Body fluid electrolytes. Water permeable membranes separate the three compartments, which contain almost the same number of osmotically active particles per kg. The sum columns of electrolyte equivalents in muscle cells are essentially higher than the extracellular sum columns of equivalents, because cells contain proteins, Ca2+, Mg 2+ and other molecules with several charges per particle (Fig. 24-4). The above columns show the ionic composition per kg of water, so we have 150 mmol of Na per kg of plasma water. Normally, one litre of plasma has a weight of 1.040 kg and contains 10% of dry material. Consequently, one litre of plasma contains 0.940 l of water, and the rest consists of plasma proteins and small ions. Thus the fraction of water in plasma (F water) is typically 0.94. 5. The indicator dilution principle Mass conservation is always the underlying principle. The amount of indicator n mol distributes in V litres of distribution volume. We measure the concentration Cp in mM, following even distribution, and calculate V: V = n/C p . Errors: Uneven distribution of indicator introduces a systematic error. - A non- representative concentration of indicator in the plasma makes it insufficient to correct for plasma proteins alone. - Loss of indicator to other compartments is inevitable. - Elimination or synthesis of indicator in the body occurs as frequent errors. - The indicator may be toxic or in other ways change the size of the compartment to be measured. Total body water, ECV, plasma volume, and the elimination rate constant are measured as follows: 5 a. Total body water Total water is measured by the help of the dilution principle. Tritium marked water is a good tracer. The equilibrium period is 3-6 hours. n mol of indicator divided by Cp mmol of indicator per l is equal to the distribution volume (V) for the indicator. Healthy adolescents and children have normal values around 60% of the body weight assuming one l of water to be equal to one kg. Adult males and females with a sedentary life style and larger fat fractions contain only 50% of water. 5 b. The extracellular fluid volume (ECV) is measured by administration of a priming dose of inulin intravenously. Then inulin is infused to maintain a steady state with constancy of the plasma concentration of inulin (Cp ). 29. The patient then urinates, and the infusion is stopped with collection of a plasma sample. For the next 10 hours the patient collects his urine, which makes it possible to measure all the body inulin present at the end of the infusion (n mol) assuming all inulin excreted. Dividing n with Cp gives the volume of distribution (V) after correcting for the difference in protein concentration between plasma and ISF (Eq. 24-1). Chromium-ethylene-diamine-tetra-acetate ( 51Cr-EDTA) is a chelate with a structure that cannot enter into cells. The chelate molecule contains radioactive Cr, making it easy to measure. The 51Cr-EDTA distributes and eliminates itself in the extracellular fluid volume (ECV) just as inulin and is therefore used to measure ECV. For clearance measurements, we inject a single dose intravenously, and draw blood samples every hour for 5 hours. The clearance of 51Cr-EDTA is independent of Cp and a good estimate of GFR just like the inulin clearance. Since the indicator is cleared from the ECV only, it is possible to measure its size. Such methods - including renal lithium reabsorption - are important during renal function studies. Normal values for ECV are approximately 20% of the body weight or 14- 17 kg. Chronically ill patients with debilitating diseases often maintain their ECV remarkably well in spite of marked reductions in the cell mass of their body. 5 c. The plasma volume Also here, the dilution principle is used. The indicator for plasma volume can be Evans Blue (T 1824) that binds to circulating plasma albumin. A small dose of albumin, marked with radioactive iodine, is also a good indicator (iodine 131 has a physical half-life of 8 days). The indicator concentration in plasma (Cp ) is measured every 10-min for an hour after the administration, and the log of Cp is plotted with time. Extrapolation to the time zero determines the maximum concentration of indicator in plasma. This corrects for the biological loss, while the indicator distributes itself in the plasma phase. The tracer dose divided by Cp at time zero provides us with the intravascular plasma volume. Normal values for the plasma volume are close to 5% of the body weight. In diabetics and hypertensive patients the tracer is lost more readily through their leaky capillaries to the interstitial fluid than in healthy persons (increased transcapillary escape). 6. The renin-angiotensin-aldosterone cascade Macula densa is described in paragraph 9 of Chapter 25. The most likely intrarenal trigger of the renin-angiotensin-aldosterone cascade is the falling NaCl concentration of the reduced fluid flow at the macula densa in the distal renal tubules (Fig. 24-5). The NaCl concentration at the macula densa falls, when we lose extracellular fluid, move into the upright position and when the blood pressure falls. Renin is a proteinase that separates the decapeptide, angiotensin I, from the liver globulin, angiotensinogen. When angiotensin I passes the lungs or the kidneys, a dipeptide is separated from the decapeptide by angiotensin converting enzyme (ACE). This process produces the octapeptide, angiotensin II. Angiotensin II has multiple actions that minimize renal fluid and sodium losses and maintain arterial blood pressure.1.Angiotensin II stimulates the aldosterone secretion by the adrenal cortex, andthrough this hormone it stimulates Na+ -reabsorption and K+ -(H+ )-secretion in the 30. distal tubules (Fig. 24-5). - Angiotensin II is in itself a potent stimulator of tubularNa+ -reabsorption.2.Angiotensin II inhibits further renin release by negative feedback.3.Angiotensin II constricts arterioles all over the body including a strong constrictionof the efferent and to some extent also the afferent arteriole. Hereby, the renalbloodflow (RBF) and to a lesser extent the glomerular filtration rate (GFR) isreduced. 4.Angiotensin II inhibits the absolute proximal tubular reabsorption contributing tothe reduction of GFR. 5.Angiotensin II enhances sympathetic nervous activity. Fig. 24-5: The renin-angiotensin-aldosterone cascade. Sympathetic stimulation of the renal nerves stimulates renin secretion directly via b- adrenergic receptors on the JG cells just as falling blood pressure in the preglomerular arterioles. - b-blocking drugs and angiotensin II inhibit the renin secretion (Fig 24-5). The combined effects from the whole renin cascade is extracellular fluid homeostasis. In contrast, exposure to stress and painful stimuli triggers the combined sympatho- adrenergic system with release of catecholamines, gluco- and mineralo-corticoids, and ACTH from the hypophysis. ACTH stimulates further the secretion of the glucocorticoid, cortisol, from the adrenal cortex. 7. Output control The body uses output control, when it is overloaded with water or with sodium. The most important osmotically active solute in ECV is NaCl, because it only passes into cells in small amounts. Urea, glucose and other molecules with modest concentration gradients are without importance, because they distribute almost evenly in the fluid compartments. Healthy persons use two primary control systems: 1) The osmolality (osmol per kg of water) or ion concentration controls our elimination of water. 2) The change of blood volume (ECV) or pressure controls sodium excretion - not osmolality. Only when the arterial blood pressure falls drastically the body will drop its protection of normal concentration. In such a disease state large amounts of ADH molecules are released in an attempt to improve the volume and blood pressure. 8. Regulation of renal water excretion The primary control of the renal water excretion is osmolality control (Fig. 24-6). Since 2/3 of the body water normally is located within the cells, this is also an intracellular volume control. Following water deprivation even an increase in plasma osmolality of only one per cent stimulates both the hypothalamic osmoreceptors and similar (angiotensin-II-sensitive) thirst receptors. Thirst may increase the water intake of the individual and thus increase the ECV, with negative feedback to the thirst receptors. Activation of the hypothalamic osmoreceptors and thirst receptors increases the hypothalamic neurosecretion to the neurohypophysis and releases antidiuretic hormone (ADH or vasopressin). Hyperosmolality elicits a linear increase in plasma ADH, which causes water retention (Fig. 24-6) until isosmolality is reached. ADH increases the reabsorption of water from the fluid in the renal cortical and medullary collecting ducts. ADH binds to receptors on the basolateral surface of the tubule cells, 31. where they liberate and accumulate cAMP. This messenger passes through intermediary steps across the cell to the luminal membrane, where the number of water channels (aquaporin 2) are increased. The luminal cell membrane is thus rendered water-permeable, which increases the renal water retention. The increased water reabsorption leads to a small, concentrated urine volume (antidiuresis), and a net gain of water that returns ECF osmolality towards normal. Initially, osmolality control overrides blood volume control. Fig. 24-6: Primary osmolality control of the renal water excretion. ADH and thirst systems maintain osmolality and ICV within narrow limits. Water overload decreases ECF osmolality and has the reverse effect, because the hypothalamic osmoreceptors suppress the ADH release, and the renal water excretion is increased already after 30 min (Fig. 24-6). When a person rapidly drinks one litre of water, the intestine absorbs water. Ions diffuse into the intestinal lumen and the blood osmolality falls causing a block of the ADH secretion (Fig. 24-6). Pure water is distributed evenly in all three body fluid compartments just like intravenous infusion of one litre of 5% glucose in water. Intake of one l of isotonic saline implies ECV expansion, without dilution of body fluids. This expansion will not increase the urine volume much, so the increased ECV can be sustained for many hours. An intravenous infusion of one l of large dextran molecules (macrodex) stays mainly in the vascular space. 9. Regulation of renal sodium excretion In healthy persons, changes of blood volume (or ECV) or blood pressure control sodium excretion (Fig. 24-7). The dominating cation of the ECV is Na+ . The sodium intake is balanced by the sodium excretion as long as the thirst and other homeostatic systems are functional. During conditions where sodium intake exceeds renal sodium excretion, total body sodium and ECV increase. Conversely, total body sodium and ECV decrease, when sodium intake is lower than renal sodium excretion. This is because volume-pressor-receptors detect the size of the circulating blood volume (ECV) or pressure, and effector mechanisms adjust the renal sodium excretion accordingly. The volume-pressor-receptors are widely distributed. Low-pressure receptors are found in the pulmonary vessels and in the atria. An increased blood volume can also increase the arterial blood pressure and stimulate the well-known high-pressure baroreceptors in the carotid sinus and the aortic arch. Increased arterial pressure reduces sympathetic tone also in the kidneys, whereas decreasing arterial pressure enhances sympathetic tone and renal salt retention. Arterial pressure receptors are also located in the renal preglomerular arterioles. Both stimuli in Fig. 24-7 release renin from macula densa, whereby angiotensin II and aldosterone is secreted (both sodium retaining hormones). A decrease in circulating blood volume leads to a decrease in NaCl delivery to the macula densa and release of the renin cascade. Conversely, an increase in circulating blood volume with increased NaCl delivery to the macula densa suppresses renin release and increases sodium excretion (Fig. 24-7).Fig. 24-7: Primary blood volume-pressure control of the renal Na+ -excretion. The effective circulating blood volume is protected also during shock (Na+ -retention) and during hypertension (natriuresis). Increased salt intake increases blood volume and leads to natriuresis, possibly augmented by release of ANP (see below), nitric oxide and other factors. The excretion of Na+ 32. depends upon several effector mechanisms out of which three are classical: The first factor is the glomerular filtration rate (GFR), which is responsible for the size of the filtered flux of Na+ across the glomerular barrier in the kidneys. Renal prostaglandins, generated in response to angiotensin II, are involved in maintaining the filtered flux of Na+ . The second factor is the renin-angiotensin-aldosterone cascade (Fig. 24-5). The third factor consists of peptides with natriuretic effects. The most well-known peptide is called atrial natriuretic peptide (ANP) and originates from granules of the atrial myocytes. A low circulating blood volume with low atrial pressure increases renal sympathetic tone, reduces the stimulus of the low-pressure receptors in the atrial wall and thus the ANP secretion. Hereby, the natriuresis is reduced. - Renal natriuretic peptide or urodilatin from the distal tubule cells is related to ANP. Urodilatin has been isolated from human urine and contains four amino acids more than ANP.An increase in effective circulating blood volume, increases atrial pressure, reduces sympathetic tone and releases ANP and urodilatin leading to increased natriuresis. The main purpose of these mechanisms is to maintain an effective circulating blood volume by an increase or a decrease of the renal excretion of Na+ . Initially, osmolality control is dominating. Finally, after a dangerous reduction in blood volume, volume-pressure receptors override the hypothalamic osmoreceptors and stimulate the ADH release and thirst. In the terminal phase, the body protects effective circulating blood volume at the expense of ECF osmolality. Pathophysiology This paragraph deals with 1. Dehydration, 2. Overhydration, 3. Hyponatraemia, 4. Hypernatraemia, 5. Hypokalaemia, and 6. Hyperkalaemia. 1. Dehydration Dehydration is an abnormal reduction of the major fluid volumes (total body water with shrinkage of ECV). When we lose more than 5% of the total body water it has clinical consequences. The condition is life threatening if the patient loses 20 %. Accidents and surgery with a period of water deprivation, imply a rise in ECF osmolality and thus stimulation of both thirst and the hypothalamic osmoreceptors, whereby ADH is released. - Symptoms and signs of dehydration are thirst, dry mucous membranes, and decreased skin elasticity or turgor due to loss of ISF. Loss of effective circulating blood volume implies a low blood pressure in both the venous and the arterial system. Loss of more than one litre of ECV causes postural hypotension with dizziness, confusion and cerebral failure. Empty veins and cold skin characterise the peripheral venoconstriction. Finally, there is extreme tachycardia, which turns into terminal bradycardia and an arterial blood pressure that approach zero. Loss of salt and water frequently develops into hypo-osmolal dehydration (Fig. 24-8). This is because the thirst forces the patient to drink (salt free) water. Water dragged into the cells further reduces the hyposmolal ECV (Fig. 24-8). The small ECV elicits a hyperaldosteronism, which is called secondary, because it is not initiated as primary hypercorticism in the adrenal cortex. A precise compensation of the water loss results in pure hyponatraemia, where water eventually is drawn from ECV into the cells. The low [Na+ ] around the swelling cells reduces the potential gradient across the cell membranes with increased neuromuscular irritability (muscular twitching) and cardiac arrhythmias. Isosmolal dehydration is a proportional loss of water and solutes. There is no concentration 33. gradient over the cell membranes, and the loss is mainly from ECV (Fig. 24-8). Fig. 24-8: Dehydration (hyperosmolal, isosmolal and hyposmolal). Hyperosmolal dehydration occurs in persons deprived of water. The hyperosmolal ECV drags water from ICV and dehydrates the cells (Fig. 24-8). This is intracellular dehydration. The hyperosmolality liberates ADH to restrict the water loss. The patient excretes a very small urine volume. Persons deprived of water at sea may drink seawater. Sea water is hypertonic saline and the victims die faster. When hypertonic saline reaches the ECV it aggravates the intracellular dehydration simultaneously with an extracellular overhydration. Intracellular dehydration leads to respiratory arrest and death of thirst. 2. Overhydration Overhydration is an abnormal increase of total body water - in particular ECV, and thus salt accumulation. The increase in the interstitial fluid volume is called oedema. Overhydration frequently occurs among patients in fluid therapy (ie, overhydration of iatrogenous origin). Increased salt intake by mouth is compensated by increased salt excretion by normal kidneys. However, a large saline infusion (0.9% NaCl) will expand ECV and total body water (isosmolal overhydration in Fig. 24-9). Inappropriately large infusions of saline lead to iatrogenous hyperosmolal overhydration, if they lose more water than salt (Fig. 24-9). Hyperosmolality drags water from the cells, so that the patient develops intracellular dehydration with hallucinations, loss of consciousness and eventually respiratory arrest. The patient with hyposmolal overhydration is typically in fluid treatment and develops muscle cramps and disorientation. The skin turgor is normal. A low serum - [Na+ ] confirms the diagnosis. The water overload in ECV is dragged into the cells in hyposmolal overhydration until osmolality balance (Fig. 24-9). In the brain and the muscles this intracellular overhydration causes headache, disorientation, increased spinal pressure, coma and muscle cramps. Both hyposmolal and hyperosmolal intracellular overhydration conditions are characterised by cerebral symptoms and signs. Fig. 24-9: Overhydration (hyperosmolal, isosmolal, and hyposmolal). Acute renal failure with decreased GFR reduces the flux of filtered NaCl (first factor) and thus the Na+ -excretion. Oedema is a clinical condition where the interstitial fluid volume (ISF) is abnormally large. A voluminous ISF is usually due to increased hydrostatic venous pressure (heart insufficiency), or a reduced colloid osmotic pressure (hypoproteinaemia) as predicted from Starlings law for transcapillary transport. Reduced protein synthesis (liver disease) and abnormal protein loss with the urine (proteinuria) causes hypoproteinaemia. Thus protein-losing kidneys are involved. Capillary damage (allergy, burns, inflammation etc) with increased capillary permeability causes local oedema. Obstruction to lymphatic drainage can also cause oedema (scarring after radiation therapy, elephantiasis etc). Cardiac insufficiency with increased venous pressure and oedema formation increases 34. sympathetic tone and thus releases the renin-angiotensin-aldosterone cascade (Fig. 24-5) causing Na+ -retention. Hepatic cirrhosis activates the cascade in a similar way - possibly including the release of nitric oxide. Hypoalbuminaemia reduces the colloid osmotic pressure of plasma, whereby water is distributed from the vascular space to the ISF. The fall in effective circulatory volume activates the renin cascade and leads to Na+ -retention. NSAIDs can activate the renin-angiotensin-aldosterone cascade, and the increased aldosterone leads to Na+ -retention and overhydration. Angiotensin II-receptor antagonists and ACE-inhibitors are utilized clinically to block the effects of angiotensin II in congestive heart failure, diabetes mellitus and hypertension. Blockade of the cascade reduces both preglomerular and postglomerular resistances. The supine position at bed rest increases venous return. This implies an increased cardiac output (Starlings law), a reduced ANF secretion from the atrial walls and a reduced renin- angiotensin-aldosterone cascade. This is why bed rest is beneficial for disorders with salt accumulation. 3. HyponatraemiaHyponatraemia (ie, plasma-[Na+ ] below 135 mM) is associated with dehydration, overhydration or normohydration (ie, a normal ECV and total body sodium content). Hyponatraemia with reduced ECV (ie, salt-deficient hyponatraemia) is caused by a salt loss in excess of the high water loss (ie, hyposmolal dehydration in Fig 24-10). This is seen in any type of hypoadrenalism including the rare primary hypoadrenalism (Addisons disease). In Addisons disease the entire adrenal cortex is destroyed by autoimmune reactions (80%) or by malignancy or infection. All three types of hormones are insufficiently produced (mineralocorticoids, glucocorticoids and sex hormones). The lack of aldosterone leads to Na+ -excretion and K+ -retention with hyponatraemia combined with hyperkalaemia resulting in dehydration and hypotension. Hyponatraemia is developed in the following way (Fig. 24-10):1. The first step is the salt loss in excess of the water loss.2. Since the ECF-[Na+ ] is low, the ADH secretion is suppressed, and the water excretion is increased. Hereby, both the ISF and the vascular spaces are reduced often by more than 10%.3. This is an adequate stimulus for the volume-pressure receptors, which override the osmoreceptors, whenever the effective circulatory volume is threatened. Fig. 24-10: The three body fluid compartments in a patient with salt-deficient hyponatraemia. The volume-pressure receptors stimulate both thirst and the release of ADH. The effective circulating volume is protected at the expense of osmolality! Still the blood pressure is falling, which impairs cerebral perfusion, causing confusion, headache and coma. The hyponatraemia implies a reduced resting membrane potential and thus a low threshold for neuromuscular stimulation resulting in muscle cramps. The large renal loss is seen with osmotic diuresis (hyperglycaemia and uraemia), excessive 35. use of diuretics, renal tubular reabsorption defects, adreno-cortical insufficiency as aldosterone-antagonist-intoxication or other types of hypoaldosteronism. The extra-renal loss is often large from excessive sweating, diarrhoea, haemorrhage, vomiting, loss with ascites or bronchial secretion, and transudation from cutaneous defects. Normal kidneys normally compensate extra-renal loss. The urinary excretion of salt and water falls in response to volume depletion, so the urine is concentrated - but with less than 10 mM Na+ .Normal sweat is a hypotonic solution, because Na+ is reabsorbed in the duct system. The [Na+ ] can increase up to 80 mM with increasing sweat flow - due to the limited time for the aldosterone-controlled Na+ -reabsorption. Increased salt intake by mouth or intravenously is required as a supplement to the treatment directed at the primary cause.Low plasma- [Na+ ] in a chronically salt-deficient patient suggests a high aldosterone secretion from the adrenal zona glomerulosa. Further administration of aldosterone therefore may not have any effect. Hyponatraemia with increased ECV (water-excess hyponatraemia) is often caused by cardiac, hepatic, and renal insufficiency or by hypoalbuminaemia - see hyposmolal overhydration (Fig. 24-9). Hyponatraemia with normal ECV is often caused by stress (surgery, psychogenic polydipsia), abnormally high ADH release (in the syndrome of inappropriate antidiuretic hormone secretion, and in vagal neuropathy), increased sensitivity to ADH by drugs such as chlorpropamide and tolbutamide, or by intake of ADH-like substances (oxytocin). Pseudo-hyponatraemia is characterised by a spuriously low plasma value measured conventionally in the total volume of plasma, which includes an extra volume in cases with hyperlipidaemia or hyperproteinaemia etc. Plasma osmolality or plasma-Na+ measured with ion selective electrodes is the choise and the direct read value is normal. This is because Na+ is confined to the aqueous phase. Treatment of artefactual hyponatraemia (taking blood from an extremity into which isotonic glucose is infused) is also unnecessary. 4. HypernatraemiaThe normal plasma-[Na+ ] is 135-145 mM, and values above 170 mM are rare. Excessive infusion of saline (0.9% NaCl or 154 mM) can lead to hypernatraemia. Such alarmingly high levels create an emergency situation, where glucose infusion is indicated initially in order to reduce the high level slowly. The increased plasma osmolality elicits a strong desire to drink. The cause is sometimes water deficit due to pituitary diabetes insipidus, or to nephrogenic diabetes insipidus, where ingestion of nephrotoxic drugs have made the renal collecting ducts resistant to ADH. Osmotic diuresis also causes water deficit with hypernatraemia just as excessive loss of water through the skin or lungs. Primary hyperaldosteronism (Conns disease) and all types of secondary hyperaldosteronism also lead to hypernatraemia combined with hypokalaemia and enlarged blood volume. Cerebral failure and convulsions are alarming signs, but there are no specific symptoms and signs of hypernatraemia. 36. Polyuria, polydipsia and thirst suggest diabetes. Diabetes mellitus is easy to diagnose, and diabetes insipidus shows a low urinary osmolality. Pituitary diabetes insipidus is treated with an analogue of ADH (desmopressin, with a low pressor-effect). 5. Hypokalaemia The normal potassium ion concentration in blood plasma is 3.5-5 mM. Hypokalaemia is caused by renal or extra-renal K+ -loss or by restricted intake. Long standing use of diuretics without KCl compensation is a frequent cause of hypokalaemia. Hyperaldosteronism (increased aldosterone secretion) is another cause.Vomit fluid only contains 5-10 mM of K+ . Still, prolonged vomiting develops into hypokalaemia, because the Na+ -loss stimulates the aldosterone secretion, which increases K + -excretion in the kidneys. Profuse diarrhoea causes marked hypokalaemia, also because the diarrhoea fluid contains up to 50 mM of K + . Hypokalaemia is seen in cardiac patients receiving digoxin treatment. Digoxin toxicity is imminent, because digoxin firmly binds to myocardial cells in hypokalaemia. Treatment must be directed towards the underlying cause. Infusion of potassium -rich fluid is dangerous, because of the marginal distance to hyperkalaemia.The reduced extracellular K+ hyperpolarises the cell membrane (increases the negativity of the voltage across the membrane). This reduces the excitability of neurons and muscle cells. Thus, hypokalaemia can result in muscle weakness and paresis. Hypokalaemia is associated with an increased frequency of cardiac arrhythmias with atrial and ventricular ectopic beats in particular in patients with cardiac disease . - Hypokalaemia inhibits release of adrenaline, aldosterone and insulin. 6. HyperkalaemiaAcute hyperkalaemia (ie, plasma-[K+ ] above 5 mM) is a normal condition following severe exercise, and normal kidneys easily eliminate K+ . In disease states the causes are insufficient renal excretion or increased release from damaged body cells as during long lasting hunger, exercise or in severe burns. A plasma- [K+ ] above 7 mM is life threatening due to asystolic cardiac arrest.Long term intake of b-blocking drugs, which inhibit the Na+ -K+ -pump, leads to hyperkalaemia that is ac
