- 1. 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 Comprehensive metabolic
panelA comprehensive metabolic panel is a group of chemical tests
performed on the blood MedlinePlus Topics serum (the part of blood
that doesn't contain cells). Laboratory Tests These tests include
total cholesterol, total protein, and various electrolytes.
Electrolytes in the body include sodium, potassium, chlorine, and
many others. Read More Electrolytes The rest of the tests measure
chemicals that reflect liver and kidney function.How the Test is
PerformedA blood sample is needed. For information on giving a
blood sample from a vein, see venipuncture.How to Prepare for the
TestYou should not eat or drink for 8 hours before the test.How 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 PerformedThis test helps provide information about your
body's metabolism. It give your doctor information about how your
kidneys and liver are working, and can be used to evaluate blood
sugar, cholesterol, and calcium levels, among other things.Your
doctor may order this test during a yearly exam or routine check
up.Normal Results Albumin: 3.9 to 5.0 g/dL Alkaline phosphatase: 44
to 147 IU/L ALT (alanine transaminase): 8 to 37 IU/L AST (aspartate
aminotransferase): 10 to 34 IU/L BUN (blood urea nitrogen): 7 to 20
mg/dL Calcium - serum: 8.5 to 10.9 mg/dL Serum chloride: 101 to 111
mmol/L CO2 (carbon dioxide): 20 to 29 mmol/L Creatinine: 0.8 to 1.4
mg/dL ** Direct bilirubin: 0.0 to 0.3 mg/dL Gamma-GT
(gamma-glutamyl transpeptidase): 0 to 51 IU/L Glucose test: 64 to
128 mg/dL LDH (lactate dehydrogenase): 105 to 333 IU/L Phosphorus -
serum: 2.4 to 4.1 mg/dL
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
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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
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14.
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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
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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