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FunctionsofBlood

Bloodperformsanumberoffunctions
dealingwith:
Substancedistribution
Regulationofbloodlevelsofparticular
substances
Bodyprotection


BloodFunctions:Distribution
Bloodtransports:
Oxygenfromthelungsandnutrientsfromthe
digestivetract
Metabolicwastesfromcellstothelungsand
kidneysforelimination
Hormonesfromendocrineglandstotarget
organs


BloodFunctions:Regulation
Bloodmaintains:
Appropriatebodytemperaturebyabsorbingand
distributingheattootherpartsofthebody
NormalpHinbodytissuesusingbuffersystems
Adequatefluidvolumeinthecirculatory
system


BloodFunctions:Protection
Bloodpreventsbloodlossby:
Activatingplasmaproteinsandplatelets
Initiatingclotformationwhenavesselisbroken
Bloodpreventsinfectionby:
Synthesizingandutilizingantibodies
Activatingcomplementproteins
ActivatingWBCstodefendthebodyagainstforeign
invaders


PhysicalCharacteristicsofBlood
Averagevolumeofblood:
56Lformales;45Lforfemales(Normovolemia)
Hypovolemialowbloodvolume
Hypervolemiahighbloodvolume
Viscosity(thickness)45(wherewater=1)
ThepHofbloodis7.357.45;x=7.4
Osmolarity=300mOsmor0.3Osm
Thisvaluereflectstheconcentrationofsolutesintheplasma
Salinity=0.85%
ReflectstheconcentrationofNaClintheblood
Temperatureis38C,slightlyhigherthannormalbody
temperature
Bloodaccountsforapproximately8%ofbodyweight

CompositionofBlood
Bloodisthebodysonlyfluidtissue(a
connectivetissue)
2majorcomponents
Liquid=plasma(55%)
Formedelements(45%)
Erythrocytes,orredbloodcells(RBCs)
Leukocytes,orwhitebloodcells(WBCs)
Plateletsfragmentsofmegakaryocytesinmarrow


ComponentsofWholeBlood

Plasma
(55% of whole blood)

Buffy coat:
leukocyctes and
platelets
(<1% of whole blood) Formed
elements
Erythrocytes
1 Withdraw blood 2 Centrifuge (45% of whole blood)
and place in tube

Hematocrit
Males: 47% 5%
Females: 42% 5%
BloodPlasma
Bloodplasmacomponents:
Water=9092%
Proteins=68%
Albumins;maintainosmoticpressureoftheblood
Globulins
Alphaandbetaglobulinsareusedfortransportpurposes
Gammaglobulinsaretheimmunoglobulins(IgG,IgA,etc)
Fibrinogen;aclottingprotein
Organicnutrientsglucose,carbohydrates,aminoacids
Electrolytessodium,potassium,calcium,chloride,
bicarbonate
Nonproteinnitrogenoussubstanceslacticacid,urea,
creatinine
Respiratorygasesoxygenandcarbondioxide

FormedElements
Formedelementscomprise45%ofblood
Erythrocytes,leukocytes,andplatelets
makeuptheformedelements
OnlyWBCsarecompletecells
RBCshavenonucleiororganelles,and
plateletsarejustcellfragments
Mostformedelementssurviveinthe
bloodstreamforonlyafewdays
Mostbloodcellsdonotdividebutare
renewedbycellsinbonemarrow

Erythrocytes(RBCs)
Biconcavedisc
Foldingincreasessurfacearea(30%moresurfacearea)
Plasmamembranecontainsspectrin
Giveerythrocytestheirflexibility
Anucleate,nocentrioles,noorganelles
Endresultnocelldivision
NomitochondriameanstheygenerateATPanaerobically
PreventsconsumptionofO2beingtransported
Filledwithhemoglobin(Hb)97%ofcellcontents
Hbfunctionsingastransport
Hb+O2HbO2(oxyhemoglobin)
Mostnumerousoftheformedelements
Females:4.35.2millioncells/cubicmillimeter
Males:5.25.8millioncells/cubicmillimeter

Erythrocytes(RBCs)

Figure 17.3
ErythrocyteFunction
Erythrocytesarededicatedtorespiratorygas
transport
Hemoglobinreversiblybindswithoxygenand
mostoxygeninthebloodisboundtohemoglobin
Compositionofhemoglobin
Aproteincalledglobin
madeupoftwoalphaandtwobetachains
Ahememolecule
Eachhemegroupbearsanatomofiron,whichcanbindtoone
oxygenmolecule
Eachhemoglobinmoleculethuscantransportfourmolecules
ofoxygen


StructureofHemoglobin

Figure 17.4
Hemoglobin
Oxyhemoglobinhemoglobinboundtooxygen
Oxygenloadingtakesplaceinthelungs
Deoxyhemoglobinhemoglobinafteroxygen
diffusesintotissues(reducedHb)
Carbaminohemoglobinhemoglobinboundto
carbondioxide
Carbondioxideloadingtakesplaceinthetissues


LifeCycle
ofRed
BloodCells


FateandDestructionof
Erythrocytes
Thelifespanofanerythrocyteis100120days
Travelsabout750milesinthattime(LAtoAlbuquerque)
Olderythrocytesbecomerigidandfragile,andtheir
hemoglobinbeginstodegenerate
Dyingerythrocytesareengulfedbymacrophages
Hemeandglobinareseparated
Ironisremovedfromthehemeandsalvagedforreuse
Storedashemosiderinorferritinintissues
Transportedinplasmabybetaglobulinsastransferrin


FateandDestructionof
Erythrocytes
Hemeisdegradedtoayellowpigmentcalled
bilirubin
Liversecretesbilirubinintotheintestinesasbile
Intestinesmetabolizebilirubinintourobilinogen
Urobilinogenleavesthebodyinfeces,inapigment
calledstercobilin
Globinismetabolizedintoaminoacidswhichare
thenreleasedintothecirculation


Stagesof
Differentiationof
BloodCells

Figure 17.9
ProductionofErythrocytes
Hematopoiesisbloodcellformation
Occursintheredbonemarrow(myeloidtissue)
Axialskeletonandgirdles
Epiphysesofthehumerusandfemur
Marrowcontainsimmatureerythrocytes
Composedofreticularconnectivetissue
HemocytoblastsgiverisetoALLformedelements
Lymphoidstemcellsgiverisetolymphocytes
Myeloidstemcellsgiverisetoallotherbloodcells


ProductionofErythrocytes:
Erythropoiesis
Ahemocytoblastistransformedintoacommittedcell
calledtheproerythroblast
Proerythroblastsdevelopintoearlyerythroblasts
Thedevelopmentalpathwayconsistsofthreephases
Phase1ribosomesynthesisinearlyerythroblasts
Phase2hemoglobinaccumulationinlateerythroblastsand
normoblasts
Phase3ejectionofthenucleusfromnormoblastsandformation
ofreticulocytes
Reticulocytesthenbecomematureerythrocytes
Reticulocytesmakeupabout12%ofallcirculatingerythrocytes


ProductionofErythrocytes:
Erythropoiesis


RegulationandRequirementsfor
Erythropoiesis
Circulatingerythrocytesthenumberremains
constantandreflectsabalancebetweenRBC
productionanddestruction
Toofewredbloodcellsleadstotissuehypoxia
Toomanyredbloodcellscausesundesirableblood
viscosity
Erythropoiesisishormonallycontrolledand
dependsonadequatesuppliesofiron,amino
acids,andBvitamins

HormonalControlof
Erythropoiesis
Erythropoietin(EPO)releasebythekidneys
istriggeredby:
HypoxiaduetodecreasedRBCs
Decreasedoxygenavailability
Increasedtissuedemandforoxygen
Enhancederythropoiesisincreasesthe:
RBCcountincirculatingblood
Oxygencarryingabilityoftheblood


ErythropoietinMechanism
Imb
ala
nce
Start
Normal blood oxygen levels Stimulus: Hypoxia due to
I mb decreased RBC count,
ala decreased availability of O2
nce
to blood, or increased
Increases tissue demands for O2
O2-carrying
ability of blood

Reduces O2
levels in blood

Erythropoietin
Kidney (and liver to a
Enhanced stimulates red
smaller extent) releases
erythropoiesis bone marrow
erythropoietin
increases RBC
count

Figure 17.6
DietaryRequirementsof
Erythropoiesis
Erythropoiesisrequires:
Proteins,lipids,andcarbohydrates
Iron,vitaminB12,andfolicacid
ThebodystoresironinHb(65%),theliver,
spleen,andbonemarrow
Intracellularironisstoredinproteiniron
complexessuchasferritinandhemosiderin
Circulatingironislooselyboundtothetransport
proteintransferrin


ErythrocyteDisorders
Polycythemia
Abnormalexcessoferythrocytes
Increasesviscosity,decreasesflowrateofblood
Anemiabloodhasabnormallylow
oxygencarryingcapacity
Itisasymptomratherthanadiseaseitself
Bloodoxygenlevelscannotsupportnormal
metabolism
Signs/symptomsincludefatigue,paleness,
shortnessofbreath,andchills

Anemia:Insufficient
Erythrocytes
Hemorrhagicanemiaresultofacuteor
chroniclossofblood
Hemolyticanemiaprematurelyruptured
erythrocytes
Aplasticanemiadestructionorinhibition
ofredbonemarrow


Anemia:DecreasedHemoglobin
Content
Irondeficiencyanemiaresultsfrom:
Asecondaryresultofhemorrhagicanemia
Inadequateintakeofironcontainingfoods
Impairedironabsorption
Perniciousanemiaresultsfrom:
DeficiencyofvitaminB12
LackofintrinsicfactorneededforabsorptionofB12
TreatmentisintramuscularinjectionofB12

Anemia:AbnormalHemoglobin
Thalassemiasabsentorfaultyglobinchainin
hemoglobin
Erythrocytesarethin,delicate,anddeficientin
hemoglobin
Sicklecellanemiaresultsfromadefectivegene
Codesforanabnormalhemoglobincalledhemoglobin
S(HbS)
ThisdefectcausesRBCstobecomesickleshapedin
lowoxygensituations


Polycythemia
PolycythemiaexcessRBCsthatincrease
bloodviscosity
Threemainpolycythemiasare:
Polycythemiavera
Secondarypolycythemia
Blooddoping


Leukocytes(WBCs)
Leukocytes,theonlybloodcomponentsthatarecompletecells:
4,80010,000/cubicmillimeter
Protectthebodyfrominfectiousmicroorganisms
Canleavecapillariesviadiapedesis
Movethroughtissuespaces(amoeboidmotion)
Manyarephagocytic(possessnumerouslysosomes)
Twomajortypesofleukocytes
Granulocytes:Neutrophils,Eosinophils,Basophils
Agranulocytes:Monocytes,Lymphyocytes
LeukocytosisWBCcountover11,000/mm3
Normalresponsetobacterialorviralinvasion
LeukopeniaadecreaseinWBCcountbelow4,800/mm3
LeukemiaacancerofWBC

Granulocytes
Granulocytesneutrophils,eosinophils,
andbasophils
Containcytoplasmicgranulesthatstain
specifically(acidic,basic,orboth)with
Wrightsstain
ArelargerandusuallyshorterlivedthanRBCs
Havelobednuclei
Areallphagocyticcells


Granulocytes:Neutrophils
(Polymorphonuclearleukocytes)
Accountfor6575%oftotalWBCs
Neutrophilshavetwotypesofgranulesthat:
Takeupbothacidicandbasicdyes
Givethecytoplasmalilaccolor
Containperoxidases,hydrolyticenzymes,and
defensins(antibioticlikeproteins)
Neutrophilsareourbodysbacteriaslayers
AKApolysorPMNs(polymorphonuclear)

Granulocytes:Eosinophils

Eosinophilsaccountfor14%ofWBCs
Haveredstaining,bilobednuclei
Haveredtocrimsongranules
Function:
Leadthebodyscounterattackagainstparasitic
infections
Lessentheseverityofallergiesbyphagocytizing
immunecomplexes(endingallergicreactions)


Granulocytes:Basophils

Accountfor0.51%ofallWBCs
HaveUorSshapednucleiwithtwoorthree
conspicuousconstrictions
Arefunctionallysimilartomastcells
Havelarge,purplishblack(basophilic)
granulesthatcontainhistamine
Histamineinflammatorychemicalthatactsasa
vasodilatorandattractsotherWBCs(antihistamines
counterthiseffect)


Agranulocytes:Lymphocytes

Accountfor2025%ormoreofWBCsand:
Havelarge,darkpurple,circularnucleiwithathinrim
ofbluecytoplasm
Arefoundmostlyenmeshedinlymphoidtissue(some
circulateintheblood)
Mostimportantcellsoftheimmunesystem
Therearetwotypesoflymphocytes:TcellsandB
cells
Tcellsattackforeigncellsdirectly
Bcellsgiverisetoplasmacells,whichproduce
antibodies

Monocytes

Monocytesaccountfor37%ofleukocytes
Theyarethelargestleukocytes
Theyhavepurplestaining,Uorkidneyshaped
nuclei
Theyleavethecirculation,entertissue,and
differentiateintomacrophages


ProductionofLeukocytes
Leukopoiesisishormonallystimulatedbytwo
familiesofcytokines(hematopoieticfactors)
interleukinsandcolonystimulatingfactors(CSFs)
Interleukinsarenumbered(e.g.,IL1,IL2),whereas
CSFsarenamedfortheWBCstheystimulate(e.g.,
granulocyteCSFstimulatesgranulocytes)
MacrophagesandTcellsarethemostimportant
sourcesofcytokines
Manyhematopoietichormonesareusedclinically
tostimulatebonemarrow


FormationofLeukocytes
Allleukocytesoriginatefromhemocytoblasts
Themotherofallbloodstemcells
Hemocytoblastsdifferentiateintomyeloidstemcells
andlymphoidstemcells
Myeloidstemcellsbecomemyeloblastsor
monoblasts
Granulocytesformfrommyeloblasts
Monoblastsenlargeandformmonocytes
Lymphoidstemcellsbecomelymphoblasts
Lymphoblastsdevelopintolymphocytes


Formation
of
Leukocytes

Figure 17.11
LeukocytesDisorders:
Leukemias
Leukemiareferstocancerousconditionsinvolving
whitebloodcells
Leukemiasarenamedaccordingtotheabnormal
whitebloodcellsinvolved
Myelocyticleukemiainvolvesmyeloblasts
Lymphocyticleukemiainvolveslymphocytes
Acuteleukemiainvolvesblasttypecellsand
primarilyaffectschildren
Chronicleukemiaismoreprevalentinolderpeople


Leukemia
Immaturewhitebloodcellsarefoundinthe
bloodstreaminallleukemias
Bonemarrowbecomestotallyoccupiedwith
cancerousleukocytes
Severeanemiaensuesduetoexcessproductionof
WBCs
Thewhitebloodcellsproduced,thoughnumerous,
arenotfunctional
Deathiscausedbyinternalhemorrhageand
overwhelminginfections
Treatmentsincludeirradiation,antileukemic
drugs,andbonemarrowtransplants

Platelets
Plateletsarefragmentsofmegakaryocytes
Theirgranulescontainserotonin,Ca2+,
enzymes,ADP,andplateletderivedgrowth
factor(PDGF)
Plateletsfunctionintheclottingmechanism
byformingatemporaryplugthathelpsseal
breaksinbloodvessels
Plateletsnotinvolvedinclottingarekept
inactivebyNitricOxide(NO)and
prostaglandins

HumanBloodGroups
RBCmembraneshaveglycoproteinantigenson
theirexternalsurfaces
Theseantigensare:
Uniquetotheindividual
Recognizedasforeigniftransfusedintoanother
individual
Promotersofagglutinationandarereferredtoas
agglutinogens
Presenceorabsenceoftheseantigensisusedto
classifybloodgroups


BloodGroups

Humanshave30varietiesofnaturally
occurringRBCantigens
TheantigensoftheABOandRhblood
groupscausevigoroustransfusionreactions
whentheyareimproperlytransfused
Otherbloodgroups(M,N,Dufy,Kell,and
Lewis)aremainlyusedforlegalities


ABOBloodGroups

TheABObloodgroupsconsistsof:
Twoantigens(AandB)onthesurfaceoftheRBCs
Twoantibodiesintheplasma(antiAandantiB)
AnindividualwithABObloodmayhavevarious
typesofantigensandspontaneouslypreformed
antibodies
Agglutinogensandtheircorrespondingantibodies
cannotbemixedwithoutserioushemolytic
reactions


ABOBloodGroups

Table 17.4
RhBloodGroups
PresenceoftheRhagglutinogensonRBCsis
indicatedasRh+;85%ofpopulationis+
LackofantigenindicatedasRh;15%ofpopn.
AntiRhantibodiesarenotspontaneouslyformed
onlyinRhindividuals
However,ifanRhindividualreceivesRh+blood,
antiRhantibodiesform
AsecondexposuretoRh+bloodwillresultina
typicaltransfusionreaction


HemolyticDiseaseoftheNewborn
MayoccurinanRhmompregnanetwithanRh+fetus
HemolyticdiseaseofthenewbornRh+antibodiesofa
sensitizedRhmothercrosstheplacentaandattackand
destroytheRBCsofanRh+baby
RhmotherbecomessensitizedwhenRh+blood(froma
previouspregnancyofanRh+babyoraRh+transfusion)
causesherbodytosynthesisRh+antibodies
ThedrugRhoGAMcanpreventtheRhmotherfrom
becomingsensitized
Treatmentofhemolyticdiseaseofthenewborninvolves
prebirthtransfusionsandexchangetransfusionsafterbirth


TransfusionReactions

Transfusionreactionsoccurwhenmismatched
bloodisinfused
Donorscellsareattackedbytherecipientsplasma
agglutininscausing:
Diminishedoxygencarryingcapacity
Clumpedcellsthatimpedebloodflow
RupturedRBCsthatreleasefreehemoglobinintothe
bloodstream
Circulatinghemoglobinprecipitatesinthekidneys
andcausesrenalfailure

BloodTyping

WhenserumcontainingantiAorantiB
agglutininsisaddedtoblood,agglutination
willoccurbetweentheagglutininandthe
correspondingagglutinogens
Positivereactionsindicateagglutination


BloodTyping

Bloodtypebeingtested RBCagglutinogens SerumReaction

AntiA AntiB

AB AandB + +

B B +

A A +

O None