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BIO202 BloodPartIaBloodCompositionandFormedElements FunctionsandCompositionofBlood Bloodhelpsmaintainhomeostasisinseveralways: Transportofgases,nutrients,waste products Transportofprocessedmolecules Transportofregulatorymolecules RegulationofpHandosmosis Maintenanceofbodytemperature Protectsagainstforeignsubstancessuchas microorganismsandtoxins Bloodclottingpreventsfluidandcellloss andispartoftissuerepair FunctionsandCompositionofBlood

ionofBlood Bloodisaconnectivetissueconsistingofplasma andformedelements Bloodisthebodysonlyfluidtissue Itiscomposedofliquidplasmaandformed elements Formedelementsinclude: Erythrocytes,orredbloodcells(RBCs) Leukocytes,orwhitebloodcells(WBCs) Platelets Hematocrit:thepercentageofRBCsoutofthe totalbloodvolume FunctionsandCompositionofBlood Bloodisasticky,opaquefluidwithametallictaste Colorvariesfromscarlettodarkred ThepHofbloodis7.357.45 Temperatureis38C Bloodaccountsforapproximately8%ofbody weight Averagevolume:56L(1.5gallons)formales,and 45Lforfemales

Plasma Paleyellowfluidcontainingover100solutes Mostlywater(91%) Proteins(7%) Albumin(58%oftheplasmaproteins) Helpsmaintainosmoticpressure Globulins(38%oftheplasmaproteins) Immunity:antibodiesandcomplement Transport:bindtomoleculessuchas hormones ClottingFactors Fibrinogen(4%oftheplasmaproteins) Convertedtofibrinduringclotformation Othersubstances(2%) Ions(electrolytes):sodium,potassium, calcium,chloride,bicarbonate Nutrients:glucose,carbohydrates,amino acids Wasteproducts:lacticacid,urea,creatinine Respiratorygases:oxygenandcarbondioxide

FormedElements Erythrocytesorredbloodcells(RBCs) About95%offormedelements RBCshavenonucleiororganelles Leukocytesorwhitebloodcells(WBCs) Mostoftheremaining5%offormedelements OnlyWBCsarecompletecells FivetypesofWBCs Platelets Cellfragmentsformedbymegakaryocytes Importantforbloodclotting ProductionofFormedElements Hemocytoblastsgiverisetoallformedelements Mostbloodcellsdonotdivide Hematopoiesis:bloodcellproduction Occursindifferentlocationsbeforeandafterbirth Fetus Liver,thymus,spleen,lymphnodes,andredbonemarrow Afterbirth Intheredbonemarrowofthe Axialskeletonandgirdles Epiphysesofthehumerusandfemur Growthfactorsdeterminethetypeofformedelementderivedfromthestemcell

BloodPartIbRedBloodCellsandWhiteBloodCells RedBloodCells(RBCs) Biconcavediscs,anucleate,essentiallynoorganelles RBCsarededicatedtorespiratorygastransport Filledwithhemoglobin(Hb),aproteinthatfunctionsingas transport RBCsareanexampleofhowstructurefitsfunction Biconcaveshapehasahugesurfacearearelativetovolume Structuralcharacteristicscontributetoitsgastransport function BiconcaveshapealsoallowsRBCstobendorfoldaround theirthincenter Giveserythrocytestheirflexibility Allowthemtochangeshapewhenmovingthrough capillaries

RedBloodCells Hemoglobin(Hb)consistsof Theproteinglobin,madeupoftwoalphaandtwobetachains,eachboundtoahemegroup Eachhemegroupbearsanatomofiron,whichcanbindtooneoxygenmolecule Hememoleculestransportoxygen(ironisrequired) Oxygencontentdeterminesbloodcolor Oxygenated:brightred Deoxygenated:darkerred Globinmoleculestransportcarbondioxide OneRBCcontains250millionHbgroupsthusitcancarry1billionmoleculesofO2 RedBloodCells TransportofOxygenandCarbonDioxide Oxygen Transportedboundtohemoglobin~98.5% Dissolvedinplasma~1.5% EachHbmoleculebindsfouroxygenatomsinarapidandreversibleprocess Carbondioxide Dissolvedinplasma~7% Transportedasbicarbonate(HCO3)~70% Chemicallyboundtohemoglobin~23% RedBloodCells TransportandExchangeofCarbonDioxide CarbondioxidediffusesintoRBCsandcombineswithwatertoformcarbonicacid(H2CO3),whichquickly dissociatesintohydrogenionsandbicarbonateions

CO2 Carbon dioxide

H2O Water

H2CO3 Carbonic acid

H+ Hydrogen ion

HCO3 Bicarbonate ion

InRBCs,carbonicanhydrasereversiblycatalyzestheconversionofcarbondioxideandwatertocarbonicacid

Erythropoiesis Ahemocytoblastistransformedintoaproerythroblast Proerythroblastsdevelopintoearlyerythroblasts Ejectionofthenucleusfromlateerythroblastsandleadstoformationofreticulocytes Reticulocytesarereleasedfromtheredbonemarrowintothecirculatingblood,whichcontains~13%reticulocytes Reticulocytesthenbecomematureerythrocytes

Erythropoiesis Circulatingerythrocytes:Thenumberremainsconstantandreflectsa balancebetweenRBCproductionanddestruction ToofewRBCsleadstotissuehypoxia ToomanyRBCscausesundesirablebloodviscosity Erythropoiesisishormonallycontrolledanddependsonadequate suppliesofiron,aminoacids,andBvitamins(folateandB12) Erythropoietin(EPO)releasebythekidneysistriggered by HypoxiaduetodecreasedRBCs Decreasedoxygenavailability Increasedtissuedemandforoxygen Enhancederythropoiesisincreasesthe RBCcountincirculatingblood Oxygencarryingabilityoftheblood RecyclingofRBCs Thelifespanofanerythrocyteis100120days OldRBCsbecomerigidandfragile,andtheirHbbeginsto degenerate DyingRBCsareengulfedbymacrophageslocatedinthe spleenorliver Hemeandglobinareseparatedandtheironissalvagedfor reuse Globinchainsarebrokendowntoindividualaminoacids andaremetabolizedorusedtobuildnewproteins Ironreleasedfromhemeistransportedtotheredbone marrowandisusedtoproducenewhemoglobin Hemebecomesbilirubinthatissecretedinbile Intheintestinesbilirubinisconvertedbybacteria intootherpigments Givesfecesitsbrowncolor Givesurineitsyellowcolor

ErythrocyteDisorders Anemia:bloodhasabnormallylowO2carryingcapacity Asignratherthanadiseaseitself BloodO2levelscannotsupportnormalmetabolism Accompaniedbyfatigue,paleness,shortnessofbreath,andchills CausesofAnemia Insufficienterythrocytes Hemorrhagicanemia:acuteorchroniclossofblood Hemolyticanemia:RBCsruptureprematurely Aplasticanemia:destructionorinhibitionofredbonemarrow Lowhemoglobincontent Irondeficiencyanemia Secondaryresultofhemorrhagicanemiaor Inadequateintakeofironcontainingfoodsor Impairedironabsorption Perniciousanemia DeficiencyofvitaminB12 LackofintrinsicfactorneededforabsorptionofB12 TreatedbyintramuscularinjectionofB12orapplicationofNascobal CausesofAnemia Abnormalhemoglobin Thalassemias Absentorfaultyglobinchain RBCsarethin,delicate,anddeficientinhemoglobin Sicklecellanemia Defectivegenecodesforabnormalhemoglobin(HbS) CausesRBCstobecomesickleshapedinlowoxygensituations ErythrocyteDisorders Polycythemia:excessofRBCsthatincreasebloodviscosity Resultsfrom: Polycythemiaverabonemarrowcancer SecondarypolycythemiawhenlessO2isavailable(highaltitude)orwhenEPOproductionincreases Blooddoping WhiteBloodCells Onlybloodcomponentsthatarecompletecells ArelessnumerousthanRBCs Makeup1%ofthetotalbloodvolume Canleavecapillariesviaameboidmovementandmovethroughtissuespaces TwofunctionsofWBCs Protectthebodyagainstinvadingmicroorganisms Removedeadcellsanddebrisfromtissuesbyphagocytosis Namedaccordingtotheirappearanceinstainedpreparations Granulocytes:containlargecytoplasmicgranules Agranulocytes:verysmallgranulesthatcannotbeeasilyseenwiththelightmicroscope

Granulocytes Neutrophils,Eosinophils,andBasophils Containcytoplasmicgranulesthatstainspecifically(acidic,basic,orboth)withWrightsstain ArelargerandusuallyshorterlivedthanRBCs Havelobednuclei Areallphagocyticcells Neutrophils NeutrophilsmostcommontypeofWBC Aremultinucleate Havetwotypesofgranulesthat: Takeupbothacidicandbasicdyes Givethecytoplasmalilaccolor Containperoxidases,hydrolyticenzymes, anddefensins(antibioticlikeproteins) Neutrophilsareourbodysbacteriaslayers Pusisanaccumulationofdeadneutrophils,bacteria,celldebrisandfluidatsitesofinfections Eosinophils Eosinophilsaccountfor14%ofWBCs Haveredstaining,bilobednucleiconnectedviaabroadbandofnuclearmaterial Haveredtocrimson(acidophilic)large,coarse,lysosomelikegranules Lessentheseverityofallergiesbyreducinginflammation Leadthebodyscounterattackagainstparasiticworms Basophils Basophilsaccountfor0.5%ofWBCs Havelarge,purplishblack(basophilic)granulesthatcontain Histamine:inflammatorychemicalthatactsasavasodilatorandattractsotherWBCs(antihistamines counterthiseffect) Heparin:preventstheformationofclots Agranulocytes Lymphocytesandmonocytes Lackvisiblecytoplasmicgranules Aresimilarstructurally,butarefunctionallydistinctandunrelatedcelltypes Havespherical(lymphocytes)orkidneyshaped(monocytes)nuclei Lymphocytes Lymphocytesaccountfor25%ormoreofWBCs Havelarge,darkpurple,circularnucleiwithathinrimofbluecytoplasm Arefoundbothinlymphoidtissuesandintheblood Therearetwotypesoflymphocytes:TcellsandBcells Bcells Stimulatedbybacteriaortoxins Giverisetoplasmacells,whichproduceantibodies Foundprimarilyinblood Tcells Protectagainstvirusesandotherintracellularmicroorganisms Attackanddestroythecellsthatareinfected Foundprimarilyintissuesandlymph

Monocytes Monocytesaccountfor48%ofleukocytes Theyarethelargestleukocytes Theyhaveanabundantpalebluecytoplasm Theyhavepurplestaining,Uorkidneyshapednuclei Theyleavethecirculation,entertissue,anddifferentiateintomacrophages Arehighlymobileandactivelyphagocytic Activatelymphocytestomountanimmuneresponse LeukocyteDisorders Leukopenia AbnormallylowWBCcountdruginduced Leukemias CancerousconditionsinvolvingWBCs NamedaccordingtotheabnormalWBCcloneinvolved Myelocyticleukemiainvolvesmyeloblasts Lymphocyticleukemiainvolveslymphocytes Acuteleukemiainvolvesblasttypecellsandprimarilyaffectschildren Chronicleukemiaismoreprevalentinolderpeople

Platelets Fragmentsofmegakaryocyteswithabluestainingouterregionandapurplegranularcenter Functioninclottingbytwomechanisms Formationofplateletplugs,whichsealholesinsmallvessels Formationofclots,whichhelpsealofflargerwoundsinthevessels TheirgranulescontainADPandthromboxanes

BloodPartIIBloodClottingandCoagulation HemostasisBloodClotting ThreeSteps Vascularspasm Plateletplugformation Coagulation(bloodclotting) VascularSpasm Vasoconstrictionofdamagedbloodvessel Triggers Directinjury Chemicalsreleasedbyendothelialcellsandplatelets Painreflexes PlateletPlugFormation Positivefeedbackcycle Atsiteofbloodvesselinjury,platelets Sticktoexposedcollagenfiberswiththehelpofvon Willebrandfactor,aplasmaprotein Swell,becomespikedandsticky,andreleasechemical messengers ADPcausesmoreplateletstostickandreleasetheir contents SerotoninandthromboxaneA2enhancevascularspasm andmoreplateletaggregation Coagulation Asetofreactionsinwhichbloodistransformedfromaliquidto gel Reinforcestheplateletplugwithfibrinthreads Threephasesofcoagulation Prothrombinactivatorisformed(intrinsicandextrinsic pathways) Prothrombinisconvertedintothrombin Thrombincatalyzesthejoiningoffibrinogentoformafibrin mesh

Phase1:PathwaytoProthrombinActivator Initiatedbyeithertheintrinsicorextrinsicpathway (usuallyboth) Triggeredbytissuedamagingevents Involvesaseriesofprocoagulants EachpathwaycascadestowardfactorX Intrinsicpathway Istriggeredbynegativelychargedsurfaces (activatedplatelets,collagen,glass) Usesfactorspresentwithintheblood(intrinsic) Extrinsicpathway Istriggeredbyexposuretotissuefactor(TF)or factorIII(anextrinsicfactor) Bypassesseveralstepsoftheintrinsicpathway, soisfaster CoagulationPhase2:PathwaytoThrombin Prothrombinactivatorcatalyzesthetransformationof prothrombintotheactiveenzymethrombin Coagulation CoagulationPhase3:PathwaytoFibrinMesh Thrombinconvertssolublefibrinogenintofibrin Fibrinstrandsformthestructuralbasisofaclot Fibrincausesplasmatobecomeagelliketrapforformed elements Thrombin(withCa2+)activatesfactorXIIIwhich: Crosslinksfibrin Strengthensandstabilizestheclot ClotRetractionandRepair ClotRetraction Actinandmyosininplateletscontractwithin3060minutes Plateletspullonthefibrinstrands,squeezingserumfromtheclot ClotRepair Plateletderivedgrowthfactor(PDGF)stimulatesdivisionofsmooth musclecellsandfibroblaststorebuildbloodvesselwall Vascularendothelialgrowthfactor(VEGF)stimulatesendothelialcellsto multiplyandrestoretheendotheliallining DisordersofHemostasis Thromboembolyticdisorders:undesirableclotformation Bleedingdisorders:abnormalitiesthatpreventnormalclotformation

ThromboembolyticConditions Thrombus:clotthatdevelopsandpersistsinan unbrokenbloodvessel Mayblockcirculation,leadingtotissuedeath Embolus:athrombusfreelyfloatingintheblood stream Pulmonaryemboliimpairtheabilityofthe bodytoobtainoxygen Cerebralembolicancausestrokes Preventedby Aspirin Antiprostaglandinthatinhibits thromboxaneA2 Heparin Anticoagulantusedclinicallyforpreand postoperativecardiaccare Warfarin Usedforthosepronetoatrialfibrillation BleedingDisorders Thrombocytopenia:deficientnumberofcirculating platelets Petechiaeappearduetospontaneous, widespreadhemorrhage Duetosuppressionordestructionofbone marrow(e.g.,malignancy,radiation) Plateletcount<50,000/mm3isdiagnostic Treatedwithtransfusionofconcentrated platelets Impairedliverfunction Inabilitytosynthesizeprocoagulants CausesincludevitaminKdeficiency,hepatitis, andcirrhosis Liverdiseasecanalsopreventtheliverfrom producingbile,impairingfatandvitaminK absorption BloodPartIIIABOBloodGroups BloodGrouping RBCmembraneshaveglycoproteinantigenson theirexternalsurfaces Theseantigensare: Uniquetotheindividual Recognizedasforeigniftransfusedinto anotherindividual Promotersofagglutinationandarereferredto asagglutinogens Presenceorabsenceoftheseantigensisusedto classifybloodgroups Humanshave30varietiesofnaturallyoccurring RBCantigens AntigensoftheABOandRhbloodgroupscause vigoroustransfusionreactions

BleedingDisorders Hemophiliasincludeseveralsimilarhereditary bleedingdisorders HemophiliaA:mostcommontype(77%ofall cases);duetoadeficiencyoffactorVIII HemophiliaB:deficiencyoffactorIX HemophiliaC:mildtype;deficiencyoffactor XI Symptomsincludeprolongedbleeding,especially intojointcavities Treatedwithplasmatransfusionsandinjectionof missingfactors Transfusions Wholebloodtransfusionsareusedwhenblood lossissubstantial Packedredcells(plasmaremoved)areusedto restoreoxygencarryingcapacity Transfusionofincompatiblebloodcanbefatal

Otherbloodgroups(MNS,Duffy,Kell,andLewis) areusuallyweakagglutinogens

BloodGrouping Transfusionreactionsoccurwhenmismatched bloodisinfused AntibodiescanbindtothedonorsRBCantigens, resultinginagglutinationorhemolysisofRBCs, leadingto Diminishedoxygencarryingcapacity Clumpedcellsthatimpedebloodflow RupturedRBCsthatreleasefreehemoglobin intothebloodstream

ABOBloodGroup TheABObloodgroupsconsistsof: Twoantigens(AandB)onthesurfaceoftheRBCs Twoantibodiesintheplasma(antiAandantiB)

Blood type

Antigens Present A B + +

Antibodies Present Anti-A + + Anti-B + +

AB B A O

+ +

RhBloodGroup RhpositivebloodhascertainRhantigens(theDantigen),whereasRhnegativeblooddoesnot AntibodiesagainsttheRhantigenareproducedwhenaRhnegativepersonisexposedtoRhpositiveblood TheRhbloodgroupisresponsibleforhemolyticdiseaseofthenewborn,whichcanoccurwhenthefetusisRh positiveandthemotherisRhnegative DiagnosticBloodTests Laboratoryexaminationofbloodcanassessanindividualsstateofhealth Microscopicexamination: VariationsinsizeandshapeofRBCs:predictionofanemia TypeandnumberofWBCs:diagnosticofvariousdiseases Chemicalanalysiscanprovideacomprehensivepictureofonesgeneralhealthstatusinrelationtonormalvalues DiagnosticBloodTests

Redbloodcellcount(million/mL)

Whitebloodcellcount(WBCs/mL)

Male4.66.2million/mL Female4.25.4million/mL

MaleandFemale50009000WBCs/mL

Hemoglobinmeasurement(gramsofhemoglobin per/mLofblood

Differentialwhitebloodcellcount(thepercentage ofeachtypeofWBC)

Male1418g/100mL Female1216g/100mL

Hematocritmeasurement(percentvolumeofRBCs)

Neutorphils60%70% Lymphocytes20%25% Monocytes3%8% Eosinophils2%4% Basophils0.5%1%

Male40%52% Female38%48%

DiagnosticBloodTests Clotting Plateletcountandprothrombintimemeasuretheabilityofthebloodtoclot BloodChemistry Thecompositionofmaterialsdissolvedorsuspendedinplasmacanbeusedtoassessthefunctioningand statusofthebodyssystems Glucose Urea Nitrogen Bilirubin Cholesterol