TurkJMedSci 33(2003)347-355 ©TÜB‹TAK PERSPECTIVES IN MEDICAL SCIENCES PathophysiologicalSignificanceofBloodRheology O¤uzKerimBAfiKURT DepartmentofPhysiology,FacultyofMedicine,AkdenizUniversity,Antalya-Turkey Received:September16,2003 Abstract: Tissueperfusionisdeterminedbybothbloodvesselgeometryandtherheologicalpropertiesofblood.Bloodisanon- Newtonianfluid,itsviscositybeingdependentonflowconditions.Bloodandplasmaviscosities,aswellastherheologicalpro perties ofbloodcells(e.g.,deformabilityandaggregationofredbloodcells),areinfluencedbydiseaseprocessesandextremephysio logical conditions.Theserheologicalparametersmayinturnaffectthebloodflowinvessels,andhencetissueperfusion.Unfortunatel yit isnotalwayspossibletodetermineifachangeinrheologicalparametersisthecauseortheresultofadiseaseprocess.The hemorheology-tissueperfusionrelationshipisfurthercomplicatedbythedistinctinvivobehaviorofblood.Besidesthespecia l hemodynamicmechanismsaffectingthecompositionofbloodinvariousregionsofthevascularsystem,autoregulationbasedon vascularcontrolmechanismsfurthercomplicatesthisrelationship.Hemorheologicalparametersmaybeespeciallyimportantfor adequatetissueperfusionifthevascularsystemisgeometricallychallenged. KeyWords: Hemorheology,tissueperfusion,metabolicautoregulation,shearstress Introduction resistance.Adequatebloodflowtoagiventissuerequires Itisaverybasicmedicalfactthatpropertissue/organ themaintenanceofasufficientpressuregradientacross functionstronglydependsonadequatebloodflow. thetissuethatisgeneratedbytheheart. Obviously,“adequacy”doesnotdenoteasteadystate Thevascularcomponentofflowresistanceis condition,buttheabilitytomatchthesupplywiththe determinedbythegeometryofthebloodvessels demandofagiventissue.Anydisturbanceofthisdelicate network.Thiscomponentisusuallycalledvascular balanceresultsinclinicalproblems.Higherlevelliving hindrance(1).Jean-MariePoiseuilledescribedthe organismsarewellequippedwithpowerfulcontrol vascularhindranceofagivenbloodvesselsegmentas mechanismstomaintainthisbalanceandtokeepthe beingdirectlyproportionaltothelengthofthesegment organismingoodhealth,accordingly. andinverselyproportionaltothefourthpowerofthe vesselradius(2),basedonhisexperimentalstudies.Flow resistanceisalsodirectlyproportionaltotheviscosityof Factorsaffectingbloodflow bloodflowinginthatsegment.Thissimplerelationshipis Bloodflowinthevascularsystemisdeterminedbythe knownsincethe19th century;however,underthestrong pressuredifference(i.e.perfusionpressure),hydraulic influenceofcellularpathologytheory,medicalscientists conductivityofthebloodvesselsandthefluidityofthe ignoredtheroleofbloodviscosityinflowthroughagiven blood.Thelast2factorscanbecombinedintoa vascularnetworkmainlyfor3reasons(3):1).Thefourth resistanceparameter(R),yieldingasimplerelationship powerfactorofthebloodvesselradiusdefinitely betweenperfusionpressure(∆P)andbloodflow(Q):∆P suppressedtheimportanceoftheviscosityfactorthatis =QxR.Inotherwords,bloodflowunderagiven representedbyapowerof1.2).Static,microscopic perfusionpressureisinverselyproportionaltohydraulic observationsofdead,fixedtissueshadlongbeentheonly 347 PathophysiologicalSignificanceofBloodRheology basisofmedicaldiagnosis,andfunctionalparameters,like RBCs,whichconstitute99%ofcellularelements(6,7). bloodviscosity,havebeenignoredforalongtime.3). WBCsandplateletsdonotplayasignificantrolein Theviscosityfactorwasconsideredaconstant,rather determiningthefluidityofbloodunderbulkflow thanavariableinthefamousPoiseuilleequation. conditions,becauseoftheirsmallernumber,butshould Despitetheeffortsofseveraldistinguishedmedical beconsideredwhenstudyingmicrocirculation(10). scientists(e.g.,RobinFahraeus)(4,5),theimportanceof TwospecialfeaturesofRBCsthatunderliethenon- bloodrheology(i.e.theflowpropertiesofblood)wasnot Newtonianrheologicalbehaviorarecellulardeformability appreciatedduringthefirst60yearsofthe20thcentury. andaggregation(11-14).Deformability(i.e.theabilityof theentirecelltoreversiblyadoptanewshapeinresponse todeformingforces)isauniqueproperty(13)andpartly Bloodrheologyasadeterminantofbloodflow contributestothethinningofbloodunderhighshear Theroleofbloodrheologyasadeterminantofblood conditions(9,14)bypromotingtheorientationofRBCs flowandtissueperfusionreceivedconsiderableattention totheflowstreamlinestherebyreducingthefriction withthedevelopmentofhemorheologicaltheoryafter betweenthem(Figure1).Aggregationdenotesthe the1960s.Boththebasicscienceandclinicalaspectsof formationofreversibleclumpsofRBCsundersufficiently thisrelationshiphavebeeninvestigatedextensively, lowshearstresses(15-17).Thisbehaviortendsto togetherwiththeuniquerheologicalbehaviorofblood. increasetheparticlesizeunderlowshearconditionsand Therheology(i.e.flowbehavior)ofafluidcan increasethedistortionoftheflowstreamlines(Figure1), physicallybedescribedbyitsviscosity.Inlaminarfluid andhencefrictionalresistancebetweenthem(11). flowasdescribedbyNewton(6),viscosityistheratioof Therefore,theeffectofRBCaggregationistoincrease theforcethatmovesthefluidlayersorlaminae(shear bloodviscosityundersmallershearforces,contributing stress)tothevelocitygradientinthefluid(shearrate), tothenon-Newtonianbehavior.Adetaileddescriptionof representinginternalresistancebetweenthelaminae themechanismsrelatedtoRBCdeformabilityand (6,7).Suchafluidflowcanbemodeledasflowstream- aggregationcanbefoundintheliterature(18-21);this linesmovingonasteadysurfaceor,morerealistically,as topicisoutsidethescopeofthisreview. concentriccylindersmovinginthedirectionofflowina Followingtheabovediscussion,itcanbestatedthat cylindricaltube(8). anyalterationsintheabove-mentionedparameters(e.g., Bloodisa2-phaseliquid.Itcanbeconsideredasolid- hematocrit,plasmaviscosity,RBCdeformabilityand liquidsuspensionifthecellularelements(redbloodcells aggregation)mayresultinalterationsofbloodflow (RBG),whitebloodcells(WBCs)andplatelets)are resistanceandtissueperfusion.Unfortunately,the regardedassolidparticles.Itcanalsobeconsidereda liquid-liquidemulsionbasedonthefluiddrop-like 100 behaviorofRBCsundercertainconditions(i.e.underhigh shearforces)(9).Therefore,dependingontheflow conditions,bloodtissuecanberegardedasasuspension oranemulsion.Thistransitionisoneofthemainreasons forthespecialrheologicalbehaviorofblood. 10 Bloodisanon-Newtonian,shearthinningfluid(7);its Viscosity(mPa.s) viscosityisnotconstant,evenwithunchanged composition,andvariesastheflowconditionschange. Bloodbecomesthinner(ormorefluid)astheshearforces 1 0.1 1 10 100 thatgenerateflowincrease.Thisisareversiblechange Shearrate(s-1) andbloodviscosityincreasesasshearforcesgetsmaller. Figure1. Shearrate-viscositycurveofnormalblood.RBC Theviscosityofbloodunderagivenshearstressis deformabilityreducestheresistancebetweenflowstream determinedbyhematocritvalue,plasmaviscosity(asthe linesathighershearrates,whiletheresistanceisincreased duetoincreasedRBCaggregation(henceincreasedparticle suspendingphase)andtherheologicalpropertiesof size)atlowershearrates. 348 O.K.BAfiKURT interactionbetweenbloodrheologyfactorsand RBCaggregationisdeterminedbybothplasmaand hemodynamicmechanismsarehighlycomplexandthe cellularfactors(17).Increasedplasmafibrinogen exactroleofbloodrheologyinphysiopathological concentrationisoneofthemaincausesofenhancedRBC processesisstilldebatable.However,thisuncertaintydid aggregation(16).Suchanalterationisacommon notpreventtheextensiveinvestigationof consequenceofacutephasereactionandaccompanies hemorheologicalparametersunderawidevarietyof mostinflammatoryprocessesyieldingenhancedRBC clinicalandexperimentalconditions. aggregation(30).Considerableevidencehasbeen accumulatedimplyingthatRBCsurfacepropertiesalso playsignificantroleintheaggregationprocess(17,31). Alterationsinbloodrheology Changesundertheinfluenceofmetabolicdisturbancesin Pathophysiology damagedtissues(e.g.,increasedproductionofoxidants) mayresultinalteredRBCaggregation(29). Hematocritvalueisadynamicparameterandmay varydependingonthefluidbalanceofthebody.Under variousphysiologicaland/orpathologicalconditions Clinicalconsiderations hematocritmayreachvalueshighenoughtoincrease Thepathophysiologicalconsiderationsaboveare bloodviscosityconsiderably(22).Plasmaviscosityisalso backedupbyahugenumberofclinicalobservationsthat sensitivetobothgeneralandlocalhomeostasis(23). canbeaccessedthroughspecificjournalsinthefield(e.g., RBCdeformabilityisdeterminedbythematerial Biorheology,ClinicalHemorheologyandMicrocirculation) properties,aswellasthemetabolicstatusofRBCs. andanumberoftextbooks(32,33).Mostofthese Variousgenetic,structuralalterationsinthecytoplasm observationsarebasedonthemeasurementof andmembraneleadtoalteredRBCdeformability hemorheologicalparametersinbloodsamplesoutsidethe (13,24).RBCdeformabilityalsodependsonintact vascularsystem(i.e.exvivo).Averybriefclassified metabolicpathwaysandanadequateATPsupplyto summaryofclinicalobservationsinimportantdisease supporttheiontransportsystems(25).Failureofthese categoriesispresentedbelow. systemswouldresultinincreasedintracellularsodium andcalciumconcentrations.Impairedsodiumexclusionis thecauseofalteredfluid-electrolytebalanceofthissimple Cardiovasculardiseases cellandisusuallyaccompaniedbyalterationsincellular Cardiovasculardiseasesareamongtheclinical volumeinmetabolicallydepletedRBCs.Anincreased conditionswithwellestablishedhemorheological cytosoliccalciumconcentrationhasbeenshowntobe consequences.Increasedbloodviscosity,impairedRBC relatedtoimpairedRBCdeformabilitybyaffectingthe deformabilityandincreasedRBCaggregationare RBCmembraneskeleton(26,27). reportedinavarietyofcardiovasculardiseases(32). Amongthese,peripheralvasculardiseasesarethemost Itshouldbenotedthatsuchametabolicdepletion