WELCOMETOHumanPhysiology(LECTURESESSION)Department of PhysiologyYangzhou University School of MedicineSpring2020
WELCOME TO Human Physiology (LECTURE SESSION) Department of Physiology Yangzhou University School of Medicine Spring 2020
RedBloodCells-deliveringO,viahemoglobin120day(human),40day(mouse)lifespan--2.4millionnewproducedpersecondStemcellCommittedcellDevelopmental pathwayPhase1Phase2iobinacoumulatosomesymhosHemonotnEathLateHemocytoblastProerythroblaserythroblastenythroblastReticulocyleErythrocyleProduction ofErythrocytes:Erythropoiesis1).Hemocytoblast stem cell2).Stemcellbecomescommitted3).Early erythroblasts have ribosomes4).Erythroblastsaccumulateironandhemoglobin5).Normoblasts ejectorganellesWhymatureRBCsfrombirds and chickens havenuclei?6).Released as erythrocyte
- delivering O2 via hemoglobin - 120 day (human), 40 day (mouse) lifespan - 2.4 million new produced per second Red Blood Cells Why mature RBCs from birds and chickens have nuclei?
Hemoglobin (Hb)Heme&Ironiron-containing oxygen-transport metalloprotein inthe red blood cellsCH.OCOONH.EMolecularStructureofHemoglobinβglobinchain02globinchainLOOCHCH.CHCactHemeDr.MaxHeme(a ringed moleculewith iron ion [Fe2+]inthecenter)Nobel PrizeforChemistry(1962)β2globin chainαglobinchain
Hemoglobin (Hb) Heme & Iron
Hemoglobin(Hb),Hemeand IronInmammals,theproteinmakesupabout97%of theredbloodcellsdry content, and around 35% of the total content (including water)Hemoglobinproteins4polypeptidechains&4-hemepigmentthatcontain ironO2WhyRBCsarered?bindingHb + O2 <>HbO2hemoglobin+oxygenoxyhemoglobin(darkred)(red)
Hemoglobin (Hb), Heme and Iron Why RBCs are red?
Beta-thalassemia:a GeneticAnemiaβ-Thalassemia ischaracterizedbythedeficientproductionof theβ-globinchains ofhemoglobin(Hb).Thistypicallyarises duetomutations intheβ-globingene.Over20o mutations havebeen identified in this geneandthetypeofmutationcaninfluencetheseverityofthedisease.Homozygous disorderβ-ThalassemiaSignificantimbalanceofa/β-globinchainsmajorSevereanemiapresenting earlyin lifeRequireslifelongRBCtransfusionsIfuntreated(i.e.noHSCTorsupportivecare)leadstodeathusuallyinfirstdecadeVariousgeneticinteractionsB-ThalassemiaGlobin-chainproductionmoderatelyimpairedintermedia-Mildanemia,diagnosed usually in late childhoodOccasionalbloodtransfusionsmayberequiredHeterozygousconditionβ-ThalassemiaAsymptomatictiedminorMayrequiregeneticcounsellingforlife
Beta-thalassemia: a Genetic Anemia
TransferrinandFerritinTf-FellgbindingtoTfR-Fe()Receptor-mediatedPlasmaTfR-(pH7.2)endocytosismembraneSOClathrin-coatedpitRecyclingendosomeSTEAPDMTOTFe(u)Fe0Oreln(pH5.5)Fe(ll)-VEndosomeTransferrin:proteinto caryFe3+Ferritin:Storagefor Fe2+老烩餐FeFe祥FeFeSTEAP3:anendosomalreductaseTFerritinHaemoglobinDMT1:divalentmetaltransporter-1NatureReviews|Molecular Cell Biology
Transferrin and Ferritin Transferrin: protein to carry Fe3+ Ferritin: Storage for Fe2+ STEAP3: an endosomal reductase DMT1: divalent metal transporter-1
Recycling the Components ofAgedorDamagedErythrocytesErythrocytes form in red bonemarrow.Erythrocytemembrane proteinsandglobinproteins are broken down into amino acids,someofwhichareused lomakenewerythrocytes.Erythrocytes circulate inbloodstreamfor120days.Hemecomponentsofbloodarerecycled.Heme(minus iron)(iron ions)HemeiscomvertedintobiliverdinandIronistransportedinthen tobilirubin.thebloodbytheproteinwhichissecretedtransteinand storedSpleenLiverinbilefromthe liver.bytheprotein ferritinin the liver.Agoderythrocytes are phagocytizedintheliverandspleen
DestructionofRBCsFe2+transported in circulationBONEOld,damagedRBCsengulfedbymacrophagesFe2+MARROWbytransferrinMACROPHAGE-AminoRBCacidsformationHemeBLOODPLASMANewRBCsBiliverdin120-dayRemainingironrecycledhemereleasedintoaveragecirculationlifespanBilirubin90%OldandMacrophages10%Becomebilirubindamagedin spleen, liver,HemolysisRBCSbonemarrow中具Goesto the liverKIDNEYS具HbBilirubinBilirubin secreted in bile (turnsbileyellow)BilirubinBilirubin-derived具productsLIVERBile enters the intestineAbsorbedintoExcretedEliminatedthe circulationinblleinurine果Bilirubin-derivedUrobilinsSMALLproductsStercobilinsBilirubinINTESTINEConverts to urobilinogenEliminatedLARGEINTESTINEinfecesExcretedinfeces(turnsfecesbrown)
Destruction of RBCs
FeedbackControlofRBCProductionSomestimulusdisruptshomeostasisbyLow O2Decreasing人Oxygendeliverytokid-neys (andothertissues)Kidneyreleases erythropoietin人ReceptorsKidneycellsdetectlowerythropoiesis in the red bone marrowoxygenlevelInputIncreased erythropoietinsecreted intobloodControl centerReturntohomeostasisRBCs are releasedProerythroblasts inwhenoxygendeliveryredbonemarrowtokidneysincreasesmaturemorequicklytonormalintoreticulocytesOutputMore reticulocytesentercirculating blood(100 to 120 days later)EffectorsLargernumberofRBCsin?circulationOld, damagedRBCs engulfed by macrophagesIncreasedoxygendeliverytotissues
Feedback Control of RBC Production
What Is Anemia?Anemiaisaconditionthatdevelopswhenyourbloodlacksenoughhealthyreobloodcellsorhemoglobin.Hemoglobinisamainpartof redbloodcellsandbinds oxygen.If youhavetoofeworabnormal redblood cells,oryourhemoglobinisabnormal orlow,thecellsinyourbodywill notgetenoughO21.RBCnumberandquality2.Hbnumberandquality3.OrbothRBCandHbThereare 4ootypesofanemia,butthemost commontypesare.Iron-deficiency anemia.Pernicious anemia·Aplasticanemia·Sickle Cellanemia.Trauma related anemia
1. RBC number and quality 2. Hb number and quality 3. Or both RBC and Hb