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