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1、MEGALOBLASTIC ANEMIA,MARROW FAILURE,Metabolically highly active,2 to rapid cell turnoverWhite cell life span 12-24 hoursPlatelet life span 7 daysRed blood cell lifespan 120 daysAny slowing of DNA production marrow failure,MEGALOBLASTIC ANEMIA,Hemoglobin production probably normalDefect in nuclear re
2、plication&divisionAffects all marrow elements,MEGALOBLASTIC ANEMIA,Trademark cell:Oval macrocyte,(MCV 100 fl)Hypersegmented neutrophils-98%Pancytopenia,esp if anemia severeReticulocytopeniaLDH elevated(90%)Serum Fe normal or elevatedSerum B12 or folate lowMarrow classic megaloblastic changes,FOLIC A
3、CID,OH,N,N,N,N,NH,CONH,COCH2CH2CHCOOH,(GLU)n,Pteridine,PABA,Glutamic Acids,H2N,1,2,3,4,5,6,7,8,9,10,FOLIC ACID,OH,N,NH,N,N,NH,CONH,COCH2CH2CHCOOH,(GLU)n,H2N,1,2,3,4,5,6,7,8,9,10,NH,NH,FOLIC ACIDOne Carbon Fragment Forms,NH,NH,CH2,N5,10 methylene THF,Thymidylatebiosynthesis,NH,NH2,CH3,N5 methyl THF,T
4、ransport,N,NH,NH,NH,CH,HC O,N5,10-methenyl THF,N10-formyl THF,H2O,Purine biosynthesis,FOLATE ABSORPTION,FOLATE DEFICIENCYCauses,Folate-poor dietAlcoholismSevere povertyIncreased folate requirementPregnancySevere hemolytic anemiaSevere PsoriasisDrug therapyMalabsorptionTropical sprue,FOLATE DEFICIENC
5、YManifestations,Megaloblastic anemiaGlossitis/stomatitisGI malabsorption 2 to impaired GI epithelium(rare),COBALAMIN(Vitamin B12)Functions,Folate metabolism-Required for demethylation of methyl-THFMethylation of myelinConversion of methylmalonyl CoAto succinyl CoA,COBALAMINStructure,-groupsCN-Cyano;
6、inactiveOH-Hydroxyl;inactiveMethyl-Folate metabolismAdenosyl-Mutase activity,COBALAMIN REACTIONS,NH,NH,CH3,THF,Homocysteine,Methionine,MethylCobalamin,Methylmalonyl CoA,Succinyl CoA,AdenosylCobalamin,GI ABSORPTION OF COBALAMIN,COBALAMIN DEFICIENCYCauses,Gastric FailurePernicious AnemiaTotal gastrect
7、omyIleal FailureRegional enteritis(Crohns disease)Ileal resectionTropical sprueCompeting organismsBacterial overgrowth(Blind loop)Diphyllobothrium latum,PERNICIOUS ANEMIA,Autoimmune destruction of parietal cellsAntibodies vs.parietal cells,intrinsic factorAchlorhydria is universalIncreased incidence
8、 of gastric cancerIncreased incidence American blacks,northern EuropeansOften associated with other immune diseases(eg Hashimotos thyroiditis),COBALAMIN DEFICIENCYPeripheral Folate Depletion,N5-methyl-THF,N5-methyl-THF,THF,Conjugated folates,THF,Cbl,Homocysteine,Methionine,COBALAMIN DEFICIENCYPeriph
9、eral Manifestations,Megaloblastic anemia-Indistinguishablefrom folate deficiency DONT DO THIS!,COBALAMIN DEFICIENCYManifestations-Central,Both brain and spinal cordBrain:DementiaPsychological disturbancesSpinal cord:Demyelinating diseaseLoss of posterior&lateral columns-hence name Combined system di
10、seaseNeurologic disease stabilized with treatment,but usually not reversedTreatment with folate does nothing for neurologic disease,SUBACUTE COMBINED DEGENERATION,COBALAMIN DEFICIENCYUsual Sequence of Events,Serum homocysteine neutrophil hypersegmentationMCV rises above normalAnemiaSymptoms,FOLATE/C
11、OBALAMINProperties,MEGALOBLASTIC ANEMIA Diagnosis/Therapy,Draw levels at first suspicion of problem,BEFORE ANY THERAPYOnce levels drawn,begin treatment with both B12 and folateOnce levels are back,can stop the normal vitaminTransfusions to be avoided unless hemodynamic compromise is present,or patie
12、nt having angina,MEGALOBLASTIC ANEMIAResponse to Therapy,SCHILLING TEST,MEGALOBLASTIC ANEMIASSummary,Deficiency in folate or B12Macrocytic anemia;other cytopeniasSlowly developing anemia,usually wellcompensatedResponse to therapy rapid and dramaticTreatment essential to avoid other complicationsAnemia is secondary to an underlying disease process,
