Iron, Transferrin & Alternative Measurements (University of Portsmouth) PDF

Iron, Transferrin & alternative measurements Gavin Knight  Learning Objectives Upon completion of this session, you should be able to: 1) Outline the basic process of iron absorption 2) Describe the role of transferrin in the transport of iron 3) Describe transferrin dependent measurements a...

Iron, Transferrin & alternative measurements Gavin Knight  Learning Objectives Upon completion of this session, you should be able to: 1) Outline the basic process of iron absorption 2) Describe the role of transferrin in the transport of iron 3) Describe transferrin dependent measurements and recognise the patterns of results associated with iron deficiency 4) Consider the contribution each test makes to the diagnosis or exclusion of iron deficiency Iron absorption & transport Iron absorption: Anatomy Iron is absorbed in the duodenum and proximal jejunum Iron must be in the ferrous state or bound by a protein such as haem The acidic environment of the proximal duodenum allows duodenal cytochrome B (Dcytb) - a ferric reductase enzyme - to convert the insoluble Fe3+ to absorbable Fe2+ Iron absorption: cell biology Iron is absorbed by the enterocyte via DMT1, stored as ferritin, or exported into the plasma by ferroportin Upon exit, Fe2+ is oxidised by the copper-dependent hephaestin or ceruloplasmin prior to binding to apotransferrin > holotransferrin Following internalisation of holotransferrin by target cells and introduction of H+, Fe3+ dissociates and is reduced by STEAP3 and transported to the cytoplasm by DMT1 Fe2+ is incorporated into protoporphyrin IX by ferrochelatase Transferrin cycle Apo-transferrin – iron free PLASM transferrin A Apo- Fe3+ Fe3+ Holo- Holo-transferrin – iron-bound transferrin transferrin transferrin Fe3+ Fe3+ Transferrin receptor CELL MEMBRANE CELL Fe2+ H+ H + Fe2+ H+ H+ H+ Fe3+ Fe3+ H+ ATPase Key measurements Serum iron This is not a valuable measurement in isolation Measures Fe3+ bound to transferrin Free iron is not measured Does not indicate if iron is bioavailable Subject to daily variation but will often be low in iron deficiency Is used to established Transferrin Saturation levels Transferrin Saturation (TSAT) Transferrin is a negative acute phase reactant The ratio of serum iron to transferrin (reported in %) Represents the proportion of serum transferrin binding sites occupied with iron molecules Requires serum iron measurements Diurnal fluctuations can be as large as 70% Malnutrition and chronic disease decrease transferrin synthesis TSAT of