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34 Cards in this Set
- Front
- Back
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Where does haem synthesis occur? |
Mi up to retic stage
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What does Fe2+ combine with to form haem?
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Protoporphyrin
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How many haems combine with each globin?
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One
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What type of anaemias result from abnormal Hb synthesis?
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Microcytic Hypochromic
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Source of iron?
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Non-haem: inorganic - nuts, fruit, Heam: organic - read meat, sea food |
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How is inorganic non-haem Fe absorbed?
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Via acidic duodenal active transport
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What are the two states for non-haem Fe absorption? |
Negative iron state- low hepcidin. Fe exported via ferroportin. Fe binds to transferrin (Fe-carrier). Positive ion state- enterocyte Fe is stored within ferritin and not transported. |
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How is organic haem-Fe absorbed?
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Jejunum (after duodenum so more alkaline) Haem-Fe from ingested Hb/myoglobin taken up by enterocytes by endocytosis Liberated from haem |
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Which factors favour the absorption of Fe?
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Fe2+ Inorganic iron Iron deficiency - negative Fe status Increased erythropoiesis Pregnancy - foetal priority |
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Which factors reduce the absorption of Fe?
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Fe3+ Organic iron (haem) Iron excess Decreased erythropoiesis Tea |
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How is iron transported?
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2 Fe3+ bound to transferrin (synth - liver) in portal blood 30% saturated |
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Which cells are rich in transferrin receptors?
What is the receptor? |
Erythroblasts (incorporate iron to Hb) Retics CD71 |
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How does Fe3+ enter cells?
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CD71-tranferrin is endocytosed Fuses with acid lysozyme freeing Fe3+ from transferrin |
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How does Fe2+ enter Mi?
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Mi iron importer - mitoferrin-1 Avoids oxidation of Fe2+ to highly toxic free-Fe3+ within oxygen-rich erythroblast/reticulocyte cytosol |
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How much Hb is synthesised a day? How much Fe is required for that? |
6g 20mg Fe |
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What is hepcidin? |
pp produced by liver cells Major hormonal regulatory of iron homeostasis Inhibits iron release from macrophages and intestinal epithelial cells by interaction with TM Fe exporter ferroportin Raised levels - reduce Fe absorption and Fe release from macrophages |
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How is iron stored? |
In macrophages as Fe3+ as ferritin and haemosiderin Regulated via iron regulatory protein (IRP) IRP normally binds & inhibits ferritin-mRNA - prevents transcription High Fe - comp inhibitor for IRP |
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How else is iron stored? |
Haemosiderin - BM Composed of protein and ferric oxide (Fe3+) Higher iron content than ferritin |
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What does RE stand for?
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Reticulo-endothelial cell
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What inhibits hepcidin?
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Cytokines - TFG-B - GDF-15 - growth differentiation factor. Downregs hepcidin and suppresses pro-inflammatory macrophage cytokines - TWSg1 HIF blocks hepcidin promoter |
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How is iron deficiency developed? |
First, BM stores depleted rbc production impaired - hypochromic, microcytic Last, tissue Fe depleted - liver, skin, skeletal muscles |
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What do lab tests for iron status show?
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Higher iron binding capacity and TIBC Fall in rbc vol and colour Fall in retics |
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Other than iron deficiency, what else causes an iron blockade?
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Chronic inflammation or malignancy
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What causes an iron blockade?
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Anaemia of Chronic disease (ACD) - related to severity of inflammatory/malignant disease Caused by: decreased Fe release from RE cells, hepcidin increased - impairs Fe release |
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What is the normal response to Fe-restricted anaemia?
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increase Fe absorption Increase storage release - low hepcidin Increase epo |
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Name two cytokines associated with infection, inflammation and malignancy? |
- stimulates hepcidin via JAK/STAT3 which binds and internalises ferroprotin IL6 IFN-y - downregs epo and activates macrophages |
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How does GDF-15 influence ACH? |
High concs: Downregs hepcidin - releasing Fe for haemopoiesis Low : attenuates macrophages Upregulated by IL6 |
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How is protoporphyrin produced?
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Condensation of glycin + succinyl CoA - Vit B6 coenzyme, stimulated by epo, inhibited by haem |
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Where is Haem mostly synthesised? |
Mi |
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What is the defect with sideoblastic anaemia? What is the cause? |
D-ALA synthetase is impaired X-linked but mostly acquired by drugs and heavy metals (Pb) |
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Where does globin synthesis occur? |
Ribosomes up to retic stage Hb A1 (adult) a2ß2 (95%) Hb A2 (adult) a2 d2 (3%) Hb F (foetal) a2 g2 (2%) |
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Why does foetal Hb have an increased O2 affinity? |
Foetal Hb gamma chains cannot bind 2,3,DPG |
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What is the result of thalassaemias? |
Reduced globin production Reduced a or ß chain production AND increased compensatory d andk../or g chain production |
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What are the features of hypochromic anaemia? |
Mean corpuscular volume and mean corpuscular Hb are reduced |
