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34 Cards in this Set

  • Front
  • Back

Where does haem synthesis occur?

Mi up to retic stage

What does Fe2+ combine with to form haem?

How many haems combine with each globin?

What type of anaemias result from abnormal Hb synthesis?

Microcytic Hypochromic

Source of iron?

Non-haem: inorganic - nuts, fruit,

Heam: organic - read meat, sea food

How is inorganic non-haem Fe absorbed?
Via acidic duodenal active transport

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.

How is organic haem-Fe absorbed?

Jejunum (after duodenum so more alkaline)

Haem-Fe from ingested Hb/myoglobin taken up by enterocytes by endocytosis

Liberated from haem

Which factors favour the absorption of Fe?


Inorganic iron

Iron deficiency - negative Fe status

Increased erythropoiesis

Pregnancy - foetal priority

Which factors reduce the absorption of Fe?


Organic iron (haem)

Iron excess

Decreased erythropoiesis


How is iron transported?

2 Fe3+ bound to transferrin (synth - liver) in portal blood

30% saturated

Which cells are rich in transferrin receptors?

What is the receptor?

Erythroblasts (incorporate iron to Hb)



How does Fe3+ enter cells?

CD71-tranferrin is endocytosed

Fuses with acid lysozyme freeing Fe3+ from transferrin

How does Fe2+ enter Mi?

Mi iron importer - mitoferrin-1

Avoids oxidation of Fe2+ to highly toxic free-Fe3+ within oxygen-rich erythroblast/reticulocyte cytosol

How much Hb is synthesised a day?

How much Fe is required for that?


20mg Fe

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

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

How else is iron stored?

Haemosiderin - BM

Composed of protein and ferric oxide (Fe3+)

Higher iron content than ferritin

What does RE stand for?

Reticulo-endothelial cell
What inhibits hepcidin?

Cytokines - TFG-B

- GDF-15 - growth differentiation factor. Downregs hepcidin and suppresses pro-inflammatory macrophage cytokines

- TWSg1

HIF blocks hepcidin promoter

How is iron deficiency developed?

First, BM stores depleted

rbc production impaired - hypochromic, microcytic

Last, tissue Fe depleted - liver, skin, skeletal muscles

What do lab tests for iron status show?

Higher iron binding capacity and TIBC

Fall in rbc vol and colour

Fall in retics

Other than iron deficiency, what else causes an iron blockade?

Chronic inflammation or malignancy
What causes an iron blockade?

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

What is the normal response to Fe-restricted anaemia?

increase Fe absorption

Increase storage release - low hepcidin

Increase epo

Name two cytokines associated with infection, inflammation and malignancy?

- stimulates hepcidin via JAK/STAT3 which binds and internalises ferroprotin


IFN-y - downregs epo and activates macrophages

How does GDF-15 influence ACH?

High concs: Downregs hepcidin - releasing Fe for haemopoiesis

Low : attenuates macrophages

Upregulated by IL6

How is protoporphyrin produced?

Condensation of glycin + succinyl CoA

- Vit B6 coenzyme, stimulated by epo, inhibited by haem

Where is Haem mostly synthesised?


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)

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%)

Why does foetal Hb have an increased O2 affinity?

Foetal Hb gamma chains cannot bind 2,3,DPG

What is the result of thalassaemias?

Reduced globin production

Reduced a or ß chain production AND increased compensatory d andk../or g chain production

What are the features of hypochromic anaemia?

Mean corpuscular volume and mean corpuscular Hb are reduced