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Flashcards in Iron metabolism Deck (20):
1

Normal red cell Production requires 

  • Drive for erythropoiesis
    • Erythropoietin (kidney)
  • ‘Recipe’ for erythropoiesis
    • Genes
  • ‘Ingredients’ for erythropoiesis
    • Iron, B12, Folate, minerals
  • Functioning Bone Marrow
    • (No increased loss/destruction of red cells)

2

Normal haemoglobin is the balance between? 

Red cell productiona and red cell destruction/losss

3

Anaemia definition

too little blood, from reduced production or increased destruction 

4

Polycythaemia definition

Too much blood , increased red cell production, decreased destruction 

5

Major role of RBC 

  • CO2 removal 
  • o2 delivery from lungs to tissues 

6

CO2 removal involves? 

Renal tubules, lungs and RBCs 

7

O2 delivery is carried out by which molecule? and describe its structure 

Carried out by Haemoglobin  (Hb)

1 molecule Hb =

4 globin chains (2a,2b)
4 Haem groups (1/globin chain)

8

Total body content of iron

4g

9

how much iron is in the Bone marrow and RBC?

3g (of total 4g) 

10

how much iron is in the RES (reticuloendothelial system)? 

200-500mg 

11

how much iron is in myoglobin (muscle) 

200-300mg 

12

how much iron is in: 

  • enzymes (iron containing/haemcontaing) 
    • cytochromes 
    • peroxidases 
    • xanthine oxidase 
    • catalases 
    • RNA reductase 

100mg

13

What molecule transfers iron to the cells of the body and give features? 

Iron is transported to the cells of the body by Transferrin (Tf):

  • Glycoprotein
  • Synthesized in hepatocytes
    • When ↓Iron  liver↑ Tf
    • When ↑Iron liver ↓ Tf
  • 2 iron binding domains
  • 30% saturated with Fe
  • Tf delivers iron to all tissues, erythroblasts, hepatocytes, muscle etc

14

Erythroblast control of iron 

-transferrin iron accepted by erythroblast through transferrin receptor (TfR)
-predominantly engaged with taking iron and making haem
-majority of erythroblast iron will go to the mitochondria where it is used to synthesize haem
-In mitochondria the rate-limiting step involves aminolevulinic acid synthase (ALA-S2) to produce haem
-the rest of the erythroblast iron is stored as EB ferritin

In vtiro, feed erythroblasts radio labelled iron on transferrin, radioactive haem is synthesized within minutes 

A image thumb
15

What do macrophages of the RES do? 

  • Red cells last for 120 days, after which Macrophages of the RES digest
  • However, iron is recycled.
  • Red cells are ingested by macrophages:
  • Haem is broken down à bilirubin + iron,
    • iron is stored in RE cells  and offered to transferrin as required
    • Controlled by hepcidin
    • Bilirubin à transported to liver, conjugated and exrected in the bile
  • globin is broken down to à amino acids that return to the amino acid pool

16

Two forms of iron in the circulation? 

  • haem iron (easily absorbed) -> in red meat
  • non-haem iron (difficult to absorb) --> in white meat, green vegetables, cereals
    •  

17

The process of iron absorption 

  1. Absorption predominantly in duodenum
  2. Duodenal enterocytes responsible for iron and other nutrient absorption
  3. 25% of haem iron will be absorbed into the enterocytes without difficulty
  4. As more difficult to absorb, non haem iron released from foodstuffs by acid digestion and proteolytic enzymes in stomach
  5. non-haem iron must be reduced from the ferric to the ferrous form by duodenal cytochrome b1(dCytb1). This process is influenced by Vitamin C and alcohol

Route of haem Iron absorption:

  1. haem easily absorbed
  2. taken up by the enterocyte
  3. broken down by the enzyme haem oxygenase --> Fe2+

Route of Non-haem Iron:

  1. Non haem iron is reduced from the ferric to the ferrous from by duodenal cytochrome b1(dctb1)
  2. iron is taken into the enterocyte through the divalent metal transporter 1 (DMT1)
  3. DMT1 is an electro genic pump. Its expression is upregulated in iron deficiency

Iron can take many different routes once inside the enterocyte:

  1. Can transfer to mitochondria to form haem
  2. Storage form as ferritin
  3. Iron can be exported from the enterocyte to the circulating plasma through ferroportin

Ferroportin is a transmembrane protein which is also essential for the release of iron from macrophages

  • ferroportin is influenced by hormone hepcidin
  • once iron is getting through the enterocyte it must be oxidised to the ferrate form (Fe3+) and bound to transferrin for transport through the plasma 

A image thumb
18

RES and recycling 

  • effete red blood cells are removed by the macrophages of the RES (RBC lifespan =120days)
  • The RES stores around 500mg of iron
  • RES iron is stored in ferritin/haemosiderin
  • RES releases iron to Tf in plasma
  • Tf-Iron take up via Tf receptors on erythroblasts, hepatocytes etc

19

Role of hepcidin in iron metabolism?

  • Hepcidin is the most important influence of iron metabolism
  • It is the “low iron” hormone; it reduces the levels of iron in plasma
  • Hepcidin binds ferroportin and degrades it –reducing iron absorption (enterocyte) and decreasing iron release from the RES
  • Hepcidin is synthesized in the liver (this requires expression of HFE)

20