82-85. Iron metabolism

Question 1

What is the total body content of iron?

Answer 1

4g

Question 2

What two intracellular proteins are responsible for the storage of iron?

Answer 2

Ferritin (soluble)
- readily available from RES
- tiny amount in serum in proportion to amounts in RES
Haemosiderin (insoluble conglomerates of ferritin)
- iron only slowly available

Question 3

In what conditions would serum ferritin:

a) Decrease
b) increase

Answer 3

a) Iron deficiency anaemia
b) iron overload

Ferritin is also an acute phase protein which is raised in response to damage/infection/inflammation

Question 4

What is responsible for the transport of iron?

Answer 4

Transferrin (Tf) - a glycoprotein synthesised by hepatocytes with two iron binding domains
- is 30% saturated with Fe

Synthesis of transferrin increases with lowered iron levels

Question 5

How many mg of iron are lost during menstruation?

Answer 5

1-2mg/day

Question 6

What is the daily need of iron?

What is the average intake of iron in the Western diet?

Answer 6

1-2mg/d
15-20mg/d

Therefore iron deficiency anaemia is very rare in adults

Question 7

What are the dietary sources for:

a) Haem iron
b) non-haem iron

Answer 7

a) Red meat

b) White meat, green vegetables, cereal

Question 8

Why is regulation of iron absorption important?

Answer 8

It’s the single physical mechanism for maintaining our iron balance - there is no excretory mechanism

Question 9

Where is most iron absorbed?

Answer 9

Duodenum (duodenal enterocytes)

Question 10

How is non-haem iron released from food?

Answer 10

By acid digestion and proteolytic enzymes in stomach

Question 11

What is the role of duodenal cytochrome b1 (dCytb1)?

What is the process influenced by?

Answer 11

Reduced non-haem iron from the ferric to the ferrous form

Vitamin C

Question 12

What is the role of divalent metal transporter 1 (DMT1)?

Answer 12

Allows iron (Fe2+) to be taken up into the cell

Question 13

What is DMT1 and what causes it’s expression to be upregulated?

Answer 13

Divalent metal transporter 1 is an electrogenic pump. It’s expression is upregulated by iron deficiency

Question 14

Iron is transported from the enterocyte to the circulating plasma through _______ and _______

Answer 14

ferroportin; hepcidin

Question 15

What is ferroportin?

Answer 15

A transmembrane protien which is also responsible for the release of iron from macrophages

Question 16

What is the most important regulator or GI absorption and RES release?

Answer 16

the interaction between ferroportin and hepcidin

Question 17

Describe RES iron uptake, storage and release and then recycled

Answer 17

RES macrophages acquire iron from effete RBCs with the breakdown of haem into iron and bilirubin

Iron is stored in RES macrophages as ferritin (stores around 500mg)

Iron release from RES macrophages is regulated by ferroportin and hepcidin
RES released iron to transferrin in plasma - iron in plasma transported by transferrin

Tf-iron taken up via Tf receptors on erythroblasts (80% of Tf receptors), hepatocytes etc

Question 18

Where is transferrin synthesised? How many binding sites does it have for iron?

Answer 18

Liver; 2

Question 19

How much iron is bound to transferrin per day? How much iron can be transported by transferrin at any one time?

Answer 19

50mg/day; 4mg at any one time

Question 20

When Tf-iron enters an erythroblast, what are it’s two possible fates?

Answer 20

Enters mitochondria to be a component of haem (by ALA-S2)
OR
Stored in erythroblast as ferrin

Question 21

True or false: Hb can reversibly bind to O2 without being oxidised or reduced.

Answer 21

True

Question 22

What is the golden rule with patients who have iron deficiency anaemia?

Answer 22

In males and post-menopausal women, IDA is caused by GI blood loss until proven otherwise

In young women; caused by menstrual blood loss and/or pregnancy

(GI investigations should only be carried out with GI symptoms or blood in stool)

Question 23

Define haematinic

Answer 23

The general term for the nutrients required for the production of RBCs in bone marrow (iron, bit B12, folic acid)

Question 24

What are the three haematinic deficiencies possible in coeliac disease (list from most likely to least likely)

Answer 24

1. Folate deficiency (in green veg, orange juice, liver)
2. Iron deficiency (in haem and non-haem)
3. Vitamin B12 deficiency (meat & dairy)

Question 25

What are the signs of hyposplenism in coeliac disease on a blood film?

Answer 25

Target cells, Howell-Jolly bodies (nucleated RBC), irregular RBC count

Question 26

Hepcidin is the most important influence on iron metabolism. Where is it produced, and what is it’s role?

Answer 26

Produced in the liver.
Role is to reduce the iron content in the circulation
Does this by binding to and degrading ferroportin to reduce the GI absorption of iron and reducing macrophage release of iron from RES

Question 27

What is required for the synthesis of hepcidin?

Answer 27

HFE (human haemochromatosis protein)/ High iron Fe

Question 28

Hepcidin loss causes…..

Answer 28

Increased GI absorption of iron and increased RES iron release
Increased Tf% saturation parenchymal overload (HH)

Question 29

What is hereditary haemochromatosis and what causes it?

Answer 29

An autosomal recessive disorder causing iron overload

Caused by abnormalities of the HFE gene (most cases)

Question 30

What is the most common mutation of the HFE gene?

Answer 30

homozygous C282Y

Question 31

How does a mutation of the HFE gene cause HH?

Answer 31

Reduction in the production of hepcidin

Question 32

How does iron overload affect the:

a) liver
b) pancreas
c) joints
d) skin

Answer 32

a) Cirrhosis
b) Diabetes
c) arthritis (of the 3rd metacarpophalangeal joint)
d) Bronzing

Question 33

What is restrictive cardiomyopathy?

Answer 33

Walls of ventricles become stiff but not necessarily thickened

Question 34

How can HHC be treated?

Answer 34

Venesection - initially up to weekly (500ml whole blood gives 250mg iron)

Monitor ferritin and transferrin saturation

Prevent/limit organ damage

Question 35

What is the total body iron in someone with HHC?

Answer 35

20g