chemical pathology: iron metabolism

Question 1

Where is iron stored

Answer 1

Spleen & liver

Question 2

What is the two functions of iron

Answer 2

1. Readily exchange electron: in cytochrome for oxidative phosphorylation for ATP production
2. Readily binds soluble gasses: oxygen

Question 3

How is iron absorbed

Answer 3

1. Iron is absorbed at proximal duodenum as Fe3+
2. Fe 3+ gets reduced to Fe2+ before taken up by DMT-1 to enter the enterocyte reduction reaction requires gastric acids or vitamin C
3. Once in enterocyte Fe2+ can be converted to ferritin & stored or transported via ferroportin out of the cell
4. Once in circulation converted back to Fe3+ via enzymes (hephaestin/caeruloplasmin) & binds to transferrin

Question 4

How is iron taken up by the cell

Answer 4

1. For a cell to be able to take up iron it requires a transferrin receptors
2. Iron is released inside the cell due to acidic environment, reduced & can be transported into cytoplasm via DMT-1
3. In cytoplasms it can be stored as ferritin or form heme in mitochondria

Question 5

How is iron recycled

Answer 5

Iron mostly comes from senescent RBC that are phagocytosed by macrophages in the spleen
Iron can be released, oxidised & picked up by transferrin or be stored in the macrophage

Question 6

What is the function of DMT-1

Answer 6

Transports iron from gut into cell in reduced form

Question 7

What is the function of ferroportin

Answer 7

Transport iron out the cell in reduced form

Question 8

What is the function of hephaestin

Answer 8

At the basolateral membrane of GIT cells to oxidise to ferric form to be carried by transferrin

Question 9

What is the function of caeruloplasmin

Answer 9

In circulation to oxidise iron to ferric form to be carried by transferrin

Question 10

What is the function of transferrin

Answer 10

Transports iron in the blood

Question 11

What is the function of transferrin receptors

Answer 11

On surface of cells to internalise iron bound to transferrin

Question 12

What inhibits ferroportin

Answer 12

Hepcidin

Question 13

What 2 factors increases transferrin

Answer 13

ID & high estrogen

Question 14

What 4 factors decrease transferrin

Answer 14

Chronic iron overload, inflammation, liver disease & protein losing states

Question 15

What is ferritin

Answer 15

Storage form of iron

Question 16

What is responsible for regulation of iron metabolism & uptake

Answer 16

Hepcidin

Question 17

What is the action of hepcidin

Answer 17

Block ferroportin that preventing iron transport, absorption or release from stores & decrease availability

Question 18

What two instances stimulate hepcidin action

Answer 18

Iron overload or inflammation

Question 19

What three things inhibits hepcidin action

Answer 19

Iron deficiency, hypoxia & erythropoeisis

Question 20

What is the gold standard for ferritin biochemical investigation

Answer 20

BMA

Question 21

What is two reasons for decreased s-iron levels

Answer 21

ID
Anemia of chronic disease

Question 22

What is a reason for increase s-iron levels

Answer 22

Iron overload

Question 23

What is two factors that influence s-iron

Answer 23

Diurnal rhythm (highest at morning)
Affected by diet

Question 24

What is a reason for decreased % saturation transferrin levels

Answer 24

ID

Question 25

What is a reasons for increased % saturation transferrin levels

Answer 25

Iron overload

Question 26

What is a reason for decreased s-ferritin levels

Answer 26

ID (DEFINITE DIAGNOSIS)

Question 27

What is three reasons for increased s-ferritin levels

Answer 27

Iron overload Inflammation Severe liver damage

Question 28

What is two reasons for increase s-soluble transferrin receptors levels

Answer 28

ID & erythropoiesis

Question 29

What is two reasons for primary chronic iron overload

Answer 29

1. **Genetic mutation:** unregulated iron uptake 2. **Abnormal hepcidin-ferroportin action:** increased uptake & accumulation

Question 30

What is two reasons for secondary chronic iron overload

Answer 30

1. **Iron loading anaemias:** ineffective erythropoiesis due to suppressed by hepcidin secretion (b-thalassemia) 2. **Transfusion iron overload**

Question 31

What is used to diagnose primary chronic iron overload

Answer 31

Liver biopsy, MRI & DNA testing

Question 32

What is the treatment for secondary chronic iron overload

Answer 32

Desferrioxamine (iron chelation therapy)

Question 33

How is iron overload excluded

Answer 33

Raised ferritin levels BUT normal s-transferrin

Question 34

What is the treatment for acute iron toxicity

Answer 34

Resuscitation & chelation with desferrioxamine

Question 35

Diagnosis table for different types

Answer 35

Table