Iron Metabolism - Goueli

Question 1

Iron deficiency in male or post-menopausal female. Look at?

Answer 1

GI tract for bleeding!

Don’t miss this!

Question 2

How is iron excreted?

Answer 2

NO physiologic pathway for excreting excess iron!

• Absorption is highly regulated so you don’t get too much
• Obligatory losses to to sloughing of cells in intestine, GU and skin.

Question 3

Major use of iron?

Answer 3

Making hemoglobin (Hgb)

Question 4

Transferrin?
Ferritin?
Hemosiderin?

Answer 4

Transferrin– transfers iron in blood
Ferritin- stores iron
Hemosiderin- long term storage

Question 5

Two forms of Iron:

1. Heme Iron (Fe2+)
2. Ferric Iron (Fe3+)

Answer 5

1. Heme Iron (Fe2+)= best absorbed. Get from meat.

2. Ferric Iron (Fe3+) = get from veggies. This doesn’t absorb as well so sometimes worry about vegan’s iron levels.

Question 6

Effect of acidic pH of stomach on iron?

Answer 6

Favors conversion of ferric (Fe3+) to ferrous (F2+) which is more soluble.

the better to absorbed version :)

Question 7

Effect of acidic pH of stomach on iron?

Answer 7

Favors conversion of ferric (Fe3+) to ferrous (F2+) which is more soluble.

the better to absorbed version :)

Question 8

DMT1

Answer 8

Transporter that brings Fe2+ iron into enterocyte

Question 9

Ferroportin

Answer 9

ONLY iron exporter we have.

Question 10

What form is needed to attach to transferrin?

Answer 10

Fe3+!

Haephestin converts Fe2+ –> Fe3+

Question 11

Keystone regulator of systemic iron homeostasis?

Answer 11

Hepcidin

Works by regulating ferroportin and controlling the release of iron from macrophages, enterocytes, and hepatocytes

-Binds to ferroportin and triggers its internalization and degradation in lysosomes.

Question 12

When is hepcidin produced?

Answer 12

In response to inflammation and increased iron stores.

Question 13

Excess hepcidin?

Answer 13

Anemia of Chronic Disease (AOCD)

Question 14

Hepcidin deficiency?

Answer 14

Iron Overload

Question 15

Hepcidin deficiency?

Answer 15

Iron Overload

Question 16

Pathway to hepcidin production?

Answer 16

1. Inflammation
2. cytokines –> activats JAK/STAT
3. Transcription of HAMP gene

OR

1. High transferrin saturation
2. HFE/TFR2 activate
3. increase HAMP gene expression to make more hepcidin

Question 17

Indirect indicators of Fe status

Answer 17

1. serum iron concentration
2. TIBC
3. Transferrin saturation
4. Serum ferritin

Question 18

Iron Deficiency Anemia:

Answer 18

Reticulocytes are NOT increased

Serum Test:
-reduced Fe, Tf Sat, Ferritin (makes sense- you don’t have much iron so you won’t be storing it and Tf wont get saturated)

Increased: TIBC, transferrin, transferrin receptors (b/c you want to increase the ability to transport the Fe that you have)

Question 19

Anemia of Chronic Disease (AOCD)

Answer 19

• Hypoproliferative anemia secondary to inflammation
• Iron stores increased, but decreased iron utilization (unavailable)
• IL’s induce hepcidin

Question 20

AOCD serum levels:

Answer 20

Low: serum iron, TIBC
Normal to elevated ferritin concentration

Normal transferrin receptors

Question 21

AOCD serum levels:

Answer 21

Low: serum iron, TIBC

Normal to elevated ferritin concentration

Normal transferrin receptors

Question 22

AOCD: MOA

Answer 22

Hepcytin binds ferroportin so iron can’t get out of cell.

Question 23

Mechanism of hemochromatosis:

Answer 23

Autosomal Recessive
-Cysteine to tyrosine sub at amino acid 282 (C282Y) == HFE gene mutation

Normally HFE interacts w/ TFR1/2 to regulate hepcidin expression.

Question 24

HFE gene mutation –>

Answer 24

Decreased hepcidin expression

• increased Fe absorption
• increased serum iron and Tf Sat
• decreased storage of iron in macs

Question 25

Triad of hemochromatosis

Answer 25

1. DM
2. Hepatomegaly
3. Hyperpigmentation

Question 26

Hemochromatosis serum levels

Answer 26

Elevated: serum iron, ferritin, Tf Sat (>45%)

Decreased: TIBC, Transferrin

Question 27

Therapies for hemochromatosis:

Answer 27

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