IRON Metabolism Flashcards Preview

IHO Week 1 > IRON Metabolism > Flashcards

Flashcards in IRON Metabolism Deck (31):
1

In post-menopausal female or male, if they have iron deficiency with no obvious cause. . .

. . you HAVE to look in the GI tract - must send to colonoscopy and not miss a GI bleed!

2

What is the mechanism by which anemia of chronic disease works?

-There is too much hepcidin
-Bioavailability is the issue

3

What is ferritin?

Your storage iron

4

What is the concept of heme iron and ferric iron in iron absorption (why vegetarians don't absorb as well)?

-Dietary iron is present in two forms in the diet
-Heme iron (hemoglobin and myoglobin in beef, chicken, fish, etc.) = best absorbed [O2 binds Fe2+ better- ferrous]
-Non-heme iron/Fe3+ (cereal, vegetables) = taken up less avidly
-Greater than 1/3 of iron is from fortification of flour

5

Hepatocyte?

-Master regulator

6

Hepatocyte?

-Master regulator via its production of hepcidin
-Hepcidin is the keystone regulator of systemic iron homeostasis

7

What is Hepcidin?

-Master regulator of systemic iron homeostasis
-25 AA polypeptide produced in response to inflammation (AOCD, IL6) and increased iron stores
-Binds to ferroportin and triggers its internalization and degradation to lysosomes
-Decreases Fe release from macrophages, enterocytes, and hapatocytes
-Results in increased IC iron

8

What does Hepcidin deficiency cause?

Iron overload

9

What does excess hepcidin cause?

AOCD

10

What happens in iron overload?

1. When a lot of iron is around, transferrin saturation is high
2. Hepcidin will then be generated
3. Hepcidin will bind the enterocyte in the liver - this doesn't allow for the release of iron at the enterocyte.
4. No absorption occurs and no iron gets into the circulation!

11

What happens in the body when you have excess iron?

More hepcidin is produced!
-Hepcidin binds to duodenal enterocytes and triggers their degradation

12

When there is high iron, transferrin saturation is ____. When there is low iron, transferrin saturation is ___.

high, low

13

When transferrin saturation is low. . .

. . .the cell does not make hepcidin.

14

What is the primary therapy for hemochromatosis?

Hemachromatosis = too much iron and the number one way to get rid of it = REMOVING BLOOD FROM PATIENT

15

Increase in transferrin saturation signals to hepatocytes to increase hepcidin expression via . . .

a HFE and TfR2 dependent manner.

16

What is TIBC?

Total iron binding capacity - number of iron binding sites on transferrin molecules - serum transferrin concentration

17

What iron indices are found in iron deficiency?

Decreased Serum iron
Increased TIBC
Decreased Transferrin saturation
Decreased Ferritin

18

What iron indices are found in anemia of chronic disease?

Decreased Serum Iron
Decreased TIBC
Decreased Transferrin saturation
Increased Ferritin (optional)

19

What iron indices are found in hemochromatosis?

Increased Serum Iron
Decreased TIBC
Increased Transferrin saturation
Increased Ferratin

20

When you have low iron. . .

. . .body increases transferrin!

21

What is the mechanism by which anemia of chronic disease works?

-Increased inflammatory cytokines (IL-6, IL-1B, etc.) induce hepcidin
-There is too much hepcidin
-Bioavailability is the issue

22

AOCD Dx

-Chronic inflammatory process
--Increased ESR, CRP
--Look at other acute phase reactants (reduced albumin, transferrin)

23

What is the treatment for hemochromatosis?

Phlebotomy!

24

What is the mechanism for which HFE mutations cause hemochromatosis?

HFE is a transmembrane protein that regulated hepcidin expression.
-Mutation results in lack of interaction of HFE with TFR2 and reduced cell surface expression

25

What is the mechanism for which HFE mutations cause hemochromatosis?

HFE is a transmembrane protein that regulates hepcidin expression.
-Mutation results in lack of interaction of HFE with TFR2 and reduced cell surface expression:
--Decreased hepcidin expression
--Increased FE absorption
--Increased serum iron and Tf Sat
-Decreased storage of iron in macrophages

26

What is hereditary hemochromatosis?

-HH, or primary iron overload is a collective label for a group of autosomal inherited iron overload disorders
-Hereditary conditions affecting the hepcidin/ferroportin access

27

What is type I hereditary hemochromatosis?

Classical HFE gene mutations resulting in cysteine-to-tyrosine substitution at amino acid 282 (C282Y) or an aspartate-to-histidine substitution at amino acid 63 (H63D)

28

What is HFE?

A transmembrane protein belonging to MHC Class I and expressed at high levels in the liver

29

What does hereditary hemachromatosis cause?

-Sever symptoms not usually seen until decades or iron loading have passed
-Classic triad
---DM
---Hepatomegaly
---Hyperpigmentation
-Death from cirrhosis, hepatocellular carcinoma, or CHF
-Goal is to make dx and tx in pre symptomatic stage

30

What does hereditary hemachromatosis cause?

-Sever symptoms not usually seen until decades or iron loading have passed
-Classic triad
---DM
---Hepatomegaly
---Hyperpigmentation
-Death from cirrhosis, hepatocellular carcinoma, or CHF
-Goal is to make dx and tx in pre symptomatic stage
-Normal life expectancy if phlebotomy caught before DM or cirrhosis

31

HFE Genetic Defect:

-Penetrance C282Y/C282Y incomplete
---Elevated serum ferritin in