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Old 07-16-2013
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RBC Why Increased Serum Iron Decreases TIBC?

How increase in serum iron :

Increase ferritin.
Decrease total iron binding capacity.
Decrease transferrin.
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Old 07-17-2013
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Is it really tough to answer this question?
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Originally Posted by medicalbiology View Post
How increase in serum iron :

Increase ferritin.
Decrease total iron binding capacity.
Decrease transferrin.
Ferritin goes up because its storage form, and if u have high fe ur body wants to store it. Tibc is going down because of the same reason. U have more than enough fe to use. U dont need them to bind.
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Old 07-18-2013
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Thanks but why TIBC is going down it should increase because more iron is avaialable
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Old 07-18-2013
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Tibc correlates with the concentration of transferrin. Increase ferritin stores causes decreased liver synthesis of transferrin-->decrease of transferrin~decrease of tibc in iron overlode

-goljan rapid review

I hope it helped u )
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Originally Posted by medicalbiology View Post
Thanks but why TIBC is going down it should increase because more iron is avaialable
TIBC is Transferrin. And Transferrin is TIBC. Both are 2 ways of describing the same thing.

Total Iron Binding Capacity, is the amount of Carrier protein you have, which can Bind Iron. And that is basically definition of what Transferrin is (a carrier protein for iron).
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As far as relationships go, just remember that Ferritin levels are inversely related to Transferrin (TIBC) levels.

And this makes sense, because if ferritin levels are high (meaning, you already have enough iron), then it tells your body "hey, I already have enough Iron, I don't need anymore"....so a signal gets sent to your Liver, telling it to stop making Transferrin (TIBC), so levels of Transferrin (TIBC) go down.

On the other hand, when you are short of iron, Ferritin levels (storage levels) will decrease. This tells your body "hey, I need more Iron"...so a signal gets sent to your liver, and tells it to make Transferrin (TIBC), so levels of Transferrin (TIBC) go up.
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I know this will help me too (b/c i also find this confusing at times), but I'm going to try summarize Goljan's notes here, to make this clear to myself, and hope it helps you too.

Serum Ferritin

First of all, Ferritin is a soluble iron-binding storage Protein. It is found in the Serum (so it can easily be measured). In addition, the same Protein is also synthesized by Macrophages in the Bone Marrow.

The great thing about Serum Ferritin, is that it's levels directly correlate with the Levels of Ferritin (i.e, Iron Stores) in the Macrophages.

For example, an increase in Serum Ferritin means that your body has 'increased levels of macrophage ferritin (inc. iron stores)', and a decrease in Serum Ferritin means that your body has 'decreased levels of macrophage ferritin' (dec. iron stores).

So to make a long story short: Serum Ferritin is an 'indicator' of iron stores in the body.

Serum Iron

Quite simply, this is the Iron that is bound to Transferrin. Note that normal Iron levels = 100 ug/Dl.

TIBC

This correlates directly with Transferrin. And it's logical. If you increase your capacity to bind Iron (Total Iron Binding Capacity), that means you increase Transferrin Levels - because that's what Transferrin does! - it increases your capacity to bind and transport Iron in the serum! So inc TIBC = inc Transferrin. Dec TIBC = dec Transferrin. Note that normal Transferrin levels = 300mg/dL.

Iron Saturation %

This is the percent of binding sites on transferrin, which is occupied by Iron. Given the normal parameters above (For Serum Iron, and Serum TIBC), it comes out to 100/300 = 33% (which is normal)

Once you have those concepts down, it's very easy to understand all the Iron studies without having to memorize which direction all those arrows go in (up or down).

Iron Deficiency Anemia

You're losing Iron from the body (so you have decreased Serum Iron), so it's only logical that you're iron stores are gonna go down too (Iron is not being sequestered and reused, instead, it's being lost by heavy menstrual bleeding, etc). So decreased iron stores, means Dec Ferritin Levels (Recall that Serum Ferritin correlates directly with iron stores...which is why a decreased Serum Ferritin is diagnostic for iron deficiency anemia) (the decreased Serum iron is an indicator that your serum iron stores are depleted - which is a hallmark of Iron Deficiency.

So now you have decreased ferritin stores in the macrophages. This will send a signal to your liver to 'make more transferrin'. Why? Because you need Iron! So Transferrin (TIBC) levels increase. (Note the inverse relationship between Ferritin and Transferrin (TIBC) levels - this relationship holds true for both ACD and Iron Overload too.

So you have decreased Serum iron, and Increased Transferrin (TIBC) levels, which is why you have a Decreased % Saturation in Iron deficiency anemia.

In Summary

Dec Serum Iron
Dec Ferritin
Inc Transferrin
Dec Iron Saturation

Anemia of Chronic Disease

This is anemia in the background of a Chronic Disease. Here's how it can be explained.

1) You get chronic inflammation
2) In response to this inflammation, liver releases Hepcidin (a peptide)
3) Hepcidin goes to Macrophages in bone marrow (it's site of action...
4) ...where it prevents the release of Iron from the Macrophages
In Summary: You do have Iron in the Macrophages, but it's being prevented from leaving...so that's why your serum Iron Levels drop. (but ferritin is high..can get in, but can't get out!!!)

Why does your body do this? Because it gets tricked into thinking, that the inflammation was caused by bacteria. And that's why the body responds by sequestering all that iron in the macrophages, by blocking its release. Because that way, the body tries to kill off the bacteria by not allowing it access to the iron.

So the sequence of events is this:

You will have dec Serum Iron (because macrophages don't release it onto transferrin). Increased Ferritin, (because iron can get in, but can't get out). Decreased Transferrin (TIBC) (because of the inverse relationship...if Ferritin is Increased, Transferrin (TIBC) must be decreased). Basically, the body sends a message "I have high ferritin...i don't need more...and liver responds by making less Transferring (dec TIBC). I know that both Serum Iron is decreased, AND Transferrin (TIBC) is decreased...and logically, you'd think that Iron Saturation would stay the same. But my goljan book says: Iron Saturation decreases too...so that just means Serum Iron decreases more than Transferrin does.

Summary:

Dec Serum Iron
Inc Ferritin
Dec Transferrin (TIBC)
Dec Iron Saturation

Iron Overload

I think this one is pretty simple to understand. Too much Iron (eg, blood multiple transfusions), so Increased Serum Iron...which leads to Increased Ferritin (because all that iron gets dumped into macrophages)...[i]remember the inverse relationship[/b]...if Ferritin is increased (sends a message to liver to stop making transferrin)...so decrease Transferrin (TIBC). Finally, if Serum iron is increased, and Transferrin (TIBC) is decreased, that means you have increased iron saturation of Transferrin

Summary:

Inc Serum Iron
Inc Ferritin
Dec Transferrin (TIBC)
Inc Percent Saturation

Last edited by ReggieMiller; 07-18-2013 at 11:30 AM.
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Old 07-18-2013
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Quote:
Originally Posted by ReggieMiller View Post
As far as relationships go, just remember that Ferritin levels are inversely related to Transferrin (TIBC) levels.

And this makes sense, because if ferritin levels are high (meaning, you already have enough iron), then it tells your body "hey, I already have enough Iron, I don't need anymore"....so a signal gets sent to your Liver, telling it to stop making Transferrin (TIBC), so levels of Transferrin (TIBC) go down.

On the other hand, when you are short of iron, Ferritin levels (storage levels) will decrease. This tells your body "hey, I need more Iron"...so a signal gets sent to your liver, and tells it to make Transferrin (TIBC), so levels of Transferrin (TIBC) go up.
For me the most confusing thing on this topic is ACD. I always forget why ferritin level is high. Everytime i read it again i think i will not forget this anymore
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Originally Posted by arazis View Post
For me the most confusing thing on this topic is ACD. I always forget why ferritin level is high. Everytime i read it again i think i will not forget this anymore
In ACD, you have to recall that the anemia is happening in a background of some sort of chronic inflammatory disease', e.g.. Rheumatoid Arthritis.

And an state of 'chronic inflammation' will increase hepcidin release from the liver. But the main point is this: Hepcidin acts on those Macrophages in the Bone marrow, and inhbits the iron transporters, so that the Iron can't get out! It's trapped!!

Reason it does this, I explained above. But that's why Ferritin levels are high. And that's the same reason why Transferrin levels are low.

Recall: high Ferritin tells your body it has enough Iron, so no need to make Transferrin. So Transferin decreases (which is what happens in ACD).
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Hepcidin Mechanism of action


Quote:
The 25-amino acid peptide of hepcidin is secreted by the liver and is considered the "master regulator" of iron metabolism. Hepcidin inhibits iron transport by binding to the iron export channel ferroportin, which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages). Inhibiting ferroportin prevents iron from being exported and the iron is sequestered in the cells.[7] By inhibiting ferroportin, hepcidin prevents enterocytes of the intestines from secreting iron into the hepatic portal system, thereby functionally reducing iron absorption. The iron release from macrophages is also prevented by ferroportin inhibition; therefore, the hepcidin maintains iron homeostasis. Hepcidin activity is also partially responsible for iron sequestration seen in anemia of chronic inflammation such as Inflammatory Bowel Disease, Chronic Heart Failure, Carcinomas, Rheumatoid Arthritis and renal failure.[8]
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