Iron Deficiency Vs Anemia Of Inflammation

[Galixie]

This is something I'm mildly curious about because I was just reading a thread about dizziness. I wasn't sure where to post this question. I'm not even sure exactly how to word this question.

 

I know celiac can cause iron deficiency because iron is just not getting absorbed. But I've also heard a few people mention having low iron that they can't seem to improve even after going gluten free. My question is: Do many celiacs suffer from Anemia of Inflammation (also known as Anemia of Chronic Disease)? The only way to know is to have complete iron panels done, rather than just serum iron levels. I'm sure that, for most people, a complete iron panel isn't ordered.

 

Unlike iron deficiency, anemia of inflammation is an immune system response. As I understand it, it can be triggered by an autoimmune condition such as celiac disease.

 

The book these excerpts are taken from is called Understanding Anemia by Ed Uthman, M.D. The following excerpts start at page 126 and relate to anemia of chronic disease (the italics are part of the original work):

 

"Briefly defined, anemia of chronic disease (ACD) is that anemia which accompanies general systemic illnesses, especially those characterized by inflammation. The underlying disease can be any from a long list of chronic ailments, including infections, collagen-vascular diseases (such as lupus and rheumatoid arthritis), and cancer (even though a cancerous tumor is not an inflammatory process, the body’s immune system may react to the tumor with some manifestations of the inflammatory response). Under our cytometric classification, ACD is a hyporegenerative normocytic/microcytic, normochromic/hypochromic anemia. This means that the reticulocyte count is low, the MCV is normal or low, and the MCHC is normal or low. Before going into more detail, let us consider the inflammatory response; for this we have to break away from our exclusive interest in the red cell and visit the even more complex world of the white cell.
White cells, or leukocytes, are the individual instruments in the great symphony that is the immune response. There are three major types of leukocytes involved in the inflammatory response, all of which not only circulate in the blood, but also reside and work in the solid tissues throughout the body. These major categories of white cells are neutrophils, monocytes, and lymphocytes.
Neutrophils, the most numerous of the circulating white cells, are considered the shock troops of the inflammatory response. When a microbial invader enters a normally sterile area of the body, millions of neutrophils accumulate at the site and attempt to destroy the invader by engulfing it and exposing it to an armamentarium of highly toxic substances. In the process of doing this, the neutrophils also fall victim to their own weapons. The innumerable dead neutrophils pile up and break down, to the point where their mass grave becomes visible to the naked eye as a creamy yellow material, called pus. One of the deadly chemicals produced by theses turned-on neutrophils before they die is an iron-containing substance called lactoferrin. When the inflammatory response is activated, neutrophils respond by markedly increasing their synthesis of lactoferrin and secreting it into the plasma (more on this later).
Monocytes, the least numerous of the three main leukocyte types, circulate around in the blood until they are needed at the battlefield to combat an unfriendly microbe. When they leave the circulation and enter the tissues, they transform into macrophages. (Remember from chapter 5 that macrophages are also a part of the reticuloendothelial system, charged with getting rid of aged red cells and readily scarfing up red cells coated with antibodies.) Macrophages are equally enthusiastic about engulfing and destroying infections agents, especially those that are coated with antibodies. Another function of macrophages is to take some of these engulfed organisms and “present” them to the cells that actually make the antibodies. You can think of the macrophage as the big goon who picks up the trouble-making punk by the collar, drags him before the local kingpin, Mr. Lymphocyte (see below), and then beats up his hapless victim at the behest of the boss.
Another function of macrophages in the marrow is to store iron and transfer it to developing red cell precursors for hemoglobin production. For the marrow macrophages to get their iron in the first place, they have to receive it from transferrin, the major iron transport protein in the blood. In conditions where the immune response is turned on, much of the lactoferrin produced by the neutrophils ends up going into the macrophages. Presumably this lactoferrin will be put to good use by the macrophages out on the battlefield, because lactoferrin is quite capable of killing bacteria. Back home in the marrow, however, the lactoferrin competes with transferrin for receptor sites on the macrophages. The iron in lactoferrin is not available for transfer to the developing red cells, so these go hungry, while more and more iron is piling up unused in the macrophages. The result is that, in ACD, the amount of storage iron is increased, but the transfer of that iron to erythroblasts is blocked. This explains why some cases of ACD resemble iron deficiency to the extent that the red cells are small and pale. In true iron deficiency anemia, of course, storage iron is absent. Because of the marked difference between iron deficiency and ACD in respect to the disposition of iron, evaluation of the amount of storage iron in a marrow biopsy can be a very valuable test in distinguishing between the two conditions.
Lymphocytes are the second most numerous of the three major types of white cells. They not only circulate in the blood but also reside in large numbers in so-called “lymphoid tissues” throughout the body. The classic example of lymphoid tissue is the lymph nodes, which are solid packages of lymphocytes. Other prominent areas of lymphoid tissue are found in the upper throat and digestive tract.
If the neutrophils and monocytes are the brawny enforcers in the war on microbes, then the lymphocytes are the brains. These little cells cannot engulf bacteria and other germs directly, but they can perform two other functions that are just as deadly. First, one class of lymphocytes, called B cells, can produce antibodies specific to the molecules sticking out on the surface of the invader. When functioning properly, these antibodies stick only onto those specific molecules that signify an enemy. Macrophages and neutrophils respond to the antibody tag by eating whatever the tag is attached to and leaving untagged cells alone. This is why the immune response can kill outsiders while leaving our own tissues untouched. The second deadly weapon at the lymphocyte’s command is the lymphokines, a motley assemblage of substances secreted by lymphocytes involved in the inflammatory/immune response. Lymphokines act as intermediaries among lymphocytes, variously hiking up and toning down inflammatory activity so as to meet infectious threats with measured response and minimal collateral damage. Several of these lymphokines have the property of being able to inhibit cell growth. The influence of these cells on erythroblasts is to make them less responsive to erythropoietin stimulation. The effects of this growth-inhibiting property of lymphokines are not limited to RBC precursors; other cells are similarly affected. For instance, during periods of acute or chronic inflammation, nails and hair also grow more slowly. Finally, some lymphokines inhibit the excretion of erythropoietin by the kidney, further enhancing the slowdown of red cell production.
As a result of the combined effect of these manifestations of the inflammatory response, anemia of chronic disease is characterized by:
(1) Accumulation of iron in macrophages, causing lack of iron for hemoglobin synthesis.
(2) Decreased responsiveness of red cells to erythropoietin stimulation.
(3) Decreased production of erythropoietin by the kidney.
From the above, it is easy to see how a hyporegenerative anemia can develop, and how such an anemia may impersonate iron deficiency by showing microcytosis and hypochromia. Another phenomenon reflecting the hoarding of iron by macrophages is that the serum iron level is typically low, as in iron deficiency. Unlike iron deficiency, which is characterized by a compensatory increase in transferrin in the serum, ACD is accompanied by a decrease in tranferrin (or, as is measured in many labs, total iron binding capacity, TIBC). The serum ferritin, which is an indirect reflection of body iron stores, is elevated as expected (cf. iron deficiency, in which ferritin is low).
The diagnosis of anemia of chronic disease is usually straightforward, but does require clinical judgement and a few strategically selected lab tests. Typically the patient has a history of some chronic disease. The hemoglobin is low, but usually above 10 grams per deciliter. The reticulocyte count is low. Serum iron and transferrin/TIBC are low, but ferritin is high. Rarely it may be necessary to perform a bone marrow biopsy to assess iron stores, but this is necessary only in complex or confusing cases (for instance, just because a patient has a chronic disease does not mean iron deficiency anemia could not also occur as the result of a bleeding ulcer or other significant abnormality).
A summary of typical lab test results in ACD is given in the following table. This should be compared with the similar table in chapter 3.

Test------------------------------Expected Result
hemoglobin-------------------------low
MCV---------------------------------normal or low
MCHC-------------------------------normal or low
serum iron -------------------------low
serum transferrin (or TIBC)------low
percent iron saturation-----------normal
serum ferritin----------------------high

Anemia of chronic disease is usually so mild that it does not require treatment. Cases severe enough to cause symptoms may respond to injections of recombinant erythropoietin. Doctors mainly need to know what not to do in treatment of ACD: blood transfusions should almost never be used, and oral or injectable iron should not be given."

 

I disagree a bit with the author about treatment. It is true that oral iron is pointless, but iron injections or infusions do work well. Open Original Shared Link

Here is the table from chapter 3 showing the typical results in iron deficiency anemia:

"Test---------------------Expected Result
hemoglobin------------------------low
MCV---------------------------------low (microcytic)
MCHC-------------------------------low (hypochromic)
serum iron -------------------------low
serum transferrin (or TIBC)------high
percent iron saturation-----------low
serum ferritin----------------------low"

 

I thought this information might be helpful, so I wanted to share it.

[cyclinglady]

Very interesting!  I always try to remind folks that you can have more than one type of anemia.  I had iron-defciency anemia due to celiac disease, but also have Thalassemia which is a genetic anemia (and will never go away!)  

[Galixie]

Yes, it's very true that anemias can co-exist. And, worse yet, if you have a microcytic anemia (like iron deficiency) at the same time as you have a macrocytic anemia (like B12 or folate deficiency) it can actually cause blood tests to show a false normal results. I had never even heard of false normal test results until I was pretty much in that situation. It's crazy. (And it also sucks because you have all these anemia-like symptoms and your doctors look at your blood tests and try to tell you it's all in your mind when it really isn't...)

 

I realize now that this topic should probably have gone under the 'related disorders' section. Maybe a moderator could move it?