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Anemia of chronic disease

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Try it free today! Anemia of chronic disease refers to a low
red blood cell, or RBC, count that may be associated with many chronic disease states
like infections, malignancy, diabetes, or autoimmune disorders. The disease used to
be called anemia of chronic inflammation because the underlying cause anemia is the continuous
inflammation generated by chronic disease, which impairs iron metabolism and, in turn,
RBC production. The anemia itself is usually mild and it’s the second most common type
of iron deficiency anemia. RBCs are produced in the bone marrow, in response
to erythropoietin – which is a molecule secreted by the kidneys in response to low levels of
oxygen in the blood. Taking a closer look at our RBCs, we can see they’re loaded with
millions of copies of the same exact protein called hemoglobin, which binds to oxygen and
turns our RBCs into little oxygen transporters that move oxygen to all the tissues in our
body. Zooming in even closer, each hemoglobin molecule is made up of four smaller heme molecules,
which have iron right in the middle. Oxygen binds to the iron, so each hemoglobin molecule
can bind four molecules of oxygen. In addition, iron is also an important part of proteins
like myoglobin, which delivers and stores oxygen in muscles; and mitochondrial enzymes
like cytochrome oxidase, which help generate ATP. Now, we get the iron required for RBC production
from our diet. Following breakdown of food in the stomach, iron is released, and then
it’s absorbed in the small intestine – specifically, the duodenum. Inside the duodenal cells, iron
molecules bind to a protein called ferritin, which temporarily stores the iron. When iron
is needed in the body, some iron molecules are released from ferritin and transported
into the blood, where they bind to an iron transport protein called transferrin that
carries iron to various target tissues and releases them there. Now, the mechanisms that underlie anemia of
chronic disease are complex and still under investigation. In general, the disease mechanism
is a two fold process; decreased RBC lifespan and decreased RBC production. Shortened RBC lifespan is a result of direct
cellular destruction via toxins from cancer cells, viruses, or bacterial infections. Decreased
RBC production is a bit more complex and involves several mechanisms. The most important one, and the one that most
researchers agree upon, involves dysregulation of iron homeostasis and the signals that control
RBC production. In chronic disease states, chemical messengers called cytokines mediate
this pathologic process in the kidney, immune system, and the GI tract. Two cytokines called TNF-a and IFN-y inhibit
the production of erythropoietin in the kidney, which subsequently prevents RBC production
in the bone marrow. Additionally, TNF-a promotes RBC degradation in macrophages via phagocytosis,
and IF-Y increases the expression of a protein channel called divalent metal transporter
one on the surface of macrophages. This channel serves as a pathway for iron to enter the
macrophage at increased rates, so less iron is available for the production of hemoglobin. Another cytokine called IL-10 mediates the
expression of increased ferritin receptors on the surface of macrophages, which then
sequesters even more iron. Finally, IL-6 also works in the liver by increasing
production of a molecule called hepcidin, which blocks further uptake of iron from the
small intestine. The culmination of all these processes results
in inadequate iron available for the production of hemoglobin. So with iron either being locked
up in macrophages, or unable to be absorbed, fully productive hemoglobin laden RBCs cannot
be produced. Symptoms of anemia of chronic disease are
usually mild, including fatigue, pallor, and shortness of breath – and the latter is usually
associated with physical activity, like walking up 3 flights of stairs. Anemia of chronic disease is usually discovered
incidentally, during the workup for the chronic disease process. A complete blood count usually
shows mildly decreased hemoglobin, usually between 10 and 12 grams per deciliter. Initially,
the anemia is normocytic, which means that RBCs have a normal size, but eventually it
can become microcytic, meaning RBCs get smaller. Iron studies show low serum iron levels, normal
to low serum iron transferrin or total iron binding capacity, low transferrin saturation,
and normal or increased serum ferritin levels. Hepcidin levels are also usually elevated,
although assays to detect hepcidin levels are not widely available. Bone marrow examination,
while not routinely performed in the assessment of anemia of chronic disease can demonstrate
macrophages with increased iron stores and erythroid precursor cells. Treatment of anemia of chronic disease requires
correcting the underlying problem or disease process. For example, if the anemia is due
to an infection, appropriate treatment with antibiotics may be necessary. If a person
has a tumor, surgical removal of the tumor may lead to resolution of the anemia. Similarly
if the anemia is due to diabetes, improved blood glucose control may result in an improvement
in the anemia. Intravenous iron therapy can sometimes be
useful, and when hemoglobin levels fall below 7 grams per deciliter, transfusions with packed
RBCs, or erythropoietic agents like epoetin alfa or darbepoetin alfa may be given to improve
symptoms. All right, as a quick recap, anemia of chronic
disease occurs in the context of chronic disease states like infections, malignancy, diabetes
and autoimmune conditions. The mechanism of disease is largely mediated by inflammatory
factors including hepcidin. Treatment involves correcting the underlying condition, or, in
severe cases, RBC transfusions or erythropoietin injections.

7 thoughts on “Anemia of chronic disease

  1. Hello I'm your subscriber from SOMALIA

    I really really like your videos, I understand easily❤ thank you OSMOSIS ORG

  2. Thank you for a very good video. Just small note: TNF-alfa and IFN-gamma is blocking EPO, and thereby blocking the production of RBC, just as you say in the video. But just looking at the screen, it looks like there is a blocking-blocking mechanism. Better of by drawing an arrow which indicates that EPO is stimulating production and then making a red cross over that "stimulating arrow" .

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