Anemia of chronic disease

Definitions & Key takeaways

Anemia of chronic disease (ACD) is a form of anemia that occurs in people with chronic medical conditions such as cancer, autoimmune diseases, and certain infections. ACD is caused by the body's inflammatory response to chronic illness, which can lead to iron deficiency. Symptoms of ACD include fatigue, weakness, and shortness of breath.

Chapters:

Watch video only

Introduction0:00–0:37

Anemia of chronic disease refers to a low red blood cell or RBC 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 of 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 is the second most common type of iron deficiency anemia.
RBC S 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.

Physiology0:37–2:06

Taking a closer look at our RBC S. We can see they're loaded with millions of copies of the same exact protein called hemoglobin, which binds to oxygen and turns our RBC S 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 as fe two plus ions and then it's absorbed in the small intestine, specifically the duodenum inside the duodenal cells.
An enzyme called he festin oxidizes iron two plus to iron three plus ions. This form of iron binds 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.

Causes2:06–2:54

Now, the mechanisms that underlie anemia of chronic disease are complex and still under investigation in general, the disease mechanism is a twofold 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 tumor necrosis factor alpha and interferon gamma inhibit the production of erythropoietin in the kidney which subsequently prevents RBC production in the bone marrow.

Pathology2:54–4:08

Additionally, tumor necrosis factor alpha promotes RBC degradation in macrophages via phagocytosis. And interferon gamma 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 six 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 either being locked up in macrophages or unable to be absorbed fully productive hemoglobin laden RBC S can not be produced.

Symptoms4:08–4:22

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 three flights of stairs.

Diagnosis4:22–5:15

Anemia of chronic disease is usually discovered incidentally during the work up for a chronic disease process. A complete blood count usually shows mildly decreased hemoglobin, usually between 10 and 12 g 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.

Treatment5:15–5:57

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 g per deciliter transfusions with packed RBC S or erythropoietic agents like epoetin alpha or Darbepoetin alpha may be given to improve symptoms.

Summary5:57–6:26

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