Anemia of chronic disease


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Anemia of chronic disease

Hematological system


Iron deficiency anemia



Sideroblastic anemia

Anemia of chronic disease

Lead poisoning

Hemolytic disease of the newborn

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Autoimmune hemolytic anemia

Pyruvate kinase deficiency

Paroxysmal nocturnal hemoglobinuria

Sickle cell disease (NORD)

Hereditary spherocytosis

Anemia of chronic disease

Aplastic anemia

Fanconi anemia

Megaloblastic anemia

Folate (Vitamin B9) deficiency

Vitamin B12 deficiency

Fanconi anemia

Diamond-Blackfan anemia

Heme synthesis disorders

Acute intermittent porphyria

Porphyria cutanea tarda

Lead poisoning

Coagulation disorders


Vitamin K deficiency

Platelet disorders

Bernard-Soulier syndrome

Glanzmann's thrombasthenia

Hemolytic-uremic syndrome

Immune thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Mixed platelet and coagulation disorders

Von Willebrand disease

Disseminated intravascular coagulation

Heparin-induced thrombocytopenia

Thrombosis syndromes (hypercoagulability)

Antithrombin III deficiency

Factor V Leiden

Protein C deficiency

Protein S deficiency

Antiphospholipid syndrome


Hodgkin lymphoma

Non-Hodgkin lymphoma


Chronic leukemia

Acute leukemia

Leukemoid reaction

Leukemoid reaction

Dysplastic and proliferative disorders

Myelodysplastic syndromes

Polycythemia vera (NORD)

Myelofibrosis (NORD)

Essential thrombocythemia (NORD)

Langerhans cell histiocytosis

Mastocytosis (NORD)

Plasma cell dyscrasias

Multiple myeloma

Monoclonal gammopathy of undetermined significance

Waldenstrom macroglobulinemia

Hematological system pathology review

Microcytic anemia: Pathology review

Non-hemolytic normocytic anemia: Pathology review

Intrinsic hemolytic normocytic anemia: Pathology review

Extrinsic hemolytic normocytic anemia: Pathology review

Macrocytic anemia: Pathology review

Heme synthesis disorders: Pathology review

Coagulation disorders: Pathology review

Platelet disorders: Pathology review

Mixed platelet and coagulation disorders: Pathology review

Thrombosis syndromes (hypercoagulability): Pathology review

Lymphomas: Pathology review

Leukemias: Pathology review

Plasma cell disorders: Pathology review

Myeloproliferative disorders: Pathology review


Anemia of chronic disease


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Anemia of chronic disease

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Anemia of chronic disease p. 429

rheumatoid arthritis p. 476

Erythropoietin (EPO)

anemia of chronic disease p. 429

Ferritin p. 211

anemia of chronic disease p. 429

Hepcidin p. 211

in anemia of chronic disease p. 429


anemia of chronic disease p. 429

Kidney disease

anemia of chronic disease and p. 429


anemia of chronic disease and p. 429

Rheumatoid arthritis p. 476

anemia of chronic disease and p. 429


anemia of chronic disease p. 429

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Content Reviewers

Viviana Popa, MD

Robyn Hughes, MScBMC


Sean Watts, MD

Evode Iradufasha, MD

Jung Hee Lee, MScBMC

Robyn Hughes, MScBMC

Evan Debevec-McKenney

Jake Ryan

Victoria Cumberbatch

Jennifer Montague, PhD

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 as Fe2+ ions, and then it’s absorbed in the small intestine - specifically, the duodenum. Inside the duodenal cells, an enzyme called hephaestin oxidizes Fe2+ to Fe3+ 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.

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.


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.


  1. "Anemia of Chronic Disease" New England Journal of Medicine (2005)
  2. "Robbins Basic Pathology" Elsevier (2017)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "Anemi ved kronisk sykdom" Tidsskrift for Den norske legeforening (2017)
  5. "Understanding anemia of chronic disease" Hematology (2015)
  6. "Anaemia of Chronic Disease: An In-Depth Review" Medical Principles and Practice (2016)
  7. "Hephaestin—a ferroxidase of cellular iron export" The International Journal of Biochemistry & Cell Biology (2005)
  8. "The exchange of Fe3+ between pyrophosphate and transferrin. Probing the nature of an intermediate complex with stopped flow kinetics, rapid multimixing, and electron paramagnetic resonance spectroscopy." Journal of Biological Chemistry (1986)

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