Pathophysiology
Summary
Iron deficiency anemia (IDA) is a prevalent form of anemia originating from insufficient iron stores. Iron is predominantly absorbed in the duodenum and retained in duodenal enterocytes as ferritin. It is transported into the circulation via the ferroportin channel and associates with transferrin for tissue distribution. Iron is also stored within macrophages as ferritin, mainly in the bone marrow. Serum ferritin levels reflect the total amount of stored ferritin and act as a surrogate marker for iron reserves. When iron stores are sufficient, the liver secretes hepcidin, which degrades ferroportin channels, inhibiting iron release from both enterocytes and macrophages.
IDA can result from various factors including a vegetarian diet, heavy menstrual bleeding, pregnancy, delivery, & lactation, as well as from GI conditions like GI cancers, benign hamartomatous polyps, erosive gastritis, & gastric ulcers. Parasitic infections like hookworms & whipworms can cause IDA through chronic blood loss. Additionally, chronic atrophic gastritis—both H. pylori-related and autoimmune—and celiac disease impair iron absorption and can induce IDA. Symptoms manifest only after bone marrow ferritin is depleted, leading to reduced hemoglobin levels and consequent anemia.
Initially, IDA is a normocytic anemia but becomes a microcytic anemia as it progresses. Lab markers include low ferritin in both bone marrow and serum, increased transferrin, and low transferrin saturation, leading to increased TIBC. Clinical signs include fatigue, skin pallor, and a hyperdynamic state manifested as tachycardia and palpitations in severe cases. IDA can also cause Plummer-Vinson syndrome (dysphagia, esophageal webs, iron deficiency), atrophic glossitis , angular cheilitis, koilonychia, and pagophagia.
In contrast, anemia of chronic disease (ACD) is principally driven by inflammation. Elevated cytokine levels, such as IL-6, induce the release of hepcidin from hepatocytes, resulting in intracellular iron sequestration, particularly within bone marrow macrophages. Consequently, serum iron is low, and transferrin levels are low, resulting in decreased TIBC. Initially, ACD is a normocytic anemia, later evolving into a microcytic anemia anemia. Common causes include chronic inflammatory conditions like rheumatoid arthritis and inflammatory bowel disease, although malignancies and alcohol can also contribute.
Lesson Outline
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FAQs
The duodenum is the primary site for iron absorption. Iron is stored in duodenal enterocytes in the form of ferritin, a protein that helps to regulate the body's iron reserves. When iron levels are low, ferritin releases stored iron to be used by the body. Ferritin serves as a beneficial tool in managing iron levels in the body, responding to need by either storing or releasing iron.
While iron is primarily stored inside of cells (such as macrophages in the bone marrow) as ferritin, small amounts of this protein are also present in the bloodstream or serum. The amounts of ferritin in the serum can be used as a surrogate marker for iron reserves as they reflect the total amount of stored ferritin. Hence, a blood test measuring ferritin levels helps determine if the body has enough iron or if it is iron deficient.
Iron deficiency anemia can be caused by a variety of factors, including a vegetarian diet, heavy menstrual bleeding, pregnancy, gastrointestinal conditions like celiac disease, gastritis, and hookworm or whipworm infections. Symptoms usually appear only after ferritin stores in the bone marrow are depleted and include fatigue, weakness, skin pallor, rapid heartbeat and pagophagia. More specific signs can include a smooth red tongue, inflamed corners of the mouth, brittle or spoon-shaped nails (koilonychia), and esophageal webs accompanied by difficulty swallowing (Plummer-Vinson syndrome).
In iron deficiency anemia, the body's ferritin stores are low due to decreased iron availability leading to reduced heme and hemoglobin formation, the key components of red blood cells. Iron deficiency anemia initially presents as normocytic anemia but later becomes microcytic. Additionally, serum transferrin levels are elevated due to increased transferrin production, but transferrin saturation is low due to decreased iron. This results in an increased total iron binding capacity (TIBC).
Anemia of chronic disease is primarily caused by an increase in cytokines due to ongoing inflammation and is associated with conditions like rheumatoid arthritis, inflammatory bowel disease, malignancies, and chronic alcohol use. In this condition, there is increased release of hepcidin which locks iron inside cells, inhibiting its release for heme production. Unlike iron deficiency anemia, ferritin levels are increased as it remains stored in macrophages of the bone marrow. Serum iron levels and transferrin are low, causing a low total iron binding capacity (TIBC). Similar to iron deficiency anemia, it initially presents as normocytic and later becomes microcytic.
