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Megaloblastic anemia, also called macrocytic anemia, is a condition where large, structurally abnormal, immature red blood cells, or RBCs, are produced by the bone marrow.
First, let’s look at the physiology of red blood cell production, or erythropoiesis. This process takes place in the bone marrow, where a stem cell differentiates into an erythroblast, which starts synthesizing hemoglobin. This is a protein that’s able to bind and carry oxygen.
Erythroblasts then lose their nucleus and differentiate into immature RBCs, called reticulocytes. These immature cells are released from the bone marrow into the bloodstream, to ultimately become mature RBCs, called erythrocytes.
Now, RBCs normally have a limited lifespan, of 120 days, so they require continuous replacement through erythropoiesis. To do so, the body needs important vitamins and minerals, including vitamin B12, also known as cobalamin, and vitamin B9, better known as folic acid or folate; these vitamins are used for the synthesis of DNA, which is essential for cell division and maturation.
Now, these vitamins are primarily obtained from a balanced diet that includes all types of foods. Once ingested, food passes through the gastrointestinal tract, where nutrients are slowly absorbed. Some nutrients, such as vitamin B12, require a specific carrier protein like intrinsic factor, which is produced by gastric parietal cells, to be absorbed into the circulation.
Alright, so megaloblastic anemia is most often caused by a deficiency in vitamin B12 or folate. Now, vitamin B12 deficiency can be caused by impaired gastrointestinal absorption or decreased dietary intake. Impaired absorption may have a number of risk factors, including medications that interfere with absorption such as proton pump inhibitors, H2 receptor blockers, or metformin; a lack of intrinsic factor, which could be caused by gastrectomy, gastric bypass surgery, or autoimmune gastric atrophy, which results in pernicious anemia. Gastrointestinal infections or inflammatory disorders of the gastrointestinal tract can also cause decreased absorption.
Macrocytic anemia is a type of anemia characterized by abnormally large red blood cells. These red blood cells are unable to carry enough oxygen to the body's tissues, resulting in symptoms such as pallor, fatigue, weakness, and shortness of breath. Main causes of macrocytic anemia include Vitamin B12 or folate deficiency, certain drugs such as methotrexate, excessive alcohol consumption, and several diseases such as multiple myeloma.
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