Content Reviewers:Anna Hernández, MD, Lisa Miklush, PhD, RNC, CNS, Antonella Melani, MD, Viviana Popa, MD, Gabrielle Proper, RN, BScN, MN
Contributors:Zachary Kevorkian, MSMI, Mathew Pietri, Evan Debevec-McKenney, Corinne Tarantino, Katrina Mikitik, BSN
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.
On the flip side, decreased dietary intake of vitamin B12-rich foods is seen primarily in clients with chronic alcoholism; or those who have adopted a strict vegan diet for a long-time, but are not taking B12 supplements. That’s because vitamin B12 is found primarily in animal and dairy products, like meat, eggs, or milk.
On the other hand, folate deficiency can be caused by decreased dietary intake, increased body demand, or impaired gastrointestinal absorption. Decreased intake can occur in clients who don’t consume foods that contain folate, such as leafy greens, legumes, or fruits like oranges and bananas.
On the other hand, folate deficiency due to increased demand can occur during pregnancy, lactation, and puberty. Certain medications like phenytoin, as well as chronic alcohol use, can interfere with folate absorption, as well as certain inflammatory disorders of the gastrointestinal tract.
Alright, so the pathology of megaloblastic anemia develops when there is a depletion of vitamin B12 or folate stores in the body. Vitamin B12 or folate deficiency causes impaired DNA synthesis, and the bone marrow starts producing macrocytic, or large, structurally abnormal RBCs called megaloblasts, that then mature into abnormally large RBCs. These RBCs also tend to have flimsy membranes, making them fragile, easily hemolyzed or broken apart, resulting in a shorter lifespan than normal RBCs. Finally, impaired DNA synthesis also affects the maturation of white blood cells like neutrophils.
Megaloblastic anemias develop slowly, so clients will often remain asymptomatic until anemia becomes severe, at which time they will present with pallor, as well as fatigue, dizziness, reduced exercise tolerance, exertional dyspnea, and tachycardia. Some clients can also develop glossitis, which can manifest as a sore tongue, or oral ulcers. In severe cases, clients with megaloblastic anemia can have decreased oxygen saturation, chest pain, and an irregular heartbeat. Hemolysis may cause jaundice.
Now, vitamin B12 also plays a role in helping to maintain the myelin sheath surrounding peripheral nerves. As a consequence, clients with vitamin B12 deficiency can also experience neurological symptoms from defective myelination, such as weakness, paresthesia or a feeling of pins and needles, as well as ataxia or impaired coordination. They can also experience neuropsychiatric symptoms, including confusion, memory loss, and even delusions and hallucinations.