Etiology: Causes of Deficiency
Vitamin B12 deficiency is relatively rare. The main cause lies in impaired intestinal absorption. Several key factors are distinguished:
- Autoimmune mechanisms. This is the most common cause (over 75% of cases). The body produces autoantibodies against intrinsic factor, the vitamin B12-intrinsic factor complex, or gastric parietal cell proton pump proteins. The latter leads to chronic atrophic gastritis and achlorhydria.
- Gastrointestinal disorders accompanied by malabsorption syndrome.
- Fish tapeworm (Diphyllobothrium latum) infection, which actively and competitively consumes the vitamin.
- Severe intestinal dysbiosis.
Folate deficiency is much more widespread. It is provoked by:
- Dietary factors (low vitamin content in food).
- Insufficient placental transfer to the fetus (in maternal folate deficiency).
- Genetic defects impairing folate transport and metabolism.
- Increased bodily demand for the vitamin (e.g., during severe infections).
Pathogenesis of Megaloblastic Hematopoiesis
The key event in the development of the disease is impaired thymidine nucleotide synthesis. Consequently, DNA replication is critically disrupted, leading to a sharp decrease in bone marrow cell division rates. The end result of this process is pancytopenia—a drop in the levels of all formed blood elements.
The formation of the pathological cell—the megaloblast—occurs via a specific mechanism. It is important to note that protein synthesis in precursor cells is entirely unaffected. This creates a phenomenon known as nuclear-cytoplasmic asynchrony. Due to impaired DNA replication, nuclear maturation is significantly delayed. Meanwhile, the cytoplasm continues to mature normally, and erythroblasts continuously accumulate hemoglobin. Because the cell cannot divide on time, it grows to a pathological size.
Bone Marrow and Biochemical Findings
Pathological precursor cells—megaloblasts—as well as numerous megalocytes appear in the bone marrow. A picture of ineffective erythropoiesis develops:
- Degeneration of megaloblast nuclei is observed.
- Normal maturation of myeloid cells is disrupted.
Because megaloblasts and the erythrocytes derived from them are defective, they undergo premature destruction (hemolysis). In biochemical blood tests, this is reflected by the development of hyperbilirubinemia.
Peripheral Blood: Quantitative and Morphological Shifts
A complete blood count reveals pronounced erythropenia, which often progresses to pancytopenia (reduction of all cell lines). Megaloblasts and megalocytes are found on the blood smear.
Erythrocyte morphology undergoes major changes:
- Anisocytosis: macrocytes and giant megalocytes predominate in the blood.
- Poikilocytosis: cells lose their normal biconcave shape.
- Hyperchromia: erythrocytes are supersaturated with hemoglobin, showing a high mean corpuscular hemoglobin concentration (MCHC).
- Polychromasia: erythrocytes take up both acidic and basic stains simultaneously.
- Basophilic stippling of erythrocytes.
- Presence of nuclear remnants inside erythrocytes: Howell-Jolly bodies and Cabot rings are identified.