Causes of development
The etiology of megaloblastic anemias boils down to a deficiency of two key factors: vitamin B12 (cyanocobalamin) and folic acid.
Vitamin B12 deficiency most commonly occurs due to:
- Impaired absorption. The leading cause (about 75% of cases) is pernicious anemia (Addison–Biermer disease). It is associated with autoimmune destruction of gastric parietal cells, leading to a cessation of intrinsic factor production. Absorption is also impaired by surgical interventions (gastrectomy, small bowel resection), gastrointestinal diseases (ileitis), and competitive uptake (fish tapeworm infestation, blind loop syndrome).
- Dietary factors. Strict vegetarianism, as B12 is found exclusively in animal products (liver, eggs, milk).
Folic acid deficiency develops due to:
- Low dietary intake of plant foods, especially in children and individuals suffering from alcoholism.
- Impaired absorption in the proximal small intestine (e.g., in tropical sprue).
- Increased demand (pregnancy, hyperthyroidism, malignant tumors).
- Use of certain medications (anticonvulsants).
Clinical presentation
Symptoms include general anemia syndrome and specific deficiency manifestations.
General signs of anemia develop slowly. Patients complain of weakness, shortness of breath, and palpitations upon physical exertion. Characteristic appearance includes pallor with a mild yellow tint (subicterus) and facial puffiness. In severe cases, myocardial dystrophy may develop with cardiac chamber enlargement and heart failure.
Vitamin B12 deficiency anemia is characterized by a classic triad:
- Hematological syndrome: macrocytic hyperchromic anemia.
- Gastroenterological syndrome: Hunter's glossitis («beefy red» tongue) and atrophic gastritis with decreased secretion.
- Neurological syndrome (funicular myelosis): a consequence of nerve fiber demyelination. It manifests as symmetric paresthesias, impaired proprioception, spastic ataxia, and neuropsychiatric disorders.
In folate-deficiency anemia, neurological symptoms are absent, and gastrointestinal manifestations are rare.
Diagnostics
The diagnosis is established based on laboratory and instrumental data.
- Peripheral blood: decreased hemoglobin, macrocytosis (elevated MCV, color index > 1.1). Anisocytosis, poikilocytosis, and nuclear remnants in erythrocytes (Howell–Jolly bodies, Cabot rings) are characteristic. The reticulocyte count is initially low (hypogenerative anemia).
- Myelogram: sternal puncture reveals megaloblastic hemopoiesis, erythroid hyperplasia, and the appearance of giant metamyelocytes.
- Biochemistry: determination of serum vitamin B12 and folic acid levels.
- Instrumental methods: upper gastrointestinal endoscopy (EGD) to confirm gastric mucosal atrophy when pernicious anemia is suspected.
Principles of treatment
Treatment must be comprehensive:
- Etiotropic therapy: elimination of the underlying cause (e.g., deworming, treatment of gastrointestinal diseases).
- Pathogenetic therapy: replacement administration of the deficient vitamin.
The primary criterion for treatment efficacy is a reticulocyte crisis — a sharp increase in the reticulocyte count on days 3–7 of therapy. It is important to remember that administering high doses of folic acid in B12 deficiency may improve the blood picture but will not halt the progression of neurological disorders.
Briefly: answers to topical questions
What causes lead to folic acid deficiency?
Folic acid deficiency is caused by dietary factors, malabsorption syndrome, the use of certain medications, and conditions with increased demand or increased excretion.
Main causes:
- Dietary deficiency — lack of raw vegetables in the diet, advanced age, feeding newborns with goat's milk.
- Malabsorption syndrome — jejunal resection, celiac disease, chronic enteritis, amyloidosis, scleroderma, small bowel tumors, chronic alcohol intoxication.
- Iatrogenic causes — use of antiepileptic drugs, methotrexate, co-trimoxazole, metformin.
- Increased demand — pregnancy, rapid child growth, heavy physical exertion, hereditary hemolytic anemias, prematurity and low birth weight, hyperthyroidism, malignancies.
- Increased excretion — hemodialysis.
In which part of the intestine does vitamin B12 absorption occur?
Vitamin B12 absorption occurs in the ileum.
For successful absorption, the vitamin first forms a complex in the stomach with intrinsic factor, which is secreted by mucosal parietal cells. Subsequently, this formed complex binds to the ileal epithelium, ensuring the delivery of the vitamin necessary for normal hemopoiesis into the body.
What is the daily requirement of the body for vitamin B12 and folic acid?
The daily requirement for these vitamins is estimated differently depending on the source.
Indicators:
- Vitamin B12 — the daily requirement is 2.4 mcg, 2.5 mcg, or 3 mcg.
- Folic acid — the requirement is stated as 50 mcg per day, however, daily intake with a diet containing sufficient fresh vegetables and fruits is 400–600 mcg.
Pernicious anemia triad: Blood (anemia), Belly (gastritis/glossitis), Brain/Nerves (funicular myelosis).
Class and exam questions
Intrinsic factor is a glycoprotein secreted by gastric parietal cells. It is absolutely essential for the binding and subsequent intestinal absorption of vitamin B12.
Intrinsic factor is a glycoprotein secreted by gastric parietal cells. It is absolutely essential for the binding and subsequent intestinal absorption of vitamin B12.
How to clinically differentiate B12-deficiency anemia from folate-deficiency anemia?
The main clinical difference is the presence of funicular myelosis (neurological disorders) in B12 deficiency. In folic acid deficiency, the nervous system is not affected.
What is a reticulocyte crisis?
This is a sharp surge in the reticulocyte count in peripheral blood on days 5–10 after the initiation of replacement therapy. It serves as proof of correct diagnosis and treatment efficacy.
What else to study on this topic
- Mechanisms of autoimmune destruction in pernicious anemia
- Differential diagnosis of causes of altered serum B12 levels
- Features of myelogram interpretation
- Folate metabolism in the cell
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