Prevalence and causes The incidence of megaloblastic anemia in various population groups depends on dietary habits, the prevalence of specific gastrointestinal diseases and surgical interventions performed on the digestive organs, the use of chemotherapeutic drugs that interfere with folic acid metabolism and DNA synthesis, and, to a lesser extent, on the prevalence of primary. net In Western countries, disorders of folic acid and vitamin B12 metabolism are still the leading causes of megaloblastic anemia.

However, in selected groups of the population, for example, those receiving chemotherapy drugs, the leading etiological factor in the violation of DNA synthesis may be the use of specific drugs..

Folic acid metabolism disorders The most common causes of folic acid metabolism disorders are given in Table. Despite the fact that congenital disorders of folic acid metabolism are quite rare, the possibility of their occurrence must be taken into account in the differential diagnosis of the causes of megaloblastic anemia in children..

Table 4. Disturbances of folic acid metabolism Congenital disorders Congenital malabsorption malabsorption cells Deficiency formiminotransferazy deficit methyltransferase acquired metabolic disorders Alcoholism Deficiency of vitamin B12 deficiency of vitamin C. The use of folic acid antagonists, inhibitors of dihydrofolate reductase (methotrexate, triamterene, trimethoprim, hloridin) Anticonvulsants Peororalnye contraceptives deficient state Inadequate intake.

In adults, conditions are quite common due to a combination of a congenital defect in folic acid metabolism and its deficiency. In many Western countries, severe alcoholism is the leading cause of megaloblastic folate deficiency anemia. In the process of its occurrence, at least two mechanisms are involved..

The point is not only in the consumption of insufficient amounts of folic acid by chronic alcoholics with food, leading over time to depletion of the folic acid depot in the body and a true deficiency state, but also in the fact that alcohol affects metabolic processes that ensure the supply of folic acid to tissues..

It has been shown that the constant use of wildcat prevents the re-participation of folic acid in the intestinal-hepatic cycle, quickly leads to a decrease in the level of folic acid in the blood serum and reduces its intake into rapidly multiplying tissues, for example, the bone marrow. This can explain the development of megaloblastic anemia in alcoholics for several weeks, despite the presence of sufficient depots of folic acid in the liver..

At the same time, the intake of folic acid with food can weaken the effect of alcohol, which consists in blocking the intestinal-hepatic folic acid cycle.. Megaloblastic anemia does not develop in alcoholics who consume adequate amounts of folate.

Megaloblastic anemia due to impaired folic acid metabolism is also observed as a result of the intake of the chemotherapeutic drug methotrexate. This drug inhibits dihydrofolate reductase and prevents the reverse conversion of dihydrofolic acid, which is necessary for the synthesis of thymididate, to tetrahydrofolic acid [T].

Drugs such as triamterene, trimethoprim and chloridine are weaker dihydrofolate reductase inhibitors, but they can also cause the described disorders in patients with a borderline state of folic acid metabolism.. Anticonvulsants and oral contraceptives also affect folate metabolism, but the mechanism of their effect has not yet been understood..

For normal metabolism of folic acid, along with vitamin B12, vitamin C is needed. As mentioned earlier, severe vitamin B12 deficiency deprives cells of the sufficient amount of tetrahydrofolic acid necessary for the synthesis of purine, pyrimidine and thymidylate. Thus, patients with vitamin B12 deficiency have functional folate deficiency..

Some people with scurvy have megaloblastic anemia, which is only partially treatable with folic acid, and vitamin C is needed for full recovery.. However, the mechanism of this interaction has not yet been clarified..

An absolute deficiency of folic acid can develop as a result of a low content of it in food, a malabsorption in the intestine or an increase in the need for it. Folate fasting occurs in newborns who are fed goat milk or if their diet is low in folic acid. Lack of dietary folic acid intake is also common in chronic alcoholics..

Folic acid malabsorption occurs in patients with tropical sprue, celiac disease, and advanced bowel lymphoma. Since folic acid is absorbed throughout the small intestine, signs of its deficiency appear only with significant intestinal damage, on the contrary, malabsorption and vitamin B12 deficiency can occur in diseases that limitedly affect the ileum.

Perhaps the most acute folate deficiency occurs in patients with tropical sprue.. In this condition, the absorption of folic acid in the intestine is disturbed so much that the symptoms of megaloblastic anemia prevail over complaints from the gastrointestinal tract..

In conditions characterized by accelerated cell division, such as pregnancy, severe hemolytic anemia, or a rapidly growing tumor, the requirement for folic acid may exceed its intake with normal food.

During pregnancy, the fetus is in a more privileged position than the mother, and the placenta extracts folic acid to the detriment of the mother's body.

Consequently, the mother may develop megaloblastic anemia with an adequate supply of folic acid to the fetus..

Vitamin B12 Metabolic Disorders.

The most important clinical disorders of vitamin B12 metabolism are listed in Table. As with disorders of folate metabolism, congenital defects in vitamin B12 metabolism are quite rare..

medbe. ru.