(i) Disease Knowledge.
Folic acid and vitamin B12 are important coenzymes in the process of DNA synthesis in the nucleus, when deficient, it will affect DNA synthesis, resulting in delayed DNA replication, stagnation of cell nuclear development, while the cytoplasm (plasma) continues to develop and mature, the cell shows an imbalance in nuclear plasma development, so the formation of a larger than normal cell size “megaloblasts This results in the formation of “megaloblasts”, which are larger than normal. Since blood cells are the fastest renewing cells in the body, when there is a lack of folic acid or vitamin B12, bone marrow hematopoietic cells are most likely to undergo “megaloblastic transformation”, and the precursor cells of these “unqualified” blood cells will die early when they do not leave the bone marrow as a hematopoietic factory. Early death of these “substandard” precursor cells occurs before they leave the bone marrow as a hematopoietic plant, i.e., “in situ hemolysis in the bone marrow”, resulting in a decrease in hemoglobin, leukopenia, and thrombocytopenia in the peripheral blood, which is called “macrocytopenia”. This is the reason for the name “megaloblastic anemia”. In addition, when vitamin B12 is deficient, the synthesis of neuromyelin phospholipids will also be affected, and various neurological symptoms will appear clinically. In severe folic acid and/or vitamin B12 deficiency, impaired DNA synthesis not only involves hematopoietic tissues resulting in a decrease in whole blood cells, but also all rapidly proliferating tissues, such as causing megaloblastic changes and atrophy of the epithelium of the digestive tract mucosa, leading to a number of clinical symptoms accordingly.
Causes of folic acid deficiency and vitamin B12 deficiency.
1. Causes of folic acid deficiency.
The amount of folic acid stored in our body is 5~20mg, while the daily consumption is 50~100μg, so the lack of intake for 3~4 months can show the performance of folic acid deficiency. The folic acid requirement of infants, pregnant and lactating women should be increased 3~10 times, and folic acid deficiency can also occur if the supplementation is insufficient. The main causes of folic acid deficiency are
(1) Inadequate intake
Folic acid deficiency can be caused by partial diet, poor diet quality, lack of fresh green vegetables or meat and eggs, or long cooking time at high temperature (folic acid is destroyed), improper artificial feeding of infants or goat milk feeding. Folic acid deficiency occurs more rapidly in alcoholics.
(2) Increased need
Infants and children during the growth period, pregnant women, hyperthyroidism, malignant tumors, hemolytic diseases, infections, etc. can increase the need for folic acid, which can lead to deficiency if not supplemented with care.
(3) Absorption disorders
Various jejunal (upper part of the small intestine) disorders, such as stomatitis diarrhea, celiac disease, and post-small intestine resection, can lead to impaired absorption of folic acid. Some drugs such as anti-epileptic drugs, salazosulfapyridine and ethanol can also inhibit the absorption of folic acid.
(4) Utilization disorders
Methotrexate, aminoglutethimide, methotrexate (TMP) and ethanol can antagonize folate and affect folate metabolism and utilization. If the body is congenitally lack of certain enzymes such as dihydrofolate reductase can also affect the utilization of folic acid.
2. Causes of vitamin B12 deficiency.
(1) Reduced intake
Vitamin B12 stores in the human body is 2~5mg, the daily consumption of human is only 1μg, completely vegetarian, it takes more than 3 to 10 years to deplete the body’s stores and cause vitamin B12 deficiency.
(2) Malabsorption
The absorption of vitamin B12 can be reduced by congenital or acquired causes of reduced production of endogenous factors or by the production of anti-endogenous antibodies in the body. Malabsorption syndrome and excessive proliferation of intestinal bacteria can also cause vitamin B12 deficiency. Certain drugs such as metformin can also affect vitamin B12 absorption.
Internal factors and vitamin B12 absorption
Endogenous factor is a protein secreted by cells in the stomach lining. It binds to vitamin B12 to form a complex, which protects vitamin B12 from being destroyed by hydrolytic enzymes. This complex binds to specific receptors in the wall of the ileum (lower part of the small intestine) and promotes vitamin B12 absorption. In patients with pernicious anemia, atrophic gastritis, and gastric acid deficiency, reduced secretion of endocannabinoids leads to impaired absorption of vitamin B12. In addition, the presence of endokine antibodies in the blood of patients with pernicious anemia can also inactivate endokine, preventing it from binding to vitamin B12 and blocking the specific receptors on the ileal wall, thus also leading to impaired absorption of vitamin B12.
(3) Utilization disorders
Deficiency of certain proteins in the body, such as congenital transcobalamin II, often results in impaired vitamin B12 transport and utilization.
(ii) Clinical manifestations.
1.Hematological manifestations
The onset of the disease is slow, often with pallor, weakness, decreased endurance, dizziness, palpitations and other anemia symptoms, about 20% of patients are accompanied by leukopenia and thrombocytopenia. The incidence of infection is high, and some patients have obvious bleeding manifestations. Hepatosplenomegaly and mild jaundice may occur in a few cases.
2. Non-hematological manifestations
(1) Gastrointestinal symptoms, especially loss of appetite is the most obvious, there can also be angular inflammation, tongue inflammation, the most typical sign is the formation of “mirror tongue” or “beef tongue” due to tongue papillae atrophy resulting in a smooth tongue surface.
(2) Neurological manifestations: symmetrical numbness of hands and feet; deep sensory disorders (loss of position of limbs, etc.); ataxia (unstable walking, staggering gait); reduced sense of taste and smell; reduced vision; incontinence of urine and stool in severe cases; psychiatric symptoms such as irritability, depression, insomnia, memory loss, hallucinations, delusions and even personality perversion, etc.
(iii) Diagnosis and treatment.
The doctor will think of the diagnosis of “megaloblastic anemia” based on the patient’s medical history and the manifestations of anemia, especially when the patient is found to have a “mirror tongue”. If the blood test shows “macrocytic anemia”, this diagnosis is highly suspected. The doctor will order further tests for serum folate and vitamin B12 levels and, if necessary, a bone marrow aspiration, if the tests indicate a decrease in serum folate and/or vitamin B12 levels, and if the bone marrow aspiration report shows a pathological hematopoietic pattern characterized by “macrocytic changes” in the bone marrow nuclei. The diagnosis can be confirmed if the bone marrow aspiration report shows pathological hematopoiesis characterized by “megaloblastic changes” and “old pulpy nuclei”. Of course, if the test is not available, experimental treatment with folic acid and vitamin B12 can be used.
Once the diagnosis is confirmed, folic acid and/or vitamin B12 supplementation can be started, and the specific treatment methods are as follows.
1. Folic acid supplementation: 5 to 10 mg each time, 3 times/day until the blood picture is completely normalized. For those caused by folic acid antagonists, calcium tetrahydrofolate can be used as treatment. If accompanied by vitamin B12 deficiency, treatment with folic acid alone may aggravate the neurological damage, and simultaneous application of vitamin B12 is required.
2. Vitamin B12 supplementation: Since the cause of vitamin B12 deficiency is often related to impaired absorption in the gastrointestinal tract, vitamin B12 should be injected intramuscularly at 500μg each time, twice a week until the blood picture returns to normal. Subsequent intramuscular injections should be given weekly to increase the reserve. In case of pernicious anemia or total gastrectomy, lifelong maintenance treatment should be given. Symptoms improve 48 to 72 hours after vitamin B12 application and reticulocytes begin to rise, followed by a rise in hemoglobin. 6 to 8 hours later the bone marrow megaloblasts decrease.
If iron deficiency is present at the same time or appears during the treatment, iron supplements should be given. And attention should be paid to the supplementation of vitamin B and vitamin C.
(iv) Prevention.
Correction of partial diet and poor cooking habits. Patients diagnosed with megaloblastic anemia should take folic acid and/or vitamin B12 supplementation as needed, in addition to folic acid and/or vitamin B12 supplementation as prescribed by the doctor. Patients diagnosed with megaloblastic anemia should take folic acid and/or vitamin B12 supplements as prescribed by their physician, in addition to folic acid and/or vitamin B12 supplements as needed.
Folic acid-rich foods.
Green vegetables: lettuce, spinach, tomatoes, carrots, bok choy, lobelia, cauliflower, rape, chard, lentils, bean pods, mushrooms, etc.
fresh fruits: oranges, strawberries, cherries, bananas, lemons, peaches, plums, apricots, prunes, begonias, sour dates, hawthorn, pomegranates, grapes, kiwis, pears, pecans, etc.
animal foods: animal liver, kidney, poultry meat and eggs, such as pork liver, chicken, beef, lamb, etc.
legumes and nut foods: soybeans, soy products, walnuts (walnut oil), cashew nuts, chestnuts, almonds, pine nuts, etc.
cereals: barley, rice bran, wheat germ, brown rice, etc.
Vitamin B12-rich foods.
The main source of vitamin B12 is animal food, because plant foods (except for a very few) do not contain vitamin B12.
Animal liver, kidney, beef, pork, chicken, fish, clams, eggs, milk, cheese, dairy products, etc.
[Characteristics of megaloblastic anemia in the elderly].
Among all age groups, the chance of megaloblastic anemia is the highest in the elderly, often related to the loss of teeth, overcooking of food, often combined with stomach disorders and autoantibody formation due to abnormal immune regulation. Clinically, in addition to anemia manifestations, there is often severe loss of appetite and malnutrition, also often accompanied by neuropsychiatric manifestations or combined with autoimmune diseases such as Hashimoto’s thyroiditis and dry syndrome. Vitamin B12 and/or folic acid supplementation can often have a “miraculous” effect. However, care should be taken to treat the cause, and if the cause is difficult to remove, lifelong supplementation is required.