megaloblastic anemia in the elderly

Introduction

Introduction to megaloblastic anemia in the elderly Megaloblastic anemia is anemia caused by defects in nuclear DNA synthesis caused by folic acid and/or vitamin B12 deficiency or other causes, which is characterized by a typical "macro" of bone marrow. Cell nuclear development disorder, cell division slows down, and is not synchronized with the development of cytoplasm, that is, cell growth and division imbalance. The increase in cell volume presents a dramatic change in morphology and function. This change can involve red blood cells, granulocytes and megakaryocytes, and the cells are destroyed in the bone marrow when they are not matured, and are ineffective, except for hematopoietic cells. Similar changes are also observed in faster-renewed cells, such as gastrointestinal epithelial cells, which are often clinically manifested as complete cytopenia with gastrointestinal symptoms. In the absence of vitamin B12, in addition to the above performance, the nervous system and medulla often change, and neurological symptoms may occur. According to the epidemiological survey of this disease, Western giant cytoplasmic anemia is mainly caused by vitamin B12 deficiency. China's megaloblastic anemia is dominated by folate deficiency. May be related to nutritional conditions, diet and cooking habits. In addition to the main manifestations of this disease, the symptoms of the nervous system are obvious, mainly peripheral neuropathy. However, a small number of people have undergone mental changes, mental retardation, and disorientation disappeared. They are called macro dementia. The treatment method is to use vitamin B12 and folic acid. basic knowledge Proportion of the disease: the probability of illness in the elderly is 2.3% Susceptible people: the elderly Mode of infection: non-infectious Complications: mental disorders

Cause

The cause of megaloblastic anemia in the elderly

Reasons for folic acid deficiency (30%):

(1) Insufficient intake: If there is a lack of fresh vegetables in the food, excessive cooking or pickling can cause folic acid to be lost. Ethanol can interfere with the metabolism of folic acid. Alcohol abusers often have folic acid deficiency and inflammation of the small intestine (especially the jejunum segment). After surgical resection of the tumor, tropical inflammatory diarrhea can lead to insufficient absorption of folic acid.

(2) Increase in demand: pregnancy, breastfeeding, chronic repeated hemolysis, chronic inflammation, infection, hyperthyroidism and leukemia, malignant tumors, etc., the need for folic acid will increase, such as insufficient supplementation will occur folic acid deficiency.

(3) Drugs: methotrexate, pyrimethamine, phenytoin, phenobarbital and sulfasalazine can affect the absorption of folic acid.

Causes of vitamin B12 deficiency (30%):

The lack of vitamin B12 is associated with gastrointestinal diseases or dysfunction.

1Intake reduction: Absolute vegetarians and the elderly, atrophic gastritis is easy to reduce vitamin B12 intake, because vitamin B12 daily needs are very small and can be reabsorbed by the enterohepatic circulation, the occurrence of vitamin B12 deficiency often takes several years Only appeared, because the lack of intake in the diet caused anemia to be less than folic acid.

2 Intrinsic factor deficiency: mainly seen in patients with pernicious anemia and total gastrectomy, patients with pernicious anemia have idiopathic gastric mucosal atrophy and internal factor antibodies, which have obstacles to vitamin B12 in food and vitamin B12 reabsorption in bile. Therefore, it is easy to cause vitamin B12 deficiency.

3 ileal diseases or bacteria, parasitic infections, blind syndrome after surgery can affect the absorption of vitamin B12.

4 Others: If congenital transcobaltin II deficiency, long-term exposure to nitrous oxide (N2O) can affect the plasma transport and intracellular transformation of vitamin B12.

Other reasons (10%):

Factors such as personal physical differences.

Pathogenesis

Both folic acid and vitamin B12 have important coenzymes in the process of DNA synthesis. If they are lacking, they will lead to DNA synthesis. When deoxyuridine (Dump) is converted to deoxythymidine (Dtmp), methylenetetrahydrogen is required. Folic acid provides one methylene group and two hydrogen atoms. If the folic acid is deficient, it will affect the progress of the above biochemical reaction and affect the synthesis of DNA.

Vitamin B12, in the process of converting homocysteine to methionine, promotes methylation of methyltetrahydrofolate, conversion to tetrahydrofolate, methylenetetrahydrofolate, and methyltetrahydrofolate Entering the cell, tetrahydrofolate is the main form of folic acid involved in various biochemical activities in the body. Methylenetetrahydrofolate is an important coenzyme in the process of DNA synthesis, so vitamin B12 deficiency directly affects the entry of folic acid into cells and various biochemical reactions.

The second role of vitamin B12 is: adenosine cobalamin can convert methylmalonyl-CoA into succinyl-CoA. If vitamin B12 is deficient, a large amount of malonyl-CoA accumulates, affecting the formation of neuromyelin. Neurological symptoms, when folic acid or vitamin B12 is deficient, the rate of DNA synthesis in the nucleus slows down, the RNA in the cytoplasm continues to mature, the ratio of RNA to DNA is dysregulated, resulting in imbalance of nucleoplasmic development, large cell size and nuclear development. It is more naive, this giant young change can also occur in granulocytes and megakaryocytes, and most of the cells that are young and young are destroyed when they are immature in the bone marrow, which is called ineffective hematopoiesis.

1. Folic acid metabolism

Folic acid, also known as pteroyl glutamic acid, is composed of pteridine, p-aminobenzoic acid and glutamic acid. It is a water-soluble B vitamin. Its properties are extremely unstable and easily destroyed by light and thermal decomposition. The human body must be from food. To obtain the desired folic acid, the folic acid in the food is a compound in which the polyglutamate is combined with pteroyl, and the solubility is low, and the glutamine carboxypeptidase secreted by the small intestine is first decomposed into monoglutamate. The proximal end of the jejunum is absorbed, about 80% of the synthetic folic acid can be absorbed, and the folic acid is converted into N5-methyltetrahydrofolate during the absorption of the jejunum. After the action of vitamin B12, the tetramethyl folate enters the cell after demethylation. The monohydro acid of monoglutamic acid is formed by the action of ATP synthase, and then forms polyglutamate, which is stored in hepatocytes. The storage amount of folic acid in the human body is 5 to 10 mg, and the daily requirement of folic acid is 200 g. Therefore, when the food is deficient in folic acid, folic acid deficiency is easily caused in a short time. Folic acid and its metabolites are mainly excreted from the urine, and a small amount of folic acid can be excreted in bile and feces. The folic acid concentration in the bile is 2 to 10 in the blood. Times, Most can be reabsorbed after the jejunum.

2. Metabolism of vitamin B12

Vitamin B12, also known as cyanocobalamin, is also a water-soluble B vitamin. The main form of vitamin B12 in the blood is methylcobalamin. It is mainly in the form of adenosine cobalamin in the liver and other tissues. The source also depends on food, animal liver, kidney, heart, muscle tissue and eggs. The vitamin B12 is rich in dairy products. Vitamin B12 in food is first combined with R-protein in the stomach, after the duodenum, in the pancreas. With the participation of protease, it binds to the internal factor secreted by the parietal cells to form a vitamin B12-inner factor complex, enters the intestinal epithelial cells at the end of the ileum, and is transferred to various tissues by transcobalt protein II, most of which are stored in hepatocytes, adults There are 4 to 5 mg of vitamin B12 in the body. The daily requirement is only 2 to 5 g. The daily vitamin B12 excreted from the urine is about 30 ng. When a large amount of vitamin B12 is ingested, the amount discharged from the urine increases. In tears, saliva And a small amount of vitamin B12 is excreted in the milk, and a small amount of vitamin B12 is excreted by the bile, 2/3 of which is reabsorbed from the intestine by the internal factor, so unless it is an absolute vegetarian or vitamin B12 absorption disorder Generally not prone to vitamin B12 deficiency.

Prevention

Prevention of megaloblastic anemia in the elderly

Folic acid is widely found in vegetables, fruits, liver, kidneys and dairy products. The folic acid content of adults in daily diet is 50 to hundreds of milligrams. Folic acid is sensitive to heat and light, is susceptible to damage during cooking, and contains more folic acid in food. Glutamate, in the gastrointestinal tract by the depolymerase to mono-alkate, mainly in the proximal end of the jejunum, vitamin B12 is present in animal food, the average daily vitamin B12 content in human food is 5 ~ 30g, The body's absorption is only 1 ~ 5g, vitamin B12 in food must be combined in the stomach and internal factors, form a vitamin B12-inner factor complex, can be absorbed in the distal part of the ileum, should educate patients to eat rich in folic acid And vitamin B12 food, correct partial eclipse and incorrect cooking habits. In February 1996, the US Food Administration announced that most of the cereal staples sold in the United States must be supplemented with folic acid to prevent congenital diseases such as neonatal spina bifida. Pregnant women have insufficient folic acid intake and are susceptible to this disease at birth.

Complication

Complications of megaloblastic anemia in the elderly Complications

Common complications include infection, bleeding, and mental disorders.

Symptom

Symptoms of megaloblastic anemia in the elderly Common symptoms Malignant anemia bleeding tends to be weak, thrombocytopenia, loss of appetite, gastrointestinal symptoms, severe anemia, constipation, bloating, dizziness

Anemia

Most of the onset is slow, especially those with vitamin B12 deficiency, which often take several months. Due to the low folic acid storage in the body, some patients with nitrous oxide, ICU wards or hemodialysis patients, and pregnant women also have clinical manifestations. Degree ~ severe anemia, in addition to general anemia symptoms, such as fatigue, dizziness, shortness of breath after activity, severe anemia outside the heart can have mild jaundice, can have both white blood cells and thrombocytopenia, patients with occasional infection and bleeding tendency.

2. Gastrointestinal symptoms

It is characterized by recurrent tongue inflammation, smooth tongue, disappearance of mastoid and taste, loss of appetite, abdominal distension, diarrhea and constipation.

3. Nervous system symptoms

Occurs in patients with vitamin B12 deficiency, especially pernicious anemia, mainly caused by damage to the lateral and peripheral nerves of the spine. It is characterized by fatigue, symmetry numbness of the hands and feet, unstable gait of the lower limbs, difficulty walking, and children. The elderly often show mental disorders of cranial nerve damage, depression, lethargy or mental confusion. When folic acid deficiency occurs, they often manifest as psychiatric symptoms. The mechanism is still unclear. Some neurological symptoms of megaloblastic anemia patients can occur before anemia. .

The above three groups of symptoms can exist simultaneously in patients with megaloblastic anemia, or they can occur separately, and their severity is also inconsistent.

Examine

Examination of megaloblastic anemia in the elderly

Blood picture

For large cell positive anemia (MCV>100fl), the blood picture tends to show a decrease in whole blood cells, neutrophils and platelets can be reduced, but the degree of anemia is lighter. Most large oval red blood cells can be seen in blood smears. Neutral and neutrophil lobulation, there may be 5 leaves or more than 6 leaves of lobes, even large platelets can be seen, reticulocyte counts are normal or slightly increased.

2. Bone marrow

The proliferation of myeloid cells was active, and the proliferation of red blood cells was significantly increased. The cells of each line showed giant and young variants, with the most prominent erythroid cells. The cells in the erythroid cells were larger than normal, and the cytoplasm was more mature than the nucleus (nuclear pulp development imbalance). Chromatin is dispersed in dispersed particles, and similar morphological changes can also be seen in granulocyte and megakaryocyte lines, with more prominent late-onset and rod-shaped granulocytes.

3. Biochemical examination

(1) Determination of serum folic acid and vitamin B12 levels: Both can be determined by radioimmunoassay, the normal range of serum folic acid is 2.5-20 ng/ml, and the normal range of serum vitamin B12 is 200-900 pg/ml, due to some adults. There may be serum vitamin B12 below 200pg/ml, and because the effects of these two types of vitamins are in the cells, rather than in plasma, megaloblastic anemia patients also have serum vitamin B12 or folic acid in the normal range, so this item The test can only be used as a preliminary screening test. The determination of folic acid or vitamin B12 deficiency cannot be determined by simple serum folic acid or vitamin B12 assay.

(2) Determination of erythrocyte folate: It can be determined by microbiological method or radioimmunoassay. The normal range is 140-250 ng/ml. The erythrocyte folic acid is not affected by short-term folic acid intake, which can accurately reflect the stock of folic acid in the body, <100ng /ml indicates folate deficiency.

(3) Determination of serum homocysteine and methylmalonic acid levels: for the diagnosis and identification of folate or vitamin B12 deficiency, serum homocysteine (normal value 5 ~ 16mol / L) level in folate deficiency or Vitamin B12 deficiency is elevated, up to 50 ~ 70mol / L, and serum methylmalonic acid levels (normal value of 70 ~ 270nmol / L) only found in vitamin B12 deficiency, up to 3500nmol / L.

The urinary imidoylglutamic acid (FlGlu) excretion test is helpful for differential diagnosis.

Diagnosis

Diagnosis and diagnosis of megaloblastic anemia in the elderly

Diagnostic criteria

According to the medical history and clinical manifestations, the blood picture shows a large cell change (MCV>100fl), and the neutrophil lobulation is excessive (5 leaves account for more than 5%, or 6 leaves) should consider the possibility of megaloblastic anemia. The typical macroscopic changes in bone marrow cells can confirm the diagnosis.

To further clarify the lack of folic acid or vitamin B12 deficiency, further examinations are required:

1. If folic acid deficiency is suspected, serum and erythrocyte folate levels should be determined. Serum folate levels <6.81 nmol/L and erythrocyte folate <227 nmol/L can be confirmed. Otherwise, serum homocysteine levels can be determined.

2. If vitamin B12 deficiency is suspected, serum vitamin B12 levels should be determined, such as <74pmol/L, indicating lack, further determination of serum homocysteine or methylmalonic acid to confirm the cause of vitamin B12 deficiency. The inner factor blocking antibody can be measured under conditions and the vitamin B12 absorption test can be performed.

3. When the above experiments are performed unconditionally, the purpose of diagnosis can be achieved by experimental treatment by administering a physiological dose of folic acid (0.2 mg/d) or intramuscular injection of vitamin B12 (1 g/d) for 10 days. Folic acid or vitamin B12 deficiency, the patient's clinical symptoms, blood and bone marrow will improve and recover after treatment, physiologically measured folic acid (or vitamin B12) is only effective in patients with folic acid (or vitamin B12) deficiency, vitamin B12 deficiency Invalid, in this way can be the differential diagnosis of the two.

Differential diagnosis

It should be differentiated from diseases that cause a decrease in whole cells, large cell anemia, and macroscopic changes in the bone marrow.

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