B12 deficiency anemia (pernicious anemia). What is b12 deficiency anemia B12 deficiency anemia mercury

B12 deficiency anemia - pathological condition caused by a violation of hematopoiesis due to a lack of vitamin B12 (cyanocobalamin) in the body. Synonyms: pernicious anemia, megaloblastic anemia, Addison-Birmer disease.

B12 deficiency anemia was first described by Addison in 1849, and in 1872 Biermer called it "progressive pernicious anemia". Vitamin B12 deficiency in the body can be either acquired or hereditary, i.e., be genetically determined.

Etiology and pathogenesis

Vitamin B12 deficiency occurs when:

• malnutrition (vegetarianism, chronic alcoholism, unbalanced diets);
• inadequate absorption (lack of internal factor, pathology of the small intestine, competitive use in helminthiases - invasion of the tapeworm wide);
• inadequate utilization (diseases of the liver, kidneys, malignant tumors, transport protein abnormalities).

Vitamin B12 is not synthesized in the human body and comes only from food. Most of all it is found in meat, liver, milk, cheese, eggs, legumes. Normally, the level of vitamin in the blood ranges from 200 - 750 pg / ml, which is about 0.1% of its total content in the body, mainly in the liver. The excretion of the vitamin occurs in the bile and, to a lesser extent, in the urine.

The reserves of vitamin B12 in the body of an adult are quite large (2-5 mg) and are mainly located in the liver. For the development of cyanocobalamin deficiency (due to malabsorption or insufficient intake of it with food), a long time is required - from 6 months to 3-6 years.

Pure vitamin B12 cannot be absorbed in the intestines. For its absorption, the presence of an internal factor (Castle factor) is necessary - a secret secreted by the parietal cells of the stomach. Intrinsic factor is a thermolabile, alkali-resistant glycoprotein. In the presence of vitamin B12 ( external factor) two molecules of intrinsic factor combine to form a dimer that transports vitamin B12 across the intestinal mucosa. The transfer of absorbed vitamin B12 by the blood to the bone marrow for participation in hematopoiesis is carried out with the help of specific transport proteins - transcobalamins I, II and III.

Vitamin B12 consists of two coenzymes - methylcobalamin and deoxyadenosylcobalamin. Deficiency of the first coenzyme causes a violation of DNA synthesis, as a result of which the division and maturation of red cells are disrupted and their excessive growth occurs without loss of the nucleus. Large cells containing nuclei are called megaloblasts. They do not mature into megalocytes (giant red blood cells without nuclei) and are easily hemolyzed while still in the bone marrow. Deficiency of vitamin B12 causes dysplasia of leukocyte and platelet cells, but this does not affect their morphology and number of cells as much as erythropoiesis disorders.

With a lack of a second coenzyme, metabolism is disturbed fatty acids, resulting in the accumulation of toxic products in the body - propionic and methylmalonic acid: damage to the posterolateral cords develops spinal cord- funicular myelosis.

Along with impaired intake of vitamin B12, there is also an autoimmune mechanism for the development of anemia. In most patients, antibodies to the parietal cells of the stomach are found in the blood serum. In more than 50% of cases, antibodies against intrinsic factor are detected.

In the pathogenesis of vitamin B12-deficient anemia, the lack of intrinsic factor is of primary importance, which develops with atrophy of the cells of the gastric mucosa that secrete this factor, and leads to classic Addison-Birmer pernicious anemia.

Thus, a lack of vitamin B12 in the body leads to impaired hematopoiesis, the appearance of megaloblasts in the bone marrow, intramedullary destruction of erythrocytes, a decrease in the number of erythrocytes and hemoglobin, leukopenia, neutropenia and thrombocytopenia, as well as changes in a number of organs and systems (GIT, CNS). Bone marrow and tissues are especially sensitive to deficiency of this vitamin. nervous system.

Symptoms

The clinical picture consists of the following syndromes:

• circulatory-hypoxic (with sufficient severity of anemia and oxygen starvation tissues);
• gastroenterological (symptoms of gastrointestinal lesions);
• neurological (symptoms of CNS damage);
• hematological (hyperchromic type anemia).

In addition to these syndromes, the clinical picture is also determined by the disease on the basis of which vitamin B12 deficiency anemia has developed.

The clinical picture of anemia develops gradually as the depletion of vitamin B12 in the liver. Patients may experience symptoms due to circulatory-hypoxic syndrome (weakness, fatigue, shortness of breath when physical activity, pain in the region of the heart, palpitations). The skin acquires a lemon-yellow tint, sometimes spotted brown pigmentation appears, body weight decreases, and subfebrile temperature is observed.

In most patients, glossitis is detected, accompanied by burning and pain in the tongue. The papillae atrophy, the tongue becomes smooth, shiny ("varnished" tongue). Sometimes the mucous membranes of the cheeks and esophagus are affected. Most patients develop atrophy of the gastric mucosa with secretory insufficiency. Diarrhea may develop, probably associated with achlorhydria. The liver and spleen are usually slightly enlarged.

All patients have clinical signs of anemia syndrome (shortness of breath, palpitations, extrasystole, tinnitus, dizziness, increasing weakness, etc.).

B12-deficiency anemia develops damage to the white matter of the posterior and lateral columns of the spinal cord (funicular myelosis), cerebral disorders and degeneration peripheral nerves. Patients complain of tingling in the fingertips and impaired sensitivity to cold. With the progression of anemia, ataxia appears, gait is disturbed, general weakness increases, and hyperreflexia develops.

Course of the disease

Perhaps a sharp exacerbation of the disease. In such cases, a coma develops: loss of consciousness, decrease in body temperature and blood pressure, shortness of breath, vomiting, areflexia and involuntary urination. There is no clear relationship between the development of a coma and a decrease in hemoglobin concentration (in patients with a sharply reduced content of hemoglobin, there is no coma). The main role in the pathogenesis of coma is played by the rapid rate and degree of decrease in hemoglobin, as well as severe ischemia and hypoxia of the central nervous system.

Diagnostics

There are two stages in the diagnosis:

1. evidence of vitamin B12 deficiency as a cause of anemia;
2. determining the causes of vitamin B12 deficiency.

At laboratory research in the blood, macrocytosis, anisocytosis and poikilocytosis, basophilic granularity of erythrocytes are determined. Erythrocytes are large, often oval in shape, in many nuclei are found (Jolly bodies, Cabot rings).

Anemia is often hyperchromic, the color index can rise to 1.3. In the blood serum, the amount of vitamin B12 decreases to less than 150 pg / ml. The content of serum iron is usually normal or slightly elevated, there is moderate hyperbilirubinemia due to bone marrow hemolysis of erythrokaryocytes.

With megaloblastic erythropoiesis, the maturation of all cellular elements of the bone marrow is disrupted. As a rule, leukopenia and thrombocytopenia occur. Characterized by the appearance of hypersegmented neutrophils in the blood.

To quantify the absorption of vitamin B12, the Schilling test is performed and the bowel is examined. For the diagnosis of macrocytic anemia, the diagnosis of bone marrow punctate is of exceptional importance.

To determine the cause of anemia, X-ray, endoscopic (stomach tumor, diverticulosis of the small intestine), helminthological examination (wide tapeworm invasion), functional examination of the liver with biopsy (chronic hepatitis, cirrhosis) and determination of neutral fat in the intestine (spru) should be performed.

Diagnostic criteria:

• decrease in the content of erythrocytes (less than 3.0×10 12 /l);
• increase in color index (more than 1.1);
• increase in hemoglobin content in erythrocytes (more than 34 pg);
• an increase in the average volume of an erythrocyte (more than 120 microns 3);
• shift of the erythrocytometric curve to the right (an increase in the number of macrocytes, the presence of megalocytes - erythrocytes with a diameter of more than 12 microns);
• detection in smears of bone marrow punctate elements of megaloblastic hematopoiesis;
• increase in content serum iron more than 30.4 µmol/l;
• decrease in urine radioactivity after taking vitamin B12 labeled with radioactive cobalt

B12 deficiency anemia should be differentiated from folate deficiency anemia. With a deficiency of folic acid, macrocytic hyperchromic anemia is found, and megaloblasts are found in the bone marrow. It should be noted that folic acid deficiency is recorded much less frequently. Unlike vitamin B12 deficiency anemia, folic acid deficiency in the blood and erythrocytes is reduced in folate deficiency anemia. In addition, when a bone marrow preparation is exposed to alizarin red, only megaloblasts associated with vitamin B12 deficiency stain, and megaloblasts associated with folic acid deficiency do not stain.

The formulation of a detailed clinical diagnosis should take into account:

• etiology of B12-deficiency anemia (anemia caused by Addison-Birmer's disease should be singled out separately);
• stage of the process (relapse or remission);
• the severity of individual syndromes (as a rule, with neurological disorders caused by funicular myelosis).

Treatment

Treatment should be carried out taking into account the etiology, severity of anemia and the existence of neurological disorders.

The patient is shown a balanced diet with sufficient protein and vitamins, as well as a complete prohibition of alcohol consumption - this is an indispensable condition for the treatment of this anemia. In case of helminthic invasion, deworming should be carried out (niclosamide or male rhizome fern are prescribed according to a certain scheme to expel a wide tapeworm).

For organic bowel diseases and diarrhea, enzyme preparations (pancreatin, hemicellulase + bile components + pancreatin) should be used, as well as fixing agents (calcium carbonate in combination with dermatol). To normalize the intestinal microflora, enzyme preparations are prescribed (pancreatin, hemicellulase + bile components + pancreatin), and a diet is selected that helps to eliminate the syndromes of putrefactive or fermentative dyspepsia.

Pathogenetic treatment of B12 deficiency anemia consists in elimination of vitamin B12 deficiency, normalization of central hemodynamic parameters and neutralization of antibodies to gastromucoprotein (intrinsic factor) or gastromucoprotein + vitamin B12 complex (use of glucocorticoids).

The elimination of vitamin B12 deficiency is carried out with the help of parenteral administration of a vitamin preparation. Two preparations of vitamin B12 are important - cyanocobalamin and oxycobalamin. Assign cyanocobalamin (400-500 mcg intramuscularly 1 time per day daily), oxycobalamin (1 mg / day every other day) for 4-6 weeks until the blood picture normalizes.

Criteria for the normalization of the blood picture: sharp increase the number of reticulocytes in the peripheral blood (reticulocyte crisis) and the transformation of megaloblastic hematopoiesis into normoblastic. The development of a reticulocyte crisis on the 5-6th day of treatment is an early criterion for its effectiveness. During treatment with cyanocobalamin, the number of red blood cells increases faster than the hemoglobin content, so the color index usually decreases.

After normalization of bone marrow hematopoiesis and blood composition (usually after 1.5-2 months), the drug is administered once a week for 2-3 months, and then 2 times a month (in the same doses as at the beginning of the course) within half a year. In the future, patients are put on dispensary records and, for prophylactic purposes, cyanocobalamin is administered to them (1-2 times a year in short courses of 5-6 injections or monthly at 200-500 mcg for life).

In funicular myelosis, large doses of vitamin B12 (1000 mcg daily) are prescribed in combination with the vitamin B12 coenzyme cobamide (500 mcg 1 time per day intramuscularly). This dose is administered for 10 days, and then 1-3 times a week until the manifestations of myelosis disappear.

Hemotransfusion (transfusion of erythrocyte mass) is carried out only for health reasons: coma with B12-deficiency anemia; drop in hemoglobin level less than 50-40 g/l; development of anemic encephalopathy, heart failure. It is recommended the introduction of erythrocyte mass at a dose of 250-300 ml (5-6 transfusions).

Prednisolone (20-30 mg / day) is prescribed for a disease of autoimmune etiology.

Forecast

The prognosis is favorable. With timely and proper treatment, patients live for a long time.

Prevention

Mer primary prevention does not exist. In persons with the previously listed etiological factors, blood should be periodically examined for the timely detection of anemia.

In megaloblastic anemia caused by vitamin B12 deficiency, the production of red blood cells in the bone marrow is disrupted, their destruction occurs prematurely (ineffective erythropoiesis) and the life span of abnormal red blood cells in the blood is shortened. The minimum daily requirement for vitamin B12, the main source of which is meat and milk, is ≤5 mcg (mean 2.4 mcg). The reserves of vitamin B12 after the cessation of its intake into the body are enough for 4 years. Vitamin B12 is absorbed in the distal small intestine after binding to intrinsic factor (IF), which is synthesized by the parietal cells of the gastric mucosa. In the blood, it binds to proteins - haptocorin and transcobalamins and is transported to organs and tissues. B12 deficiency leads to a disruption in the synthesis of purine bases necessary for building DNA, manifested by disorders in tissues with a high proliferative activity of cells (for example, the mucous membrane of the gastrointestinal tract), and in the nervous system (impaired myelin metabolism and degeneration of nerve fibers) .

Causes of severe vitamin B12 deficiency:

1) malabsorption (due to the incorrect structure of the intrinsic factor of the Castle or the receptor for absorption of the IF-B12 complex in the ileum): Addison-Birmer anemia, condition after gastrectomy, bariatric surgery, condition after resection of the ileum, congenital deficiency of the intrinsic factor of Castle, gastritis caused by H. pylori, Crohn's disease, Zollinger-Ellison syndrome, bacterial overgrowth syndrome;

2) congenital metabolic disorders, including transcobalamin deficiency;

3) nitric oxide used in anesthesiology.

Causes of minor or moderate vitamin B12 deficiency:

1) moderate and minor malabsorption (reduced availability of vitamin B12 contained in food): moderate non-immunological chronic atrophic gastritis, metformin, drugs that inhibit the secretion of hydrochloric acid, chronic pancreatitis, congenital selective malabsorption;

2) veganism or vegetarianism, malnutrition;

3) alcoholism.

Most common cause- this is Addison-Birmer's disease (syn. pernicious anemia), caused by the presence of autoantibodies to the parietal cells of the gastric mucosa and to the internal factor Castle →. The median incidence is age ≈70–80 years.

CLINICAL PICTURE AND NATURAL COURSE

1. General symptoms:

2. Biochemical and immunological studies: decreased plasma vitamin B12 levels (high false positive and false negative rates), elevated serum or plasma homocysteine ​​and/or serum methylmalonic acid (MMA) (>400 nmol/l), signs of moderate hemolysis (increased serum LDH activity , a decrease in the level of haptoglobin, a slight increase in the level of unbound bilirubin, an increase in the content of serum iron), the presence of autoantibodies to the parietal cells of the stomach and to Castle WF (in Addison-Birmer disease).

3. Aspiration biopsy and trepanobiopsy of the bone marrow: hypercellular bone marrow with abnormal megaloblastic erythropoiesis and signs of impaired erythropoiesis and intramedullary hemolysis, numerous giant metamyelocytes and stab granulocytes, granulocyte hypersegmentation, large megakaryocytes with a hypersegmented nucleus.

4. Gastroscopy: signs of atrophic gastritis (with Addison-Birmer disease).

Differential Diagnosis Folic acid deficiency anemia and other dyserythropoietic anemias (sideroblastic anemia, myelodysplastic syndrome [MDS]), other conditions with erythrocyte macrocytosis (alcoholism, liver cirrhosis; drugs that interfere with purine synthesis [methotrexate, mercaptopurine, cyclophosphamide, azidothymidine, trimethoprim] , hypothyroidism).

TREATMENT Give vitamin B 12 (cyanocobalamin) 1 mg IM or deep s.c. daily for 7–14 days, then once a week until anemia is eliminated (4–8 weeks). Supportive care (especially in patients with neurological symptoms): 1 mg IM monthly for life. Oral administration vitamin B12 at high doses (1–2 mg/day) is as effective as parenteral administration. In severely deficient patients, hypokalemia may occur early in treatment due to the use of potassium to produce new cells.

2. 4-5 days after the appointment of cyanocobalamin, a study should be made of the number of reticulocytes, a significant increase in which (reticulocyte crisis!) indicates the adequacy of the appointment of cyanocobalamin and the transformation of megaloblastic hematopoiesis into normoblastic. In the absence of a reticulocyte crisis, the diagnosis of B12 deficiency anemia should be reconsidered.

3. In the case of severe anemia with symptoms from the circulatory system (heart failure, increased angina attacks), red blood cell transfusion is indicated. Treatment leads to the elimination of anemia and associated hematological disorders. An increase in the number of reticulocytes and a decrease in MCV is observed after 4–5 days of treatment. An increase in the level of Hb, the number of erythrocytes and Ht occurs after 7 days, and the normalization of these indicators occurs after ≈2 months. Symptoms of peripheral neuropathy may partially decrease (usually within 6 months), damage to the spinal cord is irreversible. Addison-Birmer disease is associated with a 2- to 3-fold increased risk of gastric adenocarcinoma. Vitamin B12 (or folic acid) deficiency can lead to hyperhomocysteinemia, which contributes to the development of atherosclerosis and thrombosis.

PREVENTION For the purpose early detection Vitamin B12 deficiency should be observed in patients after gastrectomy or bariatric surgery, as well as those on a strict vegetarian or vegan diet (especially during pregnancy and breastfeeding) and consider the prophylactic use of cyanocobalamin parenterally or p / o.

Description of B12 deficiency anemia:

Malabsorption of vitamin B12 (cobalamin) causes pernicious anemia. This vitamin, present in meat and vegetables, is normally actively absorbed in the ileum (the lower part of the small intestine that connects to the large intestine). However, vitamin B12 can be absorbed and enter the bloodstream only in combination with the so-called intrinsic factor - a protein formed in the stomach. Without intrinsic factor, vitamin B12 remains in the intestine and is excreted in the feces. In pernicious anemia, intrinsic factor is not produced in the stomach, vitamin B12 is not absorbed, and anemia develops even with sufficient intake of this vitamin from food. But since the liver has a large supply of vitamin B12, anemia develops only 2-4 years after its normal absorption in the intestine stops.

With a deficiency of vitamin B12, not only the maturation of red blood cells is delayed, but the nervous system is also affected - tingling appears in the hands and feet, loss of sensation in the legs (feet) and hands, muscle spasms. Other symptoms may include a specific type of color blindness (impaired perception of yellow and blue), inflammation or burning of the tongue, weight loss, darkening of the skin, confusion, depression, and decreased intellectual ability.

Pathogenesis of B12 deficiency anemia:

Cyanocobalamin is a cofactor in the methyltransferase catalytic reaction, which resynthesises methionine and simultaneously regenerates 5-methyltetrahydrofolate to tetrahydrofolate and 5,10 methylenetetrahydrofolate.

With folate and (or) cyanocobalamin deficiency, the process of incorporating uridine into the DNA of developing hematopoietic cells and the formation of thymidine is disrupted, which causes DNA fragmentation (blocking its synthesis and disruption of cell division). In this case, megaloblastosis occurs, the accumulation of large forms of leukocytes and platelets, their early intramedullary destruction and shortening of the life of circulating blood cells occur. As a result, hematopoiesis is ineffective, anemia develops, combined with thrombocytopenia and leukopenia.

In addition, cyanocobalamin is a coenzyme in the conversion of methylmalonyl-CoA to succinyl-CoA. This reaction is necessary for the metabolism of myelin in the nervous system, and therefore, with cyanocobalamin deficiency, along with megaloblastic anemia, damage to the nervous system is noted, while with folate deficiency, only the development of megaloblastic anemia is observed.

Cyanocobalamin is found in foods of animal origin - liver, kidneys, eggs, milk. Its reserves in the body of an adult (mainly in the liver) are large - about 5 mg, and given that the daily loss of vitamin is 5 μg, then complete exhaustion stocks in the absence of intake (malabsorption, with a vegetarian diet) occurs only after 1000 days. Cyanocobalamin in the stomach binds (against the background of an acidic reaction of the environment) with an intrinsic factor - a glycoprotein produced by the parietal cells of the stomach, or other binding proteins - R-factors present in saliva and gastric juice. These complexes protect cyanocobalamin from destruction during transport through the gastrointestinal tract. AT small intestine at an alkaline pH value, under the influence of pancreatic juice proteinases, cyanocobalamin is cleaved from R-proteins and combined with intrinsic factor. In the ileum, the intrinsic factor complex with cyanocobalamin binds to specific receptors on the surface. epithelial cells, the release of cyanocobalamin from the cells of the intestinal epithelium and transport to tissues occurs with the help of special blood plasma proteins - transcobalamins 1,2,3, and the transport of cyanocobalamin to hematopoietic cells is carried out mainly by transcobalamin 2.

Folic acid is found in green leaves of plants, fruits, liver, kidneys. Folate reserves are 5-10 mg, the minimum requirement is 50 mcg per day. Megaloblastic anemia can develop after 4 months total absence dietary folate intake.

Symptoms of B12 deficiency anemia:

Thus, a triad is characteristic of B12-deficiency anemia:
- blood damage;
- damage to the gastrointestinal tract;
- damage to the nervous system.

Diagnosis of B12 deficiency anemia:

2. In stained smears - a typical picture: along with the characteristic oval macrocytes, there are normal-sized erythrocytes, microcytes and schizocytes - poikilo- and anisocytosis.

3. Serum bilirubin level increased due to indirect fraction

4. Mandatory puncture of the bone marrow, since such a picture on the periphery can be with leukemia, hemolytic anemia, aplastic and hypoplastic states (however, it should be noted that hyperchromia is characteristic of B12 deficiency anemia). Bone marrow cellular, the number of nucleated erythroid elements is increased by 2-3 times against the norm, but erythropoiesis is ineffective, as evidenced by a decrease in the number of reticulocytes and erythrocytes in the periphery and a shortening of their life expectancy (normally, an erythrocyte lives 120-140 days). Find typical megaloblasts - the main criterion for the diagnosis of B12-deficiency anemia. These are cells with "nuclear-cytoplasmic dissociation" (with a mature hemoglobinized cytoplasm, a delicate, reticulated nucleus with nucleoli); large granulocytic cells and giant megakaryocytes are also found.

Treatment for B12 deficiency anemia:

This type of anemia is not uncommon, and, as a rule, a lot of mistakes made by patients are associated with it, making any amateur method of treatment annoyingly meaningless, although in principle, everything is solved quite easily.

Vitamin B 12 deficiency anemia usually develops in the elderly, and very rarely in the young. The reason is that due to long-term atrophic gastritis (i.e. gastritis with thinning of the inner lining of the stomach), which is usually not accompanied by any symptoms, the body ceases to produce (or is inactivated by antibodies) the intrinsic factor that ensures the absorption of vitamin B 12 (cobalamin) from food in the intestines. This vitamin is necessary primarily for hematopoiesis - the absence leads to anemia, however, other organs also suffer (the construction of the nuclear substance of the cells is disrupted), including the nervous system (exposed nerve fibers). As a result of damage to the nerves, the sensitivity in the limbs, especially in the legs, worsens, and "woolness of the legs" appears.

In nothing else within a person, nature has shown such thriftiness as in relation to vitamin B 12 - in the liver, its warehouses can be empty only 3-4 years after the moment when the supply from the outside is completely stopped. Since the decrease in the rate of accumulation of cobalamin in atrophic gastritis occurs gradually, with the appearance of signs of the disease, you can be sure that about 5 years have passed before it would be necessary to start prophylactic treatment for anemia.

Unfortunately, the desired moment cannot be determined. And over a five-year period, this is what happens: regarding sciatica (at least 90% of people suffer from back pain in old age), one of the doctors manages to prescribe vitamin injections (popularly “red injections”) in a short course, and ... the moment of detection the underlying disease moves away for an indefinitely long period.

Vitamin B 12 deficiency anemia is manifested by pallor, puffiness, slight icteric skin tone, shortness of breath, significant weakness. The appearance of the patient is very similar to that of a cancer patient, and this can disorient the patient or his relatives, lead to depression from a sense of hopelessness, or to the old person's refusal to see a doctor.

Examination of a typical patient is carried out quite quickly, since blood tests completely solve almost all issues, in addition, however, you have to examine the stomach - do not give up on this. Only previous attempts at self-treatment can interfere with the diagnosis: taking many drugs very quickly and sharply distorts the whole picture. The result is the formation of the doctor's impression of the "incomprehensible" nature of anemia and the excruciatingly long execution of a heap diagnostic procedures to rule out other pathologies. The “extreme” will be the one who was self-medicating - he will not receive timely correct therapy.

Treatment of vitamin B 12 deficiency anemia consists in replenishing a known deficiency. Since taking the drug through the mouth is meaningless (the substance is not absorbed), it is necessary to prescribe injections of cyanocobalamin (oxycobalamin is often used abroad: it is more effective). Intramuscular injections are given frequently at first, i.e. once a day until normalization of blood hemoglobin, then once a week in order to create a reserve in the liver and then one injection per month throughout the WHOLE FURTHER LIFE (!). The most common mistake made by patients is that they stop treatment when the desired result is achieved.

Indeed, vitamin B 12, when administered in deficient conditions, has a "magic" effect: complexion and well-being improve before our eyes. However, you should be aware that the conditions for the absorption of the vitamin in the intestines have been broken forever and will never be restored (by the way, you should not be very upset about this). Accordingly, a legitimate conclusion follows: a vitamin deficiency will develop again if cyanocobalamin is not administered regularly.

By the way, this deficiency cannot be eliminated by any special nutrition. It is absurd to talk about "red diets" (carrots, beets, red caviar, etc.): as in the case of all other types of anemia, they do not make the slightest sense. Iron preparations are also not needed, since there is a deficiency of a specific substance - cobalamin (vitamin B 12), and iron stores in the body are most likely normal (mixed deficiency is extremely rare, but this problem is only within the competence of a specialist). With a pronounced lack of vitamin B 12, it is risky to use multivitamins, especially those that contain folic acid, since the latter will indirectly aggravate damage to the nervous system. On the background effective therapy this ban will be lifted, although the need for a bunch of other vitamins will still not appear.

At proper treatment Vitamin B 12-deficiency anemia does not impose any life restrictions. Doing 1 intramuscular injection per month is completely easy. It does not hurt to have a package of medicine with a good expiration date in stock. Difficulties arise in the presence of an allergy to the usual preparation of cyanocobalamin, but they are surmountable.

After the operation of removing the entire stomach (gastrectomy), vitamin B 12 injections should be started immediately in the mode of 1 injection per month.

With any type of anemia, the supply of tissues with oxygen to one degree or another decreases. In old age, this leads to the appearance (if not before) or aggravation of the symptoms of impaired blood circulation in the heart, in the brain - angina pectoris, heart failure, dizziness, memory, etc. may increase. With the narrowing of the lumen of the vessels of the legs (far advanced atherosclerosis), intermittent claudication becomes unbearable and the person is unable to walk the same distance without stopping as before. In those who suffer lung diseases, which are accompanied by shortness of breath, the latter increases. In this regard, the exact implementation of the doctor's recommendations for the treatment of anemia will be the key to the prevention of these situations.

Different types of anemia are manifested by pallor skin and mucous membranes. A person who is attentive to himself will always pay attention to this, and if he does not pay attention, then let those around him tell him. Anemia is a strong argument in favor of visiting a doctor and getting an exhaustive full examination and effective treatment. Neither excessive employment (at work, with children around the house, etc.), nor elderly age cannot justify a passive attitude towards their health.

Candidate of Medical Sciences, Associate Professor V.A. Tkachev

AT 12 -DEFICIENCY ANEMIA

AT 12 -deficiency anemia- this is a severe progressive anemia that occurs when there is a violation of the absorption of vitamin B 12 from food, due to reduced (or in the absence) secretion of internal gastric factor.

The nomenclature of the name of this disease is different, and it is often referred to in the literature as pernicious anemia (perniciosa - fatal), malignant Addison-Birmer disease (by the names of the authors), and megaloblastic anemia (by the type of hematopoiesis).

Persons older than 40 years are ill. Women are twice as likely to be affected by this disease as men, and especially those over the age of 50-60. There are known cases of B 12 deficiency anemia in children fed with goat milk or powdered milk mixtures. The incidence is 20 to 60 cases per 10,000 population.

History reference. The first description of this disease was made by Coombs in 1822 and called it severe primary anemia. In 1855, the physician Addison described this suffering under the name "idiopathic anemia." In 1872, Birmer published the results of monitoring a group of patients suffering from progressive pernicious anemia. However, the possibility of curing this disease appeared only in 1926, when Minot and Murphy discovered a pronounced therapeutic effect from the administration of raw liver.

Three years later, the American physiologist Castle showed that raw meat, liver, yeast, treated with gastric juice healthy person, have the property of inducing remission in a patient with pernicious anemia. Castle's research formed the basis of the concept, according to which, as a result of the interaction of two factors - external, contained in raw meat, raw liver, yeast, and internal, produced by the gastric mucosa, an anti-anemic compound is created that ensures the physiological maturation of bone marrow cells.

The nature of the external factor has been established - it is cyanocobalamin (vitamin B 12 ) . Vitamin B 12, according to the needs of the body, is used not only for hematopoiesis in the bone marrow, but also for the normal functioning of the nervous tissue and digestive organs.

A complex compound consisting of peptides (appearing during the conversion of pepsinogen to pepsin) and mucoids (secreted by additional cells of the gastric mucosa) was named gastromucoprotein or intrinsic factor of Castle. The role of the internal factor (gastromucoprotein) is the formation of a complex with vitamin B 12, which ensures the transport of cyanocobalamin through the intestines and prevents its decay and inactivation. Resorption (absorption) of vitamin B 12 occurs in the ileum. Its further entry into the portal circulation is carried out with the help of protein carriers: transcobalamin-1 (-globulin) and transcobalamin-2 (-globulin), which form a protein-B 12-vitamin complex that can be deposited in the liver.

Etiology. The leading factor in the etiology of the disease is endogenous vitamin B deficiency 12 , arising from a violation of its absorption due to the cessation of secretion of the internal factor (gastromucoprotein).

B12 malabsorption may occur as a result of damage to the gastrointestinal tract by an inflammatory or malignant process, after subtotal or total removal of the stomach, after extensive resection of part of the small intestine. In rare cases, pernicious anemia develops with normal secretion of internal gastric factor and is due to congenital absence of transcobalamin-2, with which vitamin B 12 binds and is delivered to the liver, or as a result absence of a protein acceptor in the intestine(perceiving) vitamin B 12, necessary for the entry of cyanocobalamin from the intestine into the bloodstream. In some cases there is genetic developmental factor In 12-deficiency anemia due to a congenital disorder in the production of gastric factor or the presence of antibodies against parietal cells.

The following factors can also lead to the occurrence of B 12 deficiency anemia:

malabsorption 12v small intestine as a result chronic enteritis or celiac disease;

competitive uptake of vitamin B12 in the small intestine wide ribbon or microorganisms;

complete exclusion of food of animal origin;

prolonged decreased exocrine secretory activity of the pancreas, resulting in a violation of the breakdown of protein R, without which vitamin B 12 cannot bind to mucopolysaccharide;

long term appointment some medicines : methotrexate, sulfasalazine, triamterene, 6-mercaptopurine, azathioprine, acyclovir, fluorouracil, cytosar, phenobarbital, etc.

Pathogenesis. Violation of hematopoiesis in B 12 deficiency anemia is characterized by megaloblastic type for all three blood sprouts: erythroid, granulocytic and megakaryocytic. The inefficiency of red hematopoiesis is noted: a violation of the differentiation of erythroid cells and the appearance of abnormal cells such as promegaloblasts, megaloblasts (large cells with basophilic cytoplasm and a nucleus containing nucleoli).

As a result of defective metabolism of folic acid (due to deficiency of B 12), which is involved in the formation of DNA, cell division is disrupted. The consequence of this is a pronounced intramedullary death of erythroid elements and a decrease in the number of erythrocytes in the periphery.

Due to the failure of the cellular elements of the blood, it is strengthened hemolysis, which is manifested by hyperbilirubinemia, urobilinuria, an increase in stercobilin in the feces.

Pathological changes characterized by general anemia, icterus of the skin and mucous membranes, fatty degeneration of the myocardium, liver, kidneys. The bone marrow is juicy, crimson in color due to hyperplasia.

On the part of the digestive organs, atrophic changes in the papillae of the tongue (their smoothness), its inflammatory changes (glossitis), aphthous rashes, cracks (Gunter's glossitis), as well as atrophy of the mucous membrane of the cheeks, palate, pharynx, and esophagus are revealed. The greatest atrophy is recorded in the stomach, which is characterized by thinning of its walls, the formation of polyps. The intestinal mucosa is also atrophied. The spleen is usually normal or enlarged.

Hepatomegaly is unexpressed. Hemosiderosis is detected in the liver, spleen, kidneys (rusty shade on the cut) as a result of hemolysis of erythrocytes.

In the nerve fibers of the tongue (the nerve plexuses of Meissner and Auerbach), as well as in the posterior columns of the spinal cord (focal swelling with the breakdown of myelinated nerve fibers), dystrophic changes are noted.

Clinical manifestations In 12-deficiency anemia, they often develop gradually: weakness, malaise, dizziness, dyspeptic disorders, tinnitus, and a tendency to obesity increase. Rarely, the disease begins acutely, with a rise in body temperature to 38 C, severe weakness.

Anemia syndrome characterized by lethargy, pallor of the skin with a lemon-yellow tint, sometimes (in 12% of patients) subicteric sclera. Anemia is recorded in the peripheral blood, more often (58%) severe, with an increase in the color index to 1.4, a decrease in reticulocytes to 0.5 - 1.0% (reticulocytosis in a third of patients), poikilocytosis and the presence of Jolly bodies and Cabot rings in erythrocytes. Leukopenia, lymphocytosis, but thrombocytopenia are often detected.

In the bone marrow, signs of a megaloblastic type of hematopoiesis are determined.

Syndrome of gastric dyspepsia(37.% of observations) is manifested by belching, nausea, loss of taste sensations, decreased appetite up to aversion to food, heaviness in the epigastrium, sometimes dysphagia, a burning sensation of the tongue, oral mucosa. Endoscopy reveals atrophic changes in the mucous membrane of the esophagus and stomach.

Intestinal dyspepsia syndrome characterized by unstable stool, weight loss.

Glossitis manifested by the presence of a "scalded" (red) or "varnished" tongue with cracks. Pain in the tongue is observed in 30% of patients with B 12 deficiency anemia.

jaundice syndrome occurs in 50% of patients and is manifested by subicteric sclera and hyperbilirubinemia.

funicular myelosis syndrome(sensory ataxia - impaired coordination of movements) is observed in patients with B 12 -deficiency anemia in 11% of cases and develops as a result of impaired proprioceptive sensitivity due to atrophic processes in the posterior horns of the spinal cord. There may be other symptoms of damage to the nervous system: paresthesia, dysfunction of the pelvic organs, decreased reflexes.

Syndrome of intercostal neuralgia occurs significantly more often (up to 30% of cases) than the signs of funicular myelosis, manifests itself with neuralgic pain along the intercostal space and is also due to functional insufficiency of the nerve tissue of the conductors.

In some patients, damage to the cranial nerves (visual, auditory, olfactory) is noted, the presence of symptoms of spinal paralysis (spastic paraparesis with increased reflexes and clonuses) Central scotoma (visual field defect) with loss of vision can be detected.

Changes from central nervous system may appear psychomotor agitation syndrome(manic state with euphoria or depression syndrome with impaired memory and criticism - megaloblastic dementia).

Cardiac syndrome(in 15–20% of cases) is characterized by shortness of breath, palpitations, pain in the region of the heart, myocardial dystrophy. Auscultation of the heart reveals a functional anemic murmur. The ECG is determined by the decrease in ST, the expansion of the ventricular complex.

Edema syndrome occurs in B 12 deficiency anemia in 80% of cases and is manifested by peripheral edema, which can reach the degree of anasarca, as a result of circulatory failure.

Liver enlargement ( hepatomegaly syndrome) occurs in 22% of patients, enlargement of the spleen ( splenomegaly syndrome) in 10% of cases.

Untreated B12 deficiency anemia can develop pernicious coma syndrome, manifested by cerebral ischemia, loss of consciousness, areflexia, drop in body temperature, decrease in blood pressure, vomiting, involuntary urination.

With the aim of disease diagnosis a thorough hematological examination is carried out, including the study pictures of peripheral blood, sternal punctate and serum factors involved in hematopoiesis. Accurate diagnosis is very important, because. these patients in some cases require lifelong treatment.

Hypersegmentation of neutrophils(more than five nuclear lobes) of peripheral blood is the first hematological pathology with megaloblastic status. In a healthy person, up to 2% of hypersegmented neutrophils can circulate in the blood. In patients with megaloblastic anemia, the number of hypersegmented neutrophils exceeds 5%.

Bone marrow hematopoiesis is characterized by megaloblastic type, for which irritation of the red germ and the appearance of megaloblasts are typical. The bone marrow is hypercellular due to an increase in the number of nucleated red cells. As a result of a violation of cell division, erythroid cells become very large ( megaloblasts). They are characterized by large size, delicate structure and unusual arrangement of chromatin in the nucleus, asynchronous differentiation of the nucleus and cytoplasm.

In the blood serum of patients with B12-deficiency anemia increased concentration of bilirubin, iron, ferritin(iron-containing liver protein). Serum lactate dehydrogenase (LDH) activity is significantly increased and increases as the disease progresses. Level serum cyanocobalamin usually low, but may be normal.

Differential Diagnosis held with folate deficiency anemia. Folic acid deficiency is usually observed at a younger age, is not accompanied by atrophic changes in the gastric mucosa and neurological symptoms.

To exclude folic deficiency anemia, a Schilling test is performed: vitamin B 12 is administered parenterally, which is determined in the urine in minimal amounts with B 12 deficiency anemia and in large quantities with folic deficiency. It is important to consider that the appointment of folic acid to patients with B 12 deficiency anemia quickly contributes to the development of funicular myelosis.

It should be remembered that symptomatic megaloblastic anemia is caused by tumors of the stomach, small and caecum, as well as helminthic invasion(helminthic B 12 deficiency anemia), which must be excluded when verifying the diagnosis.

It is necessary to differentiate with erythromyeloses(initial forms of manifestation of leukemia), which are accompanied by anemia that occurs with an increased content of vitamin B 12 in the blood and is resistant to treatment with cyanocobalamin.

When conducting a differential diagnosis of B 12 -deficiency anemia, it is necessary to establish its causes.

Treatment In 12-deficiency anemia includes parenteral administration of vitamin B 12 or hydroxocobalamin (a metabolite of cyanocobalamin) in doses that meet the daily requirement and double the depot reserves. Vitamin B 12 is administered at 1000 mcg intramuscularly daily for two weeks, then once a week until the hemoglobin level normalizes, after which they switch to the introduction of 1 time per month throughout life.

Oxycobalamin on pharmacological properties close to cyanocobalamin, but compared with the latter, it quickly turns into an active coenzyme form in the body and lasts longer in the blood. Oxycobalamin is administered at a dose of 500–1000 mcg every other day or daily. In the presence of neurological symptoms, it is necessary to administer the drug at a dose of 1000 mcg every two weeks for six months.

With funicular myelosis, massive doses of cyanocobalamin 1000 mcg daily for 7-10 days are prescribed, then twice a week until the neurological signs disappear.

The beginning of therapy with cobalamin quickly improves the well-being of patients. Bone marrow erythropoiesis turns from megaloblastic to normoblastic within 12 hours after the administration of vitamin B12. Therefore, the appointment of vitamin B 12 in a coma is an urgent measure. Reticulocytosis appears on days 3–5, its peak (reticulocytic crisis) is most pronounced on days 4–10. The concentration of hemoglobin is normalized in 1-2 months. Hypersegmentation of neutrophils persists for up to 10–14 days.

RBC transfusions indicated for the urgent elimination of symptoms of hypoxia.

After cobalamin therapy may develop severe hypokalemia. Therefore, during treatment with vitamin B 12, it is necessary to carefully monitor the content of potassium in the blood and, if necessary, carry out replacement therapy.

Treatment with cobalamin should be given to all patients after total gastrectomy. To prevent exacerbation, vitamin B 12 is administered once every two weeks, 100-200 mcg.

Medical examination. Patients with B 12 deficiency anemia are subject to dispensary observation, during which the state of peripheral blood is monitored 1-2 times a year, as well as the treatment of diseases and conditions that led to the development of this type of anemia.

There are different schemes for maintenance therapy with cobalamins. When appointed cyanocobalamin life-long annual preventive three-week courses of 400-500 mcg every other day or monthly administration of 500-1000 mcg of the drug are recommended. Hydroxycobalamin recommended by annual preventive courses of one injection per week (1 mg) for 2 months.