Pernicious anemia (Addison-Biermer disease, B12 deficiency anemia). Addison-Birmer disease - symptoms, treatment

Pernicious anemia(Addison-Birmer disease or megaloblastic anemia) is characterized by a disorder of hematopoiesis that occurs when there is a deficiency folic acid and vitamin B12 in the body. Previously, this pathological process was called malignant anemia. The nervous system and bone marrow are particularly sensitive to a deficiency of this vitamin. At the same time, many immature large precursors of megaloblasts (erythrocytes) are formed in the body.

Causes of pernicious anemia

In the body, vitamin B12 is absorbed in the area ileum, or rather in the lower part. Anemia can develop due to insufficient amounts of this vitamin in foods included in the diet. Also the reason for the development pathological process may be due to insufficient production of Carls factor (intrinsic) in the area of ​​parietal gastric cells.

Vitamin B12 deficiency with the development of a clinical anemic picture or in its absence can cause the appearance of neurological disorders, which occurs due to the inevitable synthesis fatty acids. This may result in irreversible damage nerve cells and demyelination, which is accompanied by tingling or numbness of the extremities, as well as ataxia.

Symptoms of pernicious anemia

The pernicious form of anemia develops slowly, so at the very beginning it is not accompanied by pronounced symptoms. In this case, there are such manifestations as fast fatiguability, weakness, rapid heartbeat, shortness of breath and dizziness.

Symptoms of pernicious anemia as it progresses include the appearance of the following signs:

• pale icteric skin;
• yellowness of the sclera;
• swallowing disorder;
• tongue pain;
• development of glossitis (inflammatory process of the tongue);
• enlarged liver, spleen.

A characteristic symptom of pernicious anemia is damage to nerve cells, which is called funicular myelosis. As it develops, sensitivity is impaired and constant painful sensations in the area of ​​the extremities, reminiscent of tingling. In this case, there is numbness and a feeling of “crawling goosebumps”. Patients note the presence of pronounced muscle weakness, which leads over time to gait disturbances and muscle atrophy.

Diagnosis of pernicious anemia

The diagnosis is made based on the results of the following research activities:

• A blood test for pernicious anemia is the most informative method diagnostics, as it allows you to determine the level of vitamin B12 in the serum.
• A urine test is a mandatory research measure, which also makes it possible to determine how much vitamin is excreted from the body.
• Stool examination reveals the presence of helminthic infestations.

Diagnosis of pernicious anemia also includes determining the root cause of the disease. First of all, the condition is examined gastrointestinal tract for the presence of gastritis, ulcers and other pathologies affecting the absorption nutrients. It is mandatory to check the condition of the kidneys, since in the presence of diseases such as pyelonephritis or renal failure Treatment with vitamin B12 injections does not produce results.

Treatment of pernicious anemia

Pernicious anemia requires timely treatment, otherwise there is Great chance defeats spinal cord. First, there is a symmetrical disruption of the functioning of systems and muscle structures in area lower limbs, and then a violation of pain and superficial sensitivity develops.

Treatment of pernicious anemia should be carried out under the supervision of a physician. All measures are aimed at eliminating the causes of development pathological changes. First of all, measures are taken to treat diseases of the gastrointestinal tract, and the patient is also prescribed balanced diet. To normalize hematopoiesis in the area bone marrow appointed replacement therapy, which is an inflammation of vitamin B12 deficiency.

After the first injections, there is an improvement in well-being and normalization of blood levels.

The duration of treatment ranges from 1 month or more, which depends not only on the stage of the disease, but also on the intermediate results of therapy. In order to achieve stable remission it is necessary to carry out therapeutic measures for six months, it is recommended to adhere to the following actions:

• Administer cyanocobalamin daily for 2 months.
• After 2 months, inject the drug once every 2 weeks.

Addison's disease has another name - bronze disease. This means a violation of the functioning of the adrenal glands. In turn, this violates hormonal balance, as a result, the synthesis of glucocorticoids decreases or completely disappears.

Addison-Beermer disease has a large number of symptoms, which mainly arise from the involvement of most of the crust. The cause of this disease can be different. In 8 out of 10 cases, Addison-Biermer disease develops due to an autoimmune process in the body.

But sometimes the disease can be accompanied by tuberculosis, which affects the adrenal glands. Pathology can be congenital and inherited. Autoimmune type The disease is most common in the female half of the population.

The most common symptoms of Addison's disease are painful sensations, disturbances in the functioning of the gastrointestinal tract and hypotension. Pathology can lead to metabolic disorders. This disease can also be treated with the help of traditional medicine, which will strengthen the functioning of the adrenal glands and also help in the fight against microbes and inflammation.

General characteristics of the disease

Addison's disease, photos of which clearly show the affected area, can be either primary or secondary. secondary failure. As many people know, pathology affects the glands internal secretion, responsible for the production of some of the most important hormones in the human body. These organs have 2 zones:

• crust;
• brain matter.

Each zone is responsible for synthesizing different types hormones. The medulla produces norepinephrine and adrenaline. They are especially necessary for people in stressful situation, these hormones will help use all the body's reserves.

Other hormones are also synthesized in the cortex.

• Corticosterone. It is necessary for the balance of water and salt metabolism in the body, and is also responsible for the regulation of electrolytes in blood cells.
• Deoxycorticosterone. Its synthesis is also required for water-salt metabolism, and it also affects the efficiency and duration of muscle use.
• Cortisol is responsible for the regulation of carbon metabolism, as well as the production of energy resources.

The pituitary gland has a great influence on the adrenal cortex; it is a gland that is located in the brain area. The pituitary gland produces a special hormone that stimulates the adrenal glands.

As mentioned above, Addison-Biermer disease has two types. Primary is the disease itself, when the functioning of the adrenal glands is completely disrupted due to negative factors. Secondary involves a decrease in the amount of ACTH synthesized, which, in turn, impairs the functioning of the endocrine glands. In a situation where the pituitary gland does not produce enough hormones a long period– dystrophic processes may begin to develop in the adrenal cortex.

Causes of the disease

The primary form of Addison-Biermer disease is quite rare. It can be found with equal probability in both men and women. In most cases, the diagnosis is made to people aged between 30 and 50.

There is also chronic form diseases. Such development of pathology is possible due to various negative processes. In almost all cases, namely in 80%, the cause of Addison-Biermer disease is an autoimmune condition of the body. In 1 out of 10 cases, the cause of the pathology is damage to the adrenal cortex by an infectious disease, for example, tuberculosis.

For the remaining 10% of patients, the causes may vary:

• this may be affected long-term use medicines, in particular, glucocorticoids;
• types of fungal infection;
• injury to the endocrine glands;
• amyloidosis;
• tumors of both benign and malignant nature;
• bacterial infections with a weakened human immune system;
• pituitary dysfunction;
• genetic predisposition to the disease.

Addison's disease can also cause other syndromes, such as adrenal crisis, which occurs when the concentration of adrenal hormones is too low.

There are most probable reasons occurrence of a crisis:

• severe stress condition;
• violations in dosage when drawing up a course of treatment with hormonal drugs;
• may worsen the disease infectious lesion adrenal cortex;
• adrenal gland injury;
• circulatory problems, such as blood clots.

Symptoms of the disease

Symptoms of Addison's disease directly depend on the disruption of the synthesis of certain types of hormones. Clinical manifestations of the disease may vary. The determining factors are the form of the pathology and its duration.

The most common clinical manifestations of the pathology are as follows:

• Addison's pathology has its name bronze disease for a reason. Most a clear sign This disease is a pigmentation disorder. The skin changes its color. The shade of the mucous membranes changes. It's all about too much pigmentation. With a lack of adrenal hormones, significantly more ACTH is produced, this is explained by the need to stimulate the functioning of the endocrine glands.
• One of the common clinical manifestations diseases are chronic hypotension. This may lead to dizziness and fainting, sensitivity to low temperatures increases.
• If the endocrine glands are not functioning sufficiently, the entire body as a whole weakens. If you have constant fatigue, fatigue, you should consult a medical specialist.
• With this pathology, disturbances in the functioning of the gastrointestinal tract often occur; this can manifest itself in the form of vomiting, constant nausea and diarrhea.

• The disease can affect the emotional component. Depressive state is one of the clinical manifestations of Addison's disease.
• Patients noted increased sensitivity to irritants. The sense of smell and hearing are enhanced, and a person feels the taste of food better. In most cases, patients prefer to eat salty foods.
• Painful sensations in muscle tissue can also be a symptom of Addison's pathology. This is explained by an increase in potassium concentration in blood vessels.
• As mentioned above, one of the clinical manifestations of the disease is adrenal crisis, which occurs as a result of a sharp decrease in the level of hormones of the endocrine glands. The most popular symptoms of a crisis are pain in the abdomen, low blood pressure, and disturbed salt balance.

Diagnosis of the disease

First of all, patients pay attention to changes in shade skin. This phenomenon signals lack of activity adrenal hormones. When contacting a medical specialist in this situation, he determines the ability of the adrenal glands to increase the synthesis of hormones.

Diagnosis of Addison's disease occurs by administering ACTH and measuring the cortisol content in the blood vessels before administration of the drug and 30 minutes after vaccination. If a potential patient does not have problems with adrenal function, cortisol levels will increase. If the concentration of the test substance has not changed, the person has disturbances in the functioning of the endocrine glands. In some cases, for a more accurate diagnosis, the hormone content in urea is measured.

Treatment of pathology

Up to date with treatment Special attention should be given to the diet. It must be varied, it must contain the necessary amount of proteins, fats and carbohydrates to provide the body. It is especially worth paying attention to vitamins B and C. They can be found in bran, wheat, fruits and vegetables. In addition, the patient is recommended to drink more decoctions based on rose hips or black currants.

With Addison's disease, the sodium content in the body decreases, for this reason it is recommended to focus on salty foods. In addition, the pathology is characterized by an increased concentration of potassium in the blood vessels; it is recommended not to include foods that are rich in potassium in the diet. These include potatoes and nuts. Patients are advised to eat as often as possible. Before going to bed, medical experts recommend eating dinner to reduce the chance of hypoglycemia in the morning.

Almost all folk recipes are aimed at stimulating the adrenal cortex. ethnoscience has a mild effect, side effects practically absent. Application folk recipes will not only improve the functioning of the adrenal glands, but will also have a positive effect on the condition of the entire body as a whole. Using this approach, you can normalize the functioning of the gastrointestinal tract and counteract inflammatory processes of a chronic nature. It is recommended to use several recipes in turn, this will avoid the body becoming addicted.

Prevention and prognosis

If therapy was started in a timely manner and all recommendations of a medical specialist were followed, the outcome of the disease will be favorable. The disease will not affect life expectancy in any way. In some cases, Addison's disease is accompanied by a complication - adrenal crisis. In such a situation, you should immediately seek advice from a medical specialist. A crisis can be fatal. Addison's disease is accompanied by fatigue, weight loss and loss of appetite.

Changes in the shade of the skin do not occur in all cases; deterioration in the functioning of the endocrine glands occurs gradually, so it is difficult for a person to detect this on their own. In such situation critical condition develops sharply and unexpectedly for the patient. Most often, the reason is some negative factor, such as stress, infection or injury.

Since Addison's disease is often autoimmune in nature, there are practically no preventive measures. You should keep an eye on your immune system, avoid consumption alcoholic drinks, smoking. Medical experts recommend paying attention to manifestations in a timely manner infectious diseases, especially tuberculosis.

Otherwise, Addison-Beermer anemia, relatively rare disease, usually occurs in adults aged 45-60 years.

Interestingly, it is more common in people with blood group 2 and Blue eyes. Belongs to the group of megaloblastic anemias.

Causes of vitamin B12 deficiency

The cause of this disease is antibodies directed against Castle factor (IF - intrisic factor), which, by binding to vitamin B12 in the stomach, ensures its transport through the intestinal wall into the blood; and antibodies directed against the stomach lining cells that produce acid. As a rule, vitamin B12 deficiency is accompanied by a diagnosis of inflammation of the gastric mucosa.

Other reasons leading to vitamin B12 deficiency This:

• improper diet (vegetarianism);
• alcoholism;
• congenital Castle factor deficiency;
• condition after gastrectomy – condition after resection of the small intestine;

Symptoms of Addison-Birmer's disease

Symptoms characteristic of any other anemia appear, that is:

• weakness and fatigue;
• pain and dizziness;
• fast heart rate (in severe forms of the disease);
• pallor of the skin and mucous membranes.

Diseases associated with the gastrointestinal tract may also occur:

• signs of inflammation of the tongue (dark red or very pale tongue, burning);
• inflammation of the oral cavity: redness, soreness, swelling;
• loss of sense of taste;
• constipation or diarrhea, nausea.

Neurological symptoms also develop:

• feeling of numbness in the arms and legs;
• feeling of “tingling in the limbs”;
• sensation of current passing through the spine when tilting the head forward;
• unsteady gait;
• memory loss and mental changes, such as depression, hallucinations.

The more time has passed since the appearance neurological symptoms before treatment begins, the less likely it is to recover. Changes that last longer than six months tend to last a lifetime.

Diagnosis of pernicious anemia

Having noticed that a patient has symptoms of anemia, the doctor should order a blood test. If a decrease in hemoglobin levels and red blood cells is detected blood cells, other blood parameters are also assessed.

When megaloblastic anemia and pernicious anemia, there is an increased size of red blood cells (MCV → 110). Then you must find out the reason for the improper metabolism of vitamins. In particular, evaluate the level of cobalamin in the blood: less than 130 pg/ml indicates its deficiency.

The content of methylmalonic acid in the blood and urine is also examined. It is formed in increased quantities in case of a lack of vitamin B12, so its increased content confirms the malabsorption of the vitamin. When cobalamin levels decrease, testing for antibodies that attack Castle factor is recommended. When the result is negative, a Schilling test must be performed.

A deficiency of this vitamin is also evidenced by the body's favorable response to treatment. An increase in the number of young red cells in the blood after 5-7 days indicates their recovery. Pernicious anemia is effectively reversible with the addition of vitamin B12. Usually prescribed 1000 mcg per day for 2 weeks. After anemia symptoms change, the drug administration regimen is changed and the drug is prescribed for the rest of life.

Before the discovery of vitamin B12, the disease was fatal and therefore was called malignant; today this name has only historical value.

The disease, described by Addison in 1855 and Biermer in 1868, became known among doctors as pernicious anemia, that is, a fatal, malignant disease. Only in 1926, in connection with the discovery of hepatic therapy for pernicious anemia, the idea that had prevailed for a century about the absolute incurability of this disease was refuted.

Clinic. People over 40 years of age usually get sick. The clinical picture of the disease consists of the following triad: 1) disturbances from digestive tract; 2) disorders of the hematopoietic system; 3) violations by nervous system.

Symptoms of the disease develop unnoticed. Already many years before the pronounced picture of malignant anemia, gastric achylia is detected, and in rare cases, changes in the nervous system are noted.

At the onset of the disease, increasing physical and mental weakness appears. Patients quickly get tired, complain of dizziness, headaches, tinnitus, “flying spots” in the eyes, as well as shortness of breath, palpitations at the slightest physical exertion, drowsiness during the day and night insomnia. Then dyspeptic symptoms (anorexia, diarrhea) occur, and patients consult a doctor already in a state of significant anemia.

Other patients initially experience pain and a burning sensation in the tongue, and they turn to specialists in oral diseases. In these cases, one examination of the tongue, revealing signs of typical glossitis, is sufficient to make the correct diagnosis; the latter is supported by the anemic appearance of the patient and the characteristic blood picture. The symptom of glossitis is very pathognomonic, although not strictly specific for Addison-Biermer disease.

Relatively rarely, according to various authors, in 1-2% of cases, pernicious anemia begins with symptoms of angina pectoris provoked by myocardial anoxemia. Sometimes the disease begins as a nervous disease. Patients are concerned about paresthesia - a feeling of crawling, numbness in the distal parts of the extremities or radicular pain.

The appearance of the patient during an exacerbation of the disease is characterized by severe pallor of the skin with a lemon-yellow tint. The sclera is subicteric. Often the integument and mucous membranes are more icteric than pale. Brown pigmentation in the form of a “butterfly” is sometimes observed on the face - on the wings of the nose and above the cheek bones. The face is puffy, and swelling in the ankles and feet is quite common. Patients are usually not emaciated; on the contrary, they are well nourished and prone to obesity. The liver is almost always enlarged, sometimes reaching significant sizes, insensitive, and soft in consistency. The spleen has a denser consistency and is usually difficult to palpate; splenomegaly is rarely observed.

The classic symptom - Hunter's glossitis - is expressed in the appearance of bright red areas of inflammation on the tongue, very sensitive to food intake and medications, especially acidic ones, causing the patient a burning sensation and pain. Areas of inflammation are most often localized along the edges and at the tip of the tongue, but sometimes they involve the entire tongue (“scalded tongue”). Aphthous rashes and sometimes cracks are often observed on the tongue. Such changes can spread to the gums, buccal mucosa, soft palate, and in in rare cases and on the mucous membrane of the pharynx and esophagus. Subsequently, the inflammatory phenomena subside and the papillae of the tongue atrophy. The tongue becomes smooth and shiny (“varnished tongue”).

Patients have a capricious appetite. Sometimes there is an aversion to food, especially meat. Patients complain of a feeling of heaviness in the epigastric region, usually after eating.

X-rays often reveal smoothness of the folds of the gastric mucosa and accelerated evacuation.

Gastroscopy reveals nested, less often total atrophy of the gastric mucosa. A characteristic symptom is the presence of so-called pearlescent plaques - shiny, mirror-like areas of mucosal atrophy, localized mainly in the folds of the gastric mucosa.

Analysis of gastric contents usually reveals achylia and increased mucus content. In rare cases, free hydrochloric acid and pepsin are contained in small quantities. Since the introduction of histamine testing into clinical practice, cases of pernicious anemia with preserved free hydrochloric acid in gastric juice began to occur more often.

The Singer test - a rat-reticulocyte reaction, as a rule, gives a negative result: the gastric juice of a patient with pernicious anemia, when administered subcutaneously to a rat, does not cause an increase in the number of reticulocytes in it, which indicates the absence of internal factor(gastromucoprotein). Glandular mucoprotein is not detected even when special methods research.

The histological structure of the gastric mucosa obtained by biopsy is characterized by thinning of the glandular layer and a decrease in the glands themselves. The chief and parietal cells are atrophic and replaced by mucous cells.

These changes are most pronounced in the fundus, but can affect the entire stomach. Conventionally, three degrees of mucosal atrophy are distinguished: in the first degree, simple achlorhydria is noted, in the second, the disappearance of pepsin, in the third, complete achylia, including the absence of gastromucoprotein secretion. With pernicious anemia, the third degree of atrophy is usually observed, but there are exceptions.

Gastric achylia, as a rule, persists during remission, thereby acquiring a certain diagnostic value during this period. Glossitis may disappear during remission; its appearance portends an exacerbation of the disease.

The enzymatic activity of the intestinal glands, as well as the pancreas, is reduced.

During periods of exacerbation of the disease, enteritis with abundant, intensely colored feces is sometimes observed, which is caused by an increased content of stercobilin - up to 1500 mg in daily quantities.

Due to anemia, an anoxic state of the body develops, which primarily affects the circulatory and respiratory systems. Functional myocardial failure in pernicious anemia is caused by impaired nutrition of the heart muscle and its fatty degeneration.

The electrocardiogram shows symptoms of myocardial ischemia - a negative T wave in all leads, low voltage, widening of the ventricular complex. During the period of remission, the electrocardiogram takes on a normal appearance.

The temperature during the period of relapse often rises to 38°C or higher, but is more often subfebrile. The increase in temperature is mainly associated with the process of increased breakdown of red blood cells.

Changes in the nervous system are very important in diagnostic and prognostic terms. The pathomorphological basis of the nervous syndrome is degeneration and sclerosis of the posterior and lateral columns of the spinal cord, or the so-called funicular myelosis. The clinical picture of this syndrome consists of combinations of spastic spinal paralysis and tabetic symptoms. The first include: spastic paraparesis with increased reflexes, clonus and pathological reflexes of Babinsky, Rossolimo, Bekhterev, Oppenheim. Symptoms simulating tabes dorsalis (“pseudotabes”) include: paresthesia (crawling sensation, numbness of the distal limbs), girdle pain, hypotension and decreased reflexes up to areflexia, impaired vibration and deep sensitivity, sensory ataxia and dysfunction of the pelvic organs. .

Sometimes symptoms of damage to the pyramidal tracts or posterior columns of the spinal cord dominate; V the latter case a picture is created that resembles a tabes. In the most severe, rare forms of the disease, cachexia develops with paralysis, complete loss of deep sensitivity, areflexia, trophic disorders and disorders of the pelvic organs (our observation). More often we see patients with initial symptoms of funicular myelosis, expressed in paresthesia, radicular pain, mild disturbances of deep sensitivity, unsteady gait and a slight increase in tendon reflexes.

Lesions are less common cranial nerves, mainly visual, auditory and olfactory, in connection with which corresponding symptoms from the sensory organs appear (loss of smell, decreased hearing and vision). A characteristic symptom is central scotoma, accompanied by loss of vision and quickly disappearing under the influence of treatment with vitamin B12 (S. M. Ryse). In patients with pernicious anemia, peripheral neuron damage also occurs. This form, designated as polyneuritic, is caused by degenerative changes in various nerves - sciatic, median, ulnar, etc. or individual nerve branches.

Mental disorders are also observed: delusions, hallucinations, sometimes psychotic phenomena with depressive or manic moods; Dementia is more common in old age.

During a severe relapse of the disease, a coma (coma perniciosum) may occur - loss of consciousness, drop in temperature and blood pressure, shortness of breath, vomiting, areflexia, involuntary urination. There is no strict relationship between the development of comatose symptoms and a drop in red blood counts. Sometimes patients with 10 units of hemoglobin in the blood do not fall into a coma, but sometimes coma develops with 20 units or more of hemoglobin. In the pathogenesis of pernicious coma, the main role is played by the rapid pace of anemia, leading to severe ischemia and hypoxia of the centers of the brain, in particular the region of the third ventricle (A. F. Korovnikov).

Rice. 42. Hematopoiesis and blood destruction in pernicious B12 (folate) deficiency anemia.

Picture of blood. At the center of the clinical picture of the disease are changes in the hematopoietic system, leading to the development of severe anemia (Fig. 42).

The result of impaired bone marrow hematopoiesis is a kind of anemia, which during the period of relapse of the disease reaches extremely high degree: observations are known when (with a favorable outcome!) hemoglobin decreased to 8 units (1.3 g%), and the number of red blood cells - to 140,000.

No matter how low hemoglobin decreases, the number of red blood cells drops even lower, as a result of which the color index always exceeds one, in severe cases reaching 1.4-1.8.

The morphological substrate of hyperchromia is large, hemoglobin-rich erythrocytes - macrocytes and megalocytes. The latter, reaching a diameter of 12-14 microns and more, are the end product of megaloblastic hematopoiesis. The apex of the erythrocytometric curve is shifted to the right from normal.

The volume of a megalocyte is 165 μm 3 or more, i.e., 2 times the volume of a normocyte; Accordingly, the hemoglobin content in each individual megalocyte is significantly higher than normal. Megalocytes are somewhat oval or elliptical in shape; they are intensely colored and do not show central clearing (Tables 19, 20).

During the period of relapse, degenerative forms of erythrocytes are observed - basophilically punctured erythrocytes, schizocytes, poikilocytes and microcytes, erythrocytes with preserved remnants of the nucleus in the form of Jolly bodies, Cabot rings, etc., as well as nuclear forms - erythroblasts (megaloblasts). More often these are orthochromic forms with a small pyknotic nucleus (incorrectly designated “normoblasts”), less often - polychromatophilic and basophilic megaloblasts with a nucleus of a typical structure.

The number of reticulocytes during an exacerbation is sharply reduced.

The appearance of reticulocytes in the blood in large quantities portends an imminent remission.

Changes in white blood are no less characteristic of pernicious anemia. During a relapse of pernicious anemia, leukopenia (up to 1500 or less), neutropenia, eosinopenia or aneosinophilia, abasophilia and monopenia are observed. Among the cells of the neutrophil series, a “shift to the right” is noted with the appearance of peculiar giant polysegmented forms containing up to 8-10 nuclear segments. Along with a shift of neutrophils to the right, a shift to the left is also observed with the appearance of metamyelocytes and myelocytes. Among monocytes there are young forms - monoblasts. Lymphocytes in pernicious anemia do not change, but their percentage is increased (relative lymphocytosis).

Table 19. Pernicious anemia. Blood picture in severe relapse of the disease. In the field of view, megaloblasts of various generations, megalocytes, erythrocytes with nuclear derivatives (Cabot rings, Jolly bodies) and basophilic punctation, a characteristic polysegmented neutrophil are visible.

Table 20. Pernicious anemia. The blood picture is in remission. Macroanisocytosis of erythrocytes, polysegmented neutrophil.

The number of blood platelets during an exacerbation is slightly reduced. In some cases, thrombocytopenia is observed - up to 30,000 or less. Platelets may be atypical in size; their diameter reaches 6 microns or more (so-called megaplatelet); Degenerative forms also occur. Thrombocytopenia in pernicious anemia is usually not accompanied by hemorrhagic syndrome. Only in rare cases are bleeding phenomena observed.

Bone marrow hematopoiesis. The picture of bone marrow hematopoiesis in pernicious anemia is very dynamic (Fig. 43, a, b; table 21, 22).

During the period of exacerbation of the disease, bone marrow puncture macroscopically appears abundant, bright red, which contrasts with the pale, watery appearance of peripheral blood. Total nucleated elements of the bone marrow (myelokaryocytes) are increased. The ratio between leukocytes and erythroblasts leuco/erythro instead of 3:1-4:1 normally becomes equal to 1:2 and even 1:3; therefore, there is an absolute predominance of erythroblasts.

Rice. 43. Hematopoiesis in pernicious anemia.

a - bone marrow punctate of a patient with pernicious anemia before treatment. Erythropoiesis occurs according to the megaloblastic type; b - bone marrow punctate of the same patient on the 4th day of treatment with liver extract (orally). Erythropoiesis occurs according to the macronormoblastic type.

In severe cases, in untreated patients, with pernicious coma, erythropoiesis occurs entirely according to the megaloblastic type. There are also so-called reticulomegaloblasts - cells of the reticular type of irregular shape, with wide pale blue protoplasm and a nucleus of a delicate cellular structure, located somewhat eccentrically. Apparently, megaloblasts in pernicious anemia can originate from both hemocytoblasts (via the erythroblast stage) and from reticular cells (return to embryonic angioblastic erythropoiesis).

The quantitative relationships between megaloblasts of different degrees of maturity (or different “ages”) are very variable. The predominance of promegaloblasts and basophilic megaloblasts in the sternal punctate creates a picture of “blue” bone marrow. In contrast, the predominance of fully hemoglobinized, oxyphilic megaloblasts gives the impression of “red” bone marrow.

A characteristic feature of megaloblastic cells is the early hemoglobinization of their cytoplasm while the delicate structure of the nucleus is still preserved. The biological feature of megaloblasts is anaplasia, i.e. loss by a cell of its inherent ability for normal, differentiating development and eventual transformation into an erythrocyte. Only a small part of megaloblasts mature to the final stage of their development and turn into anucleate megalocytes.

Table 21. Megaloblasts in the bone marrow in pernicious anemia (color microphoto).

Table 22. Pernicious anemia in the advanced stage of the disease (bone marrow punctate).

Below at 7 o'clock there is a promyelocyte, at 5 o'clock there is a characteristic hypersegmented neutrophil. All other cells are megaloblasts in various phases of development, starting from a basophilic promegaloblast with nucleoli (at 6 o'clock) and ending with an orthochromic megaloblast with a pyknotic nucleus (at 11 o'clock). Among megaloblasts, mitoses produce two- and three-nucleated cells.

Cellular anaplasia in malignant anemia has features in common with cellular anaplasia in malignant neoplasms and leukemia. Morphological similarity with blastoma cells is especially evident in polymorphonuclear, “monstrous” megaloblasts. A comparative study of the morphological and biological characteristics of megaloblasts in malignant anemia, hemocytoblasts in leukemia, and cancer cells in malignant neoplasms led us to the idea of ​​a possible commonality of pathogenetic mechanisms in these diseases. There is reason to think that both leukemia and malignant neoplasms, like malignant anemia, arise under conditions of a deficiency of specific factors necessary for the normal development of cells in the body.

Megaloblasts are a morphological expression of a peculiar “dystrophy” of the red nuclear cell, which “lacks” a specific maturation factor - vitamin B 12. Not all cells of the red row are anaplastic to the same extent; some cells appear as if in the form of transitional cells between normo- and megaloblasts ; these are the so-called macronormoblasts. These cells, which present particular difficulties for differentiation, are usually found in the initial stage of remission. As remission progresses, normoblasts come to the fore, and cells of the megaloblastic series recede into the background and completely disappear.

Leukopoiesis during an exacerbation is characterized by a delay in the maturation of granulocytes and the presence of giant metamyelocytes and polymorphonuclear neutrophils, the size of which is 2 times larger than that of normal neutrophils.

Similar changes - impaired ripening and pronounced nuclear polymorphism - are also observed in giant cells of the bone marrow. Both in immature megakaryocytes and in “overripe”, polymorphic forms, the processes of formation and release of platelets are disrupted. Megaloblastosis, polysegmented neutrophils and megakaryocyte changes are dependent on the same cause. This reason is a deficiency of a specific hematopoietic factor - vitamin B12.

Bone marrow hematopoiesis in the stage of hematological remission, in the absence of anemic syndrome, occurs according to the normal (normoblastic) type.

Increased breakdown of erythrocytes, or erythrorrhexis, occurs throughout the reticulohistiocytic system, including in the bone marrow itself, where some of the hemoglobin-containing erythromegaloblasts undergo the process of karyo- and cytorexis, which results in the formation of erythrocyte fragments - schizocytes. The latter partly enter the blood, partly are captured by phagocytic reticular cells - macrophages. Along with the phenomena of erythrophagy, significant accumulations of iron-containing pigment - hemosiderin, derived from the hemoglobin of destroyed red blood cells, are found in the organs.

Increased breakdown of red blood cells does not provide grounds for classifying pernicious anemia as hemolytic anemias(as was assumed by older authors), since erythrorrhexis, which occurs in the bone marrow itself, is caused by defective hematopoiesis and is secondary in nature.

The main signs of increased breakdown of erythrocytes in pernicious anemia are icteric coloration of the integument and mucous membranes, enlarged liver and spleen, intensely colored golden blood serum with an increased content of “indirect” bilirubin, the constant presence of urobilin in the urine and pleiochromia of bile and feces with a significant increase in the content of stercobilin in kale.

Pathological anatomy. Thanks to the successes of modern therapy, pernicious anemia in the section is now very rare. When autopsying a corpse, one notices the anemia of all organs while maintaining fatty tissue. Fatty infiltration of the myocardium (“tiger heart”), kidneys, and liver is noted, and central fatty necrosis of the lobules is also found in the latter.

In the liver, spleen, bone marrow, lymph nodes, especially retroperitoneal ones, a significant deposition of fine-grained yellow-brown pigment - hemosiderin, which gives a positive reaction to iron, is determined. Hemosiderosis is more pronounced in Kupffer cells along the periphery of the hepatic lobules, while in the spleen and bone marrow hemosiderosis is much less pronounced, and sometimes does not occur at all (contrary to what is observed with true hemolytic anemia). A lot of iron is deposited in the convoluted tubules of the kidneys.

Changes in the digestive organs are very characteristic. The tongue papillae are atrophic. Similar changes can be observed in the mucous membrane of the pharynx and esophagus. In the stomach, atrophy of the mucous membrane and its glands is detected - anadenia. Like atrophic process also present in the intestines.

In the central nervous system, mainly in the posterior and lateral columns of the spinal cord, degenerative changes are noted, referred to as combined sclerosis or funicular myelosis. Less commonly, ischemic foci with necrotic softening of the nervous tissue are found in the spinal cord. Necrosis and foci of glial proliferation in the cerebral cortex have been described.

A typical sign of pernicious anemia is crimson-red, juicy bone marrow, which sharply contrasts with the general pallor of the integument and anemia of all organs. Red bone marrow is found not only in flat bones and epiphyses of long bones, but also in the diaphysis of the latter. Along with bone marrow hyperplasia, extramedullary foci of hematopoiesis (accumulation of erythroblasts and megaloblasts) are observed in the splenic pulp, liver and lymph nodes. Reticulo-histiocytic elements in the hematopoietic organs and extramedullary foci of hematopoiesis exhibit the phenomena of erythrophagocytosis.

The possibility of the transition of pernicious anemia to an aplastic state, recognized by previous authors, is currently denied. Sectional findings of red bone marrow indicate that hematopoiesis persists until the last moment of the patient’s life. The lethal outcome does not occur due to anatomical aplasia of the hematopoietic organ, but due to the fact that functionally defective megaloblastic hematopoiesis is not able to provide the vital processes of oxygen respiration for the body with the necessary minimum of red blood cells.

Etiology and pathogenesis. Since Biermer identified “pernicious” anemia as an independent disease, the attention of clinicians and pathologists has been attracted by the fact that with this disease gastric achylia is constantly observed (which, according to recent data, turned out to be histamine-resistant), and atrophy of the gastric mucosa is found in sections ( anadenia ventriculi). Naturally, there was a desire to establish a connection between the state of the digestive tract and the development of anemia.

According to modern concepts, pernicious anemic syndrome should be considered as a manifestation of endogenous B12 vitamin deficiency.

The direct mechanism of anemia in Addison-Biermer disease is that due to vitamin B12 deficiency, the metabolism of nucleoproteins is disrupted, which leads to a disorder of mitotic processes in hematopoietic cells, in particular in bone marrow erythroblasts. The slow pace of megaloblastic erythropoiesis is caused by both a slowdown in mitotic processes and a reduction in the number of mitoses themselves: instead of three mitoses characteristic of normoblastic erythropoiesis, megaloblastic erythropoiesis occurs with one mitosis. This means that while one pronormoblast produces 8 red blood cells, one promegaloblast produces only 2 red blood cells.

The disintegration of many hemoglobinized megaloblasts that did not have time to “denucleate” and turn into erythrocytes, along with their slow differentiation (“abortion of erythropoiesis”) is the main reason leading to the fact that the processes of hematopoiesis do not compensate for the processes of blood destruction and anemia develops, accompanied by an increased accumulation of unused products hemoglobin breakdown.

The latter is confirmed by data from determining the iron cycle (using radioactive isotopes), as well as increased excretion of blood pigments - urobilin, etc.

In connection with the indisputably established “deficient” endogenous vitamin deficiency nature of pernicious anemia, the previously dominant views on the meaning of increased decay erythrocytes in this disease.

As is known, pernicious anemia was classified as a hemolytic anemia, and megaloblastic erythropoiesis was considered as a response of the bone marrow to increased breakdown of red blood cells. However, the hemolytic theory has not been confirmed either in experiment, or in the clinic, or in medical practice. Not a single experimenter was able to obtain pictures of pernicious anemia when animals were poisoned with a hemolytic nucleus. Anemia of the hemolytic type, neither in experiment nor in the clinic, is accompanied by a megaloblastic reaction of the bone marrow. Finally, attempts to treat pernicious anemia by splenectomy to reduce the breakdown of red blood cells have also been unsuccessful.

Increased excretion of pigments in pernicious anemia is explained not so much by the destruction of newly formed red blood cells in the circulating blood, but by the disintegration of hemoglobin-containing megaloblasts and megalocytes even before their release into the peripheral blood, i.e. in the bone marrow and foci of extramedullary hematopoiesis. This assumption is confirmed by the fact that we discovered increased erythrophagocytosis in the bone marrow of patients with pernicious anemia. The increased iron content in the blood serum noted during the period of relapse of pernicious anemia is mainly explained by impaired iron utilization, since during the period of remission the blood iron content returns to normal levels.

In addition to increased deposition in tissues of iron-containing pigment - hemosiderin and high content in the blood, duodenal juice, urine and feces of iron-free pigments (bilirubin, urobilin), in patients with pernicious anemia, an increased amount of porphyrin and small amounts of hematin are found in the blood serum, urine and bone marrow. Porphyrinemia and hematinemia are explained by insufficient utilization of blood pigments by the hematopoietic organs, as a result of which these pigments circulate in the blood and are excreted from the body in the urine.

Megaloblasts (megalocytes) in pernicious anemia, as well as embryonic megaloblasts (megalocytes), are extremely rich in porphyrin and cannot be full oxygen carriers to the same extent as normal red blood cells. This conclusion is consistent with the established fact of increased oxygen consumption by megaloblastic bone marrow.

The B12-avitaminosis theory of the genesis of pernicious anemia, generally accepted by modern hematology and clinics, does not exclude the role of additional factors contributing to the development of anemia, in particular the qualitative inferiority of macromegalocytes and their “fragments” - poikilocytes, schizocytes and the “fragility” of their presence in the peripheral blood. According to the observations of a number of authors, 50% of red blood cells transfused from a patient with pernicious anemia to a healthy recipient remain in the latter’s blood for 10-12 to 18-30 days. The maximum lifespan of erythrocytes during the period of exacerbation of pernicious anemia ranges from 27 to 75 days, therefore, 2-4 times less than normal. Finally, the weakly expressed hemolytic properties of the plasma of patients with pernicious anemia are of some (by no means primary) importance, proven by observations of erythrocytes from healthy donors transfused to patients with pernicious anemia and subjected to accelerated decay in the blood of recipients (Hamilton and co-workers, Yu. M. Bala).

The pathogenesis of funicular myelosis, as well as pernicious anemic syndrome, is associated with atrophic changes in the gastric mucosa, leading to a deficiency of the vitamin B complex.

Clinical observations that have established the beneficial effect of using vitamin B12 in the treatment of funicular myelosis allow us to recognize nervous syndrome with Birmer's disease (along with anemic syndrome) a manifestation of B12-vitamin deficiency in the body.

The question of the etiology of Addison-Birmer disease should still be considered unresolved.

According to modern views, Addison-Biermer disease is a disease characterized by congenital inferiority of the glandular apparatus of the fundus of the stomach, which is revealed with age in the form of premature involution of glands producing gastromucoprotein, necessary for the assimilation of vitamin B12.

We are not talking about atrophic gastritis (gastritis atrophicans), but about gastric atrophy (atrophia gastrica). The morphological substrate of this peculiar dystrophic process is nested, rarely diffuse atrophy, affecting mainly the fundic glands of the fundus of the stomach (anadenia ventriculi). These changes, which create “pearl spots” known to pathologists of the last century, are detected intravitally during gastroscopic examination (see above) or by biopsy of the gastric mucosa.

The concept of the autoimmune genesis of gastric atrophy in pernicious anemia, put forward by a number of authors (Taylor, 1959; Roitt and co-workers, 1964), is worthy of attention. This concept is supported by the detection in the blood serum of most patients with pernicious anemia of specific antibodies to the parietal and chief cells of the gastric glands that temporarily disappear under the influence of corticosteroids, as well as immunofluorescence data showing the presence of antibodies fixed in the cytoplasm of the parietal cells.

It is believed that autoantibodies against gastric cells play a pathogenetic role in the development of atrophy of the gastric mucosa and subsequent disorders of its secretory function.

By microscopic examination of the biopsied gastric mucosa, significant lymphoid infiltration was discovered in the latter, which is considered as evidence of the participation of immunocompetent cells in unleashing an organ-specific autoimmune inflammatory process with subsequent atrophy of the gastric mucosa.

In this regard, the frequency of combinations of the histological picture of atrophy and lymphoid infiltration of the gastric mucosa, characteristic of Birmer's pernicious anemia, with Hashimoto's lymphoid thyroiditis, is noteworthy. Moreover, deceased patients with Birmer's anemia often show (at autopsy) signs of thyroiditis.

The immunological commonality of Biermer's anemia and Hashimoto's thyroiditis is supported by the fact that antithyroid antibodies were detected in the blood of patients with Biermer's anemia, and, on the other hand, antibodies against parietal cells of the gastric mucosa in patients with the lesion thyroid gland. According to Irvine et al (1965), antibodies against gastric parietal cells are found in 25% of patients with Hashimoto's thyroiditis (antithyroid antibodies in these same patients are found in 70% of cases).

The results of studies of relatives of patients with Birmer's anemia are also of interest: according to various authors, antibodies against the lining cells of the gastric mucosa and against the cells of the thyroid gland, as well as a violation of the secretory and adsorption (in relation to vitamin B 12) functions of the stomach, are observed in no less than 20 % of relatives of patients with Birmer's pernicious anemia.

According to the latest studies conducted using the radiodiffusion method on 19 patients with pernicious anemia, a group of American researchers established the existence in the blood serum of all patients of antibodies that either “block” the intrinsic factor or bind both the intrinsic factor (IF) and the CF+ complex AT 12.

Anti-HF antibodies were also found in gastric juice and saliva of patients with Birmer's anemia.

Antibodies are also found in the blood of infants (up to 3 weeks of age) born from mothers with pernicious anemia who contained anti-HF antibodies in their blood.

In childhood forms of B12-deficiency anemia, occurring with intact gastric mucosa, but with impaired production of internal factor (see below), antibodies to the latter (anti-HF antibodies) are detected in approximately 40% of cases.

Antibodies are not detected in childhood pernicious anemia, which occurs due to impaired absorption of vitamin B 12 at the intestinal level.

In light of the above data, the deep pathogenesis of B12 deficiency Biermer's anemia appears to be an autoimmune conflict.

Schematically, the occurrence of neuroanemic (B12-deficiency) syndrome in Addison-Biermer disease can be represented as follows.

The question of the relationship between pernicious anemia and gastric cancer requires special consideration. This question has long attracted the attention of researchers. Since the first descriptions of malignant anemia, it has been known that this disease is often combined with malignant neoplasms of the stomach.

According to US statistics (cited by Wintrobe), stomach cancer occurs in 12.3% (in 36 cases out of 293) of those who died from malignant anemia over the age of 45 years. According to summary data collected by A.V. Melnikov and N.S. Timofeev, the incidence of stomach cancer in patients with malignant anemia, established on the basis of clinical, radiological and sectional materials, is 2.5%, i.e. approximately 8 times more than in the general population (0.3%). The incidence of stomach cancer in patients with pernicious anemia, according to the same authors, is 2-4 times higher than that of stomach cancer in people of the same age who do not suffer from anemia.

Noteworthy is the increase in cases of stomach cancer in patients with pernicious anemia in last years, which should be explained by the prolongation of the life of patients (due to effective Bia therapy) and the progressive restructuring of the gastric mucosa. In most cases, these are patients with pernicious anemia who develop stomach cancer. One should not, however, lose sight of the possibility that gastric cancer itself sometimes gives a picture of pernicious anemia. At the same time, it is not necessary, as some authors suggested, that the cancer should strike the fundic part of the stomach, although the localization of the tumor in this part is certainly of “aggravating” significance. According to S. A. Reinberg, out of 20 patients with a combination of stomach cancer and pernicious anemia, only 4 had the tumor localized in the cardial and subcardial regions; in 5, a tumor was found in the antrum, in 11 - in the body of the stomach. A pernicious anemic blood picture can develop at any location of gastric cancer, accompanied by diffuse atrophy of the mucosa involving the glands of the fundus of the stomach. There are cases when the developed pernicious anemic blood picture was the only symptom of stomach cancer ( similar case described by us) 1.

Signs suspicious of the development of a stomach cancer in a patient with pernicious anemia should be considered, firstly, a change in the type of anemia from hyperchromic to normohypochromic, secondly, the patient’s developing refractoriness to vitamin B12 therapy, thirdly, the appearance of new symptoms, uncharacteristic for pernicious anemia as such: loss of appetite, weight loss. The appearance of these symptoms obliges the doctor to immediately examine the patient in the direction of possible gastric blastoma.

It should be emphasized that even a negative result of an X-ray examination of the stomach cannot guarantee the absence of a tumor.

Therefore, in the presence of even just clinical and hematological symptoms that inspire reasonable suspicion of the development of blastoma, it is necessary to consider surgical intervention - a trial laparotomy - as indicated.

Forecast. Liver therapy, proposed in 1926, and modern treatment with vitamin B i2 radically changed the course of the disease, which had lost its “malignancy”. Now death malignant anemia, which occurs during oxygen starvation of the body (anoxia) in a coma, is very rare. Although not all symptoms of the disease disappear during remission, nevertheless, persistent blood remission, which occurs as a result of systematic use of antianemic drugs, is actually tantamount to practical recovery. There are cases of complete and final recovery, especially for those patients who have not yet developed a nervous syndrome.

Treatment. For the first time, Minot and Murphy (1926) reported the cure of 45 patients with malignant anemia using a special diet rich in raw calf liver. The most active was low-fat calf liver, minced twice and prescribed to the patient 200 g per day 2 hours before meals.

A great achievement in the treatment of pernicious anemia has been the production of effective liver extracts. Of the parenterally administered liver extracts, the most famous was the Soviet campolon, extracted from the liver. cattle and produced in ampoules of 2 ml. In connection with reports of the antianemic role of cobalt, liver concentrates enriched with cobalt were created. A similar Soviet drug, antianemin, was successfully used in domestic clinics to treat patients with pernicious anemia. The dosage of antianemin is from 2 to 4 ml into the muscle daily until hematological remission is obtained. Practice has shown that a single administration of a massive dose of Campolon in 12-20 ml (the so-called “Campolon blow”) is equivalent in effect to a full course of injections of the same drug, 2 ml daily.

According to modern research, the specificity of the action of liver drugs in pernicious anemia is due to the content of hematopoietic vitamin (B12) in them. Therefore, the basis for the standardization of antianemic drugs is the quantitative content of vitamin B12 in micrograms or gammas per 1 ml. Campolon of various series contains from 1.3 to 6 μg/ml, antianemin - 0.6 μg/ml of vitamin B12.

In connection with the production of synthetic folic acid, the latter was used to treat pernicious anemia. Prescribed per os or parenterally in a dose of 30-60 mg or more (maximum up to 120-150 mg pro die), folic acid causes a rapid onset of remission in a patient with pernicious anemia. However, the negative property of folic acid is that it leads to increased consumption of tissue vitamin B12. According to some data, folic acid does not prevent the development of funicular myelosis, and with long-term use even promotes it. Therefore, folic acid has not been used for Addison-Biermer anemia.

Currently, due to the introduction of vitamin B12 into widespread practice, the above remedies in the treatment of pernicious anemia, which were used for 25 years (1925-1950), have lost their significance.

The best pathogenetic effect in the treatment of pernicious anemia is achieved from parenteral (intramuscular, subcutaneous) use of vitamin B12. A distinction should be made between saturation therapy, or “impact therapy”, carried out during an exacerbation, and “maintenance therapy”, carried out during a period of remission.

Saturation therapy. Initially, based on a person’s daily need for vitamin B12, which was determined to be 2-3 mcg, it was proposed to administer relatively small doses of vitamin B12 - 15  daily or 30  every 1-2 days. At the same time, it was believed that the introduction of large doses was inappropriate due to the fact that most of the vitamin B12 obtained in excess of 30  is excreted from the body in the urine. Subsequent studies, however, showed that the B12-binding capacity of plasma (depending mainly on the content of   -globulin) and the degree of utilization of vitamin B12 vary depending on the body's need for vitamin B12, in other words, on the degree of vitamin B12 deficiency in tissues . Normal content vitamin B12 in the latter, according to Ungley, is 1000-2000  (0.1-0.2 g), of which half comes from the liver.

According to Mollin and Ross, with severe B12 deficiency in the body, manifested clinically by the picture of funicular myelosis, after an injection of 1000  vitamin B12, 200-300  is retained in the body .

Clinical experience has shown that although small doses of vitamin B12 practically lead to clinical improvement and restoration of normal (or near normal) blood counts, they are still insufficient to restore tissue reserves of vitamin B12. Undersaturation of the body with vitamin B12 manifests itself in the known inferiority of clinical and hematological remission (preservation residual effects glossitis and especially neurological phenomena, macrocytosis of erythrocytes), and in the tendency to early relapses of the disease. For the reasons stated above, the use of small doses of vitamin B12 is considered inappropriate. In order to eliminate vitamin B12 deficiency during the period of exacerbation of pernicious anemia, it is currently proposed to use medium - 100-200  and large - 500-1000  - doses of vitamin B12.

Practically, as a regimen for exacerbation of pernicious anemia, we can recommend injections of vitamin B12 100-200  daily during the first week (before the onset of reticulocyte crisis) and then every other day until the onset of hematological remission. On average, with a course of treatment lasting 3-4 weeks, the course dose of vitamin B12 is 1500-3000  .

For funicular myelosis, more massive (shock) doses of vitamin B12 are indicated - 500-1000  daily or every other day for 10 days, and then 1-2 times a week until a lasting therapeutic effect is obtained - the disappearance of all neurological symptoms.

Positive results - a pronounced improvement in 11 out of 12 patients with funicular myelosis (and in 8 patients with restoration of ability to work) - were obtained by L. I. Yavorkovsky with endolubic administration of vitamin B12 at a dose of 15-200 mcg With at intervals of 4-10 days, a total of up to 840 mcg per course of treatment . Considering the possibility of complications, including severe meningeal syndrome (headache, nausea, stiff neck, fever), the indication for endolubic administration of vitamin B12 should be limited to exclusively severe cases of funicular myelosis. Other methods used in the recent past for the treatment of funicular myelosis: spinal diathermy, raw pork stomach in large doses(300-400 g per day), vitamin B1 50-100 mg per day - have now lost their importance, with the exception of vitamin B1, recommended for neurological disorders, especially the so-called polyneuritic form.

The duration of treatment with vitamin B12 for funicular myelosis is usually 2 months. The course dose of vitamin B12 is from 10,000 to 25,000  .

To obtain stable remission, Chevallier recommended long-term treatment with vitamin B12 in massive doses (500-1000  per day) until the highest red blood counts are obtained (hemoglobin - 100 units, red blood cells - over 5,000,000).

In connection with the long-term use of massive doses of vitamin B12, the question of the possibility of hypervitaminosis B12 arises. This issue is resolved negatively due to the rapid removal of vitamin B12 from the body. The accumulated wealth of clinical experience confirms the virtual absence of signs of oversaturation of the body with vitamin B12, even with long-term use.

Oral administration of vitamin B12 is effective in combination with the simultaneous administration of gastric antianemic factor - gastromucoprotein. Favorable results were obtained in the treatment of patients with pernicious anemia by oral administration of tablet preparations containing vitamin B12 in combination with gastromucoprotein.

In particular, positive results were noted when using the domestic drug mucovit (the drug was produced in tablets containing 0.2 g of gastromucoprotein from the mucous membrane of the pyloric part of the lower stomach and 200 or 500 mcg of vitamin B12).

In recent years, there have been reports of positive results in treating patients with pernicious anemia with vitamin B12 administered orally at a dose of at least 300  per day without intrinsic factor. In this case, you can expect that even 10% of the administered vitamin B12 will be absorbed, i.e. approximately 30  , quite sufficient to ensure the onset of hematological remission.

It is also proposed to administer vitamin B12 in other ways: sublingually and intranasally - in the form of drops or by spraying - at a dose of 100-200 mcg daily until the onset of hematological remission, followed by maintenance therapy 1-3 times a week.

According to our observations, transformation of hematopoiesis occurs within the first 24 hours after the injection of vitamin B12, and the final normalization of bone marrow hematopoiesis is completed 48-72 hours after the administration of vitamin B12.

The possibility of transforming the megaloblastic type of hematopoiesis into a normoblastic one is decided in the light of the unitary theory from the point of view of the genesis of erythroblasts of both types from a single parent cell. As a result of the onset of saturation of the bone marrow with the “erythrocyte maturation factor” (vitamin B12, folinic acid), the direction of development of basophilic erythroblasts changes. The latter, in the process of differentiating division, turn into cells of the normoblastic series.

Already 24 hours after the injection of vitamin B12, radical changes occur in hematopoiesis, expressed in the massive division of basophilic erythroblasts and megaloblasts with the differentiation of the latter into new forms of erythroblasts - mainly meso- and microgeneration. The only sign indicating the “megaloblastic past” of these cells is the disproportion between the high degree of hemoglobinization of the cytoplasm and the nucleus, which still retains its loose structure. As the cell matures, the dissociation in the development of the nucleus and cytoplasm is smoothed out. The closer a cell is to final maturation, the more it approaches a normoblast. The further development of these cells - their denuclearization, final hemoglobinization and transformation into erythrocytes - occurs according to the normoblastic type, at an accelerated pace.

On the part of granulopoiesis, there is an increased regeneration of granulocytes, especially eosinophils, among which there is a sharp shift to the left with the appearance of a significant number of eosinophilic promyelocytes and myelocytes. On the contrary, among neutrophils there is a shift to the right with an absolute predominance of mature forms. The most important is the disappearance of polysegmented neutrophils characteristic of pernicious anemia. During the same period, restoration of the normal morphophysiology of giant bone marrow cells and the normal process of platelet formation is observed.

Reticulocyte crisis occurs on the 5-6th day.

Hematological remission is determined by the following indicators: 1) the onset of a reticulocyte reaction; 2) normalization of bone marrow hematopoiesis; 3) normalization of peripheral blood; 4) restoration of normal levels of vitamin B12 in the blood.

The reticulocyte response, expressed graphically as a curve, in turn depends on the degree of anemia (it is inversely proportional to the initial number of red blood cells) and the speed of the bone marrow response. The faster the curve rises, the slower its decline, which is sometimes interrupted by a second rise (especially with irregular treatment).

Isaacs and Friedeman proposed a formula according to which in each special case You can calculate the maximum percentage of reticulocytes expected under the influence of treatment:

Where R - expected maximum percentage of reticulocytes; En - original number of red blood cells in millions.

Example. The number of red blood cells on the day of initiation of therapy was 2,500,000.

The immediate effect of vitamin B12 therapy in the sense of replenishing the peripheral blood with newly formed red blood cells begins to be felt only from the 5-6th day after the administration of the antianemic drug. The percentage of hemoglobin increases more slowly than the number of red blood cells, so the color indicator in the remission stage usually decreases and becomes less than one (Fig. 44). In parallel with the cessation of megaloblastic erythropoiesis and the restoration of a normal blood picture, the symptoms of increased breakdown of red blood cells also decrease: the yellowness of the integument disappears, the liver and spleen are reduced to normal sizes, the amount of pigments in the blood serum, bile, urine and feces decreases.

Rice. 44. Dynamics of blood parameters under the influence of vitamin B12.

Clinical remission is expressed in the disappearance of all pathological symptoms, including anemic, dyspeptic, neurological and ocular. The exception is histamine-resistant achylia, which usually persists during remission.

Improvement in general condition: increased strength, disappearance of diarrhea, drop in temperature - usually occurs before the disappearance of anemic symptoms. Glossitis is eliminated somewhat more slowly. In rare cases, restoration of gastric secretion is also noted. Nervous phenomena are reduced to some extent: paresthesia and even ataxia disappear, deep sensitivity is restored, and the mental state improves. In severe forms, nervous phenomena are hardly reversible, which is associated with degenerative changes in nervous tissue. The effectiveness of vitamin B12 therapy has a known limit, after which the increase in blood counts stops. Due to the faster increase in the number of red blood cells compared to the increase in hemoglobin, the color indicator decreases to 0.9-0.8, and sometimes lower, anemia becomes hypochromic. It seems that vitamin B12 therapy, while promoting the maximum use of iron to build red blood cell hemoglobin, leads to the depletion of its reserves in the body. The development of hypochromic anemia in this period is also favored by reduced absorption of dietary iron due to achylia. Therefore in this period For the disease, it is advisable to switch to treatment with iron preparations - Ferrum hydrogenio reductum 3 g per day (must be washed down with hydrochloric acid) or hemostimulin. An indication for the administration of iron to patients with pernicious anemia may be a decrease in plasma iron from elevated levels (up to 200-300%) during the period of exacerbation to subnormal levels during the period of remission. An indicator of the beneficial effect of iron during this period is an increase in the utilization of radioactive iron (Fe 59) from 20-40% (before treatment) to normal (after treatment with vitamin B12).

The issue of using blood transfusions for pernicious anemia is decided in each case according to the indications. An absolute indication is pernicious coma, which poses a threat to the patient’s life due to increasing hypoxemia.

Despite the brilliant achievements in the treatment of pernicious anemia, the problem of its final cure still remains unresolved. Even in the remission stage with normal blood counts, characteristic changes in erythrocytes (aniso-poikilocytosis, single macrocytes) and a shift of neutrophils to the right can be detected. Examination of gastric juice reveals in most cases permanent achylia. Changes in the nervous system can progress even in the absence of anemia.

With the cessation of the administration of vitamin B12 (in one form or another), there is a threat of relapse of the disease. Clinical observations show that relapses of the disease usually occur within 3 to 8 months after cessation of treatment.

In rare cases, relapses of the disease occur after several years. Thus, in a 60-year-old patient we observed, a relapse occurred only 7 (!) years after the complete cessation of vitamin B12 intake.

Maintenance therapy consists of prescribing a preventive (anti-relapse) intake of vitamin B12. In this case, one should proceed from the fact that a person’s daily need for it is, according to the observations of various authors, from 3 to 5 . Based on these data, it can be recommended that in order to prevent relapse of pernicious anemia, it is recommended to administer 100  or weekly 50 vitamin B12 to the patient in the form of injections 2-3 times a month.

As maintenance therapy in a state of complete clinical and hematological remission and for the prevention of relapses, oral drugs - mucovit with or without intrinsic factor (see above) can also be recommended.

Prevention. Prevention of exacerbations of pernicious anemia comes down to the systematic administration of vitamin B12. The timing and dosage are set individually (see above).

Taking into account age characteristics (usually the elderly age of patients), as well as the existing pathomorphological substrate of the disease - atrophic gastritis, considered as a pre-cancrosis condition, it is necessary to show reasonable (not excessive!) oncological vigilance in relation to each patient with pernicious anemia. Patients with pernicious anemia are subject to clinical observation with mandatory blood monitoring and X-ray examination of the gastrointestinal tract at least once a year (more often if there is suspicion).