Pernicious anemia is a violation of the red germ of hematopoiesis caused by a lack of cyanocobalamin (vitamin B12) in the body. With B12-deficient anemia, circulatory hypoxic (pallor, tachycardia, shortness of breath), gastroenterological (glossitis, stomatitis, hepatomegaly, gastroenterocolitis) and neurological syndromes (impaired sensitivity, polyneuritis, ataxia) develop. Confirmation is made based on the results of laboratory studies (clinical and biochemical blood analysis, bone marrow punctate). Treatment includes a balanced diet, intramuscular administration of cyanocobalamin.
ICD 10
D51.0 Vitamin-B12-deficiency anemia due to deficiency of internal factor
Meaning
Pernicious anemia is a type of megaloblastic deficiency anemia that develops with insufficient endogenous intake or assimilation of vitamin B12 in the body. “Pernicious” in Latin means “dangerous, fatal”. In modern hematology, synonyms of pernicious anemia also serve as B12-deficiency anemia, Addison-Birmer disease. The disease occurs more often in people older than 40-50 years, somewhat more often in women. The prevalence of pernicious anemia is 1%; at the same time, about 10% of elderly people over the age of 70 suffer from vitamin B12 deficiency.
Pernicious anemia causes
The daily human need for vitamin B12 is 1-5 mcg. It is satisfied by the intake of vitamin C from food (meat, dairy products). In the stomach, under the action of enzymes, vitamin B12 is separated from dietary protein, but for assimilation and absorption into the blood, it must connect with glycoprotein (Castle factor) or other binding factors. Cyanocobalamin is absorbed into the bloodstream in the middle and lower part of the ileum. The subsequent transport of vitamin B12 to tissues and hematopoietic cells is carried out by plasma proteins – transcobalamins 1, 2, 3.
The development of B12-deficiency anemia can be associated with two groups of factors: alimentary and endogenous. Alimentary reasons are due to insufficient intake of vitamin B12 from food. This can occur during fasting, vegetarianism and diets with the exception of animal protein.
Endogenous causes mean a violation of the assimilation of cyanocobalamin due to a deficiency of the internal Castle factor with its sufficient intake from outside. Such a mechanism of development of pernicious anemia occurs with atrophic gastritis, a condition after gastrectomy, the formation of antibodies to the internal Castle factor or parietal cells of the stomach, congenital absence of the factor.
Impaired absorption of cyanocobalamin in the intestine may occur with enteritis, chronic pancreatitis, celiac disease, Crohn’s disease, diverticula of the small intestine, tumors of the jejunum (carcinoma, lymphoma). Increased consumption of cyanocobalamin may be associated with helminthiasis, in particular, diphyllobothriosis. There are genetic forms of pernicious anemia.
The absorption of vitamin B12 is impaired in patients who underwent resection of the small intestine with the imposition of gastrointestinal anastomosis. Pernicious anemia can be associated with chronic alcoholism, the use of certain medications (colchicine, neomycin, oral contraceptives, etc.). Since the liver contains a sufficient reserve of cyancobalamin (2.0-5.0 mg), pernicious anemia develops, as a rule, only 4-6 years after the violation of the intake or assimilation of vitamin B12.
In conditions of vitamin B12 deficiency, there is a deficiency of its coenzyme forms – methylcobalamin (participates in the normal course of erythropoiesis processes) and 5-deoxyadenosylcobalamin (participates in metabolic processes occurring in the central nervous system and peripheral nervous system). The lack of methylcobalamin disrupts the synthesis of essential amino acids and nucleic acids, which leads to a disorder of the formation and maturation of erythrocytes (megaloblastic type of hematopoiesis). They take the form of megaloblasts and megalocytes, which do not perform an oxygen transport function and are rapidly destroyed. In this regard, the number of red blood cells in the peripheral blood is significantly reduced, which leads to the development of anemic syndrome.
On the other hand, with a deficiency of the coenzyme 5-deoxyadenosylcobalamin, the metabolism of fatty acids is disrupted, resulting in the accumulation of toxic methylmalonic and propionic acids, which have a direct damaging effect on the neurons of the brain and spinal cord. In addition, myelin synthesis is disrupted, which is accompanied by degeneration of the myelin layer of nerve fibers – this is due to the defeat of the nervous system in pernicious anemia.
Pernicious anemia symptoms
The severity of the course of pernicious anemia is determined by the severity of circulatory hypoxic (anemic), gastroenterological, neurological and hematological syndromes. The signs of anemic syndrome are nonspecific and are a reflection of a violation of the oxygen transport function of erythrocytes. They are represented by weakness, decreased endurance, tachycardia and palpitations, dizziness and shortness of breath when moving, subfebrility. During auscultation of the heart, the noise of a “top” or systolic (anemic) noises can be heard. Externally, there is a pallor of the skin with a subicteric shade, puffiness of the face. A long “experience” of pernicious anemia can lead to the development of myocardiodystrophy and heart failure.
Gastroenterological manifestations of B12-deficient anemia are decreased appetite, unstable stool, hepatomegaly (fatty liver dystrophy). The classic symptom detected in pernicious anemia is a “lacquered” crimson tongue. The phenomena of angular stomatitis and glossitis, burning and pain in the tongue are characteristic. During gastroscopy, atrophic changes in the gastric mucosa are detected, which are confirmed by endoscopic biopsy. Gastric secretion decreases sharply.
Neurological manifestations of pernicious anemia are caused by damage to neurons and pathways. Patients indicate numbness and stiffness of the limbs, muscle weakness, gait disorder. Possible urinary and fecal incontinence, the occurrence of persistent paraparesis of the lower extremities. A neurologist’s examination reveals a violation of sensitivity (pain, tactile, vibration), increased tendon reflexes, symptoms of Romberg and Babinsky, signs of peripheral polyneuropathy and funicular myelosis. With B12-deficiency anemia, mental disorders can develop – insomnia, depression, psychosis, hallucinations, dementia.
Diagnostics
In addition to a hematologist, a gastroenterologist and a neurologist should be involved in the diagnosis of pernicious anemia. Vitamin B12 deficiency (less than 100 pg/ml at a norm of 160-950 pg/ml) is established during a biochemical blood test; it is possible to detect At to the parietal cells of the stomach and to the internal Castle factor. Pancytopenia (leukopenia, anemia, thrombocytopenia) is typical for a general blood test. Microscopy of a peripheral blood smear reveals megalocytes, Jolly and Cabot corpuscles. Fecal examination (coprogram, analysis for worm eggs) can detect steatorrhea, fragments or eggs of a broad tapeworm in diphyllobothriosis.
The Schilling test makes it possible to determine a violation of the absorption of cyanocobalamin (by excretion in the urine of vitamin B12 labeled with a radioactive isotope taken orally). Bone marrow puncture and myelogram results reflect the increase in the number of megaloblasts characteristic of pernicious anemia.
To determine the causes of impaired absorption of vitamin B12 in the gastrointestinal tract, FGDS, stomach radiography, and irrigation are performed. In the diagnosis of concomitant disorders, ECG, abdominal ultrasound, electroencephalography, MRI of the brain, etc. are informative. B12-deficient anemia must be distinguished from folic deficiency, hemolytic and iron deficiency anemia.
Pernicious anemia treatment
The diagnosis of pernicious anemia means that the patient will need lifelong pathogenetic treatment with vitamin B12. In addition, regular (every 5 years) gastroscopy is indicated to exclude the development of stomach cancer.
Intramuscular injections of vitamin B12 are prescribed in order to compensate for cyanocobalamin deficiency. Correction of conditions that led to B12-deficiency anemia (deworming, taking enzyme preparations, surgical treatment) is required, and with the alimentary nature of the disease – a diet with an increased content of animal protein. In case of violation of the production of the internal Castle factor, glucocorticoids are prescribed. Hemotransfusions are resorted to only with severe anemia or signs of anemic coma.
Against the background of pernicious anemia therapy, blood counts usually normalize after 1.5-2 months. The longest (up to 6 months) neurological manifestations persist, and with late treatment they become irreversible.
Prevention
The first step towards preventing pernicious anemia should be a full-fledged diet that ensures sufficient intake of vitamin B12 into the body (eating meat, eggs, liver, fish, dairy products, soy). Timely therapy of gastrointestinal pathologies that disrupt the absorption of vitamin is necessary. After surgical interventions (resection of the stomach or intestines), it is necessary to conduct supportive courses of vitamin therapy.
Patients with B12-deficient anemia are at risk for the development of diffuse toxic goiter and myxedema, as well as stomach cancer, therefore they need the supervision of an endocrinologist and gastroenterologist.
Literature
- Lam J. R., Schneider J. L., Zhao W., et al. Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B 12 Deficiency // JAMA. — 2013; 310: 2435.link
- Donelly L. A., Dennis J. M., Coleman R. L., et al. Risk of Anemia With Metformin Use in Type 2 Diabetes: a mastermind Study // Diabetes Care. — 2020. link
- Teplitsky V., Huminer D., Zoldan J., Pitlik S., Shohat M., Mittelman M. Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults // Isr Med Assoc J. — 2003; 5 (12): 868-872. link
- De Block CEM, De Leeuw I. H., Van Gaal L. F. Autoimmune Gastritis in Type 1 Diabetes: A Clinically Oriented Review // J Clin Endocrinol Metab. — 2008; 93: 363-371. link
- Effects of vitamin B12 and folate deficiency on brain development in children / Maureen M. Black // Food Nutr Bull. — 2008; 29 (2 Suppl): S126-S131.link
- Hyperhomocysteinaemia and vitamin B12 deficiency: the long-term effects in cardiovascular disease / Martijn G. H. van Oijen, Floor Vlemmix, Robert J. F. Laheij, Lea Paloheimo, Jan B. M. J. Jansen, Freek W. A. Verheugt // Cardiology. — 2007; 107(1): 57-62.link