PERNICIOUS ANEMIA (anemia perniciosa; lat. perniciosa is disastrous, pernicious; anemia; synonym: malignant anemia, Addison's disease — Birmera, B 12 - scarce anemia, megaloblastny anemia) — the heavy progressing anemia arising at disturbance of digestion of vitamin B 12 , arriving with food, owing to lowered (or at absence) secretions of an internal gastric factor.
First description of P. and. under the name «heavy primary anemia» Kumbu belongs (J. S. Combe, 1822). T. Addison in 1855 described a disease under the name «idiopathic anemia», and A. Birmer (see) in 1872 — group of the patients who had «the progressing pernicious anemia».
Possibility of treatment of P. and. by purpose of a special diet (a crude liver) it is established by J. Minot and U. Murphy in 1926; opening in 1929 by U. Kasl of an internal gastric factor (see. Kasla factors ) and in 1948 E. L. Smith and E. L. Rickes of «anti-pernicious» vitamin B 12 — cyanocobalamine (see) promoted identification of a pathogeny of P. and. and to its successful treatment.
Item and. the hl meets. obr. at persons 40 years are more senior; more often men are ill. Exceptional cases of a disease of children because of uniform feeding are known for goat milk or dry milk blends. P.'s incidence and., according to different researchers, makes from 20 to 60 on 10 000 population.
In classification anemias (see) allocate B 12 - (foliyevo) scarce anemias. Actually the combined deficit of vitamin B 12 and folic to - you meet seldom, the isolated deficit of vitamin B is more often observed 12 less often — deficit folic to - you.
An etiology and a pathogeny
the Major factor in P.'s etiology and. endogenous insufficiency of vitamin B is 12 , arising owing to disturbance of its absorption as a result of decrease or complete cessation of secretion of an internal gastric factor (gastromucoprotein) necessary for binding and the subsequent absorption of vitamin B 12 . Item and. can result from defeat went. - kish. a path, napr, inflammatory or malignant process, and also after subtotal or total removal of a stomach and after an extensive resection of a part of a small intestine. In rare instances P. and. develops at normal secretion of an internal gastric factor and it is caused by inborn lack of transcobalamine II (protein of a blood plasma) with which vitamin B 12 it communicates and delivered in a liver and red marrow, or absence in intestines of a proteinaceous acceptor of vitamin B 12 , vitamin B, necessary for receipt 12 from intestines in a circulatory bed. Point cases of family diseases, and also P.'s emergence to a role of a genetic factor and. because of inborn disturbance of secretion of the internal gastric factor inherited on autosomal recessively type. About participation of immune mechanisms at P. and. existence in blood serum at sick P.' most testifies and. and their relatives of the antibodies directed against parietal glandulotsit of a stomach, and also antibodies (IgG) against an internal gastric factor to-rye are defined as in parietal glandulotsita (at a gastrobiopsiya), and in cytoplasm of plasmocytes of red marrow autoradiography (see). Tell cases of a combination of P. of ampere-second about existence of autoimmune processes by Hashimoto's thyroiditis (see. Hashimoto disease ), at the same time at the same time there are anti-thyroid antibodies and antibodies to parietal glandulotsita of a stomach. Autoimmune genesis of P. and. confirms successful use of corticosteroids. In some cases P. and. arises without participation of specific antibodies.
Disturbance hemopoiesis (see) it is characterized megaloblastozy red marrow with defeat of all three sprouts of a hemopoiesis — erythroidal, granulotsitarny and megakariotsitarny. Feature of a megaloblastichesky erythrocytopoiesis is its inefficiency caused by sharp disturbance of processes of differentiation of erythroidal cells as a result of which in red marrow there is an accumulation of abnormal erythroidal cells — promegaloblasts and megaloblasts. The Megaloblastichesky erythrocytopoiesis is caused by falloff of activity In the ^-dependent enzymes participating in metabolism of folates (salts folic to - you), DNA, necessary for synthesis; in particular, decrease of the activity of methyltransferase is followed by cumulation in cells of inactive methyltetrahydrofolate and decrease in synthesis of DNA that leads to disturbance of cellular division and development of a megaloblastoz.
The increased «intramedullary mortality» of megaloblasts revealed at a biopsy of marrow in the form of an intensive erythrophagocytosis and hemosiderosis (see), leads to falloff of products of erythrocytes, i.e. to anemia. At the same time as a result of the increased disintegration of gemoglobinizirovanny megaloblasts (polychromatophilous and oxyphilic) there are symptoms hemolitic anemia (see) — not - the conjugated hyperbilirubinemia, a pleyokhromiya (the increased maintenance of pigments) of bile, an urobilinuria, the increased release of stercobilin with a stake. The possibility of participation of antibodies in marrowy destruction of erit-rokariotsit is not excluded.
Fatal cases in connection with successful treatment of P. and. meet extremely seldom. During the opening of the dead in the acute period of a disease the general anemia, yellowness of skin, serous and mucous membranes, fatty dystrophy of a myocardium, liver, kidneys comes to light. Blood in heart and large vessels liquid, watery. Owing to the expressed hyperplasia of the hemopoietic elements and disappearance of fat marrow of flat bones, and also a diaphysis and epiphysis of tubular bones very juicy, crimson-red color. Atrophic changes are characteristic in went. - kish. path.
Nipples of language, especially in the field of a root, an atrofichna, are maleficiated. The mucous membrane of language contains the reddish sites of an inflammation which are located more often at the edges and on a tip, sometimes aphthous rashes, cracks (a picture of a so-called gunterovsky glossitis). Similar changes can be observed in a mucous membrane of gums, cheeks, a soft palate, a throat, a gullet. Constantly the mucosal atrophy of a stomach which is most expressed in the field of a bottom comes to light; folds of a mucous membrane are maleficiated or are not defined, the wall of a stomach is thinned, in certain cases there are polypostural growths. Atrophic changes can be observed also in a mucous membrane of intestines. The sizes of a spleen — in limits or there is slightly more norm. The liver is increased slightly, a plotnovata. Owing to adjournment of hemosiderin tissue of a spleen, liver, sometimes kidneys on a section has a rusty shade. Limf, nodes small, soft. In some: cases macroscopically in a spinal cord the small centers of a necrosis with a softening come to light. Sometimes find punctulate hemorrhages of century serous and mucous membranes, in skin.
Microscopically in red marrow the expressed hyperplasia of cells of an erythroidal row with existence among them a large number of megaloblasts — the large cells having nezhnoyacheisty structure of a kernel with clearly visible kernels and a wide zone basphilic or polychrome-tofilnoy of cytoplasm is noted. The number of cells of a leykotsitopoez is a little lowered. Megacaryocytes contain in the sufficient or reduced quantity. The expressed dystrophic changes and disintegration of cells, especially erythroidal row, abundance erythro-and siderophages are observed. In a mucous membrane of a stomach the picture of atrophic gastritis comes to light, there is a considerable reduction of amount of glands and ferruterous cells, especially obkladochny. Cells are reduced in sizes, piknotichna, flattened owing to what the gleam of glands is expanded. The quantity of muciparous ferruterous cells increases, sites of an intestinal metaplasia of a superficial epithelium meet. The stroma of a mucous membrane is sclerosed, an infiltrirovana lymphocytes, plasmocytes, single segmentoyaderny neutrocytes (fig). Changes are most expressed in a greater cul-de-sac, however intensity can vary them in various sites of a mucous membrane. Atrophic changes are not exposed to involution at treatment by vitamin B 12 also remain during remission of a disease.
At a biopsy of a mucous membrane of a small bowel shortening of intestinal fibers, dystrophic changes of ferruterous cells with decrease in figures of mitoses in them in crypts, lymphoid plazmotsitarnaya infiltration of a stroma come to light. After treatment by vitamin B 12 these changes can disappear. Along with atrophic changes dystrophy of nerve fibrils of language, nervous cells of a submucous plexus (plexus submucosus, s. Meissneri) and a muscular and intestinal texture is observed (plexus myen-tericus, s. Auerbachi).
Dystrophic changes in back and side columns of a spinal cord are characteristic, it is preferential in cervical department, expressed in focal swelling with the subsequent disintegration of myelin nerve fibrils. Merge of the small centers leads to formation of big sites of defeat. Dystrophic changes craniocereberal are in certain cases observed (cranial, T.) and peripheral nerves. The hemosiderosis of marrow, spleen, liver, limf, nodes, kidneys, expressed in various degree takes place. In a spleen, limf, nodes the centers of an extramedullary hemopoiesis quite often meet.
The clinical picture
the Clinical picture is shown by symptoms of defeat went. - kish. path, nervous system and hemopoietic fabric. Gradually there are a weakness, fatigue, heartbeat, an asthma at an exercise stress. Many of patients complain of the dispeptic frustration which resulted from a gastric akhiliya which can be found several years prior to development of an anemia at the same time a gastric juice for a number of years does not contain an internal gastric factor. In 1 — 2% of cases of P. and. begins with the phenomena of stenocardia.
As a rule, the disease proceeds with aggravations which remissions follow. Outward of the patient at an aggravation of process is characterized by pallor with a citreous shade of skin and subikterichnostyo scleras. Patients are inclined to obesity. The liver is, as a rule, increased, soft. The dense spleen is sometimes palpated. Temperature is occasionally subfebrile. Functional (anemic) cordial noise are listened; on an ECG — decrease in a tooth of T in all assignments, broadening of a gastric complex.
The gunterovsky glossitis is found in some patients: in the beginning the inflammatory phenomena (the «scalded» language), further — atrophic prevail (the «varnished» language). Inflammatory and atrophic changes can extend to gums, a mucous membrane of cheeks, a soft palate, a throat and a gullet; in the latter case there is a dysphagy (Plakhmmer's syndrome — Vinsona). These phenomena, except an akhiliya, disappear during remission. At gastroscopies (see) gnezdny comes to light, the total mucosal atrophy of a stomach is more rare.
Defeat of c. the N of page is clinically shown by symptoms of a rachioplegia (a spastic paraparesis with reinforced reflexes and clonuses) and tabic symptoms (paresthesias, girdle pains, decrease in reflexes up to a full areflexia, disturbance of vibration and deep sensitivity, a touch ataxy, disorder of functions of pelvic bodies). Defeats of cranial nerves, hl are less often observed. obr. visual, acoustical, olfactory. Central is typical scotoma (see) with loss of the sight which is quickly recovered under the influence of treatment by vitamin B 12 .
At P.'s aggravation and. in blood Hyperchromic anemia is noted; reduction of quantity of erythrocytes is characteristic of it, to-rye differ in a saturation in hemoglobin, reach in dia. 12 — 15 microns; the color indicator is equal to 1,4 — 1,8. Erythrocytes meet the remains of kernels (Joly's little body), a mitotic spindle (Cabot's ring), basphilic stippling, poly-chromophils, poikilocytes, schizocytes, and also nuclear forms of erythroidal cells — megaloblasts. The quantity of leukocytes is reduced at the expense of a granulocytopenia; are found miyelo-and metamyelocytes, huge palochko-and the segmentoyaderny neutrophils containing up to 12 and more segments. Thrombocytopenia is marked, huge plates (megathrombocytes) meet. Content of vitamin B 12 in blood it is reduced at the normal or increased level of folates in erythroidal cells (the so-called metiltetragidrofo-latny block) and at the increased content of serumal iron. During remission the picture of blood is gradually normalized.
In cases of an easy current of P. and. at 80 — 90% of patients, according to M. P. of the Nevsky, asthenic disturbances are observed (see. Asthenic syndrome ).
At one patients prevail emotional giperesteticheskaya weakness, fatigue, absent-mindedness, instability of attention, feeling of weakness, in depression - tearful mood, a hyperesthesia; at others — irritability, discontent, easy excitability, the increased insistence. Hypochiondrial statements at patients with P. and. (see. Hypochiondrial syndrome ) are often connected with real somatic frustration. In cases irogrediyentno the current P. and., especially accompanied with symptoms of funicular myelosis (see), there are acute and long psychoses which frequency, according to a number of researchers, fluctuates from 4 to 10%. Psychoses meet at women aged from 40 up to 60 years more often. Initial frustration are defined by an adynamy which duration in cases of an acute current makes weeks, and in long — months. In the subsequent at an acute current the delirium most often develops (see. Delirious syndrome ), is more rare — twilight stupefaction (see) or an amentia (see. Amental syndrome ). Weighting of mental disturbances leads to development of a sopor and coma (see).
At psychoses with a long current after an adynamy there are affective frustration, most often in the form of a depression (see. Depressive syndromes ). The alarming agitated states with a sketchy persecution complex and charges, verbal prevail illusions (see) and hallucinations (see). In some cases there is a depression with fear. Less often maniacal states meet euphoria and reduced criticism (see. Maniacal syndromes ). During the weighting the wedge, pictures develops a hallucinatory paranoid state (see. Paranoid syndrome ), at Krom there can be expressed tactile hallucinations. Feature of mental disorders at P. and. consists in variability of their intensity and change of one frustration by others throughout short intervals of time. When such «blinking» of mental disorders is absent, prolonged psychosis is exhausted by one any state, reminding schizophrenia (see) or maniac-depressive psychosis (see). At the remote stages of long psychoses there can be delirious states. In some cases their emergence — a sign of the possible death connected with a basic disease. Psychoses in cases of an easy current of P. and. can be replaced by passing symptoms of decrease in level of the personality, and in cases of a heavy current emergence various on weight and manifestations is observed psychoorganic syndrome (see).
Heavy complication of P. and. the Pernicious coma (coma perniciosum) arising owing to the bystry anemization leading to a hypoxia and ischemia of a brain is (in particular, areas III of a ventricle). At the same time the loss of consciousness, an areflexia, temperature drop of a body and the ABP, short wind, vomiting, an involuntary urination is observed.
the Diagnosis establish on the basis a wedge, data, a characteristic picture of blood and results of a research of marrowy punctate.
Differential diagnosis Items of ampere-second others carry out a megaforehead of l by astny, in particular folic and scarce, anemias on the basis of the test of the Shilling which is that at sick P. and. the radioactive vitamin B entered inside 12 and at the same time parenterally not radioactive vitamin B 12 (1000 mkg) are defined in urine only in the minimum quantities that points to the broken absorption of vitamin B 12 , which is connected or with disturbance of secretion of an internal gastric factor, or with disturbance of intestinal absorption of vitamin B 12 ; in the latter case reception of a concentrate of an internal gastric factor does not improve absorption of vitamin B 12 . Item and. differentiate with symptomatic a megaloblast-nymi (pernitsioznopodobny) anemias arising at tumors of a stomach, diverticulums and tumors of thin and blind guts and also from agastralny, anenteralny and helminthic B 12 - scarce anemias (see. Anemia ), at which megaloblastny anemia develops as a result of disturbance of secretion of an internal gastric factor or absorption of vitamin B 12 in intestines. Item and. differentiate also with general diseases, napr, an erythremic myelosis (see. Leukoses ), of which are characteristic megaloblastoz marrow at the increased content of vitamin B 12 in blood (to 1000 ng/ml and above) and lack of therapeutic effect of administration of vitamin B 12 (so-called B 12 - akhrestichesky anemia).
At an aggravation daily enter vitamin B 12 (on 100 — 200 mkg) within 1 week to reticulocytic crisis which usually comes for the 5th day from the beginning of administration of vitamin B 12 also it is characterized by the increased maintenance of reticulocytes. Further the same doses enter every other day within 4 — 5 weeks before approach gematol, remission which is defined by normalization of peripheral blood and marrowy blood formation and recovery of normal content of vitamin B 12 in blood, and normalization of blood begins after reticulocytic crisis and comes to the end in 4 — 6 weeks; normalization of a marrowy hemopoiesis (transformation of a megaloblastiche-sky erythrocytopoiesis in normoblastic) begins immediately after administration of vitamin B 12 also comes to the end in 48 — 72 hours; content of vitamin B 12 in blood it is recovered gradually. During remission the wedge, symptoms, including neurologic disappear. At a funicular myelosis enter massive doses of vitamin B 12 (500 — 1000 mkg) daily within 7 — 10 days, further two times a week before disappearance of neurologic symptoms.
At psychoses depending on a wedge, pictures apply psychotropic drugs. At quickly progressing heavy pernicious anemia (the menacing Pernicious coma) transfusion of eritrotsitny weight is shown (see. Hemotransfusion ).
The forecast and Prevention
the Forecast at timely begun treatment favorable.
Prevention. For the prevention of aggravations of P. and. make injections of vitamin B 12 on 50 — 100 mkg weekly during 1 year and further 1 times in 2 weeks during all life.
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