Anemia pathophysiology briefly. Anemia. Stages of compensation for acute blood loss

1. Hematology / O.A. Rukavitsyn, A.D. Pavlov, E.F. Morshakova [etc.] /ed. O.A. Rukavitsina. – St. Petersburg: LLC “DP”, 2007. – 912 p.

2. Cardiology. Hematology / ed. ON THE. Buna, N.R. College and others - M.: Reed Elsiver LLC, 2009. - 288 p.

3. Visual hematology / Translation from English. Edited by prof. IN AND. Ershova. – 2nd ed. – M.: GEOTAR-Media, 2008. – 116 p.: ill.

4. Papayan A.V., Zhukova L.Yu. Anemia in children: a guide for doctors. – SPb.: PETER. – 2001 – 384 p.

5. Pathophysiology: textbook: in 2 volumes/ed. V.V. Novitsky, E.D. Goldberg, O.I. Urazova. – 4th ed. – GEOTAR-Media, 2010. – T.2. – 848 p.: ill.

6. Pathophysiology: textbook, 3 volumes: [A.I. Volozhin and others]; edited by A.I. Volozhina, G.V. Poryadina. – M.: Publishing Center “Academy”, 2006.- T.2 – 256 pp.: ill.

8. Guide to hematology / Ed. A.I. Vorobyova. - M.: Newdiamed, 2007. - 1275 p.

9. Shiffman F.J. Pathophysiology of blood. – M.: Publishing house BINOM, 2009. – 448 p.

Hemolytic anemia is a group of diseases characterized by pathologically intense destruction of red blood cells, increased formation of their breakdown products, as well as a reactive increase in erythropoiesis. Currently, all hemolytic anemias are usually divided into two main groups: hereditary and acquired.

Hereditary hemolytic anemias, depending on the etiology and pathogenesis, are divided into:

I. Membranopathy of erythrocytes:

a) “protein-dependent”: microspherocytosis; ovalocytosis; stomatocytosis; pyropoikilocytosis; "Rh-zero" disease;

b) “lipid-dependent”: acanthocytosis.

II. Enzymopathies of erythrocytes caused by deficiency:

a) enzymes of the pentose phosphate cycle;

b) glycolysis enzymes;

c) glutathione;

d) enzymes involved in the use of ATP;

e) enzymes involved in the synthesis of porphyrins.

III. Hemoglobinopathies:

a) associated with a violation of the primary structure of globin chains;

b) thalassemia.

Acquired hemolytic anemia:

I. Immunohemolytic anemia:

a) autoimmune;

b) heteroimmune;

c) isoimmune;

d) transimmune.

II. Acquired membranopathies:

a) paroxysmal nocturnal hemoglobinuria(Marchiafava-Micheli disease);

b) spur cell anemia.

III. Anemia associated with mechanical damage red blood cells:

a) march hemoglobinuria;

b) arising from prosthetics of blood vessels or heart valves;

c) Moshkovich disease (microangiopathic hemolytic anemia).

IV. Toxic hemolytic anemia of various etiologies.

Developmental mechanisms and hematological characteristics of Congenital hemolytic anemias

The above classification of hemolytic anemia convincingly indicates that the most important etiopathogenetic factors in the development of erythrocyte hemolysis are disturbances in the structure and function of erythrocyte membranes, their metabolism, the intensity of glycolytic reactions, pentose phosphate oxidation of glucose, as well as qualitative and quantitative changes in the structure of hemoglobin.

I. Features separate forms erythrocyte membranopathies

As already indicated, pathology can be associated either with a change in the structure of the protein or with a change in the structure of the lipids of the erythrocyte membrane.

The most common protein-dependent membranopathies include the following hemolytic anemias: microspherocytosis (Minkowski-Choffard disease), ovalocytosis, stomatocytosis, more rare forms - piropoikilocytosis, Rh-null disease. Lipid-dependent membranopathies occur in a small percentage among other membranopathies. An example of such hemolytic anemia is acanthocytosis.

Microspherocytic hemolytic anemia (Minkowski-Choffard disease). The disease is inherited in an autosomal dominant manner. The basis for disturbances in microspherocytosis is a reduced content of the actomyosin-like protein spectrin in the erythrocyte membrane, a change in its structure and a disruption of the connection with actin microfilaments and lipids of the inner surface of the erythrocyte membrane.

At the same time, there is a decrease in the amount of cholesterol and phospholipids, as well as a change in their ratio in the erythrocyte membrane.

These disorders make the cytoplasmic membrane highly permeable to sodium ions. A compensatory increase in the activity of Na, K-ATPase does not ensure sufficient removal of sodium ions from the cell. The latter leads to overhydration of red blood cells and contributes to a change in their shape. Red blood cells become spherocytes, lose their plastic properties and, passing through the sinuses and intersinus spaces of the spleen, are injured, lose part of their membrane and turn into microspherocytes.

The lifespan of microspherocytes is approximately 10 times shorter than that of normal red blood cells, mechanical resistance is 4-8 times lower, and the osmotic resistance of microspherocytes is also impaired.

Despite the congenital nature of microspherocytic hemolytic anemia, its first manifestations are usually observed in older childhood, adolescence and adulthood, rarely in infants and the elderly.

Patients with microspherocytic anemia experience jaundice skin and mucous membranes, enlarged spleen, in 50% of patients the liver becomes enlarged, there is a tendency to form stones in the gallbladder. Some patients may have congenital anomalies of the skeleton and internal organs: tower skull, gothic palate, brady- or polydactyly, strabismus, malformations of the heart and blood vessels (the so-called hemolytic constitution).

Picture of blood. Anemia of varying severity. Reduced number of red blood cells in peripheral blood. The hemoglobin content during hemolytic crises decreases to 40-50 g/l, during the inter-crisis period it is approximately 90-110 g/l. The color index may be normal or slightly reduced.

The number of microspherocytes in peripheral blood varies - from a small percentage to a significant increase in the total number of red blood cells. The content of reticulocytes is persistently increased and ranges from 2-5% during the inter-crisis period to 20% or more (50-60%) after a hemolytic crisis. During a crisis, single erythrokaryocytes may be detected in the peripheral blood.

The number of leukocytes during the inter-crisis period is within the normal range, and against the background of a hemolytic crisis - leukocytosis with a neutrophilic shift to the left. The platelet count is usually normal.

Bone marrow puncture reveals pronounced hyperplasia of the erythroblastic lineage with an increased number of mitoses and signs of accelerated maturation.

With microspherocytic anemia, as with other hemolytic anemias, there is an increase in the level of bilirubin in the blood serum, mainly due to the unconjugated fraction.

Ovalocytic hemolytic anemia (hereditary elliptocytosis). Ovalocytes are a phylogenetically more ancient form of red blood cells. In blood healthy people they are determined in a small percentage - from 8 to 10. In patients with hereditary elliptocytosis, their number can reach 25-75%.

The disease is inherited in an autosomal dominant manner. Pathogenesis is caused by a defect in the erythrocyte membrane, in which several fractions are missing membrane proteins, including spectrin. This is accompanied by a decrease in the osmotic resistance of ovalocytes, an increase in autohemolysis and a shortening of the life span of ovalocytes.

The destruction of ovalocytes occurs in the spleen, so most patients experience its enlargement.

Picture of blood. Anemia of varying severity, most often normochromic. The presence of ovalocytes in the peripheral blood is more than 10-15%, moderate reticulocytosis. Increase in indirect bilirubin in blood serum. Ovalocytosis is often combined with other forms of hemolytic anemia, for example, sickle cell anemia, thalassemia.

Hereditary stomatocytosis. The type of inheritance is autosomal dominant. This is a rare pathology. The diagnosis is based on the detection of a peculiar appearance of red blood cells in a blood smear: an unstained area in the center of the red blood cell is surrounded by colored areas connected at the sides, which resembles an open mouth (Greek stoma). Changes in the shape of erythrocytes are associated with genetic defects in the structure of membrane proteins, which causes increased membrane permeability for Na + and K + ions (the passive penetration of sodium into the cell increases approximately 50 times and the release of potassium from erythrocytes increases 5 times). In most carriers of the anomaly, the disease is not clinically manifested.

Picture of blood. Patients develop anemia, often normochromic. During the hemolytic crisis there is a sharp decline hemoglobin, high reticulocytosis. The level of indirect bilirubin increases in the blood serum.

The osmotic resistance and lifespan of defective red blood cells are reduced.

Determination of an increased amount of sodium ions in altered red blood cells and a decrease in potassium ions is of diagnostic importance.

Acanthocytic hemolytic anemia. The disease belongs to lipid-dependent membranopathies, is inherited in an autosomal recessive manner and manifests itself in early childhood. With this pathology, peculiar red blood cells are found in the blood of patients - acanthocytes (Greek akanta - thorn, thorn). on the surface of such red blood cells there are from 5 to 10 long spike-like projections.

It is believed that in the membranes of acanthocytes there are disturbances in the phospholipid fraction - an increase in the level of sphingomyelin and a decrease in phosphatidylcholine. These changes lead to the formation of defective red blood cells.

At the same time, the amount of cholesterol, phospholipids, triglycerides in the blood serum of such patients is reduced, and β-protein is absent. The disease is also called hereditary abetalipoproteinemia.

Picture of blood. Anemia, often normochromic, reticulocytosis, the presence of red blood cells with characteristic spike-like projections.

The content of indirect bilirubin in the blood serum is increased.

II. Hereditary hemolytic anemia associated with impaired activity of erythrocyte enzymes

Hemolytic anemia associated with deficiency of pentose phosphate cycle enzymes. Insufficiency of glucose-6-phosphate dehydrogenase of erythrocytes is inherited in a sex-linked type (X-chromosomal type). According to this clinical manifestations diseases are observed mainly in men who inherited this pathology from their mother with her X chromosome, and in women who are homozygous for the abnormal chromosome. In heterozygous women, clinical manifestations will depend on the ratio of normal red blood cells and red blood cells with glucose-6-phosphate dehydrogenase deficiency.

Currently, more than 250 variants of glucose-6-phosphate dehydrogenase deficiency have been described, of which 23 variants were discovered in the USSR.

The key role of G-6-FDG is its participation in the reduction of NADP and NADPH2, which ensure the regeneration of glutathione in erythrocytes. Reduced glutathione protects red blood cells from decay upon contact with oxidants. In individuals with glucose-6-phosphate dehydrogenase deficiency, oxidants of exogenous and endogenous origin activate lipid peroxidation of erythrocyte membranes, increase the permeability of the erythrocyte membrane, disrupt the ionic balance in cells and reduce the osmotic resistance of erythrocytes. Acute intravascular hemolysis occurs.

More than 40 are known various types medicinal substances, which are oxidizing agents and provoke hemolysis of red blood cells. These include antimalarials, many sulfa drugs and antibiotics, antituberculosis drugs, nitroglycerin, analgesics, antipyretics, vitamins C and K, etc.

Hemolysis can be induced by endogenous intoxications, for example, diabetic acidosis, acidosis during renal failure. Hemolysis occurs during toxicosis of pregnant women.

Picture of blood. Hemolytic crisis provoked by taking medicinal product, is accompanied by the development of normochromic anemia, reticulocytosis, neutrophilic leukocytosis, and sometimes the development of a leukemoid reaction. Reactive erythroblastosis is noted in the bone marrow.

In newborns with a severe deficiency of glucose-6-phosphate dehydrogenase activity, hemolytic crises occur immediately after birth. This is a hemolytic disease of newborns, not associated with an immunological conflict. The disease occurs with severe neurological symptoms. The pathogenesis of these crises has not been sufficiently studied; it is assumed that hemolysis is provoked by consumption by a pregnant or nursing mother. medicines with hemolytic effect.

Hereditary hemolytic anemia caused by deficiency of erythrocyte pyruvate kinase activity. Congenital hemolytic anemia occurs in individuals homozygous for an autosomal recessive gene. Heterozygous carriers are practically healthy. The enzyme pyruvate kinase is one of the concluding enzymes of glycolysis that ensures the formation of ATP. In patients with pyruvate kinase deficiency, the amount of ATP in erythrocytes decreases and the products of glycolysis of previous stages - phosphophenolpyruvate, 3-phosphoglycerate, 2,3-diphosphoglycerate - accumulate, and the content of pyruvate and lactate decreases.

As a result of a decrease in ATP levels, all energy-dependent processes are disrupted, and primarily the work of Na+, K+-ATPase of the erythrocyte membrane. A decrease in the activity of Na+, K+-ATPase leads to the loss of potassium ions by the cell, a decrease in the content of monovalent ions and dehydration of red blood cells.

Dehydration of red blood cells makes it difficult to oxygenate hemoglobin and release oxygen from hemoglobin to tissues. An increase in 2,3-diphosphoglycerate in erythrocytes partially compensates for this defect, since the affinity of hemoglobin for oxygen decreases when it interacts with 2,3-diphosphoglycerate, and, consequently, the release of oxygen to tissues is facilitated.

Clinical manifestations of the disease are heterogeneous and can manifest as hemolytic and aplastic crises, and in some patients - in the form of mild severe anemia or even asymptomatic.

Picture of blood. Moderate anemia, often normochromic. Sometimes macrocytosis is detected; the osmotic resistance of erythrocytes is reduced or unchanged; during crises, the content of indirect bilirubin in the plasma increases. The number of reticulocytes in the peripheral blood increases sharply during a crisis, and in some patients erythrokaryocytes appear in the blood.

III. Hemoglobinopathies

This is a group of hemolytic anemias associated with a violation of the structure or synthesis of hemoglobin.

There are hemoglobinopathies caused by an anomaly in the primary structure of hemoglobin, qualitative (sickle cell anemia), and caused by a violation of the synthesis of hemoglobin chains, or quantitative (thalassemia).

Sickle cell anemia. The disease was first described in 1910 by Herrick. In 1956, Itano and Ingram established that the disease is a consequence gene mutation, as a result of which an amino acid substitution occurs in position VI of the β-polypeptide chain of glutamic acid hemoglobin with neutral valine and abnormal hemoglobin S begins to be synthesized, which is accompanied by the development of pronounced poikilocytosis and the appearance of sickle cell forms of erythrocytes.

The reason for the appearance of sickle-shaped red blood cells is that hemoglobin S in the deoxygenated state has 100 times less solubility than hemoglobin A, and high ability to polymerization. As a result, oblong crystals form inside the red blood cell, which give the red blood cell a sickle shape. Such red blood cells become rigid, lose their plastic properties and are easily hemolyzed.

In the case of homozygous carriage we speak of sickle cell anemia, and in heterozygous carriage we speak of sickle cell anomaly. The disease is common in the countries of the “malarial belt” of the globe (the countries of the Mediterranean, the Near and Middle East, North and West Africa, India, Georgia, Azerbaijan, etc.). The presence of hemoglobin S in heterozygous carriers provides them with protection against tropical malaria. In residents of these countries, hemoglobin S occurs in up to 40% of the population.

The homozygous form of the disease is characterized by moderate normochromic anemia, the total hemoglobin content is 60-80 g/l. The number of reticulocytes is increased - 10% or more. The average lifespan of red blood cells is about 17 days. A characteristic feature is the presence in the stained smear of sickle-shaped erythrocytes, erythrocytes with basophilic puncture.

Hemolysis of red blood cells contributes to the development of thrombotic complications. Multiple thromboses of the vessels of the spleen, lungs, joints, liver, and meninges may occur, followed by the development of infarction in these tissues. Depending on the localization of thrombosis in sickle cell anemia, several syndromes are distinguished - thoracic, musculoskeletal, abdominal, cerebral, etc. Worsening of anemia may be associated with a hypoplastic crisis, which most often occurs in children against the background of an infection. In this case, inhibition of bone marrow hematopoiesis is noted and reticulocytes disappear in the peripheral blood, the number of red blood cells, neutrophils and platelets decreases.

Hemolytic crisis can be triggered in patients with sickle cell anemia infectious diseases, stress, hypoxia. During these periods, the number of red blood cells sharply decreases, the level of hemoglobin drops, black urine appears, icteric discoloration of the skin and mucous membranes appears, and indirect bilirubin in the blood increases.

In addition to aplastic and hemolytic crises in sickle cell anemia, sequestration crises are observed, in which a significant part of the red blood cells is deposited in internal organs, in particular in the spleen. When red blood cells are deposited in internal organs, they may be destroyed at the deposit sites, although in some cases red blood cells are not destroyed during deposit.

The heterozygous form of hemoglobinopathy S (sickle cell anomaly) is asymptomatic in most patients, since the content of pathological hemoglobin in red blood cells is low. A small percentage of heterozygous carriers of abnormal hemoglobin during hypoxic conditions (pneumonia, rise to altitude) may have dark urine and various thrombotic complications.

Thalassemia. This is a group of diseases with a hereditary disorder of the synthesis of one of the globin chains, hemolysis, hypochromia and ineffective erythrocytopoiesis.

Thalassemia is common in the countries of the Mediterranean, Central Asia, Transcaucasia, etc. Environmental and ethnic factors, consanguineous marriages, and the incidence of malaria in a given area play a significant role in its spread.

The disease was first described by American pediatricians Cooley and Lee in 1925 (probably a homozygous form of α-thalassemia).

The etiological factor in thalassemia is mutations of regulatory genes, the synthesis of abnormally unstable or non-functioning messenger RNA, which leads to disruption of the formation of the α-, β-, γ-, and δ-chain of hemoglobin. It is possible that the development of thalassemia is based on hard mutations of structural genes such as deletions, which can also be accompanied by a decrease in the synthesis of the corresponding globin polypeptide chains. Depending on the disturbance in the synthesis of certain polypeptide chains of hemoglobin, α-, β-, δ- and βδ-thalassemia is distinguished, however, each form is based on a deficiency of the main fraction of hemoglobin - HbA.

Normally, the synthesis of various polypeptide chains of hemoglobin is balanced. In pathology, in the case of deficiency in the synthesis of one of the globin chains, excess production of other polypeptide chains occurs, which leads to the formation of excessive concentrations of unstable abnormal hemoglobins of various types. The latter have the ability to precipitate and fall out in the erythrocyte in the form of “inclusion bodies”, giving them the shape of targets.

Classification of thalassemias:

1. Thalassemia caused by impaired synthesis of the α-globin chain (α-thalassemia and diseases caused by the synthesis of hemoglobins H and Brats).

2. Thalassemia caused by impaired synthesis of β- and δ-chains of globin (β-thalassemia and β-, δ-thalassemia).

3. Hereditary persistence of fetal hemoglobin, i.e. a genetically determined increase in hemoglobin F in adults.

4. Mixed group - double heterozygous states for the thalassemia gene and the gene for one of the “qualitative” hemoglobinapathies.

α-thalassemia. The gene responsible for the synthesis of the α chain is encoded by two pairs of genes located on the 11th chromosome. One of the pairs is manifest, the other is secondary. In the case of development of α-thalassemia, gene deletion occurs. With homozygous dysfunction of all 4 genes, the globin α-chain is completely absent. Hemoglobin Brats is synthesized, which consists of four γ-chains that are unable to carry oxygen.

Carriers of homozygous α-thalassemia are not viable - the fetus dies in utero due to dropsy.

One of the forms of α-thalassemia is hemoglobinopathy H. With this pathology, there is a deletion of three genes encoding the synthesis of hemoglobin α-chains. Due to a deficiency of α-chains, abnormal hemoglobin H is synthesized, consisting of 4 β-chains. The disease is characterized by a decrease in the number of erythrocytes, hemoglobin (70-80 g/l), severe hypochromia of erythrocytes, their target appearance and basophilic punctation. The number of reticulocytes is moderately increased.

Deletion in one or two genes encoding the α chain causes a slight deficiency of hemoglobin A and is manifested by mild hypochromic anemia, the presence of basophilic puncta and target red blood cells, and a slight increase in reticulocyte counts. As with other forms of hemolytic anemia, with heterozygous α-thalassemia, icteric discoloration of the skin and mucous membranes and an increase in indirect bilirubin in the blood are noted.

β-thalassemia. It is more common than α-thalassemia and can be found in homozygous and heterozygous forms. The gene encoding the synthesis of the β chain is located on chromosome 16. Nearby are the genes responsible for the synthesis of globin γ- and δ-chains. In the pathogenesis of β-thalassemia, in addition to gene deletion, there is a violation of splicing, leading to a decrease in mRNA stability.

Homozygous β-thalassemia (Cooley's disease). The disease is most often detected in children aged 2 to 8 years. Jaundice discoloration of the skin and mucous membranes, enlarged spleen, deformations of the skull and skeleton, and stunted growth appear. In severe forms of homozygous β-thalassemia, these symptoms appear already in the first year of a child’s life. The prognosis is unfavorable.

From the blood side, signs of severe hypochromic anemia are detected (CP about 0.5), a decrease in hemoglobin to 20-50 g/l, the number of red blood cells in the peripheral blood is 1-2 million per day.

Heterozygous β-thalassemia. It is characterized by a more benign course; signs of the disease appear at a later age and are less pronounced. Anemia is moderate. The content of red blood cells is about 3 million in 1 micron, hemoglobin is 70-100 g/l. The content of reticulocins is 2-5% in peripheral blood. Aniso- and poikilocytosis, target-like erythrocytes are often detected; basophilic punctured erythrocytes are typical. The iron content in serum is usually normal, less often - slightly increased. In some patients, indirect serum bilirubin may be slightly increased.

Unlike the homozygous form, with heterozygous β-thalassemia there are no skeletal deformities and no growth retardation.

The diagnosis of β-thalassemia (homo- and heterozygous forms) is confirmed by an increase in the content of fetal hemoglobin (HbF) and HbA2 in erythrocytes.

Bibliographic link

Chesnokova N.P., Morrison V.V., Nevvazhay T.A. LECTURE 5. HEMOLYTIC ANEMIA, CLASSIFICATION. DEVELOPMENTAL MECHANISMS AND HEMATOLOGICAL CHARACTERISTICS OF CONGENITAL AND HEREDITARY HEMOLYTIC ANEMIA // International Journal of Applied and basic research. – 2015. – No. 6-1. – pp. 162-167;
URL: https://applied-research.ru/ru/article/view?id=6867 (access date: 07/18/2019). We bring to your attention magazines published by the publishing house "Academy of Natural Sciences"

PATHOPHYSIOLOGY OF THE BLOOD SYSTEM. DYSERYTHROPOETIC ANEMIA.

MINISTRY OF EDUCATION OF THE KYRGYZ REPUBLIC
KYRGYZ-RUSSIAN SLAVIC UNIVERSITY
DEPARTMENT OF NORMAL AND PATHOLOGICAL PHYSIOLOGY KRSU
Faculty of Medicine
specialty "General Medicine"
PATHOPHYSIOLOGY
BLOOD SYSTEMS.
DYSERYTHROPOETIC
ANEMIA.
The lecture was prepared by: Candidate of Medical Sciences, Associate Professor of the Department of Research and Physical Education Pak I.V.

Lecture outline

Etiology and pathogenesis of iron deficiency anemia.
Main clinical manifestations.
Etiopathogenesis of B-12 and folate deficiency anemia.
Pathophysiological basis for the main
clinical syndromes and hematological changes.
Aplastic anemia, etiology and pathogenesis.
Basic principles and methods of therapy
dyserythropoietic anemias.
Differential diagnosis of anemia.
Dyserythropoietic anemias

Dyserythropoietic anemias

N.B.!
Normal erythropoiesis
possible if the body has
sufficient quantity
amino acids, iron,
vitamins B1, B2, B6, B12, C,
folic acid,
microelements Co, Cu, etc.
substances.
Dyserythropoietic anemias

Maintenance of erythropoiesis
For effective erythropoiesis especially
the following substances are important:
Vitamin B12
Folic acid
Important for synthesis
cellular DNA
Iron
Part of hemoglobin
Dyserythropoietic anemias

Classification

Dyserythropoietic anemias

Etiopathogenesis
iron deficiency
anemia
Dyserythropoietic anemias

Epidemiology
WHO data, 2004:
Anemia
2.000.000.000
ZhDA
1.800.000.000
(90% of anemia cases are caused by iron deficiency)
Iron deficiency
3.580.000.000
Iron-deficiency anemia is the first in
list of the 38 most common diseases by
according to WHO.

Historical data
AI data
Historical
epidemiology of IDA
ZhDA
epidemiology
For centuries, chlorosis, or "pale
illness" was considered a sign of unrequited love and was attributed
to diseases of the juvenile period.
In 1832 Pierr Blaud discovered the effectiveness of sulfate
iron in chlorosis. Since that time, chlorosis began to be attributed to
blood diseases.
IDA accounts for 80-90% of all anemias.
Prevalence: 0.2% men, 2.6% women.
Russia:
IDA in 9-13% of women
Ukraine:
IDA in 20% of the population
Central Asia: IDA in 50-60% of women.
Dyserythropoietic anemias

Iron metabolism

gland
Metabolism
Iron food
10-20 mg/day
10 %
Loss of feces
10-20 %
urine, epithelium
1-2 mg/day
depot
100-400 mg
suction
in the gastrointestinal tract 1-2 mg/day
75 %
Other
processes
Plasma
transferrin 4 mg
Erythroblasts
Hb synthesis
5-15 %
macrophages
Red blood cells
destruction 1/120 day
Dyserythropoietic anemias

DISTRIBUTION OF IRON IN THE BODY

IRON DISTRIBUTION
IRON B
IN
DISTRIBUTION
ORGANISM
ORGANISM
heme (protoporphyrin and Fe++)
hemoglobin - 75% è O2 transport
myoglobin - 5-15% è O2 reserve in muscles
enzymes - 0.3% и cellular respiration
non-heme
transferrin - 0.1% è transfer of Fe+++ from plasma to tissue
ferritin and hemosiderin – 10-20% è iron depot in
liver
Dyserythropoietic anemias

The role of iron in the human body
storage and
transportation
oxygen
energetic
exchange
metabolism
BAV
division
cells
biosynthetic
processes
Dyserythropoietic anemias

Lack of iron in
body
o Iron deficiency in the body occurs when
if the supply of mineral
substances less than 1 mg per day.
Iron deficiency in the human body comes down not only to
hematological manifestations, but also determines
dysfunction of all cells (especially in high
aerobic tissues), causing negative consequences
disorders of iron metabolism in the human body.
Deficiency of this vital trace element
inevitably leads to disruption of education
hemoglobin, the development of anemia and, as a consequence, to
trophic disorders in organs and tissues.
Dyserythropoietic anemias

Iron-deficiency anemia

- This pathological condition, characterized
a decrease in the amount of hemoglobin and red blood cells due to:
lack of iron intake
increased need for iron
excess iron loss
Dyserythropoietic anemias

Iron-deficiency anemia

Iron-deficiency anemia -
pathological condition,
characterized by a decrease in the amount
hemoglobin per unit volume of blood,
which is caused by an imbalance between
receipt, use (expense
or loss) of iron in the body.
Dyserythropoietic anemias

chronic blood loss (uterine,
gastric, hemorrhoidal, tumors)
insufficient intake of Fe from food
Fe malabsorption (gastrointestinal pathology)
increased Fe intake during growth and
child development, during lactation and
pregnancy, during intense physical
loads
Dyserythropoietic anemias

Etiology of iron deficiency anemia

Dyserythropoietic anemias

PATHOGENESIS OF IDA

decreased iron reserves
▼
reduction in content serum iron
▼
increasing the total iron-binding capacity of serum with
decreased saturation of transferrin with iron
▼
decreased iron incorporation into erythroid cells
▼
decrease in heme synthesis (increase in protoporphyrin in erythroid
cells)
▼
Iron-deficiency anemia
Dyserythropoietic anemias

Main clinical manifestations of iron deficiency anemia

Hematological
syndrome
hemic
hypoxia
- pale skin and
mucous membranes
- tachycardia
- shortness of breath
- dizziness,
headache
- memory loss and
attention
- general weakness,
fatigue
Sideropenic
syndrome
↓Fe(S) content
Serum iron is normal
in men – 13-30 µmol/l,
in women – 11.5-25 µmol/l
- dry skin
- brittle nails and
hair
- taste disturbances
- impaired sense of smell
Dyserythropoietic anemias

Dyserythropoietic anemias

Sideropenic syndrome

“hyposiderosis syndrome” is caused by tissue deficiency
iron, which leads to a decrease in the activity of many enzymes
(cytochrome oxidase, peroxidase, succinate dehydrogenase, etc.).
Signs:
perversion of taste (pica chlorotica) - irresistible desire
eat anything unusual and inedible (chalk, dental
powder, coal, clay, sand, ice), as well as raw dough, minced meat, cereals; this
the symptom is more common in children and adolescents, but quite often in
adult women; addiction to hot, salty, sour, spicy foods;
perversion of smell - addiction to smells that
are perceived by most others as unpleasant (gasoline,
kerosene, acetone, the smell of varnishes, paints, shoe polish, naphthalene, etc.);
severe muscle weakness and fatigue, muscle atrophy and
decreased muscle strength due to myoglobin and enzyme deficiency
tissue respiration;
dystrophic changes in the skin and its appendages (dryness,
peeling, tendency to rapid formation of cracks in the skin;
dullness, fragility, hair loss, early graying of hair; thinning,
fragility, cross-striations, dullness of nails; symptom
koilonychia - spoon-shaped concavity of nails);
Dyserythropoietic anemias

Sideropenic syndrome

angular stomatitis - cracks; glossitis (in 10% of patients) - characterized by
a feeling of pain and swelling in the tongue area, redness of its tip, and in
further atrophy of the papillae (lacquered tongue); often observed
tendency to periodontal disease and caries;
atrophic changes in the mucous membrane of the gastrointestinal tract
- this is manifested by dryness of the mucous membrane of the esophagus and difficulties, and
sometimes pain when swallowing food, especially dry food (sideropenic dysphagia);
development of atrophic gastritis and enteritis.
symptom of “blue sclera” (characterized by a bluish color or pronounced
blue sclera. This is explained by a violation of collagen synthesis in the sclera, it
thins out and shines through choroid eyes.
imperative urge to urinate, inability to hold urine when
laughing, coughing, sneezing, possibly even bedwetting, which is caused by
weakness of the bladder sphincters;
sideropenic low-grade fever - characterized by a prolonged increase
temperatures up to subfebrile levels,
pronounced predisposition to acute respiratory viral and
other infectious and inflammatory processes, chronic infection, which
caused by a violation of the phagocytic function of leukocytes and weakening
immune systems;
reduction of reparative processes in the skin and mucous membranes.
Dyserythropoietic anemias

KOILONYCHIA

Dyserythropoietic anemias

N.B.
Sideroblasts are
bone erythrokaryocytes
brain containing iron
(normal 20-40%)
Dyserythropoietic anemias

Main criteria for IDA
low color index
hypochromia of erythrocytes
microcytosis
decreased serum iron levels
increase in total iron-binding
serum abilities
decreased serum ferritin levels
Dyserythropoietic anemias

Diagnostic signs of iron deficiency and iron deficiency anemia

Stages
deficit
gland
Ferritin
serum
Iron
serum
Prelatent
(hidden)
decrease
Latent
(hidden)
decrease
decrease
decrease
decrease
Hemoglobin
Explicit
decrease

Iron deficiency conditions

Dyserythropoietic anemias

TREATMENT OF IDA

Eliminating the causes
development of anemia
Administration of iron supplements
Diet therapy
Diet is not
is not
is the presenter
leading factor
factor in recovery
restoration
Diet
iron balance
iron at
during treatment
treatment of anemia!
anemia!
balance

Sources of nutritional iron

Sources of nutritional
nutritional iron
gland
Sources
Cheeses
1% Bread
Fruits
5%
8%
58%
meat
10%
18%
Vegetables
French fries
Dyserythropoietic anemias

Criteria for effective
effective therapy
IDA therapy
ZhDA
Criteria
Days 5-7: reticulocyte crisis
from 3 - 4 weeks: normalization of Hb, Ht,
erythrocytes
from 10 weeks:
normalization
ferritin (Fedepo)
Dyserythropoietic anemias

Reasons for ineffective
ineffective
Causes
anemia treatment
anemia
treatment
insufficient dose of iron
impaired absorption of iron in the gastrointestinal tract
refusal of iron supplements due to
side effects
premature
cancel when reached
normal HB level
Dyserythropoietic anes

Duration of therapy
iron deficiency therapy
iron deficiency
Duration
anemia (WHO,
(WHO, 2001)
2001)
anemia
Filling the deficit
iron, including
replenishment of iron depot,
should last until 6
months
for warning
relapse
Iron Deficiency Anaemia. Assessment, Prevention and Control, WHO, 2001
Dyserythropoietic anemias

Premature
drug withdrawal
gland - main
cause of relapse
anemia
Dyserythropoietic anes

NEED FOR CORRECTION

CORRECTIONS
NECESSITY
children, teenagers
athletes
pregnant, lactating
elderly
women of reproductive age,
menstruating heavily
Dyserythropoietic anemias

Etiopathogenesis
B and folate deficiency
anemia
12
Dyserythropoietic anemias

Historical reference

In 1855 English doctor Thomas Addison and then in 1872
year in more detail German doctor Anton Birmer described
a disease called malignant (pernicious)
anemia. Soon the French doctor Armand Trousseau suggested
call this disease Addison's anemia and anemia
Addison - Beerman.
In 1926, J. Whipple, J. Minot and W. Murphy reported,
What pernicious anemia can be treated by adding to the diet
nutrition of raw liver and what is the basis of the disease
congenital inability of the stomach to secrete a substance,
necessary for the absorption of vitamin B12 in the intestine. Behind
They received the Nobel Prize for this discovery in 1934.
Dyserythropoietic anemias

Anemia associated with the disorder
DNA and RNA synthesis
N.B.
Vitamin B and folic acid
take part in the main stages
exchange of purine and pyrimidine
bases in the process of DNA and RNA synthesis.
The body contains 4 mg of reserve
vitamin B12, which is enough for 4
of the year.
12
Dyserythropoietic anemias

Metabolism of B12 in the body

AT 12
methylcobalamin
DNA synthesis
cell division
adenosinecobalamin
- regulates the synthesis of fatty acids
acids
- participates in education
succinic acid from
methylmalonic acid
Dyserythropoietic anemias

Metabolism of vitamin B12 (cyanocobalamin)

Metabolism of vitamin B (cyanocobalamin)
12
B12 intake from food (daily requirement 1 mcg) +
internal factor Castla in the stomach (gastromucoprotein)
Absorbed in the ileum
Methylcobalamin
Folic acid
Tetrahydrofolic acid
DNA synthesis
Normal hematopoiesis
Portal vein
Liver (depot B1212)
In the blood B12 + transcobalamin-2
5-deoxyadenosylcobalamin
Methylmalonic acid (toxic)
+ propionic acid
succinic acid
Fatty acid metabolism

B12 - folate deficiency anemia

- pathological condition,
characterized by a decrease
amount of hemoglobin and red blood cells in
unit of blood volume that
due to the replacement of normoblastic
type of hematopoiesis on
megaloblastic type due to
disorders of nucleic acid synthesis
in conditions of vitamin B12 deficiency and/or
folic acid.
Dyserythropoietic anemias

Etiology of B12 deficiency anemia

deficit
Castle's external factor
– vitamin B12 with food
deficit
internal factor
Kastla is a gastromucoprotein synthesized by parietal
cells of the stomach, protects vital. AT 12
from destruction
Dyserythropoietic anemias

Causes of vitamin B12 deficiency

Causes of Vitamin B Deficiency
1.
2.
3.
12
Insufficient B12 content in food (external Castle factor).
Malabsorption:
a)
violation of gastromucoprotein synthesis (internal Castle factor):
atrophic gastritis of the fundus of the stomach;
autoimmune reactions with the production of antibodies to parietal cells
stomach and gastromucoprotein;
gastrectomy (after gastrectomy, the half-life of B12 is 1 year;
after gastrectomy, signs of B12 deficiency appear after 4-5 years);
stomach cancer;
congenital deficiency of gastromucoproteins;
b)
impaired absorption of B12 in the small intestine;
diseases small intestine accompanied by the syndrome
malabsorption (chronic enteritis, celiac disease (glutenenteropathy),
SPRU (tropical diarrhea), Crohn's disease)
ileal resection;
small intestine cancer;
congenital absence of receptors for the vitamin B12 + complex
gastromucoprotein in the small intestine;
c)
competitive uptake of vitamin B12;
broad tapeworm infestation;
pronounced intestinal dysbiosis.
Decreased production of transcobalamin-2 in the liver and impaired transport
vitamin B12 into the bone marrow (for cirrhosis of the liver).
Dyserythropoietic anemias

PATHOGENESIS of MBA

The main pathogenetic links in the development of B12-deficiency anemia

Impaired DNA synthesis in hematopoietic cells,
mainly erythroblasts
Cell division disorder
Embryonic type of hematopoiesis (megaloblastic)
Megaloblasts rarely mature into megalocytes due to their hemolysis in
bone marrow and do not provide hematopoietic function (increased
content of unconjugated bilirubin, urobilin, stercobilin, m.b.
increased serum iron with hemosiderosis of internal organs)
The cell nucleus matures slowly, the protoplasm has an increased content
Нb – hyperchromia (Jolly bodies, Cabot rings), hypersermonuclearity
neutrophils
Dyserythropoietic anemias

Main clinical syndromes of B12 deficiency anemia

Hematological syndrome
(manifested by pancytopenia → hypoxia,
bleeding, immunodeficiency)
Gastroenterological
syndrome (manifested by atrophic
glossitis, gastritis, enteritis → violation
gastrointestinal functions
Neurological syndrome
(manifested by funicular myelosis → shaky
gait, sensory disturbance
Dyserythropoietic anemias

Hematological syndrome
disturbance of proliferation and maturation of FEC
transition from normoblastic to
megaloblastic type of hematopoiesis
formation of FEC with low resistance,
short life expectancy
anemia, leukopenia, thrombocytopenia
Dyserythropoietic anemias

Dyserythropoietic anemias

Pathogenetic rationale for the main clinical syndromes of B12 - deficiency anemia

Gastroenterological syndrome
disruption of cell division and maturation in the mucosa
gastrointestinal tract
atrophy of the gastrointestinal mucosa
inflammation of various parts of the gastrointestinal tract (glossitis,
stomatitis, enterocolitis, etc.) – dysfunction
Dyserythropoietic anemias

Pathogenetic rationale for the main clinical syndromes of B12 deficiency anemia

Neurological syndrome
disruption of fatty acid synthesis
accumulation of methylmalonic acid
toxic effect on myelin
funicular myelosis (degeneration of the posterior and
lateral columns of the spinal cord)
Dyserythropoietic anemias

Main differential criteria for B12 deficiency anemia

Hematological syndrome:
hyperchromic anemia (CP above 1.1-1.3);
anisocytosis (megalocytosis), poikilocytosis,
basophilic granularity, Cabot rings, corpuscles
Jolly;
trilinear cytopenia;
hypersegmental neutrophilosis;
megaloblastic type of hematopoiesis (according to
data from sternal puncture);
decrease in B12 in the blood is less than 200 pg/ml;
Dyserythropoietic anemias

Dyserythropoietic anemias

Bone marrow in B12 deficiency anemia

Prevail
erythromegaloblasts with
delayed maturation
kernels.
In the preparation there are gigantic
stab and
polysegmental
neutrophils.
Dyserythropoietic anemias

Dyserythropoietic anemias

Peripheral blood picture in B12-deficiency anemia

Peripheral blood picture
B-deficiency anemia
12
Dyserythropoietic anemias

Folate deficiency anemia
Less common than B12 deficiency
The reserve of FA in the body is designed for 2-3 months.
FC is present in all products; when heated, it
is destroyed
Absorbed throughout the jejunum, maybe. diarrhea
Transport proteins are not required for FA absorption
Birth defects of FC are combined with mental
retardation and are not corrected by entering FC
Dyserythropoietic anemias

Causes of folate deficiency anemia

nutritional deficiency (frequent
cause in the elderly);
enteritis with malabsorption;
taking certain medications that depress
synthesis of folic acid (methotrexate,
triamterene, anticonvulsants,
barbiturates, metformin);
chronic alcohol intoxication;
increased need for folic acid
(malignant tumors, hemolysis,
exfoliative dermatitis, pregnancy).
Dyserythropoietic anemias

Folate deficiency anemia

anemia
Folate deficiency
Prophylactic intake of folic acid
reduces risk congenital pathology up to 70%
WHO recommends mandatory use
folic acid during pregnancy!!!
Dyserythropoietic anemias

Main differential criteria for folate deficiency anemia

History data:
pregnancy,
neonatal period,
chronic alcoholism,
chronic hemolysis,
myeloproliferative diseases,
taking medications (folic acid antagonists,
antituberculosis, anticonvulsants).
Erythropoiesis suffers.
There is no funicular myelosis or gastric damage.
There is no reticulocyte crisis when taking B12.
In the bone marrow, only megaloblasts are stained with the dye
with B12-deficiency anemia, and with folate-deficiency anemia -
No.
Reduction of folic acid in the blood less than 3 mg/ml (N – 3-25
mg\ml).
Dyserythropoietic anemias

Treatment of megaloblastic anemias

Vitamin B12 (cyanocobalamin) – 400-500 mcg intramuscularly (4-6 weeks).
For neurological disorders: B12 (1000 mcg) + cobalamide
(500 mcg) until neurological symptoms disappear.
If necessary, lifelong administration of B12 (500 mcg) 1 time every 2
weeks or preventive treatment - B12 (400 mcg) for 1015 days 1-2 times a year.
Transfusion of erythromass only vital signs(at
all anemias!):
Nv< 50 г/л,
Nv< 70 г/л с нарушением гемодинамики,
development of precoma and coma, urgent preparation for surgery and
etc.
Deworming – removal of tapeworm (fenosal,
male fern).
Folic acid 5-15 mg/day (up to 30 mg/day); preventative
dose – 1-5 mg/day.
Dyserythropoietic anemias

Criteria for treatment effectiveness

subjective improvement in
first days of treatment;
reticulocyte crisis at 5-7
day of treatment (for B deficiency anemia);
12
improvement in blood counts
second week of treatment, from
normalization after 3-4 weeks.
Dyserythropoietic anemias

Etiopathogenesis
aplastic
anemia
Dyserythropoietic anemias

Aplastic anemia

APLASTIC ANEMIA – hematological
syndrome caused by a large number endogenous and
exogenous factors, qualitative and
quantitative changes in the stem cell and its
microenvironment, cardinal morphological
a sign of which is pancytopenia in
peripheral blood and fatty degeneration
bone marrow.
P. Ehrlich (1888) first described AA.
The term “aplastic anemia” was introduced in 1904.
Shoffar.
The incidence is 4-5 people per 1 million population per year (in
Europe)
Age peaks of incidence 20 and 65 years
Dyserythropoietic anemias

Aplastic anemia

Dyserythropoietic anemias

Etiological factors of AA
medicines,
chemical substances,
viruses,
autoimmune processes;
in 50% of cases the etiology is unknown (idiopathic AA).
Pathogenesis of AA
damage to pluripotent blood stem cells
suppression of hematopoiesis
action of immune (cellular, humoral)
mechanisms
deficiency of factors that stimulate hematopoiesis
iron, B12, protoporphyrin cannot be
used by hematopoietic tissue.
Dyserythropoietic anemias

Aplastic anemia may be
1.
Congenital (with syndrome congenital anomalies or without it)
2.
Acquired
AA is released downstream
3.
Spicy
4.
I'll sharpen it up
5.
Chronic
AA Forms
6.
Immune
7.
Non-immune
Clinical syndromes of AA
8.
Circulatory-hypoxic
9.
Septic-necrotic
10.
Hemorrhagic
Dyserythropoietic anemias

Aplastic anemia

Dyserythropoietic anemias

Bone marrow aplasia

PRINCIPLES, GOALS AND METHODS OF TREATMENT
DYSERYTHROPOETIC ANEMIA
PRINCIPLES
GOALS
ETIOTROPIC
Eliminate
decrease
degree
violations
division and
differentiation
erythrokaryocyto
V
METHODS
* Termination
actions
factors,
leading
to hypoplasia
bone
brain
*Introduction
“scarce”
factors - reasons
anemia
(vitamins B12,
B6, folic
acids,
PATHOGENETIC
SYMPTOMATIC
Eliminate
decrease
degree
hypoxia
prevent,
decrease
degree
hemosiderosis
Adjust
KShchR
Eliminate
decrease
degree
consequences
hypoxia
Eliminate
unpleasant
Feel
* Usage
* Function correction
cardiovascular
system, kidneys,
liver,...
antihypoxants,
antioxidants
*Introduction
buffer
solutions
Dyserythropoietic anemias

Differential diagnosis of anemia

Dyserythropoietic anemias

Differential diagnosis of anemia

Signs
ZhDA
SAA
GA
MBA
AA
CPU
<1
<1
N (thalassemia
< 1)
>1
N
Reticulocytes
N or ↓
N or ↓

N or ↓
↓↓
Syv. Fe
↓

N or
N or
N or
Platelets
N
N
N or ↓
↓
↓↓↓
Leukocytes
N
N
N
↓
↓↓↓
Spleen
N
N
often
m/b
N
Liver
N
often
often
often
N
Bone marrow
moderate
hyperplasia
erythrocyte germ,
sideroblasts
↓↓.
moderate
hyperplasia
erythrocyte germ,
sideroblasts

pronounced
hyperplasia
erythrocyte germ.
megaloblast
long type
hematopoiesis
nia
oppression
Dyserythropoietic anemias

Thank you for attention!
Posthemorrhagic anemia. Hemolytic anemia. Anemia (anemia)- a decrease in the total level of hemoglobin (Hb), often manifested in a decrease in it per unit volume of blood; in children under 6 years of age it is below 110 g/l, in adult women it is below 120 g/l, in men it is below 130 g/l. True anemia differs from pseudoanemia in the size of the hematocrit (in adults it is 36-48%).

◊ In most cases, with the exception of iron deficiency anemia and thalassemia, anemia is accompanied by a decrease in the content of red blood cells (below 3.9 10 12 / l).

Anemia is classified based on several principles.

A. By color indicator.

1. Normochromic - 0.85-1.05

2. Hyperchromic - above 1.05, but not more than 1.60.

3. Hypochromic - below 0.85.

B. By the average diameter of red blood cells.

1. Normocytic - 7-8 µm

2. Microcytic - less than 6.5 microns

3. Macrocytic - 8-12 microns.

4. Megalocytic - more than 12 microns.

B. By the ability of the bone marrow to regenerate (by the content of reticulocytes).

1. Regenerative - 1-5%.

2. Hyporegenerative 0.5-1%.

3. Regenerative - less than 0.5%.

4. Hyperregenerative - more than 5%.

D. According to the type of hematopoiesis.

1. Normoblastic.

2. Megaloblastic.

D. According to the etiopathogenetic principle.

1. Anemia due to blood loss (post-hemorrhagic):

a) acute;

b) chronic.

2. Anemia due to impaired blood formation:

a) deficiency anemia (vitamin deficiency, iron deficiency)

protein-deficient);

b) hypo- and aplastic;

c) metaplastic;

d) dysregulatory.

3. Anemia due to increased blood destruction (hemolytic):

a) hereditary;

b) purchased.

ACUTE POSTHEMORRHAGIC ANEMIA

A condition associated with rapid loss of a significant volume of blood (20-25% of blood over approximately 1 hour). The factor determining the degree of dysfunction and their compensation is uncorrectable hypovolemia.

STAGES OF COMPENSATION FOR ACUTE BLOOD LOSS

Reflex phase of compensation. Occurs on the 1st day after acute blood loss due to activation of the sympathoadrenal system: peripheral vascular resistance increases, blood redistribution occurs (centralization of blood circulation). However, blood pressure decreases, the return of blood to the heart and, accordingly, cardiac output decreases.

Hydraemic phase of compensation. It occurs on the 2-4th day and consists of the movement of fluid from the extracellular space into the vessels. One of the mechanisms of the hydremic phase is catecholamine-induced hyperglycemia due to glycogenolysis in the liver; the content of basic electrolytes in plasma remains virtually unchanged.

Bone marrow compensation phase. In this phase (5-7 days after acute blood loss), activation of the formation of erythropoietins in the kidneys against the background of severe hypoxia is important.

In the first time after blood loss, due to a decrease in the volume of the vascular bed, a decrease in the content of hemo-

globin and red blood cells, the hematocrit indicator also does not change.

Due to hydremia, a gradual drop in the levels of hemoglobin and red blood cells begins - normochromic anemia is formed, which subsequently becomes hypochromic due to lack of iron.

CHRONIC POSTHEMORRHAGIC ANEMIA

Anemia that develops as a result of repeated losses of small volumes of blood during bleeding from the gastrointestinal tract, with renal, uterine, nasal and hemorrhoidal bleeding.

Peripheral blood is characterized by a decrease in color index to 0.4-0.6, microcytosis, moderate leukocytosis with a neutrophilic shift to the left. With a long course of the disease, anemia becomes hyporegenerative in nature.

ANEMIA ASSOCIATED WITH IMPAIRED BLOOD FORMATION

1. Dysregulatory- caused by a violation of the regulation of hematopoiesis with a decrease in the production of erythropoietins or an increase in the number of their inhibitors (chronic kidney disease, hypofunction of the pituitary gland, adrenal glands, thyroid gland).

2. Scarce- occurs when there is a lack of substances necessary for erythropoiesis (iron, vitamins, protein).

Iron-deficiency anemia accounts for up to 80% of all anemia and develops as a result of an imbalance between the intake of iron into the body, its use and loss.

Iron losses are observed with repeated and prolonged bleeding - uterine, gastrointestinal, renal, pulmonary, and with hemorrhagic diathesis.

In some cases, nutritional iron deficiency (less than 2 mg per day) is possible, for example, with a small amount of meat consumption, with artificial feeding or with late complementary feeding in childhood.

Reduced iron absorption is observed with hypoacid gastritis, chronic enteritis, or with resection of parts of the gastrointestinal tract.

Impaired iron transport is possible with hereditary or acquired hypotransferrinemia.

Increased iron consumption develops during periods of growth and maturation, during pregnancy and lactation, and in chronic inflammatory diseases.

Iron deficiency is accompanied by an increase in ineffective erythropoiesis and a decrease in the lifespan of erythrocytes.

The blood picture is characterized by a decrease in hemoglobin content (from 100 to 20 g/l), the erythrocyte content may be normal or significantly reduced, and hypochromia is detected. A tendency to microcytosis, poikilocytosis, and the regenerative or hyporegenerative nature of anemia are also typical.

In the peripheral blood there are: serum iron levels below 30 mcg/l; the total iron-binding capacity of blood serum is higher than 64.4 µmol/l; ferritin content in the blood is below 40 mcg/l.

Serum iron deficiency is manifested by increased fatigue, distortion of taste and smell, general weakness, and headaches. Iron deficiency also leads to a decrease in the level of myoglobin and the activity of tissue respiration enzymes. The consequence of hypoxia is degenerative processes in organs and tissues. Layered and brittle nails, stomatitis, caries, atrophic gastritis, etc. are common.

ANEMIA CAUSED BY VITAMIN B12 DEFICIENCY (PERNICIOUS)

Vitamin B 12 deficiency can develop due to a violation of its supply, absorption, transport, deposition and assimilation at the bone marrow level.

Malabsorption is likely in the absence of internal Castle factor (transcorrin), in atrophic processes on the part of the gastric mucosa, in a hereditary selective disorder of vitamin production, in autoimmune destruction, in the agastric form of deficiency.

The absorption of vitamin B 12 is sharply limited with widespread damage to the small intestine - with enteritis, celiac disease, as well as with its resection.

The pathogenetic role of the competitive consumption of vitamin is shown in case of invasion by the broad tapeworm, as well as in the “cecal intestine” syndrome (when anastomoses are applied, areas of the small intestine remain through which food does not pass), as well as in multiple diverticulosis of the small intestine.

In some cases, vitamin B12 deficiency is caused by a lack of transcobalamin.

Vitamin B12 deficiency causes a disruption in the formation of DNA and further a disorder in the division of hematopoietic cells, i.e. slowing down the mitotic process and reducing the number of mitoses. Under such conditions, a megaloblastic type of hematopoiesis, similar to the embryonic one, is formed. The development of anemia is associated with the following mechanisms.

1. Decreased mitotic activity.

2. Ineffective erythropoiesis due to intramedullary destruction of megaloblasts.

3. Extravascular hemolysis in the spleen due to the increased size of megalocytes.

4. Intravascular hemolysis due to a decrease in the osmotic resistance of the megalocyte membrane.

In the peripheral blood, severe anemia is detected, predominantly hyperchromic (color index - 1.3-1.5), hyporegenerative. The presence of nuclear residues, anisocytosis, and poikilocytosis are typical. Neutropenia and thrombocytopenia are also noted.

Folate deficiency anemia is close to vitamin B 12 deficiency in its development mechanism and blood picture.

ANEMIA ASSOCIATED WITH IMPAIRED SYNTHESIS OR UTILIZATION OF PORPHYRINS

Caused by hereditary or acquired deficiency of enzymes involved in the synthesis of porphyrins or heme, such anemias are usually hypochromic, with a high iron content in the body, and are often characterized by organ hemosiderosis.

A hereditary deficiency of coproporphyrinogen decarboxylase, which synthesizes protoporphyrin, has been described. Apparently, more often the disease is associated with a violation of the synthesis of aminolevulinic acid. Due to disorders of protoporphyrin synthesis, iron binding becomes impossible - sideroachrestic anemia develops.

Acquired anemia of this kind often occurs with lead poisoning. Lead blocks sulfhydryl groups in the active sites of two enzymes involved in heme synthesis: aminolevulenic acid dehydrase and heme synthetase. As a result-

aminolevulenic acid accumulates in the urine, and in erythro-

citah - protoporphyrin.

A decrease in the rate of globin biosynthesis (-chain) and increased hemolysis were also detected. Lead is also capable of weakening the activity of ion pumps in the red blood cell membrane, which reduces the level of potassium ions and the life span of cells.

HYPO- AND APLASTIC ANEMIA

These anemias are a set of syndromes in which, along with pancytopenia, inhibition of hematopoiesis in the bone marrow is detected.

According to etiology, aplastic anemia is divided as follows:

1. Genuine (idiopathic), constitutional-hereditary, caused by impaired reactivity of the body or endocrine insufficiency.

2. Aplastic anemia associated with the action of damaging factors: radiation, toxic factors (benzene, mercury), cytotoxic (chlorethylamine, ThioTEP, colchicine, 6-mercaptopurine, etc.), medicinal (amidopyrine, barbiturates, sulfonamides, chlorpromazine), infectious ( viral hepatitis A, B, generalized forms of tuberculosis, typhoid fever, salmonellosis, septic conditions).

The following mechanisms are important in pathogenesis:

1. Reduced number of stem cells or their defects.

2. Disruption of the microenvironment, leading to changes in stem cells.

3. Immune influences causing disorders of stem cell function. The blood picture is characterized by pronounced, often normochromic, macrocytic, hyporegenerative anemia. There is significant granulocytopenia and thrombocytopenia. The number of myelokaryocytes in the bone marrow decreases. The clinical picture depends on the degree of disruption of individual hematopoietic germs and their combinations; it includes anemic, thrombocytopenic and granulocytopenic syndromes.

HEMOLYTIC ANEMIA

This group includes various anemias associated either with hereditary increased destruction of red blood cells or with the action of hemolytic factors of exogenous origin.

HEREDITARY HEMOLYTIC ANEMIA

1. Anemia associated with disruption of the erythrocyte membrane (membranopathy). Hereditary microspherocytosis (Minkowski-Choffard disease) is an autosomal dominant type of inheritance, characterized by increased permeability of the erythrocyte membrane and excessive intake of sodium ions into the cell. There is swelling of red blood cells, impaired ability to deform and a decrease in their life expectancy, destruction of the spleen by macrophages.

In microspherocytosis, the absence or disruption of binding of the membrane protein spectrin to protein 4.1 was revealed. It is assumed that the formation of the tetrameric form of spectrin from the dimeric form is disrupted, as well as the absence of erythrocyte membrane proteins, designated 4.2.

Usually the anemia is normochromic, regenerative. According to the blood picture, it differs in varying degrees of severity, during a hemolytic crisis it is more severe, but at the same time high reticulocytosis develops.

Membranopathies also include elliptocytosis (ovalocytosis), stomatocytosis (mouth-shaped red blood cells).

Acanthocytosis is caused by a violation of the lipid structure of the erythrocyte membrane.

2. Anemia associated with impaired activity of erythrocyte enzymes (enzymopathies). Deficiency of enzymes involved in energy production in red blood cells can lead to disruption of the ionic composition, reduced resistance to oxidizing agents and a decrease in the lifespan of these cells.

Hereditary deficiency of enzymes of lycolysis and ATP metabolism (hexokinase, hexophosphate isomerase, phosphofructokinase, pyruvate kinase, ATPase) has been described.

Deficiency of enzymes of the pentose phosphate cycle (glucose-6-phosphate dehydrogenase) leads to a lack of NADP H2, which is necessary for the reduction of glutathione, a factor that resists the action of oxidizing agents. This happens when there is a deficiency of glutathione synthesis enzymes - glutathione synthetase, glutathione reductase, glutathione peroxidase.

In such cases, anemia of varying severity is formed. Usually normochromic, with symptoms of anisocytosis, poikilocytosis, and polychromasia. The content of reticulocytes is increased, especially during exacerbations.

3. Anemia associated with impaired structure and synthesis of hemoglobin (hemoglobinopathies). Thalassemia- a group of hereditary diseases associated with a violation of the synthesis of one of the hemoglobin chains (¸ ¸ ¸), leading to an imbalance in their balance. In this case, the excessively formed chain aggregates and is deposited in erythrokaryocytes.

Thalassemia is determined by the deletion of structural genes responsible for the synthesis of the corresponding chain. The synthesis of the α-chain is encoded by two pairs of genes located on chromosome 11 pair. The absence of the β-chain in the embryo leads to intrauterine death.

Deletion in 1 of 4 genes encoding chain synthesis causes a mild deficiency, while deletion in 2 genes causes a more severe deficiency. If 3 genes are missing, then hemoglobinopathy H develops. Hemoglobin H consists of 4 chains, is unstable, easily aggregates, and is easily removed from the circulation by the spleen.

Thalassemia is characterized by moderate hypochromic anemia with symptoms of target-like erythrocytes and basophilic punctuation, moderate reticulocytosis.

The pathogenesis of thalassemia is more complex. The gene encoding the synthesis of the -chain is located on chromosome 16, next to it are the genes responsible for the synthesis of the - and -chains.

Some -thalassemias are caused by splicing disorders (i.e., changes that mRNA undergoes on its way from the nucleus, where it is synthesized, to the cytoplasm). The latter can lead to destabilization of the structure. Due to a disorder in the synthesis of the β-chain, many free β-chains appear, which causes ineffective erythropoiesis with increased destruction of erythrokaryocytes in the bone marrow.

Anemia associated with disruption of the structure of globin chains. They are caused by the replacement of one or more amino acids in the globin chain, the absence of a section of the chain, or its lengthening.

The most common abnormality of hemoglobin structure is hemoglobinopathy S. In the case of homozygous carriage, sickle cell anemia is said, and in heterozygosity, sickle cell anomaly. Sickling is the result of reduced solubility of hemoglobin, which gives up oxygen to form a gel.

Microscopy reveals crystals measuring 1.5 microns. It is assumed that the replacement of glutamic acid with valine at the 6th position leads to increased binding of one globin molecule to another.

The blood picture is characterized by a moderate decrease in the levels of hemoglobin and red blood cells, the color index is close to one. The stained smear shows basophilic punctuation, target-like appearance, and sometimes sickle-shaped red blood cells. The sickling is more pronounced when tested with sodium metabisulfite or after applying a tourniquet to the base of the finger. The content of reticulocytes is significantly increased.

ACQUIRED HEMOLYTIC ANEMIA

IMMUNE HEMOLYTIC ANEMIA

Heterogeneous group of diseases, combined by the participation of antibodies or immune lymphocytes in the damage and death of red blood cells or erythrokaryocytes.

Iso- or alloimmune anemias may develop with hemolytic disease of the newborn or with blood transfusion, not

compatible according to the AB0, Rhesus or other system to which the patient has antibodies.

Transimmune anemias occur when antibodies from a mother suffering from autoimmune hemolytic anemia cross the placenta and cause hemolytic anemia in the fetus.

Heteroimmune anemia (haptenic) associated with the appearance of new antigens on the surface of erythrocytes (for example, as a result of fixation of drugs on erythrocytes - penicillin, sulfonamides). The hapten sometimes becomes a virus, also fixed on the surface of the erythrocyte.

Autoimmune hemolytic anemias- a group of diseases caused by the formation of antibodies against self-antigens of erythrocytes or erythrokaryocytes.

In addition to idiopathic ones, there are also symptomatic autoimmune anemias; in them, hemolysis develops against the background of other diseases (malignant tumors of various locations and hemoblastosis, systemic lupus erythematosus, rheumatoid polyarthritis, immunodeficiency states).

The most likely pathogenetic basis of autoimmune hemolytic anemia is a breakdown of immunological tolerance.

The blood picture shows mild anemia, often normochromic, with an increased content of reticulocytes. During hemolytic crises, blood counts are disturbed to a greater extent; reticulocyte crises are possible with an increase in the content of reticulocytes to 80-90%.

Hypoplastic anemia is a disease of the blood system, characterized by inhibition of the hematopoietic function of the bone marrow and manifested by insufficient formation of red blood cells, leukocytes and platelets (panhemocytopenia) or only red blood cells (partial hypoplastic anemia, erythroblastophthisis). The basis of the pathological process is a violation of the proliferation and differentiation of bone marrow cells. A characteristic sign of this disease of the blood system is complete depletion (aplasia) of the bone marrow and profound impairment of its function, which is accompanied by severe anemia, leukopenia and thrombocytopenia. Insufficient production of cells by the bone marrow determines the main mechanisms of disease development - anemic syndrome, infectious complications due to granulocytopenia and hemorrhagic syndrome.

The main etiological factors of hypoplastic anemia are: ionizing radiation; insecticides; cytostatic drugs; other medicines; antibodies against bone marrow cells; viral infections (viral hepatitis); hereditary factors; idiopathic hypo- and aplastic anemia.

Blood picture

When examining peripheral blood, pancytopenia, severe anemia with low reticulocytosis and pronounced anisopoicilocytosis are noted. The hemoglobin content drops to 15-20 g/l. Leukopenia, thrombocytopenia of varying degrees. Sharp acceleration of ESR - up to 60-80 min/h. A study of bone marrow hematopoiesis in aplastic anemia reveals a picture of almost complete depletion of the bone marrow

Pathogenesis

Currently, the main pathogenetic factors of aplastic anemia are:

· damage to pluripotent hematopoietic stem cells;
· damage to the cellular microenvironment of the hematopoietic stem cell and indirect disruption of its function;
· immune depression of hematopoiesis and apoptosis of hematopoietic stem cells;
shortening the life of red blood cells;
· metabolic disorder of hematopoietic cells.

Damage to pluripotent hematopoietic stem cells-- the most important pathogenetic factor of aplastic anemia. The stem cell is the ancestor of all hematopoietic cells. With aplastic anemia, the colony-forming ability of the bone marrow is significantly reduced, the proliferation of hematopoietic cells is disrupted, and ultimately the pancytopenia syndrome is formed - leukopenia, anemia, thrombocytopenia. The mechanism of inhibition of the activity of pluripotent hematopoietic stem cells has not been fully elucidated.

Clinical picture

The main clinical and laboratory symptoms of acquired hypo- and aplastic anemia with damage to all three hematopoietic sprouts of the bone marrow are caused by total inhibition of hematopoiesis, as well as hypoxia of organs and tissues and hemorrhagic syndrome. The severity of symptoms depends on the severity and course of anemia.

Patients present complaints characteristic of anemic syndrome. Characterized by bleeding (gingival, nasal, gastrointestinal, kidney, uterine bleeding) and frequent infectious and inflammatory diseases. In the acute form, symptoms develop quickly and the course of the disease is severe from the very beginning. But in most patients the disease develops quite slowly, gradually, and to a certain extent, patients adapt to anemia. The disease is usually recognized when symptoms are severe.

When examining patients, attention is drawn to the pronounced pallor of the skin and visible mucous membranes, often with an icteric tint; hemorrhagic rashes on the skin, often in the form of bruises of varying sizes. Often, extensive hematomas form at the injection site (intramuscular, intravenous, subcutaneous). Hemorrhagic rash is localized mainly in the area of the legs, thighs, abdomen, and sometimes on the face. Hemorrhages may be observed in the conjunctiva and visible mucous membranes - lips, oral mucosa. There may be severe nasal, gastrointestinal, renal, pulmonary, uterine, and intracerebral bleeding. Peripheral lymph nodes are not enlarged.

When examining internal organs, the following changes may be detected:

· Respiratory system - frequent bronchitis, pneumonia.
· Cardiovascular system - myocardial dystrophy syndrome.
· Digestive system - with severe hemorrhagic syndrome, erosions may be detected on the mucous membrane of the stomach and duodenum.

Hemosiderosis of internal organs often develops due to increased destruction of defective red blood cells, decreased use of iron by the bone marrow, impaired heme synthesis, and frequent red blood cell transfusions.

Laboratory data and instrumental studies

General blood analysis- marked decrease in the number of red blood cells and hemoglobin; anemia in most patients is normochromic, normocytic; characterized by the absence or sharp decrease in the number of reticulocytes (regenerative anemia); leukopenia due to granulocytopenia with relative lymphocytosis is observed; Thrombocytopenia is typical. Thus, the most significant laboratory manifestation of hypo- and aplastic anemia is pancytopenia. ESR is increased.

Blood chemistry-- Serum iron content is increased, the percentage of iron saturation of transferrin is significantly increased.

Study of sternal puncture (myelogram)-- a pronounced decrease in cells of the erythrocyte and granulocytic series, lymphocytes and a significant reduction in the megakaryocytic lineage. In severe cases, the bone marrow looks “empty”; only single cells can be found in the sternal puncture. In the bone marrow, the content of iron, located both extracellularly and intracellularly, increases significantly.

Diagnostic criteria

· Normochromic normocytic aregenerator anemia with a sharp decrease or complete absence of reticulocytes, an increase in ESR.
· Leukocytopenia, absolute granulocytopenia, relative lymphocytosis.
· Thrombocytopenia.
· A sharply expressed absolute deficiency in the myelogram of erythro-, leuko- and thrombocytopoiesis cells, a delay in their maturation.
* Increased iron content inside erythrokaryocytes and extracellularly.
· A sharp decrease in the number or complete disappearance of hematopoietic cells and replacement of hematopoietic bone marrow with adipose tissue in the trephine biopsy specimen of the ilium is the main method for verifying the diagnosis of hypo- and aplastic anemia).
· Increased serum iron levels.

Iron deficiency anemia

Most often, iron deficiency in the body is caused by blood loss, which results in a discrepancy between the intake of iron in the body from food and the level of its utilization during the formation of red blood cells.
In particular, iron deficiency anemia can be caused by: hemorrhages from vessels damaged during the formation of peptic ulcers of the stomach and duodenum, menstrual blood loss. Sometimes in newborns and children, the intensity of erythropoiesis prevails over the intake of iron, which causes anemia without blood loss.

Anemia due to chronic inflammation

In patients with long-term (more than one month) inflammatory diseases, anemia often occurs. Moreover, the severity of anemia is directly related to the duration and severity of inflammation. The diseases that most often lead to anemia of this origin are subacute bacterial endocarditis, osteomyelitis, lung abscess, tuberculosis and pyelonephritis.
Autoimmune diseases (rheumatoid arthritis, etc.) are also characterized by chronic inflammation and anemia.
One of the causes of anemia in patients with malignant neoplasms is associated chronic inflammation.

Anemia caused by chronic inflammation is caused by:
1. Inhibition of erythropoiesis due to its prolonged stimulation by cytokines (colony-stimulating factors) formed and released by activated cellular effectors of chronic inflammation.
2. Failure to compensate for the decreased life expectancy of red blood cells.

In anemia due to chronic inflammation, a decrease in iron content in erythroblasts is a consequence of impaired delivery to the developing cells of the erythroid germ of the bone marrow. Iron deficiency leads to hypochromia and microcytosis of red blood cells. A deficiency of iron available for hemoglobin synthesis leads to an increase in the content of protoporphyrin in erythrocytes. The amount of iron available for erythropoiesis, despite its normal content in the body, is reduced by excessive systemic activation of mononuclear phagocytes, as well as their hyperplasia.
As a result of hyperplasia and hyperactivation in the mononuclear phagocyte system, excess iron is captured by activated mononuclear cells, which have an increased ability to absorb this microelement. The increased ability of mononuclear cells to absorb iron is largely due to the high concentration of interleukin-1 in the circulating blood, which increases with chronic inflammation. Under the influence of interleukin-1, which circulates in the blood in increased concentrations, neutrophils throughout the body intensively release lactoferrin. This protein binds free iron, released during the destruction of dying red blood cells, and transports it in increased quantities to mononuclear cells, which capture and retain this microelement. As a result, erythropoiesis is inhibited, which is due to a decrease in the availability of iron for the formation of erythroid cells.

Presumably, one of the links in the pathogenesis of anemia due to chronic inflammation can be considered excessive destruction of erythrocytes as a result of hyperactivation and hyperplasia in the mononuclear phagocyte system.
It is evidenced by a shortening of the life of almost normal erythrocytes, the pathological changes of which are reduced to a reduced iron content and an increase in the content of protoporphyrin.

Sideroblastic anemias

These anemias are associated with impaired synthesis of heme as a component of hemoglobin. Disturbances in hemoglobin synthesis in sideroblastic anemia are characterized by the accumulation of iron in mitochondria located around the nucleus of pathological erythroid cells (sideroblasts). These cells form a ring-like outline around the cell nucleus. Disturbances in heme synthesis in patients with sideroblastic anemia cause hypochromia and microcytosis.

There are two types of sideroblastic anemia:
1. Hereditary sideroblastic anemia, which is a monogenic disease, the transmission of which from parents to the patient is associated with the X chromosome or is inherited in an autosomal recessive manner. Presumably, hereditary sideroblastic anemia is caused by a congenital deficiency in the activity of the enzyme gamma-aminolevulinic acid synthetase (the key enzyme of the first stage of porphyrin synthesis).
Inhibition of enzyme activity may be primary or result from an inborn error in the metabolism of its essential cofactor, pyridoxal-5-phosphate.

2. Acquired sideroblastic anemias occur more often than hereditary ones. Acquired sideroblastic anemia can be the result of side effects of drugs (isoniazid, etc.). In addition, they may be idiopathic.

Impaired utilization of iron for the formation of heme in sideroblastic anemia manifests itself by an increase in the content of free iron cations in the serum, as well as an increase in the concentration of ferritin in it.

Thalassemia is a monogenic disease, which is based on inhibition of the synthesis of one of the polymer chains that make up the globin molecule. Depending on the type of chain whose synthesis is insufficient, thalassemia is classified into one of two main groups:

1. Alpha thalassemia. These diseases are caused by deletion (removal) of alpha-globin genes from the genome. There are four such genes. Depending on which gene is lost in the genome, sideroblastic anemia varies in severity from minor to severe, which causes the death of the fetus in the womb.
2. Beta thalassemia, which is caused by the absence or dysfunction of the corresponding gene. When a gene is dysfunctional, transcription occurs but results in the formation of abnormal ribonucleic acid (RNA). In addition, gene dysfunction may also consist of reduced formation of normal RNA. The genome contains two different beta globin genes. Therefore, there are two types of beta thalassemias. With a more severe form of beta thalassemia (Kulei's anemia), its symptoms become obvious in childhood. Usually at the age of thirty, despite blood transfusions, death occurs. In less severe beta thalassemia, there is no indication for blood transfusions, and anemia does not limit life expectancy.

When examining a blood smear in patients with thalassemia, poikilocytosis is revealed, that is, pathological variability in the shape of red blood cells.