Lviv National Medical University Department of pathological physiology

PATHOLOGY OF RED BLOOD

PhD. Sementsiv N.G. In norm The number of erythrocytes:  in female - 3,9-4,7·1012/l  in male - 4,5-5,0·1012/l

Hemoglobin  in female - 120-140g/l  in male - 140-160g/l

 Color index(CI) - 0,85-1,15  Globular value = 3 x Hb / the first 3 figures of erythrocytes.

 Reticulocytes - 0.5-2%, 0,5-2%0 changes in total blood volume

 normovolemia  hypovolemia  hypervolemia  simple (Ht - norm),  polycitemia (Ht > 0,48),  olygocytemia (Ht < 0,36). A) Norm B) acut anaemia

б) acute hemorrhage г) hydremia Pathological forms of erythrocytes

 regenerative  degenerative  cell pathologic regeneration Regenerative forms reticulocytes

залежно від зрілості розрізняють:

 (Зернисті) Stippling

 (Сітчасті) Mesh  Norm in a blood reticulocytes - 0,2–2,0%. Regenerative forms  Basophiles substantial erythrocytes - cytoplasm remains basophilic normo blast.  Polychromatophil erythrocytes (polychromasia, polychromatophilia ) – erythrocytes with basophiles substantial ( blue cells) indicates increased RBC production by the marrow Qualitative (degenerative) changes of

 - - different shape of erythrocytes;  - - different size of erythrocytes;  - - different saturation of red blood cells by hemoglobin Degenerative forms

Anisocytosis  present in a blood different forms erythrocytes

» normocyte (7,01–8,0 мкм) » microcyte(6,9–5,7 мкм) » macrocyte(8,1–9,35 мкм) » megalocyte (10–15 мкм) Degenerative forms Poikilocytosis  present in a blood pictures erythrocytes different forms : elongate form , oval, ellipsoid and os.

ОVAlOCYTE( ) – 5% all blood.

Pathological cells regenerate

Megaloblast  mehaloblastyc cell type hematopoiesis

Megaloblast oval cells in the diameter of 1,5- 2,0 times larger than normal erythrocytes

is the final stage mehaloblastyc hematopoiesis.  - pathological inclusions in the erythrocytes : Jolly bodies

Cabot rings Jolly bodies Erythrocytosis Primary family (hereditary) forms

Secondary Absolute (increased erythropoiesis) relative Vaquez disease Erythremia (true polycythemia) - chronic leukemia with the defect of cells of precursor of mielopoesis with unlimited proliferation hematopoetic cells.

Blood picture:  Hemoglobin (over 180g/l)  Erythrocyte (over 6x1012/l)  Platelets (over 400x109/l)  Leukocyte (over 10x109/l)  Hematocrit ↑ Anaemia

Anemia -is a syndrome or disease which is characterized by the decrease of erythrocytes and hemoglobin amount in the unite of blood volume and accompanied by qualitative changes of erythrocyte. Cases of anemia

 The cases of anemia are numerous but the most important grouped whit in three major mechanisms that produce anemia:  Blood loss (excessive bleeding)  Inadequate production of red blood cells  Excessive destruction of red blood cells Classification of anemia

 I. According to etiology:  Hereditary and acquired

 II. According to pathogenesis : Diserythropoietic  Hemolytic  Posthemorragic IІІ. According to type of hematopoesis:  1. with erythroblastic  2. with megaloblastic

ІV. According to color index (globular value):  1. normochromic  2. hypochromic  3. hyperchromic  Color index(CI) - 0,85-1,15  Globular value = 3 x Hb (g/l) / the first 3 figures of erythrocytes.

ІV. According to color index (globular value):  Hypohromatic (c.i. < 0,8)  Normochromatic (c.i. = 0,8– 1,05)  Hyperchromatic (c.i. > 1,05) V. According to ability of bone marrow to regeneration:  regenerative  hyperregenerative  hyporegenerative  aregenerative Classification of anemia

Over a mean diameter of erythrocytes (MDE)

 normocytic (mde = 7,2–8,0 мкм)

 microcytic (mde < 7,2 мкм)

 macrocytic (mde = 8,1–9,5мкм)  megalocytic anaemia (mde > 12 мкм) Classification of anemia

By type hematopoiesis

Megaloblastic Erythroblastic Classification of anemia

By etiopathogenesis

 Posthemorrhagic  Hemolityc  Dyserythropoietyc Classification of Anemia According to Underlying Mechanism

 I Blood Loss  Acute: trauma  Chronic: lesions of gastrointestinal tract, gynecologic disturbances  II Increased Destruction (Hemolytic Anemias):

 III Impaired Red Cell Production Classification of Anemia According to Underlying Mechanism

II Increased Destruction (Hemolytic Anemias):  A. Intrinsic (intracorpuscular) abnormalities  1. Hereditary  2. Acquired  B. Extrinsic (extracorpuscular) abnormalities Classification of Anemia According to Underlying Mechanism

B. Extrinsic (extracorpuscular) abnormalities

 1. Antibody mediated  2. Mechanical trauma to red cells: Extrinsic (extracorpuscular) abnormalities

 1. Antibody mediated  a. Isohemagglutinins: transfusion reactions, erythroblastosis fetalis (Rh disease of the newborn)

 b. Autoantibodies: idiopathic (primary), drug-associated, systemic lupus erythematosus B. Extrinsic (extracorpuscular) abnormalities

 2. Mechanical trauma to red cells:

 a. Microangiopathic hemolytic anemias: thrombotic thrombocytopenic purpura, disseminated intravascular coagulation

 b. Infections: malaria Toxic hemolytic anemia

Poisoning by hemolytic poisons:

 Arsine  Acetic lead  Phosphorus  Nitrobenzene  Phenylhydrazine  Biliary acids  Mushroom poison  Snake venom Immune hemolytic anemia

 1. Autoimmune anemia

 2. Post transfusion anemia а) transfusion of АВ0-uncompatible blood б) transfusion of Rh- uncompatible blood

 3. Hemolytic anemia of new-born Acquired haemolytic anemia Ethiology  Immune injury : – isoimmun; – autoimmun.  Injury caused by biological factors: the endo-and Some strains of microbes.  Mechanical injury  Thermal injury .  Intoxication hemolytic poisons . A. Intrinsic (intracorpuscular) abnormalities 1. Hereditary

 a. Membrane abnormlities  Membrane skeleton proteins: , elliptocytosis:  Membrane lipids: abetalipoproteinemia  b. Enzyme deficiencies  Glycolytic enzymes: pyruvate kinase, hexokinase  Enzymes of hexose monophosphate shunt: glucose-6-phosphate dehydrogenase, glutathione synthetase Microspherocytosis or Minkowsky-Shauffard disease []. Membranopathy Blood picture :  1. The number of hemoglobin decreases.  2. The number of erythrocytes is decreases.  3. CI is normal - normochromic anemia.  4. The reticulocytes number increases - hyperregenerative anemia.  5. Decrease of erythrocytes osmotic resistance takes place.  6. Increase mean concentration of hemoglobin in the red blood cell (МСНС) more than 36%.  6. The number of unconjugated [indirect] bilirubin increases. Enzymopathy-deficiency of the enzyme Gl-6-FDG Blood picture : 1. Erythrocyte number ↓ 2. Hemoglobin amount ↓ 3. Color index (globular value) – normochromic. 4. Reticulocyte number ↑ 5. Erythrocytes osmotic resistance ↓ 6. Indirect bilirubin ↑ A. Intrinsic (intracorpuscular) abnormalities 1. Hereditary

 c. Disorders of hemoglobin synthesis  Deficient globin synthesis: thalassemia syndromes  Structurally abnormal globin synthesis (hemoglobinopathies): sickle cell anemia, unstable hemoglobins: Hemoglobinopathys are the anemias related to the violation of hemoglobin synthesis. Types of hemoglobinopathys : The 1st – is the hemoglobin chains synthesis violations; The 2nd – is the hemoglobin chains structure violations. Hemoglobinopathy

α-thalassemia

Blood picture :  1. Erythrocyte number ↓ ↓  2. Hemoglobin amount ↓  3. Color index ↓.  4. Reticulocyte number ↑  5. Erythrocytes osmotic resistance ↓  6. Indirect bilirubin ↑  7. Target erythrocytes () Sickle-cell anemia

Blood picture :

 Erythrocyte number ↓  Hemoglobin amount ↓  Color index (globular value) – normochromic  Indirect bilirubin ↑  Smear - Sickle-cell III Impaired Red Cell Production

 A.Disturbance of proliferation and differentiation of stem cells:

 2. Defective hemoglobin synthesis

 a. Deficient heme synthesis: iron deficiency  b. Deficient globin synthesis: thalassemias:  Anemia of renal failure III Impaired Red Cell Production

 B. Unknown or multiple mechanisms: myelodysplastic syndrome, anemia of chronic inflammation, anemias due to marrow infiltrations Pathology of Anemias

 CLINICAL MANIFESTATIONS  Acute: shortness of breath, organ failure, shock  Chronic:  With hemolysis: skeletal abnormalities because of expansion of marrow; growth retardation; jaundice and gallstones  With defective erythropoiesis: iron overload, heart and endocrine failure Signs and symptoms of anaemia

 Most commonly, people with anemia report non-specific symptoms of a feeling of weakness, or fatigue, general malaise and sometimes poor concentration. Posthemorrhagic anaemia

1. Acute 2. Chronic

Periods of compensation of acute blood loss 1. Reflectory 2. Hidremic 3. Medullary Iron-deficiency anemia

 Blood picture :  Erythrocyte number ↓  Reticulocyte number ↓  Hemoglobin amount ↓  Color index (globular value) ↓

 Smear: microcytes, anulocytes , aniso/poikilocytosis, Target and “pencil” cells

 serum ferritin ↓  serum iron ↓  Serum soluble transferine receptors increase State of the oral cavity in anemias • Dietary iron deficiency anemia or anemia of chronic disease should be suspected in every case of glossitis, glossodynia, angular cheilitis, erythematous mucositis, oral candidiasis, recurrent oral ulcers, and burning mouth when no other obvious causes are identified Glossodynia Iron Deficiency Anemia  IRON REFRACTORY is anemia which arises up as a result of the violation of iron including into hemoglobin, at the activity decrease or absence of enzymes which are needed for the hemoglobin synthesis (protoporphyrin ІX deficiency)

Reasons:  1. Hereditary   2. , alcoholism. Iron-refractory anemia  Blood picture : - Hemoglobin amount ↓ - Erythrocyte number ↓ - Color index (globular value) ↓ - Sideroblasts ↑

 In the blood serum the number of iron increases!!!!.

 In marrow the sideroblasts number increases. ANEMIAS OF DIMINISHED ERYTHROPOIESIS

Megaloblastic Anemia:  Caused by deficiencies of folate or vitamin B12, which lead to inadequate synthesis of thymidine and defective DNA replication. Results in enlarged abnormal hematopoietic precursors (megaloblasts) in the bone marrow, ineffective hematopoiesis, and (in most cases) pancytopenia. В12-deficiency anemia Reasons:

 insufficient intake with food  pathology of the stomach  pathology of the intestine  transcobalamin deficiency  hepatitis  pregnancy В12-deficiency anemia

 Blood picture

 Erythrocyte number ↓  Hemoglobin amount ↓  Color index (globular value) ↑ ↑  Leukopenia, hypersegmentation of neutrophils  Thrombocytopenia

 In the smear of blood: megalocytes, megaloblasts; Jolly's bodies; Cabot's rings. Aplastic anemia: which affects bone marrow erythrocyte sprout on the background of a deep bone marrow suppression and sharply reduced production of red blood cells and granulocytes and platelets (pancytopenia).

 Caused by bone marrow failure (hypocellularity) due to diverse causes, including exposures to toxins and radiation, idiosyncratic reactions to drugs and viruses, and inherited defects in DNA repair and the enzyme telomerase.