ANEMIAS OF DIMINISHED ERYTHROPOIESIS

1. ANEMIAS OF DIMINISHED ERYTHROPOIESIS • includes anemias that are caused by : 1- inadequate dietary supply of nutrients: e.g. iron, folic acid, and vitamin B12. 2- anemias associated with bone marrow failure (aplastic anemia) 3- anemia of chronic disease (systemic inflammation) 4- bone marrow infiltration by tumor or inflammatory cells (myelophthisic anemia).

2. Iron Deficiency Anemia • the most frequent cause of anemia is iron deficiency.. • developed countries 10% of people • developing countries 25% to 50% • Morphology: • red cells are microcytic and hypochromic. • low serum ferritin and iron levels, low transferrin saturation • increased total iron-binding capacity • response to iron therapy. • For unclear reasons, the platelet count often is elevated. Erythropoietin levels are increased

3. PATHOGENESIS: • Chronic blood loss is the most important cause of iron deficiency anemia in the Western world - (e.g., peptic ulcers, colonic cancer, hemorrhoids) and the female genital tract • In the developing world, low intake is the most common causes of iron deficiency. • Increased demands not met by normal dietary intake occur worldwide during pregnancy and infancy. • Malabsorption can occur with celiac disease or after gastrectomy

4. Polycythemia= erythrocytosis • an increase in red cells per unit volume of peripheral blood, usually in association with an increase in hemoglobin concentration. • Polycythemia may be absolute (defined as an increase in total red cell mass) or relative. Relative polycythemia results from dehydration, such as occurs with water deprivation, prolonged vomiting, diarrhea, or the excessive use of diuretics. • Absolute polycythemia is described as primary when the increased red cell mass results from an autonomous proliferation of erythroid progenitors, and secondary when the excessive proliferation stems from elevated levels of erythropoietin. Primary polycythemia (polycythemiavera) is a clonal, neoplasticmyeloproliferative disorder considered later in this chapter. • The increases in erythropoietin that cause secondary forms of absolute polycythemia have a variety of causes

5. MegaloblasticAnemias • The morphologic hallmark of megaloblastic anemia is the presence of megaloblasts, enlarged erythroid precursors that give rise to abnormally large red cells (macrocytes). Granulocyte precursors are also increased in size. Underlying this cellular gigantism is a defect in DNA synthesis that impairs nuclear maturation and cell division. Because the synthesis of RNA and cytoplasmic elements proceeds at a normal rate and thus outpaces that of the nucleus, the hematopoietic precursors show nuclear-cytoplasmic asynchrony

6. The bone marrow is markedly hypercellular and contains numerous megaloblasticerythroid • In the peripheral blood the earliest change is the appearance of hypersegmented • The red cells typically include large, egg-shaped • mean cell volume often is greater than 110 fL (normal, 82 to 92 fL • macro-ovalocytesneutrophilsprogenitors.

7. Pernicious anemia is the most frequent cause of vitamin B12 deficiency. This disease seems to stem from an autoimmune reaction against parietal cells and intrinsic factor itself, which produces gastric mucosal atrophy • The main neurologic lesions associated with vitamin B12 deficiency are demyelination of the posterior and lateral columns of the spinal cord; The spinal cord disease begins with symmetric numbness, tingling, and burning in feet or hands, followed by unsteadiness of gait and loss of position sense, particularly in the toes

8. The diagnostic features of pernicious anemia Include: (1) low serum vitamin B12levels (2) normal or elevated serum folatelevels (3) serum antibodies to intrinsic factor (4) moderate to severe megaloblasticanemia (5) leukopenia with hypersegmentedgranulocytes (6) a dramatic reticulocytic response (within 2 to 3 days) to parenteral administration of vitamin B12

9. Aplastic anemia • is a disorder in which multipotent myeloid stem cells are suppressed, leading to bone marrow failure and pancytopenia. • It must be distinguished from pure red cell aplasia, in which only erythroid progenitors are affected and anemia is the only manifestation

10. Causes • PATHOGENESIS • more than half of the cases, aplastic anemia is idiopathic. • In the remainder, an exposure to a known myelotoxic agent, such as a drug or a chemical, can be identified. With some agents, the marrow damage is predictable, dose-related, and reversible. Included in this category are antineoplastic drugs (e.g., alkylating agents, antimetabolites), benzene, and chloramphenicoland sulfonamides

11. certain viral infections, most often community-acquired viral hepatitis • autoreactive T cells play an important role. This is supported by a variety of experimental data and clinical experience showing that aplastic anemia responds to immunosuppressive therapy aimed at T cells in 70% to 80% of cases • 5% to 10% of patients with "acquired" aplastic anemia have inherited defects in telomerase