Introduction to Anemia PDF

Introduction to anemia Dr. Jehad Alhmoud  Anemia is derived from the Greek word anemia, meaning “without blood.” It’s a decrease in the number of RBCs or the amount of hemoglobin in the RBCs, that results in decreased oxygen delivery and subsequent tissue hypoxia. Anemia should not be...

Introduction to anemia Dr. Jehad Alhmoud  Anemia is derived from the Greek word anemia, meaning “without blood.” It’s a decrease in the number of RBCs or the amount of hemoglobin in the RBCs, that results in decreased oxygen delivery and subsequent tissue hypoxia. Anemia should not be thought of as a disease, but rather as a manifestation of other underlying disease processes. Therefore, to diagnose anemia the cause should be thoroughly investigated.  HEMOGLOBIN SYNTHESIS α= alpha β= beta γ= gama ε= epsilon δ=delta ζ= zeta  Hemoglobin synthesis results from an orderly evolution of a series of embryonic, fetal, and adult hemoglobins. At birth, Hb F constitutes 60% to 90% of the total hemoglobin. Hb F declines from 90% to 95% at 30 weeks’ gestation to approximately 7% at 12 weeks after birth and stabilizes at 3.2 ± 2.1% at 16 to 20 weeks after birth. The switch from Hb F to Hb A is genetically controlled and determined by gestational age. The concentration of hemoglobin fluctuates dramatically in the weeks and months after birth as a result of physiologic changes.  The reference interval for hemoglobin for a full-term infant at birth is 16.5 to 21.5 g/dL; levels less than 14 g/dL are considered abnormal. The average hemoglobin value for a preterm infant who is small for gestational age is 17.1 g/dL, lower than that for a full-term infant; hemoglobin values less than 13.7 g/dL are considered abnormal in preterm infants. Normal adult blood contains three types of haemoglobin: 1. The major component is haemoglobin A with the molecular structure α2β2. 2. The minor haemoglobins contain γ (fetal Hb or Hb F) or δ (Hb A2) globin chains instead of β chains. In the embryo and fetus, Gower 1, Portland, Gower 2, and fetal Hb dominate at different stages. The genes for the globin chains occur in two clusters: ε, γ, δ, and β on chromosome 11 and ζ and α on chromosome 16. Two types of γ chain occur, Gγ and Aγ, which differ by a glycine or alanine amino acid at position 136 in the polypeptide chain. The α-chain gene is duplicated and both α genes (α1 and α2) on each chromosome are active.  Switch from fetal to adult hemoglobin The globin genes are arranged on chromosomes 11 and 16 in the order in which they are expressed Certain embryonic hemoglobins are usually only expressed in yolk sac erythroblasts. The β‐globin gene is expressed at a low level in early fetal life, but the main switch to adult hemoglobin occurs 3–6 months after birth when synthesis of the γ chain is replaced by β chains.  Hemoglobin abnormalities These result from the following: 1. Synthesis of an abnormal haemoglobin. 2. Reduced rate of synthesis of normal α‐ or β‐globin chains (the α‐ and β‐thalassaemia's).  Clinical features of anemia Can be considered under 4 major headings: 1) Speed of onset: rapid progressive anemia causes more symptoms 2) Severity: mild anemia produces no symptoms. 3) Age: elder patients tolerate anemia less the well younger ages. 4) O2 dissociation curve: pyruvate kinase deficiency increases 2, 3 -DPG concentration and shifts the dissociation curve (left Hb F, Right Hb variants).  Symptoms and signs Shortness of breath, weakness, palpitation, and headache. The general sign is the pallor of mucous membranes. Less occurrence signs include tachycardia, cardiomegaly, and other cardiovascular system impairment signs. Specific signs associated with particular types of anemia e.g. Spoon nail with iron deficiency jaundice with hemolytic anemia and megaloblastic anemia. Leg ulcer with sickle cell anemia. The general classification of anemia depends on morphology: 1- Macrocytic anemia 2- Microcytic hypochromic anemia 3- Normocytic normochromic anemia Also, anemia is classified as hereditary and acquired.  General Classification of Anemia General classification of anemia depends on etiology: 1- Impaired erythrocyte production 2- Accelerated erythrocyte destruction 3- Blood loss  Impaired erythrocyte production: 1. Abnormal bone marrow 2. Aplastic anemia 3. Essential Factor Deficiency: Iron, Vit. B12, folic acid 4. Stimulation factor deficiency: Anemia of chronic disease.  Accelerated erythrocyte destruction: - Hemolytic anemia - Intracorpuscular defect: (abnormalities in the red blood cell itself/ intrinsic RBC factor). 1. Membrane defect: ex. Hereditary spherocytosis. 2. Enzyme deficiency: ex. G6PD deficiency. 3. Hemoglobin abnormalities: ex. Thalassemia. - Extracorpuscular defect: (nonintrinsic RBC factor) 1. Mechanical: ex. Microangiopathic hemolytic anemia (MAHA). 2. Others as chemical, infection. Excess blood loss: Bleeding due to accident, GI bleeding.  The general aspect of anemia Anemia: reduction in the hemoglobin concentrations below normal. Considered anemia if: Adult male below 13.5 g/dl Adult female below 11.5 g/dl Newborn infant below 14 g/dl Anemia usually but not at all times associated with a reduction in RBC count and PCV level.  Laboratory Diagnosis of Anemia Complete Blood Cell Count (CBC). Reticulocyte Count and Reticulocyte production (maturation) index (RPI). Peripheral blood examination. Bone Marrow Examination. Other Laboratory Tests:- Iron studies urinalysis stool analysis Liver and renal function tests Serum vitamin B12 and serum folate assays  Other laboratory findings Leukocytes and platelets count: Help to distinguish pure anemia from pancytopenia (reduction in all blood cells and suggest for general marrow defects such as hypoplasia). Reticulocyte count: Normal level is 50-150 X 10^9/L (0.5-2.5%). Increased in anemia due to increase in erythropoietin level. If in case of anemia reticulocyte count not increased it may suggest impaired marrow function or defect in erythropoietin synthesis. Morphologic classification of anemias and the reticulocyte count 1. Microcytic anemias are characterized by an MCV of less than 80 fL with small RBCs (less than 6 μm in diameter). - Microcytosis is often associated with hypochromia (increased central pallor in RBCs) - MCHC of less than 32 g/ dL. - Microcytic anemias are caused by conditions that result in reduced hemoglobin synthesis. - Heme synthesis is diminished in iron deficiency, iron sequestration (chronic inflammatory states), and defective protoporphyrin synthesis (sideroblastic anemia, lead poisoning). - Globin chain synthesis is insufficient or defective in thalassemia and in Hb E disease. - Iron deficiency is the most common cause of microcytic anemia; the low iron level is insufficient for maintaining normal erythropoiesis. - Early stages of iron deficiency do not result in microcytosis or anemia and are manifested only by reduced iron stores. 2. Macrocytic anemias are characterized by an MCV greater than 100 fL with large RBCs (greater than 8 μm in diameter). - Macrocytic anemias arise from conditions that result in megaloblastic or nonmegaloblastic red cell development in bone marrow. - Megaloblastic anemias are caused by conditions that impair the synthesis of DNA, such as vitamin B12 and folate deficiency or myelodysplasia. - Nuclear maturation lags behind cytoplasmic development as a result of impaired DNA synthesis. - This asynchrony between nuclear and cytoplasmic development results in larger cells. - All cells of the body are ultimately affected by the defective production of DNA - Megaloblastic anemia is characterized by oval macrocytes and hypersegmented neutrophils in the peripheral blood and by megaloblasts or large nucleated erythroid precursors in the bone marrow. - The MCV in megaloblastic anemia can be markedly increased (up to 150 fL), but modest increases (100 to 115 fL) are most common. - Nonmegaloblastic forms of macrocytic anemias are also characterized by large RBCs, but in contrast to megaloblastic anemias, they are typically related to membrane changes caused by disruption of the cholesterol-to-phospholipidcholesterol-to-phospholipid ratio. - These macrocytic cells are mostly round, and the erythroid precursors in the bone marrow do not display megaloblastic changes. - Macrocytic anemias are often seen in patients with chronic liver disease, alcohol abuse, and bone marrow failure. It is rare for the MCV to be greater than 115 fL in nonmegaloblastic anemias. 3. Normocytic anemias are characterized by an MCV in the range of 80 to 100 fL. - The RBC morphology on the peripheral blood film must be examined to rule out a dimorphic population of microcytes and macrocytes that can yield a normal MCV. - The presence of a dimorphic population can also be verified by observing a bimodal distribution on the RBC histogram produced by an automated blood cell analyzer. - Some normocytic anemias develop as a result of the premature destruction and shortened survival of RBCs (hemolytic anemias), - characterized by an elevated reticulocyte count. - The hemolytic anemias can be further divided into those that result from intrinsic causes (membrane defects, hemoglobinopathies, and enzyme deficiencies) and those that result from extrinsic causes (immune and nonimmune RBC injury). - A direct antiglobulin test helps differentiate immune-mediated RBC destruction from other causes of hemolysis. Classification and laboratory findings of anemia Blood film