Microbiology 435 Anemia

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Anemia is a condition in which the blood cannot adequately oxygenate the tissues. It shows up as a decreased RBC count, decreased hematocrit or decreased hemoglobin concentration. Laboratory diagnosis of anemia The laboratory offers a set of routine procedures relevant to the diagnosis of anemia: CBC (complete blood count) Cell counts - RBC, WBC, platelet WBC differential RBC morphology RBC indices Hemoglobin determination Hematocrit Hematocrit The percentage of RBCs in whole blood. Also called the PCV (packed cell volume). Normal values are 36 to 46%. RBC indices MCV - Mean Corpuscular Volume Gives the average volume of the RBCs in circulation. Normal values are 80-95 femtoliters. Terms that are associated with MCV evaluation are normocytic, microcytic, and macrocytic. MCH - Mean Corpuscular Hemoglobin The average weight of hemoglobin per cell. Normal values are 27-31 picograms. MCHC - Mean Corpuscular Hemoglobin Concentration The average weight of hemoglobin per cell per its volume. Normal values are 33-36% (grams per deciliter). Terms associated with MCHC evaluation are normochromic, hypochromic, and hyperchromic   RBC Morphology The variation of size (anisocytosis) and shape (poikilocytosis) of RBCs as seen on the peripheral smear provide information about RBC disorders. This is useful in classification of anemias according to size of the erythrocytes and/or according to amount of hemoglobin present. Various other disease states will also affect the RBC morphology. Membrane abnormalities, changes in the hemoglobin molecule, immune reactions (Antibodies/RBC Antigens), permeability defects, enzyme deficiencies, and hereditary factors are some of the abnormalities that affect shape and/or size.   Reticulocyte count Done to determine the number of young RBCs in the peripheral blood. It indicates the response of the bone marrow to anemia. If the patient is anemic, the bone marrow should respond by releasing more immature RBCs into peripheral blood. New Methylene Blue, a supravital stain, precipitates excess RNA in the nearly mature RBCs.   Bone marrow evaluation The sample usually consists of the aspirate and the core biopsy specimen of red bone marrow. The aspirate is used to determine the cell types and proportions in the marrow. This is useful in diagnosing acute leukemias, for example. The core biopsy determines cellularity of the bone marrow and the relationship of cells to fat and connective tissue stroma. This is useful in diagnosing Hodgkin's and non-Hodgkin's lymphomas, for example, where focal lesions are produced rather than diffuse involvement of the marrow.   Pathophysiologic Classification of Anemias Decreased production of RBCs Stem cell disorders Aplastic anemia DNA synthesis disorder megaloblastic anemias vitamin B12 deficiency folic acid deficiency Hemoglobin synthesis disorders iron deficiency thalassemias Precursor erythroid cells disorders anemia of chronic renal failure endocrine disorder anemia Unknown mechanisms anemia of chronic disease sideroblastic anemia   Increased destruction or loss Intracellular abnormality Membrane defect hereditary spherocytosis hereditary elliptocytosis Enzyme deficiency G-6-PD pyruvate kinase Globin abnormality hemoglobinopathies sickle cell disease Paroxysmal nocturnal hemoglobinuria   Extracellular abnormality Mechanical microangiopathic hemolytic anemia Infection malaria Babesia Hemobartonella Chemical and physical agents drugs toxins burns Antibody-mediated hemolytic anemia autoimmune drug-induced hemolytic disease newborn Blood loss   Morphological Classification of Anemias Microcytic Iron deficiency Thalassemias Anemia of chronic disease Normocytic Aplasic Anemia of Chronic Disease Acute and Chronic blood loss Macrocytic Liver disease, Vitamin B12 and Folate deficiency   Examples of RBC disorders Anemias Iron deficiency: Bone marrow histiocytes show decreased stored iron when viewed using Prussian Blue stain. Lead poisoning: Lead inhibits enzymes needed for heme synthesis. Basophilic stippling is associated with any heme synthesis disorder. Thalassemia major: Chain production is decreased but is normal. Alpha homozygous form is more severe. Excess beta chains form inclusions and cells are phagocytized. Sideroblastic - inability of RBCs to utilize iron, resulting in excess iron storage in the mitochondria (ringed sideroblasts) Vitamin B12 deficiency: Formerly called pernicious anemia. The gastric mucosa is unable to secrete the intrinsic factor needed for Vitamin B12 absorption (or an autoantibody is produced that inactivates the intrinsic factor). Nucleated RBCs show asynchronous maturation: the nucleus is less mature than the cytoplasm. This is called a megaloblastic cell. Mature RBCs are nucleated and macrocytic. Associated with this condition, the neutrophils may be hypersegmented. Folic acid deficiency is similar in appearance to Vitamin B12 deficiency. Folic acid also is required for normal DNA synthesis.   Membrane abnormalities Hereditary spherocytosis is a defect in the skeletal protein of the RBC. The cell has less membrane resulting in a spherical shape rather than discoid. The cells are less flexible and may fragment and lyse in the spleen. Hereditary elliptocytosis is an increase in oval and elongated cells. This condition caused by a defect in the membrane cytoskeleton. Cells may fragment. There are usually no overt signs of hemolysis and no anemia if erythropoiesis is able to compensate for the loss of the elliptocytes in the spleen. Because hemolysis takes place in the spleen splenectomy would protect the patient from chronic hemolysis but the elliptocytes would remain. Hereditary pyropoikilocytosis - This is a rare subgroup of hereditary elliptocytosis. It is a severe hemolytic anemia in infancy or early childhood. associated with poikilocytosis.   Globin abnormalities In these conditions the globin chains are abnormal. Sickle cell anemia results from the substitution of only one amino acid in the polypeptide chain. When the HgbS in oxygenated, the cell has a normal shape. When HgbS is deoxygenated it sickles. Sickle cells will be seen on the peripheral smear if the patient is in an acute crisis state. Hemoglobin C disease: Hgb C differs from Hgb A by the substitution of a single amino acid in the same position as Hgb S. Mild hemolysis results.   Unstable hemoglobins These conditions are due to amino acid substitutions or deletions. The hemoglobins may denature and precipitate in the RBCs in the form of Heinz bodies. This usually happens when there is a change in the RBC's environment caused by an oxidizing drug or infection. Hemolysis occurs because the RBCs become rigid and membrane damage occurs.   Mechanical Antibody-mediated anemia is an abnormality within the immune system. The ability for self-recognition of an individual's own RBCs is lost. As a result patients destroy their own cells by producing autoantibodies that bind to the cells and hemolyze them. Parasites in or on RBCs cause the spleen to remove infected cells. The degree of anemia correlates with load of parasites found in the blood. Cold agglutinins-Normal cold autoantibodies are present in all human sera to a greater or lesser degree and have no clinical significance. There are also pathologic cold agglutinins that cause hemolysis of RBCs in the capillaries of the extremities with temperatures between 250 and 310 C. Symptoms will be acrocyanosis of the hands, feet, ears and nose along with a sense of numbness. This condition is known as Raynaud's phenomenon.         Just a word on automated blood cell analyzers Smaller instruments measure cell numbers, hemoglobin, hematocrit and MCV. Larger instruments add MCH, MCHC, WBC differentials, histograms and RDW (the histograms and RDW [red cell distribution width] give information about RBC morphology).