Megaloblastic Anemia PDF

MEGALOBLASTIC ANEMIA Clinical Hematology 1 Lecture Megaloblastic Anemia Megaloblastic anemias are characterized by the presence of abnormally large developing red cells in the bone marrow. The marrow is usually cellular. Anemia is based on ineffective erythropoiesis. These red cells a...

MEGALOBLASTIC ANEMIA Clinical Hematology 1 Lecture Megaloblastic Anemia Megaloblastic anemias are characterized by the presence of abnormally large developing red cells in the bone marrow. The marrow is usually cellular. Anemia is based on ineffective erythropoiesis. These red cells are large in shape Megaloblastic Anemia A descriptive term that refers to the abnormal changes in blood cell formation that demonstrate a nuclear and cytoplasmic maturation dissociation in all myeloid and erythroid cell lines, leading to macrocytic anemia It is the result of abnormal DNA synthesis because of single or combined deficiency of folate or Vitamin B12 Megaloblastic Anemia Megaloblastic Anemia Classification of Macrocytic Anemia by cause Megaloblastic Anemia Etiology Cobalamin: Deficiency / abnormal metabolism. Folate: Deficiency / abnormal metabolism / antifolate drugs. Drugs interfering with synthesis of DNA. Rarely: Orotic aciduria, AML, myelodysplasia. Arsenic poisoning Nitrous oxide inhalation. Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Forms: Ado (2-deoxyadenosyl) form: Found in mitochondria Cofactor for Methyl Malonyl CoA Mutase. Methyl cobalamin: Found in plasma, cytoplasm Cofactor for Methionine synthase. Hydroxocobalamin Megaloblastic Anemia Etiology Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Normal absorption of Vitamin B12 Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Absorption Active: Intrinsic Factor Passive (!%) Buccal Duodenal Ileal Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Absorption Proteins involved in active absorption: Intrinsic factor {IF=HCl} Haptocorrins Cubilin Transcobalamin II TC I – cobalamin analogues IFs are destroyed in illeal cells Cobalamin enters portal blood after 6 hours of oral ingestion. Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Absorption Amount recirculated in bile 0.5 - 5μg. Body stores 2-3mg. Sufficient for 3-4 years without dietary intake of cobalamin. Daily requirement: 1-3μg. Only traces are excreted in urine; in pharmacological doses large part is excreted in urine. Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Causes of Cobalamin Deficiency Nutritional: Vegans (Legumes) Abnormalities - TC II deficiency; Congenital absence of IF Malabsorption Gastrectomy (total / partial) Tropical sprue Intestinal stagnant loop syndrome Selective malabsorption Ileal resection Crohn’s disease Pernicious anemia Megaloblastic Anemia Etiology Cobalamin (Vitamin B12) Neurologic Findings in B12 deficiency Peripheral Nerves: Glove and stocking paresthesia Loss of ankle reflexes Spinal Cord: Subacute combined degeneration of the cord Posterior columns: Diminished vibration sensation and proprioreception Corticospinal Tracts: Upper motor neuron signs Cerebrum: Dementia Optic Atrophy Autonomic Neuropathy Megaloblastic Anemia Etiology Folate/Folic Acid Destroyed easily by cooking especially in large amounts of water. Storage in liver (sufficient for 3-4 months) Total body folate around 10mg. Daily requirements: 200-300μg. Pregnancy: 400μg. Megaloblastic Anemia Etiology Folate/Folic Acid Megaloblastic Anemia Etiology Folate/Folic Acid Absorption: Upper small intestine Transport Plasma protein bound 1/3. Considerable enterohepatic circulation occurs Alcohol interferes with the release of methyl-THFA by hepatocytes Only traces are excreted; but in pharmacological doses 50-90% are excreted. Megaloblastic Anemia Etiology Folate/Folic Acid Megaloblastic Anemia Megaloblastic Anemia Megaloblastic Anemia Megaloblastic Anemia Clinical Features Epithelial surfaces: macrocytosis Infertility in both men and women CVD – IHD. Malignancy: Acute Lymphoblastic Leukemia of childhood. Neurologic: bilateral peripheral neuropathy and degeneration; Alzhiemer’s disease Maternal: prematurity; abortion; neural tube defects Children: poor brain development ; impaired intellectual development. Megaloblastic Anemia Megaloblastic Anemia Hematologic Findings Oval macrocytes Anisocytosis (varied sizes) Poikilocytosis (Abnormal- shaped) Hypersegmented neutrophils Howell – jolly bodies Unconjugated bilirubin Haptoglobins Urine – urobilinogen, hemosiderin. Megaloblastic Anemia Megaloblastic Anemia Laboratory Findings ELISA: Serum cobalamin normal: 160-1000 ng/L Severe anemia