Anemia I TEST ONLY.pdf

Erythropoietin (EPO) • Activates transcription factors: o GATA-1 and FOG-1 on erythroid committed precursors to enhance § Erythroid specific genes § Anti-apoptotic genes § Transferrin receptor o In late stages of erythropoiesis, it stimulates: § Erythroid proliferation § Erythroid maturation § Hb pr...

Erythropoietin (EPO) • Activates transcription factors: o GATA-1 and FOG-1 on erythroid committed precursors to enhance § Erythroid specific genes § Anti-apoptotic genes § Transferrin receptor o In late stages of erythropoiesis, it stimulates: § Erythroid proliferation § Erythroid maturation § Hb production Anemia Definition and Clinical Presentation • Reduction in RBC • Measurement(s) obtained as part of a CBC: o Hb concentration o RBC count o Hematocrit • Classification: Anemia II and III are reduction in RBC o Inherited Anemia II § Hb synthesis (Hemoglobinopathy, Thalassemia) o Acquired Anemia III § RBC metabolism (nutritional deficiency) § Marrow failure (Aplastic anemia) o Classification according to RBC indices § Mean Corpuscular volume (MCV) — Increased = macrocytic — Decreased = microcytic § Mean Corpuscular hemoglobin (MCH) — Normal = normochromic — Decreased = hypochromic § Red Cell Distribution width (RDW) — High = heterogeneous — Decreased = homogeneous Anemia I: Overview Red blood cell metabolism o Embden Meyerhof pathway o Luebering-Rapoport shunt o Hexose monophosphate shunt (aka pentose phosphate pathway) Microcytic Anemias • Microcytosis (low MCV) o <80 fL o defect in cellular hemoglobin synthesis • Common causes: o Iron deficiency o Decreased Globin chains o Decreased heme Macrocytic Anemias • Macrocytosis (high MCV) o >100 fL o Due to asynchronous maturation of nuclear chromatin • Common Causes: o Megaloblastic anemia: Asynchronous nuclear maturation due to abnormality in DNA o Megaloblastic maturation can be due to: § Vit B12 (cyanocobalamin) deficiency = pernicious anemia (chronic illness with reduced Vitamin B12) § Folate deficiency § Copper deficiency § Iatrogenic: meds interfere with DNA synthesis § not iron deficiency o Reticulocytosis § Reticulocytes are larger than mature RBCs § Reticulocytes increased in: — Hemolytic anemias (acute/chronic) — Recovery from bleeding — Replacement of iron/other nutrient in deficiency anemia — Recovery from bone marrow suppression (ex. binge drinking) & Pernicious anemia Clinical signs/symptoms of Anemia o âoxygen carrying capacity causing tissue hypoxia o Respiratory: Shortness of breath (dyspnea) esp w exercise o Cardio: Angina, palpitations, claudication, confusion o Clinical Signs: § Pallor mucous membranes (Hb < 9-10 g/dL) § Severe anemia (Hb < 5 g/dL) leads to congestive HF § Anemic Retinopathy from severe iron deficiency Serum Iron Studies • Serum iron: Measurement of transferrin-bound iron • Ferritin: Measure of storage iron • Transferrin: Transports iron to tissues w transferrin receptors • TIBC (total iron binding capacity): Concentration of iron required to fully saturate iron-binding sites of transferrin o Ex. TIBC can tell if iron does not have binding capacity, but ferritin will be normal Tissue Iron Studies • Ferritin: Labile storage form (easily altered) • Hemosiderin: Stable storage form, stains BLUE w Perls Prussian Blue Hemoglobinopathies • Hemoglobin S o Glutamate switches to Valine on codon 6 of β chain o Hb crystals distort RBCs into sickles o Diagnosis § Newborn screening § Screening test for sickling § HPLC (high performance liquid chromatography) to identify hemoglobin variants RBC Morphology in Sickle Cell Dz • Peripheral blood smear o Irreversible sickled cells o Reticulocytosis o Hyperplastic Bone Marrow o Howell Jolly bodies o Pappenheimer bodies o Hyposplenism Treatment for Sickle Cell • Vaccines o Pneumococcal, haemophilus, meningococcal, Hep B o Prophylactic Penicillin from diagnosis to puberty Beta Thalassemia • decreased synthesis of beta globin chains due to mutations • Two categories: o B0: absent B globin synthesis o B+: reduced B globin synthesis • Beta Thalassemia Major, features: o Severe anemia o Expansion of flat bones ‘chipmunk face’ o Enlarged Liver and Spleen due to: § Red cell destruction § Extramedullary hematopoiesis § Iron overload o Expansion of bones due to: § Marrow dysplasia § Characteristic facial features: — Large cheekbones — Protuberant maxilla — Depressed nasal bridge Iron Deficiency Anemia (IDA) • Labs: Feature Iron deficiency Anemia o âHb MCV/MCH Decreased o âFerritin Serum ferritin Low o âSerum iron o á TIBC Serum hepcidin Low • Morphology: Serum Reticulocytes % High o Peripheral smear: § Microcytic (<7um) § Hypochromic red cells (Hypochromasia: normal RBC have low Hb) o Bone marrow: Decreased/absent storage iron o Low RPI: reticulocyte count • Pathophysiology of IDA o Increased demand in: § Physiological state (Pregnancy, childhood) § Blood Loss o Decreased availability § Poor intake (vegetarian diet) § Poor absorption (Helicobacter pylori infection) Anemia of chronic disease Normal Increased High Low Aplastic Anemias (AA) • • • • Pancytopenia in assc w bone marrow hypoplasia/aplasia (<30% cellularity) Characterized by pancytopenia NOT anemia alone Normal Aplastic in adults: 40-60% Aplastic Anemia: <30% cellular Hemolytic Anemia • Increased RBC breakdown: o Increased bilirubin, urobilinogen, hemoglobinuria o Decreased serum haptoglobin • Peripheral Blood abnormalities: o Schistocytes (intravascular hemolysis) o Spherocytes (extravascular hemolysis) • Immune Hemolytic Anemias o Diagnosis requires detection of antibodies o Found using the Coombs tests § Direct Coombs: detects antibodies bound to red cells § Indirect Coombs: detects antibodies in serum Hemolysis due to Intrinsic RBC defects • Hb defect o Sickle cell anemia o HbC disease • Structural defect o Hereditary spherocytosis o Hemoglobinuria (paroxysmal nocturnal) Extravascular Hemolysis Clinical Features of Hemolytic Transfusion Rxn • 3 stages: o Hemolytic shock phase § Occurs after a few mm are transfused § Or 1-2hrs after transfusion o Oliguric phase § Assc w acute tubular necrosis § Renal failure o Diuretic phase § Imbalance in fluid/electrolytes during recovery of ARF • Red cells removed from circulation by reticuloendothelial system, causing: o Anemia o Splenomegaly o Jaundice • Peripheral blood abnormality: Spherocytes