RBC Disorders - Lecture Notes PDF

RBC DISORDERS 1 Dr. Geener.K. John Recommended reading pages 346-347 & 356-358 from Robbins – Basic Pathology 11th edition  imy RBC indices Mean cell volume (MCV) average volume of single RB ÉÉgtes importantAverage volume per...

RBC DISORDERS 1 Dr. Geener.K. John Recommended reading pages 346-347 & 356-358 from Robbins – Basic Pathology 11th edition  imy RBC indices Mean cell volume (MCV) average volume of single RB ÉÉgtes importantAverage volume per red cell 81-97 fL if Tyner Mean cell hemoglobin (MCH) microcytes femtoliter if larger Ferchromia Average mass of Hb per red cell 28-34 pg picogram gifyspegmia Mean cell hemoglobin concentration (MCHC) the proportion not commonly used Average concentration of Hb in a given volume of packed red cells 33-35 g/dL Red cell distribution width (RDW) Coefficient of variation of red cell volume 11.5-14.8 so Rbc with low no cmicrocytes average of me eg macrocytes 50 RBC with high Mor c is normal Lab investigations in anemia 16781 of u Hemoglobin ♂ 13.2 – 16.7 ♀ 11.9- 15 g/dL there are some Hematocrit (PCV)♂ 38- 48 differences between ♀ 35- 44% female RBC Count ♂ 4.2- 5.6 slightly male ♀ 3.8- 5x106/mm3 higher if Bu is a active Reticulocyte count 0.5-1.5 % therein reticulocytes will be be done T impo to Peripheral smear examination is done in all cases mm Specialised tests – Iron indices, Vit B12 & folate concentration, femia Coombs Iiamia Hb electrophoresis, immune test Marrow exam is required in some cases just done in case of anemia is associated with RBC platelets abnormalities Anemias of diminished erythropoiesis RBC ONTO 1.Dietary deficiency a. Iron – reduced Hb synthesis size b color (microcytic hypochromic anemia) b. Vit B12 & Folic acid – defective DNA macrocytic r size synthesis (megaloblastic anemia) 2.Bone marrow failure Aplastic anemia reticulocytes very low 3.Unknown or multiple mechanism – Anemia of chronic disease, JE Myelophthisic anemias don't worry IRON DEFICIENCY ANEMIA Iron deficiency is the most common cause of anemia Most common form of nutritional deficiency Total body iron content ♀ - 2.5gm, ♂ - 3.5gm but majority aisosyogmbin 80% of functional iron is in Hb more stable lessavailable Storage forms are hemosiderin & ferritin seen in more available liver, spleen & bone marrow Serum ferritin is a good indicator of body iron stores Iron absorption Site of absorption is duodenum Body iron balance is maintained by regulating dietary absorption Only fraction of iron that is absorbed is delivered to plasma transferrin. carry iron to blood Remaining iron is bound to cytoplasmic ferritin in the mucosal cells & lost when cells are exfoliated ↓sed iron stores - ↑se transfer to plasma ↑sed iron stores - ↓se transfer to plasma This is regulated by hepcidin a hepatic peptide Regulation of Iron Absorption Thepcidin in case of y ferroportin adequet iron 6 channels lessabsorbtion how decide iron much Fatshan if there is more it will hepcidinewith feric compine ferroportin less channels will be there fortransport ferous in yee t hepcidin in case of T ferroportin iron 9 channels deficincy more absorbtion Iron metabolism transport protien Transported by binding with protein transferrin – Total iron binding capacity is 300-350μg/dL bat594 percentage saturation be saturated Normally 33% saturated with iron giving serum iron level of 100-120μg/dL No regulated pathway for iron excretion 1-2 mg /day is lost by shedding of mucosal & skin epithelial cells by 7 Normal diet contains 10-20 mg of which 20% is absorbed, this balances the loss twixt Causes of iron deficiency 1.Low dietary intake & poor bioavailability Vegetarian diet 2.Increased requirement Pregnancy, infancy 3.Malabsorption any condition affect dudenum Um Sprue, celiac disease, after gastrectomy 4.Chronic blood loss From GIT & female genital tract Clinical features Most cases are mild & asymptomatic General – weakness, listlessness, pallor Epithelial lesions – WH Koilonychia (spooning of the nails), glossitis inflammation of toning Pica – consumption of non food stuffs Plummer – Vinson syndrome (Paterson- Kelly syndrome) IDA with esophageal web irondeficiency anemia dysphagia Abstractof food Morphology pale color less iron Red cells are microcytic & hypochromic Small red cells with iron deficiency anemia RBC a narrow rim of Hb at the periphery We Normal RBCs Diagnostic criteria Decreased Hb, PCV, RBC count Decreased MCV, MCH In cell hemoglobin Low serum transferrin saturation & serum iron levels form Low Storage ferritin& increased total iron binding capacity Response to iron therapy iron supplements i Reticulocyte response response Hb response Morphology  Regulation of Iron Absorption Storage Iron Hepcidin Ferroportin Iron absorption / Level Level Transfer Normal Adequate High Low Normal Controlled Absorption Normal Iron Def. anemia Low Low High More Absorption Hemochromatosis High Low High More Absorption Anemia of C/c Diseases Normal/High High Low Less transfer to BM  MEGALOBLASTIC & OTHER ANEMIAS Dr. Geener.K. John Recommended reading pages 358-361 from Robbins Basic Pathology 11th edition TIBC, Serum Iron, Transferrin saturation TIBC 600 500 400 300 200 100 0 Female (N) Male (N) IDA C/c Infection Series 1 Series 2  MEGALOBLASTIC ANEMIA Introduction Hallmark is enlargement of erythroid precursors megaloblasts, which give rise to abnormally large red cells macrocytes Normoblast Normocyte- 7.5 - 8 Megaloblast Macrocyte - > 8.5 Causes Deficiency of folic acid Deficiency of vitamin B12 Both required for DNA synthesis Effect on hematopoiesis is similar but causes & consequences differ Pathogenesis Inadequate biosynthesis of thymidine one of the building blocks of DNA Hence DNA synthesis is impaired due to deficiency of folic acid & vitamin B12 Synthesis of RNA & cytoplasmic elements including Hb proceed normally Nuclear maturation lags behind and cell division is delayed - So excess Hb is synthesized during delay between cell divisions enlarged cells Outcome RBC Megaloblasts Macrocytes Anemia (Anemia due to ineffective erythropoiesis & fewer cell divisions) WBC Giant metamyelocyte Hypersegmented neutrophils Granulocytopenia Platelets Thrombocytopenia Produces pancytopenia Morphology Bone marrow is hypercellular with many Megaloblasts - Larger cells Finely reticulated chromatin Abundant basophilic cytoplasm Giant metamyelocytes Large megakaryocytes Peripheral smear Macro-ovalocytes MCV > 110fL (N 81-97fL) MCH also sed Hypersegmented neutrophils - 5 or more lobes (Normal 3 or 4 lobes) Large platelets with abnormal shape seen Folate (Folic acid) deficiency Causes Dietary deficiency poor diet, elderly individuals Increased demand pregnancy Rich sources Fresh uncooked vegetables & fruits (destroyed by cooking for 10-15 mts) Absorption of Folic acid Site of absorption jejunum Malabsorptive diseases like tropical sprue & celiac disease impair absorption Drugs like phenytoin inhibit folate absorption Methotrexate inhibit folate metabolism Deficiency result in inadequate DNA synthesis  Clinical features Insidious onset with symptoms like weakness & easy fatigability GIT, which is another site of rapid cell turn over also affected sore tongue, cheilosis Neurological abnormalities are not produced unlike in Vit B12 deficiency Diagnosis Peripheral smear & bone marrow exam Measuring serum & red cell folate levels  Vit B12 (Cobalamin) deficiency Absorption of Cobalamin Peptic digestion releases dietary vitamin B12, allowing it to bind a salivary protein called haptocorrin On entering duodenum this complex separates and Vit B12 binds with intrinsic factor (IF) secreted by gastric parietal cells Site of absorption Vit distal ileum by attaching to cubilin a receptor for IF From enterocytes transferred to plasma transcobalamin which deliver to liver and other cells  Source & Causes of deficiency Food of animal origin including egg & poultry products (not destroyed by cooking or boiling) Normally stored in the liver & contains a reserve for 5- 20 years Dietary deficiency is confined to strict vegetarians Long standing malabsorption is most important Gastrectomy loss of cells producing IF Resection of ileum absorption prevented Disorders of distal ileum - tropical sprue & Crohn disease - impaired absorption  Pernicious anemia Is the most frequent cause of Vit B12 deficiency Autoreactive T cell response initiates gastric mucosal injury and triggers the formation of auto Abs, that attack gastric mucosa and suppresses the production of IF The serum of affected patients contains several types of auto Abs that block the binding of Vit B12 to IF or prevent binding of the IF - Vit B12 complex to cubilin. Histologically there is a chronic atrophic gastritis PA show association with gastric carcinoma  Clinical features General - Pallor, easy fatigability & GIT symptoms Demyelination of posterior & lateral columns of spinal cord Start with numbness, tingling & burning in feet or hand Followed by unsteadiness of the gait & loss of position sense Anemia responds to treatment but neurological manifestations will not respond Diagnosis Peripheral smear macrocytic RBCs leucopenia, hypersegmented granulocytes Low serum Vit B12 level Normal or elevated serum folate level Serum antibodies to IF Schilling test to measure Vit B12 absorption Dramatic reticulocyte response in 2-3 days following parenteral administration of Vit B12  APLASTIC ANEMIA Multipotent myeloid stem cells are suppressed Marrow failure Pancytopenia (should not be confused with pure red cell aplasia) Pathogenesis - Not fully understood but 2 mechanisms are proposed 1. Extrinsic-Immune mediated suppression of marrow stem cells Activated T cells suppress stem cells, which bare antigenically altered by drugs, radiation & infectious agents. 60-70% responds to immunosuppressive therapy 2. Intrinsic-stem cell abnormality- 5-10% patients have inherited defects in telomerase Morphology Markedly hypocellular marrow >90% of the space occupied by fat Cells present are limited to lymphocytes & plasma cells Clinical features Affect persons of all ages & both genders Slowly progressive anemia (normocytic & normochromic) weakness, pallor, dyspnea Granulocytopenia frequent & persistent minor infections Thrombocytopenia petechiae, ecchymoses Produces pancytopenia Splenomegaly is typically absent Reticulocytes are reduced in number MYELOPHTHISIC ANEMIA Anemia caused by extensive infiltration of marrow by tumors or other lesions Causes Metastatic carcinoma from lungs, breast, prostate Advanced TB Lipid storage disorders Osteosclerosis Manifestations Anemia Thrombocytopenia WBCs less affected Abnormal RBCs tear drop cells seen Immature cells Granulocytic & erythroid precursors seen in smear Produces pancytopenia with Leuco-erythroblastic