Iron Metabolism and Blood Groups PDF

Types of Anaemia, Iron Metabolism & Blood Groups Which of the following conditions is/are likely to result in decreased erythropoietin? – – – – – – A. End-stage renal disease B. Relocation to high altitudes C. Physical exercise D. Haemorrhage E. Stab wound F. Low haemoglobin levels Which of the foll...

Types of Anaemia, Iron Metabolism & Blood Groups Which of the following conditions is/are likely to result in decreased erythropoietin? – – – – – – A. End-stage renal disease B. Relocation to high altitudes C. Physical exercise D. Haemorrhage E. Stab wound F. Low haemoglobin levels Which of the following cells is produced in the highest number each day? A. Neutrophils B. Erythrocytes C. Platelets D. Monocytes Which of the following feature(s) of erythrocytes contribute to their ability to transfer oxygen A. Lack of nucleus B. High surface area to volume ratio C. Haemoglobin D. Biconcave shape True or False 1. Erythrocytes are microcytic and hypochromic in iron deficency anaemia. 2. In anaemia due to blood loss, the erythrocytes are characterized by being normochromic and normocytic. Contents Types of anaemia Daily iron circulation Iron absorption into & transport through the enterocyte Intravascular & Extravascular Haemolysis Blood Groups Laboratory Investigation of Anaemia Blood Count: RBC count, Hb, Hct, RBC indices Study of the of the peripheral blood smear Reticulocyte count These examinations serve to – (i) Classify the anaemia on the basis of RBC size – (ii) Establish the presence or absence of RBC morphological abnormalities suggestive of disordered RBC production or haemolysis – (iii) Search for morphological clues to the diagnosis from the WBCs and platelets on the peripheral blood smear. – (iv) Identify the kinetic basis for the anaemia as failure of RBC production, rapid RBC loss or both. Types of Anaemia Megaloblatic Anaemia Defect in DNA synthesis in haemopoietic cells. Oval macrocytes predominate Poikilocytosis (varying shapes) Causes – Failure to secrete intrinsic factor – Inability to absorb cobalamin (vit. B12) (ileal resetion) – Reduced intake of folate/ abnormal absorption of folate Pernicious Anaemia A decease in RBCs when the body is unable to absorb vitamin B12. Gastric atrophy which may be due to autoimmune injury. Haemolytic Disorders Intrinsic Haemolytic anaemias – haemolysis occurs because of a defect of the patient’s RBCs (i) Abnormal haemoglobin (Hgb S, Hgb H) – form aggregates within the RBC, so that cells become rigig & lose deformability (ii) Enzyme abnormalities – Deficiencies in enzymes in the main glyclytic pathway (Embeden –Meyerhof pathway) – Pyrivate kinase deficiency. – Deficiencies in enzymes of the hexose monophosphate shunt – glucose-6-phosphate dehydrogenase. - Haemolytic Disorders (iii) Membrane abnormalities Hereditary spherocytosis – abnormalities of the cytoskeletal protein, spectrin result in the formation of microspherocytes and haemolysis Hereditary elliptocytosis Extrinsic haemolytic anaemias – normal RBCs are damaged by an external factor – Transfusion of incompatable blood – Drug-related antibodies – Mechanical damage Iron Absorption Occurs in the duodenum and upper jejunum with the aid of the apical transport protein, divalent metal transporter,1. Fe3+ (ferric) is reduced to Fe2+ (ferrous) by the duodenal cytochrome reductase (DcytB) before it is taken up by DMT1 Hephaestin – permits iron transport from the enterocytes into the blood stream. Iron in the enterocyte is stored as Ferritin or transported into the bloodstream via the protein ferroportin. Regulation of Iron Absorption Hepcidin – a peptide produced by the liver; it directly binds to ferroportin, degrading it and preventing iron from leaving the cell. Storage Iron is stored in 2 forms: 1. Ferritin 2. Haemosiderin Highest concentration stored in the liver, spleen & bone marrow Hepcidin is a 25 amino acid peptide hormone that inhibits iron entry into the plasma compartment from the three main sources of iron: dietary absorption in the duodenum, the release of recycled iron from macrophages and the release of stored iron from hepatocytes The production of hepcidin is regulated by iron, so that more hepcidin is produced by hepatocytes when iron is abundant, limiting further iron absorption and release from stores. When iron is deficient, hepatocytes produce less or no hepcidin, allowing more iron to enter plasma. Haemolysis Refers to the destruction of red blood cells. Haemolysis occurs in many haematologic and non-haematologic diseases and can be defined as the removal of senescent or damaged red blood cells (RBCs) from the circulation When RBCs are destroyed rapidly, erythropoietin and unknown factors stimulate the marrow to increase RBC production. Haemolysis Intravascular haemolysis: RBCs are destroyed within the circulation and release free haemoglobin (Hb) and RBC contents into the bloodstream Extravascular haemolysis: RBCs are phagocytosed in the monocyte-macrophage system of organs such as the liver and the spleen. Causes of Haemolysis – Bone marrow failure – Complications from blood transfusion reaction If the marrow can respond, RBCs may be destroyed at several times the normal rate without a patient becoming anaemic. Evidence of haemolysis: spherocytes, reticulocytes and elevated bilirubin. Effective erythropoiesis: Results in the formation of circulating RBCs Ineffective erythropoiesis: results in the formation of defective RBCs that are destroyed within the marrow (intramedullary haemolysis) or immediately upon entering the circulation. Haemolytic Disorders Intrinsic: stems from a defect in the RBC (hereditary) Abnormal Haemoglobins: e.g. Hgb S, Hgb H ABO Blood Grouping Determined by antigens (agglutinogens) on surface of RBCs and agglutinins (antibodies) in the plasma Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs ABO Blood Groups Universal donor (no agglutinogen on red cell membrane) Universal recipient (no agglutinin in plasma) Blood group distribution O Caucasians 46% Africans 49% A 42% 25% B 9% 22% AB 3% 4% Rh (D antigen) Blood Group First studied in rhesus monkeys Types – Rh positive: Have these antigens present on surface of RBCs – Rh negative: Do not have these antigens present Rhesus blood group Rh +ve – 85% (Caucasians) 98% (Africans) 99% (Asians) Rh –ve can donate blood to Rh +ve individuals Hemolytic disease of the newborn (HDN) – Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs Erythroblastosis Fetalis