Anaemia Lecture: Hong Kong Metropolitan University (2025) - PDF

HONG KONG METROPOLITAN UNIVERSITY SCI 3009SEF Haematology & Transfusion Science I H.LEE Anaemia 20-1-2025 H.LEE SCI 3009SEF 20/1/2025 Anaemia 1 JaypeeDigital/eBookReader...

HONG KONG METROPOLITAN UNIVERSITY SCI 3009SEF Haematology & Transfusion Science I H.LEE Anaemia 20-1-2025 H.LEE SCI 3009SEF 20/1/2025 Anaemia 1 JaypeeDigital/eBookReader H.LEE SCI 3009SEF 20/1/2025 Anaemia 2 Standardoofcare.com/erythropoiesis H.LEE SCI 3009SEF 20/1/2025 Anaemia 3  Erythropoiesis As cell develops see structural changes: 1. decrease in cell volume, 2. condensation of chromatin, 3. decrease in nuclear to cytoplasmic ratio, 4. loss of nucleoli, 5. decrease of RNA in cytoplasm, 6. decrease in mitochondria, 7. and gradual increase in hemoglobin synthesis. Finally, the nucleus eventually extruded. H.LEE SCI 3009SEF 20/1/2025 Anaemia 4 Standardoofcare.com/erythropoiesis H.LEE SCI 3009SEF 20/1/2025 Anaemia 5  Erythrocytes Reference ranges varies with Sex Age Geographic location Normal RBC in adults Male 4.5-5.5 x 1012/l Female 4.0 - 5.0 x 1012/l Infants and children - normals vary by age H.LEE SCI 3009SEF 20/1/2025 Anaemia 6  Maturation of Erythrocytes Stem Cell CFU-GEMM BFU-E CFU-E EPO Mature RBC H.LEE SCI 3009SEF 20/1/2025 Anaemia 7  Maturation of Erythrocytes Stem cell - an unspecified cell that gives rise to a specific specialized cell, such as a blood cell – Multipotential and cannot be identified morphologically – Can self-renew and differentiate CFU-GEMM: granulocyte, erythrocyte, monocyte, megakaryocyte BFU-E: burst forming unit CFU-E: colony forming unit H.LEE SCI 3009SEF 20/1/2025 Anaemia 8  Maturation of Erythrocytes Reticulocyte (diffusely basophilic or polychromatophilic erythrocyte) Size: 8-10µm Cytoplasm - Diffusely basophilic due to residual RNA - Stain with new methylene blue to see fine reticulum strands No nucleus present Present in circulation for 1-2 days Elevated in anemia Reference range: 0.5% to 2% in adults ; 2% to 6% in infants H.LEE SCI 3009SEF 20/1/2025 Anaemia 9  Erythrocytes Mature erythrocyte – Size = 7-8µm – Volume = 80-100 fL – Cytoplasm Pink/red Biconcave shape – Nucleus - none – Present in circulation for about 120 days H.LEE SCI 3009SEF 20/1/2025 Anaemia 10  Bone marrow (BM) BM activity can be increased by 5–10 times its normal rate result in increased hematopoiesis in certain pathologic states. This increase is known as “Hyperplastic” i.e. more yellow marrow is replaced by red one. Hyperplastic condition occurs in either ineffective or increased hematopoiesis : - Acute or severe chronic anaemia - Malignant disease where red and yellow may be replaced by proliferating abnormal cells. H.LEE SCI 3009SEF 20/1/2025 Anaemia 11  Anaemia Anemia is the inability of the blood to supply the tissue with adequate oxygen for proper metabolic function Clinically, anemia is defined as a decrease in the normal concentration of hemoglobin or erythrocytes or haematocrit. Diagnosis of Anaemia depends on: - Age - Sex - Geographic location - others e.g. lung disease H.LEE SCI 3009SEF 20/1/2025 Anaemia 12  Haemoglobin Structure 4 polypeptide Subunits – Heme group Porphyrin ring /protoporphyrin Ferrous iron- binds O2 Globin chain – 2 Alpha Chains – 2 Beta chains H.LEE SCI 3009SEF 20/1/2025 Anaemia 13  Haemoglobin Synthesis Hemoglobin is a tetrametric molecule and each of these subunits has a heme group and a globin chain. Ferrous iron and the porphyrin ring also known as protoporphyrin IX found in Heme. Protoporphyrin IX ultimately originates from glycine & succinyl coenzyme A which are found in the mitochondria. There is a chain reaction of reactions which occurs within the mitochondria and cytoplasm to come to the end product of protoporphyrin. One protoporphyrin is formed and binds with iron, heme is made. Heme is a tetrapyrrole ring with a ferrous iron located in the center. Ferrous iron binds oxygen. Each heme subunit can carry one molecule of oxygen bound to ferrous iron, so each hemoglobin molecule can carry four molecules of oxygen. The globin chains included in the hemoglobin molecule are two alpha chains and two beta chains. H.LEE SCI 3009SEF 20/1/2025 Anaemia 14  Haemoglobin Synthesis Synthesis – Occurs in the mitochondria of developing red cells as they mature in the bone marrow – Processes necessary for normal synthesis Adequate iron supply & delivery Adequate synthesis of protoporphyrins Adequate globin synthesis H.LEE SCI 3009SEF 20/1/2025 Anaemia 15  Haem Synthesis Chain of Events – Iron delivery & supply Iron is delivered to the bone marrow by transferrin – Synthesis of protoporphyrins Occurs in the mitochondria of RBC precursors Mediated by EPO and vitamin B6 – Protoporphyrin + iron = heme H.LEE SCI 3009SEF 20/1/2025 Anaemia 16  Globin Synthesis Chain of Events – The rate of globin synthesis is proportional to the rate of porphyrin synthesis. – Proper globin synthesis depends on genes. The precise order of amino acids in the globin chains is critical to the structure and function of hemoglobin. – Chain designations are as follows Alpha α, beta β, delta δ, epsilon ε, gamma γ, zetaζ H.LEE SCI 3009SEF 20/1/2025 Anaemia 17  Globin Synthesis The globin chains included in the hemoglobin molecule are two alpha chains and two beta chains. Hb A is the major (96-98%) normal adult Hb - 2 identical α-chains, each with 141 amino acids; and 2 identical β-chains, with 146 amino acids each H.LEE SCI 3009SEF 20/1/2025 Anaemia 18  Globin Synthesis Hb F (