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Hematology & Immune Mechanisms Tutor: Prof Mohan Dikshit 1 Objectives: Composition of blood & RBC Describe the cellular and non-cellular components of blood Enumerate functions of the non-cellular part. Describe the physical characteristics of the RBC Describe functions of RBC. Describe the life cycle of RBCs Describe the process of erythropoiesis List the factors that affect erythropoiesis State the normal values for Hemoglobin percentage and RBC count in males and females Define anemia, and recognize different types of anemia, and that iron deficiency anemia is the commonest variety world wide List the common symptoms of anemia Define Polycythemia and give an example Recommended reading: Tortora & Derrickson . Principles of Anatomy and Physiology.12th edn. 2009. Volume 2 2 Physical characteristics of blood Thicker than water with a Specific gravity around 1.58 pH 7.35-7.45 Colour: bright red when oxygenated dark red when de-oxygenated 8% body weight 20% of ECF Volume about 5 l (70 ml/Kg body wt.) Sampling by venipuncture; finger pick/heel prick arterial puncture 3 Constituents of blood Plasma 55% Formed elements 45% RBCs 5 million/cumm (µl) 91.5% water 7% gm% proteins 3.8gm % albumin (54%) 2.7gm% globulin (38%) 0.5gm % fibrinogen (7%) 1.5% Electrolytes Nutrients Gases Regulatory substances Waste products WBCs 10,000/cumm (µl) Neutrophils Eosinophils Basophils Monocytes Lymphocytes Platelets 140-400000/µl 4 5 Constituents of blood 6 Functions of blood 1. Transportation of respiratory gases; nutrients ; hormones; waste products 2. Regulatory: body temperature; pH 3. Protection against disease (immune functions); against blood loss (coagulation) ( ) َت َخ ُّثر 7 Origin: STEM CELLS (stem cell pool) in the bone marrow Stem cells may be i. Pluripotent (multipotential), ii. Committed (unipotential) COLONY forming Units (CFUs). Hematopoesis : process of forming blood cells continues life long, is modulated by requirements of the body. - It increases in anemia, blood loss, infection by: i. reconversion of old yellow bone marrow into red marrow; ii. daughter cells differentiate faster; iii. faster proliferation of stem cells Some times even in adults EXTRA MEDULLARY hematopoesis occurs in liver, spleen In blood cancer, hematopoesis becomes abnormal 8 9 Red Blood Cells (eryrthrocytes) No. 4-5 million/cumm (μL) Size 7μ, bi-concave discs No nucleus: can not reproduce = More surface area & center becomes thinner (biconcave): - More O2 can be carried - Squeeze into narrow capillaries - Allow O2 & CO2 Diffusion NO mitochondria: ATP by anaerobic means (advantage: do not use up O2 they carry) Life span 120 days Destroyed in the body by RE cells: by products are recycled (mostly at Spleen) 10 Live only 120 days, Why? While Moving in and out of capillaries the RBC are torn and damaged, and due to the absence of Nucleus, healing doesn’t occur. 11 Physiology of RBCs 1. Main function: transport of OXYGEN bound to Hemoglobin 4 Heme mols Each having Iron mol Globin 2 alpha chains 2 beta chains Thus each Hb molecule carries 4 O2 molecules - Iron is what attaches Oxygen Hb and O2 binding is a loose chemical one: easily released by Hb 12 Hb : also carries CO2 but only about 15% Nitric Oxide (NO) – allows blood to go through narrow capillaries RBCs carry blood group antigens (A,B, O) on their cell membranes RBC Life cycle: 120 days Macrophages in spleen liver, marrow break up RBCs heme Iron recycled biliverdin globin Amino Acids Bilirubin in liver excreted increase leads to jaundice recycled 13 Erythropoeisis: formation of RBC Before birth in yolk sac liver and spleen After birth In bone marrow long bones up to about 20 yr flat bones later in life About 2.5 million RBC are formed/sec Extra medullary erythropeisis Under severe stress of anemia in post natal life Liver and spleen 14 Normal erythropoiesis Progenitor cell in bone marrow: Pluripotent hemopoeitic stem cell Colony forming unit Erythrocyte (Stimulated by erythropoeitin) Proerythroblast Basophil erythroblast ( Hb just introduced); B9 B12 Process takes about 1 week Polychromatophil erythroblast Orthochromatic erythro Reticulocyte In circulation for 1-2 days ERYTHROCYTE Large no of Reticulocytes means that the bone marrow is working 15 16 Factors affecting erythropoeisis: Erythropoeitin from the kidneys is most important Erythropoietin increases in hypoxia, chronic lung disease, anemia, low blood volume that’s why people living in high mountains have larger numbers of RBC = HYPOXIA (other sources of Erythropoietin: liver) - Testosterone Vit B12, Folic acid (B9), Iron Thyroid hormone Normal Reticulocyte count about 1% of RBC If bone marrow is hypoactive reticulocyte count will go down 17 Normal HB level Male: about Female about Clinical implications Anemia means a deficiency of Hb which can be caused by either too few RBCs or too little Hb in the cells. For diagnosis of anemia: Hemoglobin <13.0 g/dl for males < 12.0 g/dl. for females 13-15 gm% 12-14 gm% 18 Causes of anemia i. reduced/defective RBC formation ii. blood loss iii. excessive destruction ( ) َت ْخريب: iv. combination of all the above The commonest cause of anaemia world wide is IRON deficiency : IDA 19 Common symptoms of anemia weakness lethargy lack of concentration breathlessness – to begin with on exercise heart failure in severe anemia Investigations: Hb/RBC count Treatment: iron; diet; remove obvious cause 20 Polycythemia: Excess formation of RBC (> 6-7 million/µl) i. Classically : high altitude exposure ii. Polycythemia Rubra 21 RECAP Blood constituents Functions of the non-cellular part. RBC: characretristics, functions & and formation Life cycle of RBCs Normal values for Hemoglobin percentage and RBC count in males and females Anemia, and recognize different symptoms of anemia Iron deficiency anemia is the commonest variety world wide Define Polycythemia and give an example 22 23