Hematology& Immune Mechanisms Tutor: Prof Mohan Dikshit 1

Objectives: Composition of blood & RBC Objectives: Composition of blood & RBC Describe the cellular and non-cellular components of blood Describe the cellular and non-cellular components of blood Enumerate functions of the non-cellular part. Enumerate functions of the non-cellular part. Describe the physical characteristics of the RBC Describe the physical characteristics of the RBC Describe functions of RBC. Describe functions of RBC. Describe the life cycle of RBCs Describe the life cycle of RBCs Describe the process of erythropoiesis Describe the process of erythropoiesis List the factors that affect erythropoiesis List the factors that affect erythropoiesis State the normal values for Hemoglobin percentage and RBC count in males and females 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 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 List the common symptoms of anemia Define Polycythemia and give an example Define Polycythemia and give an example Recommended reading: Tortora & Derrickson. Principles of Anatomy and Physiology.12th edn Volume 2 Recommended reading: Tortora & Derrickson. Principles of Anatomy and Physiology.12th edn Volume 2 2

Physical characteristics of blood Thicker than water with a Specific gravity around 1.58 Thicker than water with a Specific gravity around 1.58 pH pH Colour: bright red when oxygenated Colour: bright red when oxygenated dark red when de-oxygenated dark red when de-oxygenated 8% body weight 8% body weight 20% of ECF 20% of ECF Volume about 5 l (70 ml/Kg body wt.) Volume about 5 l (70 ml/Kg body wt.) Sampling by venipuncture; finger pick/heel prick Sampling by venipuncture; finger pick/heel prick arterial puncture arterial puncture 3

Plasma 55% Formed elements 45% Constituents of blood 91.5% water 7% gm% proteins 3.8gm % albumin (54%) 2.7gm% globulin (38%) 0.5gm % fibrinogen (7%) 1.5%ElectrolytesNutrientsGases Regulatory substances Waste products RBCs 5 million/cumm (µl) WBCs 10,000/cumm (µl) NeutrophilsEosinophilsBasophilsMonocytes Lymphocytes neutrophils 60-70% lymphocytesd 25-30% lymphocytesd 25-30% monocytes 3-8% monocytes 3-8% basophils 1% basophils 1% Platelets /µl 4

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Constituents of blood 6

Functions of blood Functions of blood 1. Transportation of 1. Transportation of respiratory gases; nutrients ; hormones; respiratory gases; nutrients ; hormones; waste products waste products 2. Regulatory: body temperature; pH 2. Regulatory: body temperature; pH 3. Protection 3. Protection against disease (immune functions); against disease (immune functions); against blood loss (coagulation) ( تَخَثُّر ) against blood loss (coagulation) ( تَخَثُّر ) 7

Origin: STEM CELLS (stem cell pool) in the bone marrow Origin: STEM CELLS (stem cell pool) in the bone marrow Stem cells may be Stem cells may be i. Pluripotent (multipotential), i. Pluripotent (multipotential), ii. Committed (unipotential) COLONY forming Units (CFUs). ii. Committed (unipotential) COLONY forming Units (CFUs). Hematopoesis : process of forming blood cells continues life long, Hematopoesis : process of forming blood cells continues life long, is modulated by requirements of the body. is modulated by requirements of the body. - It increases in anemia, blood loss, infection by: - It increases in anemia, blood loss, infection by: i. reconversion of old yellow bone marrow into red marrow; i. reconversion of old yellow bone marrow into red marrow; ii. daughter cells differentiate faster; iii. faster proliferation of stem cells ii. daughter cells differentiate faster; iii. faster proliferation of stem cells Some times even in adults EXTRA MEDULLARY hematopoesis occurs in liver, spleen Some times even in adults EXTRA MEDULLARY hematopoesis occurs in liver, spleen In blood cancer, hematopoesis becomes abnormal In blood cancer, hematopoesis becomes abnormal 8

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Red Blood Cells (eryrthrocytes) No. 4-5 million/cumm (μL) No. 4-5 million/cumm (μL) Size 7μ, bi-concave discs Size 7μ, bi-concave discs No nucleus: can not reproduce = More surface area & center becomes thinner (biconcave): - More O 2 can be carried - Squeeze into narrow capillaries - Allow O 2 & CO 2 Diffusion No nucleus: can not reproduce = More surface area & center becomes thinner (biconcave): - More O 2 can be carried - Squeeze into narrow capillaries - Allow O 2 & CO 2 Diffusion NO mitochondria: ATP by anaerobic means (advantage: do not use up O 2 they carry) NO mitochondria: ATP by anaerobic means (advantage: do not use up O 2 they carry) Life span 120 days Life span 120 days Destroyed in the body by RE cells: by products are recycled (mostly at Spleen) Destroyed in the body by RE cells: by products are recycled (mostly at Spleen) 10

11 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.

Thus each Hb molecule carries 4 O 2 molecules - Iron is what attaches Oxygen Hb and O 2 binding is a loose chemical one: easily released by Hb Globin 4 Heme mols Each having Iron mol Hemoglobin Physiology of RBCs 1. Main function: transport of OXYGEN bound to 2 alpha chains 2 beta chains 12

Hb : also carries Hb : also carries CO 2 but only about 15% CO 2 but only about 15% Nitric Oxide (NO) – allows blood to go through narrow capillaries Nitric Oxide (NO) – allows blood to go through narrow capillaries RBCs carry blood group antigens (A,B, O) on their cell membranes 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 globin Iron biliverdin Bilirubin in liver excreted increase leads to jaundice recycled Amino Acids recycled 13

Erythropoeisis: formation of RBC Erythropoeisis: formation of RBC Before birth in Before birth in yolk sac yolk sac liver and spleen liver and spleen After birth After birth In bone marrow In bone marrow long bones up to about 20 yr long bones up to about 20 yr flat bones later in life flat bones later in life About 2.5 million RBC are formed/sec Extra medullary erythropeisis Extra medullary erythropeisis Under severe stress of anemia in post natal life Under severe stress of anemia in post natal life Liver and spleen Liver and spleen 14

Proerythroblast Basophil erythroblast ( Hb just introduced); B 9 B 12 ( Hb just introduced); B 9 B 12 Orthochromatic erythro Polychromatophilerythroblast Reticulocyte In circulation for 1-2 days ERYTHROCYTE Normal erythropoiesis Progenitor cell in bone marrow: Pluripotent hemopoeitic stem cell Pluripotent hemopoeitic stem cell Colony forming unit Erythrocyte (Stimulated by erythropoeitin) (Stimulated by erythropoeitin) Process takes about 1 week 15 Large no of Reticulocytes means that the bone marrow is working

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Factors affecting erythropoeisis: Factors affecting erythropoeisis: Erythropoeitin from the kidneys is most important Erythropoeitin from the kidneys is most important Erythropoietin increases in 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 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) (other sources of Erythropoietin: liver) - Testosterone Testosterone Vit B 12, Folic acid (B 9 ), Vit B 12, Folic acid (B 9 ), Iron Iron Thyroid hormone Thyroid hormone Normal Reticulocyte count about 1% of RBC Normal Reticulocyte count about 1% of RBC If bone marrow is hypoactive If bone marrow is hypoactive reticulocyte count will go down reticulocyte count will go down 17

Normal HB level Normal HB level Male: about gm% Male: about gm% Female about gm% Female about gm% Clinical implications Clinical implications Anemia means a deficiency of Hb which can be caused by either too few RBCs or too little Hb in the cells. 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: For diagnosis of anemia: Hemoglobin Hemoglobin <13.0 g/dl for males <13.0 g/dl for males < 12.0 g/dl. for females < 12.0 g/dl. for females 18

Causes of anemia Causes of anemia i. reduced/defective RBC formation i. reduced/defective RBC formation ii. blood loss ii. blood loss iii. excessive destruction ( تَخْريب ): iii. excessive destruction ( تَخْريب ): iv. combination of all the above iv. combination of all the above The commonest cause of anaemia world wide is IRON deficiency : IDA The commonest cause of anaemia world wide is IRON deficiency : IDA 19

Common symptoms of anemia Common symptoms of anemia weakness weakness lethargy lethargy lack of concentration lack of concentration breathlessness – to begin with on exercise breathlessness – to begin with on exercise heart failure in severe anemia heart failure in severe anemia Investigations: Investigations: Hb/RBC count Hb/RBC count Treatment: iron; diet; remove obvious cause 20

Polycythemia: Polycythemia: Excess formation of RBC (> 6-7 million/µl) Excess formation of RBC (> 6-7 million/µl) i. Classically : high altitude exposure i. Classically : high altitude exposure ii. Polycythemia Rubra ii. Polycythemia Rubra 21

RECAP RECAP Blood constituents Blood constituents Functions of the non-cellular part. Functions of the non-cellular part. RBC: characretristics, functions & and formation RBC: characretristics, functions & and formation Life cycle of RBCs Life cycle of RBCs Normal values for Hemoglobin percentage and RBC count in males and females Normal values for Hemoglobin percentage and RBC count in males and females Anemia, and recognize different symptoms of anemia Anemia, and recognize different symptoms of anemia Iron deficiency anemia is the commonest variety world wide Iron deficiency anemia is the commonest variety world wide Define Polycythemia and give an example Define Polycythemia and give an example 22

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