Hematology & Immune Mechanisms Tutor: Prof Mohan Dikshit

1. Hematology & Immune Mechanisms Tutor: Prof Mohan Dikshit

2. 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

3. 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

4. Constituents of blood Formed elements 45% Plasma 55% RBCs 5 million/cumm (µl) 91.5% water 7% gm% proteins 3.8gm % albumin (54%) 2.7gm% globulin (38%) 0.5gm % fibrinogen (7%) WBCs 10,000/cumm (µl) Neutrophils Eosinophils Basophils Monocytes Lymphocytes neutrophils 60-70% lymphocytesd 25-30% monocytes 3-8% basophils 1% 1.5% Electrolytes Nutrients Gases Regulatory substances Waste products Platelets 140-400000/µl

6. Constituents of blood

7. 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) (تَخَثُّر )

8. 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 cellscontinues 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 MEDULLARYhematopoesis occurs in liver, spleen • In blood cancer, hematopoesis becomes abnormal

10. 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)

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.

12. Physiology of RBCs 1. Main function: transport of OXYGEN bound to Hemoglobin 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 Globin 4 Heme mols Each having Iron mol 2 alpha chains 2 beta chains

13. RBC Life cycle: 120 days • 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 Macrophages in spleen liver, marrow break up RBCs heme globin recycled Amino Acids biliverdin Iron recycled Bilirubin in liverexcretedincrease leads to jaundice

14. 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

15. 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

17. Factors affecting erythropoeisis: • Erythropoeitinfrom the kidneys is most important • Erythropoietin increases in hypoxia, chronic lung disease, anemia, low blood volumethat’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

18. Normal HB level • Male: about 13-15 gm% • Female about 12-14 gm% • 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

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

20. 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

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

22. 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