BLOOD

1. BLOOD BY: GBADEBO ADEOLA MICHAEL Department of Physiology School of Health Sciences KIU, Dar es Salaam

2. OUTLINE • Introduction • Hematopoiesis • Red Blood Cells(Erythrocytes) • White Blood Cells(Leucocytes) • Platelets(Thrombocytes)

3. Introduction • Blood is a tissue fluid • It circulates in a closed system of vessels and heart • It is made of four components namely: - Red blood cell - White blood cell - Platelets - Plasma(liquid component of blood)

4. Composition of Blood

5. Hematopoiesis All blood cells are derived from pluripotent haematopoietic stem cells,which are found in different locations at different stages: • Yolk sac 3rd to 10th Week of gestation • Liver 6th to 32nd Week of gestation • Spleen 10th to 25th Week of gestation • Bone marrow 30th to 36th Week and also after birth and until adulthood

6. Hematopoiesis ‘Contd • A single pluripotent haematopoieticstemcellgivesrisetothe cellularcomponentsofblood • however, two major progenitor cells,bothderivedfrom the pluripotent stem cellscanbeidentified: -Thelymphoidprogenitorcell generateslymphocytes -The myeloidprogenitorcellgivesrisetoalltheothercellular components oftheblood

7. Principal sites of action of erythropoietin and various colony-stimulating factors Totipotent Stem cell

9. Changes when the cell matures • Size of the cell decreases • Cytoplasmic: Nuclear Ratio increases • Chromatin becomes thick, coarse, irregular • RNA decreases • Nucleoli become absent

10. Changes in red bone marrow cellularity with age.

11. Red Blood Cell • Red blood cells (erythrocytes) form by erythropoiesis • Myeloid progenitor cells differentiate through three stages to develop into mature red blood cells • The stages are: • normoblast, reticulocyte and mature erythrocyte

12. Characteristics of RBCs • Biconcave discs • size : 7.5 Micrometer • Membrane flexible • No Mitochondria, ribosome or RNA • Anaerobic Glycolysis • Life Span 120 days • 4.7-5.2 million/cubic mm3

13. Characteristics of human red cells

14. Factors affecting Erythropoiesis • Erythropoietin (hormone regulating erythropoiesis) • Protein diet • Vitamins e.g. Vit B12,Folic Acid, Vit C, Vit E, Riboflavin etc. • Metals e.g. Fe, Cu, Co, Mn etc • Hormones e.g. Testosterone, Growth hormone, Cortisol, Adrenaline and nor-adrenaline, estrogen

16. Production of erythropoietin by Kidney in response to its O2 Supplies

17. Factors Affecting Erythropoiesis

18. HEMOGLOBIN

19. Types of Haemoglobin • HbA ( Alpha2 Beta2) • HbF ( Alpha2 Gamma2) • Met Hemoglobin • Hb S

20. Reactions of Hemoglobin • Combine with O2 • Combine with CO2 • Combine with CO • Combine with NO • Combine with H Ions

21. Anemia Deficiency of haemoglobin content in the blood which can be caused by either too few RBCs or too little Hb in the cell for the age and sex of a patient.

22. Types of Anemia

23. Inherited Disorders of Hemoglobin • Hemoglobinopathies e.g Sickle cell anemia • Thalasemias e.g Alpha and Beta

24. Polycythemia Increased number of RBCs 1. Polycythemia Vera 2. Secondary Polycythemia • Physiological

25. Blood Types Blood types depends on surface antigens (Agglutinogen) on erythrocytes • O-A-B blood types • Rh blood type • Others: Rh, MNSs ,Kidd, Lutheran ,Kell etc

26. O-A-B blood type Depending on presence or absence of antigen (Agglutinogen),four different blood groups A--if only agglutinogen A is present B--if only agglutinogen B is present AB--if both agglutinogen A and B are present O--if neither agglutinogen A nor agglutinogen B are present

27. Relative frequencies of blood types

28. Landsteiner,s Law • If a particular agglutinogen is present on RBC, corresponding agglutinin must be absent in serum • If a particular agglutinogen is absent on RBC, corresponding agglutinin must be present in serum This law does not apply to Rh system

30. White Blood Cell(Leukocytes) Are mobile units of the body’s protective system • Granulocytes • Neutrophils • Eosinophils • Basophils • Agranulocytes • Monocytes • Lymphocytes

31. Normal Percentages Of Different WBCS • Polymorphonuclearneutrophils 62 % • Polymorphonucleareosinophils 2-3 % • Polymorphonuclearbasophils 0.4 % • Monocytes 5.3 % • Lymphocytes 30.0 %

32. Characteristics of Granulocytes Margination Migration or Diapedesis Amoeboid movement Chemotaxis Phagocytosis

33. Movement of neutrophils showing characteristics of granulocytes

34. Functions of Neutrophils • Phagocytosis • Lysosomes: Proteolytic enzymes Myeloperoxidase H2O2+Cl Hypochlorite • Bactericidal agents. e.g. Superoxide ions, Hydrogen peroxide, Hydroxyl ions

35. Neutrophilia Increased number of neutrophils in blood. Causes are: • Acute bacterial infections. e.g. Pneumonias, appendicitis, tonsillitis • Burns, hemorrhage, tissue injury • Polycythemia vera • Strenuous exercise

36. Neutropenia Decreased number of neutrophils in blood. Causes: • Bacterial infections. e.g. Typhoid fever. • viral hepatitis • Kalazar (Schistosomiasis) • Bone marrow depression • Hypersplenism

37. Characteristics of Eosinophils. • Weakly phagocytic • Lysosomes contain hydrolytic enzymes • Major basic protein • Reactive oxygen • Histaminase • Peroxidases

38. Eosinophilia Increased number of eosinophils in blood. Causes are: • Allergic conditions e.g. Bronchial asthma, hay fever • Parasitic infestations e.g. hookworm, trichinosis(Trichinella), schistosomiasis etc. • Dermatitis • Penicillin

39. Eosinopenia Decreased number of Eosinophils in blood. Causes are: Coticosteroids Over activity of adrenal cortex Diurnal variation: less in the morning ,may be in response to increased secretion of ACTH in the morning

40. Contents of Basophils • Heparin • Histamine • SRS ( slow reacting substance of anaphylaxis) • Serotonin • Leukotreins • Bradykinin • Eosinophil chemotactic factor • Neutrophil chemotactic factor • Many other lysosomal enzymes

41. Monocyte Macrophage system Monocytes in blood plus both fixed and wandering macrophages and few specialized endothelial cells in bone marrow, spleen and lymph nodes make up Reticuloendothelial system They are known by different names in different organs Brain: Microglia Skin: Histiocytes Lungs: alveolar macrophages Liver: Kupffer cells Spleen, Bone marrow: Sinusoids Lymphatic Channels: littoral cells

42. Inflammation 1st line of defense: Macrophages 2nd line of defense: Neutrophils 3rd line of defense: Second macrophage invasion 4th line of defense: increased production of granulocytes and monocytes by bone marrow

43. Platelets Size: 1 – 4 Micro meter in diameter Normal Count: 1, 50000 – 300,000 / cu mm or micro liter Live span: 10 days Megakaryocyte 35-160 micron

44. Platelet membranes contain receptors for • Collagen • ADP • Vessel wall Von Willebrand factor • Fibrinogen • Glycoprotein • Prothrombin

45. Platelets cytoplasm contain • Actin • Myosin • Thrombosthenin • Glycogen • Lysosomes • Fibrin stabilizing factor • Granules • Dense granules Contains non protein substances e.g. Serotonin, ADP, Ca and other nucleotides. II. Alpha granules: Secrete proteins e.g. Clotting factors, platelet derived growth factor (PDGF), Von Willebrand factor.

46. Regulation of Platelet Production • Thrombopoietin • Erythropoietin • Menstrual cycle • Adrenaline • Injury • Hypoxia • Smoking • Vitamin deficiency

47. Thrombocytosis Increase no of platelets in the blood Causes. • After acute haemorrhage • Splenectomy • Polycythemia vera

48. Thrombocytopenia Decreased Number of platelets in the blood Causes. • Idiopathic • Secondary • Pancytopenia • Increased destruction of platelets • Hypersplenism • Leukemia

49. Hemostasis Arrest of bleeding/ prevention of blood loss when there is vessel injury Involves three steps A. Vascular spasm • Inherent vascular response • Sympathetically induced vasoconstriction • Vasoconstrictor substance e.g Thromboxane A2. B. Formation of platelet plug • Platelet adhesion • Platelet activation • Platelet aggregation. C. Clot formation • Intrinsic system • Extrinsic system • Growth of fibrous tissue in clot

50. Whenever the vessel is damaged, the net result is formation of prothrombin activator. • Prothrombin activator is formed in two ways • The extrinsic pathway • The intrinsic pathway