Blood

blood cells, its types and composition with blood grouping and hemostasis

1. BLOOD BY SONI KUMARI SHAH

2. Introduction Blood is a fluid connective tissue. It circulates constantly around the body, allowing constant communication between tissues distant from each other. It transports: oxygen nutrients hormones heat protective substances clotting factors.

3. Blood Blood is composed of a clear, straw-colored, watery fluid called plasma in which several different types of blood cell are suspended. Plasma normally constitutes 55% of the volume of blood and the cell fraction. Blood makes up about 7% of body weight (about 5.6 liters in a 70 kg man). This proportion is less in women and considerably greater in children, gradually decreasing until the adult level is reached.

4. Characteristics Blood Volume : 5-6 Liters Normal Reaction : Slightly Alkaline pH 7.35-7.45 Specific Gravity : 1.052-1.060 Viscosity : 4.5 Times More Than Water Temperature : 36-38 C Osmotic Pressure : 25mmHg Color : bright Red(oxygenated); dark red/purplish(deoxygenated) Taste: Salty

5. Composition Cellular substance : 45% 44% RBC & 1% buffy coat containing platelets and WBC Plasma(fluid): 55% 91-92% water 8-9% solid Organic Substances : proteins, carbohydrates, fat, urea, uric acid, creatine , ammonia, enzymes, antibodies, hormones, bilirubin, etc Inorganic Substances : sodium, potassium, calcium, magnesium, phosphorous, iron, copper, etc

6. Plasma The constituents of plasma are water (90–92%) and dissolved and suspended substances, including: • plasma proteins • inorganic salts • nutrients, principally from digested foods • waste materials • hormones • gases.

7. Plasma proteins Plasma proteins, which make up about 7% of plasma, are normally retained within the blood, because they are too big to escape through the capillary pores into the tissues. They are largely responsible for creating the osmotic pressure of blood, which keeps plasma fluid within the circulation. Plasma viscosity (thickness) is due to plasma proteins, mainly albumin and fibrinogen. Plasma proteins, with the exception of immunoglobulins, are formed in the liver.

8. Important plasma proteins are Albumin Globulin Fibrinogen Prothrombin

9. Functions of plasma protein They transport hormones, iron and other substances. They exert osmotic pressure and regulate blood volume. They provide viscosity to blood(which helps in maintaining blood pressure). Fibrinogen in plasma in necessary for clotting Globulin of plasma is important for the synthesis of immune substances called antibodies.

10. Electrolytes These have a range of functions, including muscle contraction (e.g. Ca2 + ), transmission of nerve impulses (e.g. Ca2 + and Na + ), and maintenance of acid–base balance.

11. Nutrients The products of digestion, e.g. glucose, amino acids, fatty acids and glycerol, are absorbed from the alimentary tract. Together with mineral salts and vitamins they are used by body cells for energy, heat, repair and replacement, and for the synthesis of other blood components and body secretions.

12. Waste products Urea, creatinine and uric acid are the waste products of protein metabolism. They are formed in the liver and carried in blood to the kidneys for excretion. Carbon dioxide from tissue metabolism is transported to the lungs for excretion.

13. Hormones These are chemical messengers synthesized by endocrine glands. Hormones pass directly from the endocrine cells into the blood, which transports them to their target tissues and organs elsewhere in the body, where they influence cellular activity.

14. Gases Oxygen, carbon dioxide and nitrogen are transported round the body dissolved in plasma. Oxygen and carbon dioxide are also transported in combination with hemoglobin in red blood cells. Most oxygen is carried in combination with hemoglobin and most carbon dioxide as bicarbonate ions dissolved in plasma. Atmospheric nitrogen enters the body in the same way as other gases and is present in plasma but it has no physiological function.

15. Cellular Content Of Blood There are three types of blood cell • erythrocytes (red blood cells) • platelets (thrombocytes) • leukocytes (white blood cells). Blood cells are synthesized mainly in red bone marrow. Some lymphocytes, additionally, are produced in lymphoid tissue. In the bone marrow, all blood cells originate from pluripotent (i.e. capable of developing into one of a number of cell types) stem cells and go through several developmental stages before entering the blood. Different types of blood cell follow separate lines of development. The process of blood cell formation is called hemopoiesis

16. Erythrocytes (Red Blood Cells) Red blood cells are by far the most abundant type of blood cell; 99% of all blood cells are erythrocytes. They are biconcave discs with no nucleus, and their diameter is about 7 μ m . Their main function is in gas transport, mainly of oxygen, but they also carry some carbon dioxide. Their characteristic shape is suited to their purpose; the biconcavity increases their surface area for gas exchange, and the thinness of the central portion allows fast entry and exit of gases. The cells are flexible so they can squeeze through narrow capillaries, and contain no intracellular organelles, leaving more room for hemoglobin, the large pigmented protein responsible for gas transport.

17. Erythrocytes (Red Blood Cells) Because they have no nucleus, erythrocytes cannot divide and so need to be continually replaced by new cells from the red bone marrow, which is present in the ends of long bones and in flat and irregular bones. They pass through several stages of development before entering the blood. Their life span in the circulation is about 120 days. There are approximately 30 trillion (1014) red blood cells in the average human body, about 25% of the body’s total cell count, and around 1%, mainly older cells, are cleared and destroyed daily.

18. Red Blood Cells(Erythrocytes) Can be deformed into any shape Excess cell membrane Less tendency of rupture Can squeeze through capillaries

19. Functions of RBC: Transport oxygen from lungs to tissue. Transport carbon dioxide from tissue to lungs. Hemoglobin in RBC Functions as good buffer Carry the blood group antigens like A Agglutinogen, B Agglutinogen, and Rh factor. This helps in determining blood group and blood transfusion.

20. Red Blood Cells Sites of Production Yolk sac- fetus less than 2 months Liver: 2-5 months Spleen: 2-5 months Lymph nodes: adult life Bone marrows: adult life

21. Development Of Erythrocytes Formed in bone marro w The process of development of red blood cells from stem cells takes about 7 days and is called erythropoiesis . The immature cells are released into the bloodstream as reticulocytes, and mature into erythrocytes over a day or two within the circulation. During this time, they lose their nucleus and therefore become incapable of division.

22. Development Of Erythrocytes Both vitamin B12 and folic acid are required for red blood cell synthesis. They are absorbed in the intestines, although vitamin B12 must be bound to intrinsic factor to allow absorption to take place. Both vitamins are present in dairy products, meat and green vegetables. The liver usually contains substantial stores of vitamin B12, several years’ worth, but signs of folic acid deficiency appear within a few months

23. Control Of Erythropoiesis: The Role Of Erythropoietin

24. Hemoglobin hemoglobin is a large, complex molecule containing a globular protein (globin) and a pigmented iron-containing complex called hem. Each hemoglobin molecule contains four globin chains and four hem units, each with one atom of iron. As each atom of iron can combine with an oxygen molecule, this means that a single hemoglobin molecule can carry up to four molecules of oxygen.

25. Hemoglobin An average red blood cell carries about 280 million hemoglobin molecules, giving each cell a theoretical oxygen-carrying capacity of over a billion oxygen molecules. Iron is carried in the bloodstream bound to its transport protein, transferrin , and stored in the liver. Normal red cell production requires a steady supply of iron. Absorption of iron from the alimentary canal is very slow, even if the diet is rich in iron, meaning that iron deficiency can readily occur if losses exceed intake.

26. Types Of Hemoglobin Oxyhemoglobin: It is the combined form of oxygen and hemoglobin which is found in arterial blood and is the oxygen carried to the body tissue. Methemoglobin: A compound formed from hemoglobin by oxidation of its ferrous iron to ferric iron by injury or toxic substance. Carboxyhemoglobin: The inhaled carbon monoxide combines with hemoglobin binding more tightly then oxygen and rendering the hemoglobin incapable of transporting oxygen is known as carboxyhemoglobin.

27. Functions Of Hemoglobin It transports respiratory gases(oxygen and carbon dioxide). Maintenance of acid base balance. It reserves iron and protein.

28. Erythrocyte Disorder Polycythemia is excess of RBC. Primary polycythemia is due to cancer of myeloid tissue. Secondary polycythemia is caused by lung damage, high altitude or other factors leading to hypoxia.

29. Erythrocyte Disorder Anemia is deficiency of either RBC or hemoglobin. Anemia falls into three categories: inadequate erythropoiesis or hemoglobin production , hemorrhagic anemia from bleeding and hemolytic anemia from RBC destruction. Three potential consequences of anemia are hypoxia, reduced blood osmolarity and reduced blood viscosity.

30. Leukocytes (White Blood Cells) These cells have an important function in defense and immunity. They detect foreign or abnormal (antigenic) material and destroy it, through a range of defense mechanisms. Leukocytes are the largest blood cells but they account for only about 1% of the blood volume. They contain nuclei and some have granules in their cytoplasm.

31. Leukocytes (White Blood Cells) There are two main types: Granulocytes (Polymorphonuclear Leukocytes) : Neutrophils Eosinophils Basophils Agranulocytes: Monocytes Lymphocytes Rising white cell numbers in the bloodstream usually indicate a physiological problem, e.g. infection, trauma or malignancy.

32. Leucocytes(White Blood Cells) Life span Granulocytes : 4-8 hrs in blood, 4-5 days in tissue Monocytes : 10-20 hrs in blood, months in tissue Lymphocytes: circulates continually, weeks to months

33. Leucocytes (White Blood Cells)

34. Granulocytes All granulocytes have multilobed nuclei in their cytoplasm. Their names represent the dyes they take up when stained in the laboratory. Eosinophils take up the red acid dye, eosin; basophils take up alkaline methylene blue; and neutrophils are purple because they take up both dyes.

35. Eosinophils Eosinophils, although capable of phagocytosis, are less active in this than neutrophils; their specialized role appears to be in the elimination of parasites, such as worms, which are too big to be phagocytosed. They are equipped with certain toxic chemicals, stored in their granules, which they release when the eosinophil binds to an infecting organism. Local accumulation of eosinophils may occur in allergic inflammation, such as the asthmatic airway and skin allergies.

36. Neutrophils These small, fast and active scavengers protect the body against bacterial invasion, and remove dead cells and debris from damaged tissues. They are attracted in large numbers to any area of infection by chemicals called chemotaxins , released by damaged cells. Their numbers rise very quickly in an area of damaged or infected tissue. Once there, they engulf and kill bacteria by phagocytosis. Neutrophils live on average 6–9 hours in the bloodstream. Pus that may form in an infected area consists of dead tissue cells, dead and live microbes, and phagocytes killed by microbes.

37. Phagocytic Action Of Neutrophils.

38. Basophils Basophils, which are closely associated with allergic reactions, contain cytoplasmic granules packed with heparin (an anticoagulant), histamine (an inflammatory agent) and other substances that promote inflammation. Usually the stimulus that causes basophils to release the contents of their granules is an allergen (an antigen that causes allergy) of some type.

39. Neutrophils: Protect against any foreign materials that gains entry to the body To remove waste materials Eosoniphils Elimination of parasites Often found at sites of allergic inflammation Basophils: Closely associated with allergic reaction Packed with heparin, histamine,etc

40. Agranulocytes The monocytes and lymphocytes make up 25 to 50% of the total leukocyte count. They have a large nucleus and no cytoplasmic granules.

41. Monocytes: These are the largest of the white blood cells. Some circulate in the blood and are actively motile and phagocytic while others migrate into the tissues where they develop into macrophages .

42. Monocytes: Both types of cell produce interleukin 1 , which: acts on the hypothalamus, causing the rise in body temperature associated with microbial infections stimulates the production of some globulins by the liver enhances the production of activated T-lymphocytes. Macrophages have important functions in inflammation and immunity.

43. Lymphocytes: Smaller than monocytes and have large nucleus Some circulate in the blood but most are found in tissues, including lymphatic tissue such as lymph nodes and the spleen. Responds to antigens Two distinct types: T- lymphocytes & B- lymphocytes

44. Disorders of Leukocytes Leukopenia is a condition in which too few leukocytes are produced. If this condition is pronounced, the individual may be unable to ward off disease. Excessive leukocyte proliferation is known as leukocytosis . Although leukocyte counts are high, the cells themselves are often nonfunctional, leaving the individual at increased risk for disease.

45. Disorders of Leukocytes Leukemia is a cancer involving an abundance of leukocytes. It may involve only one specific type of leukocyte from either the myeloid line ( myelocytic leukemia) or the lymphoid line ( lymphocytic leukemia ). In chronic leukemia , mature leukocytes accumulate and fail to die. In acute leukemia , there is an overproduction of young, immature leukocytes. In both conditions the cells do not function properly.

46. Disorders of Leukocytes Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues. As in leukemia, the malignant leukocytes do not function properly, and the patient is vulnerable to infection. Some forms of lymphoma tend to progress slowly and respond well to treatment. Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal.

47. Functions Of Leucocytes(WBC) Protection against infection: done by neutrophils and monocytes by phagocytosis. To aid in repair of injured tissue. To produce immune substances which defense against disease. This is done by lymphocytes through synthesis of gamma globulin. Basophils secretes an anticoagulant substance called heparin.

48. Thrombocytes(platelets) The life span of platelets is between 8 and 11 days and those not used in hemostasis are destroyed by macrophages, mainly in the spleen. About a third of platelets are stored within the spleen rather than in the circulation; this is an emergency store that can be released as required to control excessive bleeding.

49. Platelets (Thrombocytes) These are very small discs, 2–4 μ m in diameter, derived from the cytoplasm of megakaryocytes in red bone marrow. Although they have no nucleus, their cytoplasm is packed with granules containing a variety of substances that promote blood clotting, which causes hemostasis (cessation of bleeding).

50. Platelets are derived from cells called megakaryocytes.

51. Functions Of Platelet Platelets are essential parts of blood coagulating mechanism. The close minute lesions in the walls of vessels.

52. Disorders of Platelets Thrombocytosis is a condition in which there are too many platelets. This may trigger formation of unwanted blood clots (thrombosis), a potentially fatal disorder. If there is an insufficient number of platelets, called thrombocytopenia , blood may not clot properly, and excessive bleeding may result.

53. Functions of Blood Carries respiratory gases, nutrients, hormones, enzymes, vitamins, metabolites(body fluid, CSF) other chemicals and wastes Regulates body temperature Maintains water and electrolyte balance Maintains acid base balance Contains agents which protects against infection Coagulation of blood by platelets.

54. Product And Functions Of Blood Cells SN Cell type Normal count Life span Main product or component Main function 1. Erythrocyte M: 47-61 lakh/mm 3 F: 42-54 lakh/mm 3 120 days Hemoglobin Gaseous transport(CO2 and O2) 2. Leucocytes 4000-11000/mm 3 1-14 days To provide immunity 2.1 Neutrophil 1000-6000/mm 3 1-5 days Azurophilic granule Phagocytosis of bacteria 2.2 Eosinophil 150-450/mm 3 7- 12 days Specific granules with modified lysozyme Defense against parasitic helminth; modulation of inflammatory process 2.3 Basophil 0-10/mm 3 12-15 days Granules containing histamine heparin Release of histamine and other inflammation mediators 2.4 Monocyte 200-600/mm 3 5-8 days Lysosomal enzyme Phagocytosis and digestion of protozoa and virus infected cells 2.5 Lymphocyte 1500-2700/mm 3 ½-1day a. T-lymphocyte 2days Interleukins Killing of virus infected cells b. B- lymphocyte 1 day Immunoglobulins Generation of antibody- producing terminal cells c. Natural killer (NK) cells 1day Attacks virus infected& cancer cells without previous stimulation Killing of some tumor and virus infected cells 3. Platelet 2 - 3.5 lakh/mm 3 7-14 days Blood clotting substance Clotting of blood

55. Blood Cells Count RBC count 4.7-6.1 million/mm 3 in male 4.2-5.4 million/mm 3 in fe male WBC count 4000-11000/mm 3 Platelets 2,00,000- 3,50,000/mm 3 Hemoglobin 12-16gm/dl for female 14-18gm/dl for male

56. Blood is composed of straw colored transparent fluid when blood cells are suspended. It is called Serum Plasma Hemocrit Fibronigen Viscosity of blood is mainly due to RBCs WBCs Platelets Electrolytes Approximate life span of platelet is: 120 days 7 days 24 hrs 6 hrs

57. Formation of blood The process of formation of blood is hemopoiesis. Sites Of Blood Formation : During intrauterine life: yolk sac (1-2 months) liver and spleen (2-5months) bone marrow, lymph node, spleen (5months till birth) After birth: Bone marrow, lymph node, spleen

58. Haemopoiesis

59. Blood Grouping(ABO System)

60. Blood Grouping(Rhesus/Rh System) Blood group RBC Antigen Antibody Frequency Positive D None 85% Negative None None by birth 15%

61. Prevalence Of Different Blood Group

62. Parents Child Blood Group Relationship

63. Purpose Of Blood Grouping Blood transfusion : if non match blood will be transferred to the patient then there will be antigen antibody reaction and hemolysis will occur. To prevent hemolytic disease of new born. Relationship of blood groups, susceptibility to various diseases.

64. Basis Of Transfusion Reaction Individual have different types of antigen on the surface of their RBCs. These antigens, which are inherited, determine the individual’s blood group . Individuals can make antibodies to these antigens, but not to their own type of antigen, since if they did the antigens and antibodies would react, causing a potentially fatal transfusion reaction . These antibodies circulate in the blood stream and the ability to make them, like the antigens, is genetically determined and not associated with acquired immunity.

65. Basis Of Transfusion Reaction If individuals are transfused with blood of the same group , i.e. possessing the same antigens on the surface of the cells, their immune system will not recognize them as foreign and will not reject them. However, if they are given blood from an individual of a different blood type , i.e. with a different type of antigen on the red cells, their immune system will generate antibodies to the foreign antigens and destroy the transfused cells. This is the basis of the transfusion reaction; the two blood types, the donor and the recipient, are incompatible .

66. H emostasis The process which causes stoppage of bleeding is called hemostasis. It keeps blood within a damaged blood vessel hence prevent bleeding. The opposite of hemostasis is hemorrhage. It is the first stage of wound healing .

67. Steps Of Hemostasis: Vasoconstriction Platelet plug formation Coagulation(blood clotting) Fibrinolysis

68. Vasoconstriction: Platelet come in contact with damaged blood vessel- become sticky-adhere to the wall- release serotonin-constrict blood vessel-reduce blood flow Platelet Plug Formation: Adherent platelet clump to each other-release ADP-attracts more platelets-forms temporary seal-platelet plug

69. Coagulation Blood clotting results in the formation of insoluble thread like mesh of fibrin which traps the blood cells and is much stronger than the rapidly formed platelet plug. In the final stage of this process prothrombin activator acts on the plasma protein prothrombi n converting it to thrombin . Thrombin acts on another plasma protein fibrinogen and converts it to fibrin .

70. Coagulation Prothrombin activator can be formed by two process : the extrinsic and intrinsic pathway. The extrinsic pathway is activated rapidly (within seconds) following tissue damage. Damaged tissue releases a complex of chemicals called thromboplastin or tissue factor, which initiates coagulation. The intrinsic pathway is slower (3–6 minutes) and is triggered when blood comes into contact with damaged blood vessel lining (endothelium) and the effects of platelets adhering to it.

71. Fibrinolysis: The breakdown of clot is called fibrinolysis. An inactive substance called plasminogen is present in clot and is converted to the enzyme plasmin by activators released from the damaged endothelial cells. Plasmin initiates breakdown of fibrin to soluble products that are treated as waste materials and are removed by phagocytosis.

72. Clotting Factors

73. Erythroblastosis Fetalis It is a clinical condition, if Rh – ve mother has Rh + ve fetus, at the time of delivery fetal RBCs enter maternal circulation and cause sensitization leading to formation of agglutin against Rh in large quantity. If next time this woman becomes pregnant and bears Rh + ve fetus, agglutin can enter from mother to fetus leading to agglutination of fetal RBC and hemolysis. Severe hemolysis in fetus causes jaundice. To compensate hemolysis more and more number of RBC are needed not only from bone marrow but also from liver and spleen. Now many large and immature proerythroblastic stage are released in circulation because of this only disease is called erythroblastosis fetalis. Ultimately due to excessive hemolysis anemia occurs and the infant dies because of severe anemia.

74. Erythroblastosis Fetalis

75. Donated blood should be used within 4 weeks 4 months 10 weeks 10 months Which blood group is called universal receiver A B AB O Universal donar is one who has blood group A B AB O

76. In blood group A there is: No antibodies, A&B antigen Anti-B antibody, A antigen Anti-A antibody, B antigen Anti-A & anti-B antibody, no antigen Donated blood is usually taken from Artery Vein Capillary artery and vein