Study of Blood. 7/3/02 Mr. Davenport 1

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1 Study of Blood Copyright 1999, Stephen G. Davenport, No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form without prior written permission. 7/3/02 Mr. Davenport 1

2 Blood Functions Transports essential substances to cells gases, nutrients, hormones, electrolytes, etc Removes waste products of metabolism urea, creatinine, ammonium ions, etc. Protection against blood loss clotting Protection against toxins and pathogens white blood cells and antibodies Stabilization of ph (bicarbonate ions and buffer system) 7/3/02 Mr. Davenport 2

3 Location of Blood Blood is a vascular connective tissue which is located in the cardiovascular system. Cardiovascular: heart, arteries, arterioles, capillaries, venules, veins. Heart is a blood pump Arteries (and arterioles) carry blood away from heart Veins (and venules) carry blood toward the heart Capillaries are the sites of exchange Breaching the walls of the cardiovascular system results in a Bleed Hematoma (blood blister) blood accumulates in tissue space Contusion (bruise) does not disrupt integrity of skin with characteristic discoloration, swelling, and pain. 7/3/02 Mr. Davenport 3

4 Composition of Blood 46-63% plasma and 37-54% formed elements Plasma is the fluid component of blood serum is fluid of blood after removal of clotting proteins (coagulation) Formed elements include red blood cells (RBCs), erythrocytes white blood cells (WBCs), leukocytes platelets A ph of Volume in one s body my change: Hypovolemic (hemorrhage, dehydration) Hypervolemic (polycythemia, overhydration) Normovolemic 7/3/02 Mr. Davenport 4

5 Plasma 92% water 7% proteins 1% other solutes 7/3/02 Mr. Davenport 5

6 Plasma Proteins -7% Plasma proteins; normally remain in vessel albumins 60% of plasma proteins which contribute to osmotic pressure and serve as transport proteins for lipids (fatty acids) and some steroid hormones, etc. globulins 35% of plasma proteins which include immunoglobulins (antibodies) and transport globulins fibrinogen 4% of plasma protein which functions in blood clotting hormones less than 1% which include insulin, TSH, FSH, etc. Liver synthesizes 90% of plasma proteins (all albumins, fibrinogen, and most globulins (additional globulins are produced by leukocytes called plasma cells 7/3/02 Mr. Davenport 6

7 Other Plasma Solutes 1% Electrolytes contribute to osmotic pressure of fluids electrical activity, muscle contraction, etc. Organic nutrients mostly nutrients picked up by digestive system or synthesized (packaged) by liver. Include lipids, carbohydrates, and amino acids. Used for ATP production, cell growth and maintenance Organic wastes urea, creatinine, bilirubin, ammonium ions, etc. 7/3/02 Mr. Davenport 7

8 Formed Elements Hemopoiesis produces the formed elements Hemocytoblasts produce both myeloid and lymphoid stem cells myeloid stem cells produce RBCs and platelets in adult located in red bone marrow lymphoid stem cells produce WBCs in adult in red bone marrow and lymphoid tissue 7/3/02 Mr. Davenport 8

9 Red Blood Cells Described as anucleate, biconcave discs, containing mostly hemoglobin which binds and transports both oxygen and carbon dioxide. Account for 99% of the formed elements Male has million RBCs microliter Female has million RBCs microliter 7/3/02 Mr. Davenport 9

10 Hematocrit Hematocrit is % volume of packed red blood cells male 40-54% (average 47%) female 37-47% (average 42%) Used as an indicator of blood dysfunction as it does not specifically identify why RBC % volume is not normal 7/3/02 Mr. Davenport 10

11 Hematocrit Determination Determination in lab is by centrifugation of a volume of blood. Then to determine % RBC volume divide volume of RBCs by total blood volume and multiply by 100 for percentage. RBC volume is 32 mm Total volume is 69 mm 32 divided by 69 =.46 x 100 = 46% 7/3/02 Mr. Davenport 11

12 FACTORS AFFECTING HEMATOCRIT Anemia is the lowered ability of blood to deliver oxygen and may be due to reduction in the number of RBC or quantity of hemoglobin Hemolytic anemia is due to RBCs having a short survival period and marrow can not keep pace Aplastic anemia is due to failure of bone marrow Polycythemia is an increase in the number of RBCs Dehydration loss of blood volume (hypovolumic) 7/3/02 Mr. Davenport 12

13 Hemoglobin (Hb) Accounts for over 95% of intracellular proteins Functions in transport of respiratory gases oxyhemoglobin (transports oxygen) carbaminohemoglobin (transports carbon dioxide) Quaternary shape -four polypeptide chains each with heme group (pigment complex containing iron ion) Binding of oxygen is weak and reversible 7/3/02 Mr. Davenport 13

14 Hemoglobin (Hb) 98.5% of oxygen is transported bound to Hb 1.5% remaining oxygen is carried dissolved in plasma 23% of carbon dioxide transported as carbaminohemoglobin Hb releases oxygen when plasma levels are low and binds carbon dioxide when its concentration is high (peripheral capillaries). This process is reversed in the lungs. 7/3/02 Mr. Davenport 14

15 Anemia the reduced ability to deliver oxygen Anemias may result from : abnormal hemoglobin decreased number of RBCs decreased hemoglobin 7/3/02 Mr. Davenport 15

16 Anemia (continued) Anemias due to abnormal hemoglobin Sickle cell anemia - due to abnormal hemoglobin (genetic) Thalassemia - due to inability to produce hemoglobin chains; thus, cells production is slow, cells are fragile and have short life span (genetic) 7/3/02 Mr. Davenport 16

17 Anemia (continued) Anemias due to decreased number of RBCs Hemolytic anemia- RBCs have short survival period and bone marrow can not compensate. May be caused by disease, genetic RBC disorders (such as sickle cell), toxins, drugs, mismatched blood. Aplastic anemia - failure of bone marrow. Hemorrhagic anemia - result from blood loss. 7/3/02 Mr. Davenport 17

18 Anemia (continued) Anemias due to decreased hemoglobin Iron deficiency anemia - decreased iron in diet or impairment of iron metabolism Pernicious anemia - due to deficiency of vitamin B12. Must have intrinsic factor, which is produced by the stomach, in order to absorbb12. If intrinsic factor is lacking then B12 can be administered by intramuscular injection. 7/3/02 Mr. Davenport 18

19 RBC Life Span Life span of about 120 days mostly due to mechanical stresses placed on cell. (Replacement rate is about 1% per day or about 3 million cells / second) Damaged or worn out RBC s are phagocytized in the liver, spleen and bone marrow. Amino acid portion of Hb is reduced to amino acids Heme portion is stripped of iron and is ultimately converted to bilirubin. Bilirubin released into blood and absorbed by hepatocytes. Jaundice - excessive amounts of and/or accumulation of bilirubin in body. Produces an yellow discoloration of skin, sclera, and mucous membranes. 7/3/02 Mr. Davenport 19

20 RBC Life Span (continued) Iron (removed from heme unit) is released into blood (or stored by phagocyte) and bonds to plasma protein called transferrin. Transferrin is picked up in bone marrow and iron is used for production of new RBCs picked up by liver and spleen and stored and bound to proteins (liver proteins - ferritin and hemosiderin) Iron deficiency anemia - decreased iron in diet or impairment of iron metabolism 7/3/02 Mr. Davenport 20

21 Erythropoiesis Erythropoiesis is the formation of RBC s and occurs in the red bone marrow (myeloid tissue) of the adult. (lymphoid tissue gives rise to lymphocytes) Series of divisions produces produces a precursor cell which sheds its nucleus and then develops into a reticulocyte. Reticulocytes still have some RNA and can be differentiated in lab. Normally comprise about 0.8% of erythrocyte population; thus, increases or decreases are used as a rough measure of erythropoiesis. 7/3/02 Mr. Davenport 21

22 Regulation of Erythropoiesis Required: amino acids, iron, vitamins (B12, B6, and folic acid) intrinsic factor produced by stomach mucosa erythropoietin - produced by kidney especially when blood oxygen levels are low (hypoxia). Hypoxia can be caused by Anemia Blood flow to kidneys declines High altitude Damage to respiratory membranes or failure to delivery oxygen to respiratory membranes 7/3/02 Mr. Davenport 22

23 Function of Erythropoietin Erythropoietin increases rate of cell division (erythroblasts) speeds rate of maturation by acceleration of hemoglobin synthesis (rate can be increased to 30 million cells /second, hematocrit can rise to + 65% ; thus straining the cardiovascular system) 7/3/02 Mr. Davenport 23

24 Blood Types - Antigens RBCs have surface antigens (agglutinogens) the presence or absence of which determines your blood type. Surface antigens are identified as A, B, and Rh (D). Cells may have either A or B -> (type A or type B) both A and B -> (type AB) neither A or B -> (type O) either have D (Rh) or lack D (Rh) -> (Rh + or -) 7/3/02 Mr. Davenport 24

25 Cell With Antigens A or B Cells may have either antigen A (Type A) -or antigen B (Type B) Type A Type B 7/3/02 Mr. Davenport 25

26 Cells With Antigens A and B Cells have both antigens A and B (type AB) Type AB 7/3/02 Mr. Davenport 26

27 Cells Without Antigens A and B Cells lack both antigens A and B (type O) Type O 7/3/02 Mr. Davenport 27

28 Antigen D Cells have antigen D (Rh pos) Cells lack antigen D (Rh neg) Rh positive Rh negative 7/3/02 Mr. Davenport 28

29 Blood Types - Antibodies Protein molecules (agglutinins) found in the plasma which clump (agglutinate) with like designated antigens. (Immunoglobulin produced by lymphocytes in response to a specific antigenic substance) Antibodies that are present in blood can not have same designation as antigen Blood type A has b antibodies Blood type B has a antibodies Blood type AB has neither a or b antibodies Blood type O has both a and b antibodies There are no preformed Rh antibodies 7/3/02 Mr. Davenport 29

30 Cells With Antibodies a or b Cells with antibodies a have antigen B Cells with antibodies b have antigen A Type B Type A 7/3/02 Mr. Davenport 30

31 Cells With Antibodies a and b Cells with antibodies a and b have neither antigens A or B Type O 7/3/02 Mr. Davenport 31

32 Cells Without Antibodies a and b Cells without antibodies a and b have both antigens A and B Type AB 7/3/02 Mr. Davenport 32

33 Rh Antibodies No preformed antibodies Rh positive Rh negative 7/3/02 Mr. Davenport 33

34 Blood Cross-Reactions Cross-reactions occur when like designated antigen meets with its antibody. Result is agglutination and cell lysis. Donors blood must have the same antigens as recipient (example type A to type A) the blood donor should NOT have antigen/s which will cross-react with recipients antibodies (example type O to type A) 7/3/02 Mr. Davenport 34

35 Agglutination Agglutination occurs when like designated antigen meets with its antibody. RBCs can lyse and blood blood vessels (especially capillaries) 7/3/02 Mr. Davenport 35

36 Cross-Reactionstype A and type B Type A Type B Type A blood and type B blood cross-react and result in agglutination (between like antigens and antibodies) blood donor should NOT have antigen/s which will cross-react with recipients antibodies 7/3/02 Mr. Davenport 36

37 Cross-Reactionstype O to type A Type O Type A Type O blood given to type A blood cross-react between like antibodies and antigens (however, antibody level (titer) is low and degree of agglutination is insignificant. blood donor should NOT have antigen/s which will cross-react with recipients antibodies 7/3/02 Mr. Davenport 37

38 Cross-Reactionstype A to type AB Type A Type AB Type A blood given to type AB blood cross-react between like antibodies and antigens (however, antibody titer is low and degree of agglutination is insignificant. blood donor should NOT have antigen/s which will cross-react with recipients antibodies 7/3/02 Mr. Davenport 38

39 Laboratory Blood Typing (based upon cross-reactions) Type A Type B Type AB Type O 7/3/02 Mr. Davenport 39

40 Transfusions Considering only the ABO Group then: Type O negative is the universal donor Type AB positive is the universal recipient A donates to A, AB and receives A and O B donates to B, AB and receives B and O AB donates to AB and receives AB, A, B, O O donates to O, A, B, AB and receives O Should Rh factor be considered? 7/3/02 Mr. Davenport 40

41 Rh Antibodies No preformed antibodies Rh positive Rh negative 7/3/02 Mr. Davenport 41

42 Formed Rh Antibodies Rh positive Rh negative NEXT EXPOSURE to Rh positive blood Rh negative produces (immune response) Rh antibodies Agglutination Rh positive Rh negative with Rh antibodies 7/3/02 Mr. Davenport 42

43 Formed Rh Antibodies Rh antibodies can be produced if a Rh negative person is exposed to Rh positive blood. In this case Rh antigens promote immune response and antibody is produced. The next exposure to Rh positive blood produces agglutination. 7/3/02 Mr. Davenport 43

44 Hemolytic Disease Hemolytic disease of the newborn (HDN) may result when mother is Rh negative and baby is Rh positive. RhoGam (anti-rh antibodes) destroy fetal blood that passes placenta and mixes into mother s blood. 7/3/02 Mr. Davenport 44

45 Laboratory Blood Typing (based upon cross-reactions) Blood should be typed for at least the ABO and Rh groups. There are at least 30 common varieties of surface antigens Taking into account both ABO and Rh groups universal donor is O negative universal recipient is AB positive Type AB negative 7/3/02 Mr. Davenport 45

46 White Blood Cells (Leukocytes) Defend against pathogens, remove toxins, phagocytosis, release chemical mediators, etc Divided into two groups (based on staining characteristics) granularinclude neutrophils, eosinophils, basophils agranularinclude lymphocytes and monocytes 6,000-9,000 per cubic microliter Mostly located outside of circulation in connective tissue and lymphatic organs 7/3/02 Mr. Davenport 46

47 WBC production Leukopoiesis - production of WBCs and is mostly hormonally stimulated Cytokines are chemical mediators of cellular immunity and include Interleukins released by macrophages promotes activated T cells to divide (positive feedback) Colony-stimulating factors; promote the production of specific lines (granulocytes-csf promotes granulocytes) production mostly by macrophages and T lymphocytes Thymosins promote T cell production 7/3/02 Mr. Davenport 47

48 WBC Disorders Leukopenia is low WBC count Common causes drugs such as glucocorticoids and for anticancer treatment. Leukocytosis is excessive numbers of WBCs typically due to infections or leukemia 7/3/02 Mr. Davenport 48

49 WBC Disorders Leukemias are cancerous conditions of WBCs suppress or impair normal bone marrow function acuteleukemias are rapid to advance chronic leukemias are slow to advance named according to abnormal type of cell lymphocytic involves lymphocytes, myelocytic involves myeloblasts, etc. Mononucleosis results from virus (Epstein-Barr virus) characterized by excessive number of atypical agranulocytes 7/3/02 Mr. Davenport 49

50 WBC Characteristics Amoeboid movement allows movement in tissues Diapedesis movement through blood vessels Positive chemotaxis toward damaged tissues, pathogens, active WBCx Phagocytosis Monocytes; macrophages in tissues Neutrophils and eosinophils; microphages in tissues 7/3/02 Mr. Davenport 50

51 WBC General Functions Nonspecific defenses defense against a wide variety of pathogens neutrophils, eosinophils, basophils, and monocytes Specific defenses- immunity defense against a specific antigen (antigenic response) Lymphocytes T lymphocytes responsible for cell to cell interactions B lymphocytes responsible for production of antibodies 7/3/02 Mr. Davenport 51

52 Neutrophils Also called polymorphonuclear (PMNs) Highly mobile, first to arrive Phagocytosis of cells (pathogens) marked with antibody or complement Release cytotoxic chemicals and enzymes Average 50-70% in differential count 7/3/02 Mr. Davenport 52

53 Eosinophils Phagocytic of antibody marked cells Release of cytotoxic chemicals Increase due to allergies and certain parasites Average 2-4 % in a differential count 7/3/02 Mr. Davenport 53

54 Basophils Promote inflammation Release histamine and heparin Average 1% or less in a differential count 7/3/02 Mr. Davenport 54

55 Monocytes Phagocytes in tissues known as macrophages Release chemicals that attract fibrocytes and other WBCs Average 2-8% in a differential count 7/3/02 Mr. Davenport 55

56 Lymphocytes T cells responsible for cellular immunity B cells responsible for humoral immunity (develop into plasma cells) Average % in a differential count 7/3/02 Mr. Davenport 56

57 Platelets Cell fragments from a precursor cell 150, ,00 per microliter Functions include initiation and control of clotting process physically clump to form a platelet plug active contraction after formation of plug reduces site of injury and further slows blood loss 7/3/02 Mr. Davenport 57

58 Hemostasis Hemostasis is the prevention of blood loss Vascular phase results in local vascular spasm Platelet phase occurs as platelets stick together to form a platelet plug Coagulation phase (blood clotting) leads to conversion of fibrinogen to fibrin resulting in a blood clot. Plasma must contain clotting factors which include calcium and 11 proteins. (Most (9) of these proteins originate from liver and some (4) require vitamin K for their production.) 7/3/02 Mr. Davenport 58

59 Hemostasis Clot retraction (by action of platelets) occurs after additional platelets and RBCs stick to fibrin threads Fibrinolysis results in the breakdown of fibrin (clot) by enzyme called plasmin. Occurs by the activation of the blood protein plasminogen which was incorporated into the forming clot. (Local signals such as chemicals produced by healing endothelial cells called tissue plasminogen activator trigger the start of fibrinolysis). 7/3/02 Mr. Davenport 59