1. Copyright 2010, John Wiley & Sons, Inc. Chapter 14 The Cardiovascular System: Blood

2. Copyright 2010, John Wiley & Sons, Inc. Functions Transportation: water, gases, nutrients, wastes, heat, etc. Regulation: pH, temperature, water balance Protection: blood clotting, defense:

3. Copyright 2010, John Wiley & Sons, Inc. Blood Volume Varies with Body size Changes in fluid concentration Changes in electrolyte concentration Amount of adipose tissue about 8% of body weight about 5 liters 14-3

4. Copyright 2010, John Wiley & Sons, Inc. Composition Plasma(~55%): soluble materials  mostly water; lighter so at top of tube Formed elements (~45%): cells  heavier so at bottom of tube  Mostly red blood cells (RBCs) Percent of blood RBCs = hematocrit (Hct) Normal hematocrit: 42-47%  Females: 38 to 46%; males: 40 to 54%  Buffy coat: white blood cells (WBCs) and platelets

5. Copyright 2010, John Wiley & Sons, Inc. Composition

6. Copyright 2010, John Wiley & Sons, Inc. Plasma: Liquid Portion of Blood Water: 91.5% Plasma proteins: 7%  Albumin:  Globulins:  Fibrinogen: Other: 1.5%  Electrolytes, nutrients, gases, hormones, vitamins, waste products

7. Copyright 2010, John Wiley & Sons, Inc. Plasma Proteins Albumins Most numerous Originate in liver Help maintain osmotic pressure of blood Fibrinogen Originate in liver Plays key role in blood coagulation Alpha and Beta Globulins Originate in liver Transport lipids and fat- soluble vitamins Gamma Globulins Originate in lymphatic tissues Constitute the antibodies of immunity 14-22

8. Copyright 2010, John Wiley & Sons, Inc. Plasma Lipoproteins Chylomicrons High concentration of triglycerides Transport dietary fats to muscles and adipose cells HDLs Relatively high concentration of proteins Transport remnants of chylomicrons to liver LDLs Relatively high concentration of cholesterol Formed from VLDLs Deliver cholesterol to various cells VLDLs Relatively high concentration of triglycerides Produced in the liver Transport triglycerides from liver to adipose cells 14-24

9. Copyright 2010, John Wiley & Sons, Inc. Gases and Nutrients Gases Oxygen Carbon dioxide Nitrogen Nutrients Amino acids Simple sugars Nucleotides Lipids Lipoproteins 14-23

10. Copyright 2010, John Wiley & Sons, Inc. Nonprotein Nitrogenous Substances Urea – product of protein catabolism; about 50% Uric acid – product of nucleic acid catabolism Amino acids – product of protein catabolism Creatine – stores phosphates Creatinine – product of creatine metabolism BUN – blood urea nitrogen; indicate health of kidney 14-25

11. Copyright 2010, John Wiley & Sons, Inc. Plasma Electrolytes Sodium – most abundant Potassium – most abundant Calcium Magnesium Chloride Bicarbonate Phosphate Sulfate 14-26

12. Copyright 2010, John Wiley & Sons, Inc. Formed Elements I. Red Blood Cells (RBCs) II. White blood cells (WBCs) A.Granular leukocytes 1.Neutrophils 2.Eosinophils 3.Basophils B.Agranular leukocytes 1.Lymphocytes and natural killer (NK) cells 2.Monocytes III Platelets

13. Copyright 2010, John Wiley & Sons, Inc. Formation of Blood Cells Called hemopoiesis or hematopoiesis Occurs throughout life  Specific hormones  stem cells  form blood cells Pluripotent stem cells in red marrow  Lymphoid stem cells  lymphocytes (in lymphatic tissues)  Myeloid stem cells  all other WBCs, all RBCs, and platelets

14. Copyright 2010, John Wiley & Sons, Inc. Formation of Blood Cells

15. Copyright 2010, John Wiley & Sons, Inc. Formation of Blood Cells

16. Copyright 2010, John Wiley & Sons, Inc. Erythrocytes (RBCs) Hemoglobin (red pigment)  Carries 98.5% of O 2 and 23% of CO 2 RBC count: about 5 million/µl  Male: 5.4 million cells/µl; female: 4.8 million/µl Structure of mature RBC  No nucleus/DNA Biconcave disc shape with extensive plasma membrane Maximal gas exchange Flexible for passing through capillaries RBCs live only 3 to 4 mos

17. Copyright 2010, John Wiley & Sons, Inc. Red Blood Cells 14-6

18. Copyright 2010, John Wiley & Sons, Inc. RBC Synthesis: Erythropoiesis Stimulus - low O 2 delivery (hypoxia) in blood passing to kidneys  Kidneys release erythropoietin (EPO)  Stimulates erythropoiesis in red marrow  Increased O 2 delivery in blood (negative feedback mechanism)

19. Copyright 2010, John Wiley & Sons, Inc. RBC Synthesis: Erythropoiesis Cells lose nucleus; then released into bloodstream as reticulocytes  Develop into erythrocytes after 1-2 days in bloodstream  High reticulocyte count - Indicates high rate of RBC formation

20. Copyright 2010, John Wiley & Sons, Inc. Red Blood Cell Production 14-8

21. Copyright 2010, John Wiley & Sons, Inc. RBC Synthesis: Erythropoiesis Lower-than-normal RBC count  changes in skin, mucous membranes, & finger nail beds  Cyanosis: bluish color  Anemia: pale color

22. Copyright 2010, John Wiley & Sons, Inc. RBC Recycling Cleared by macrophages (liver and spleen) Recycled components  Globin  amino acids recycled to form proteins  Heme broken down into: Fe  Carried in blood by transferrin  Recycled in bone marrow; proteins and vitamin B 12 required also Non-Fe portion of heme  biliverdin  bilirubin  Bilirubin to liver  bile  helps absorb fats  Intestinal bacteria convert bilirubin into other chemicals that exit in feces (stercobilin) or urine (urobilin)

23. Copyright 2010, John Wiley & Sons, Inc. Life Cycle of Red Blood Cell 14-9

24. Copyright 2010, John Wiley & Sons, Inc. Red blood cell death and phagocytosis Key: in blood in bile Macrophage in spleen, liver, or red bone marrow 1 Globin Red blood cell death and phagocytosis Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Heme 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Heme 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Heme 4 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Liver Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Ferritin Heme 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Ferritin Heme 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Ferritin Heme Fe 3+ 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Circulation for about 120 days Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Fe 3+ 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Circulation for about 120 days Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Biliverdin Bilirubin Fe 3+ 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Circulation for about 120 days Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Biliverdin Bilirubin Fe 3+ 10 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Stercobilin Bilirubin Urobilinogen Feces Small intestine Circulation for about 120 days Bacteria Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Biliverdin Bilirubin Fe 3+ 12 11 10 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Urine Stercobilin Bilirubin Urobilinogen Feces Small intestine Circulation for about 120 days Bacteria Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Kidney Macrophage in spleen, liver, or red bone marrow Ferritin Urobilin Heme Biliverdin Bilirubin Fe 3+ 13 12 11 10 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Urine Stercobilin Bilirubin Urobilinogen Feces Large intestine Small intestine Circulation for about 120 days Bacteria Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Kidney Macrophage in spleen, liver, or red bone marrow Ferritin Urobilin Heme Biliverdin Bilirubin Fe 3+ 14 13 12 11 10 9 8 7 6 5 4 3 2 1 Formation and Destruction of RBC’s

25. Copyright 2010, John Wiley & Sons, Inc. Regulation of Erythropoiesis

26. Copyright 2010, John Wiley & Sons, Inc. Types of Anemia Aplastic anemia Bone marrow damaged Toxic chemicals Radiation Iron deficiency anemia Hemoglobin deficient Lack of iron Pernicious anemia Excess of immature RBCs Inability to absorb B 12 Sickle cell anemia Abnormal shape of RBCs Defective gene Thalassemia Hemoglobin deficient RBCs short-lived Defective gene 14-10

27. Copyright 2010, John Wiley & Sons, Inc. Hemolytic Anemia 14-11 RBCs destroyed Toxic chemicals

28. Copyright 2010, John Wiley & Sons, Inc. White Blood Cells (WBCs or Leukocytes) Appear white  lack hemoglobin Normal WBC count: 5,000-10,000/µl  usually increases in infection Two major classes - presence or absence of granules (vesicles)  Granular: Neutrophils usually make up 2/3 of all WBCs  Agranular: Major function: defense against  Infection and inflammation  Antigen-antibody (allergic) reactions

29. Copyright 2010, John Wiley & Sons, Inc. Neutrophils First responders to infection Phagocytosis Release bacteria-destroying enzyme - lysozyme light blue granules in acid-base stain lobed nucleus elevated in bacterial infections 14-13

30. Copyright 2010, John Wiley & Sons, Inc. Basophils Intensify inflammatory responses and allergic reactions Release chemicals that dilate blood vessels: histamine and serotonin heparin (anticoagulant) deep blue granules in basic stain 14-14

31. Copyright 2010, John Wiley & Sons, Inc. Eosinophils Phagocytose antibody-antigen complexes Help suppress inflammation of allergic reactions Respond to parasitic infections  deep red granules in acid stain bilobed nucleus 14-15

32. Copyright 2010, John Wiley & Sons, Inc. White Blood Cell Functions Lymphocytes About the size of RBC Large spherical nuclei - thin rims of cytoplasm  Three types T cells B cells Natural killer (NK) cells  Play major roles in immune responses B lymphocytes  foreign substances (antigens) cause cells to produce antibodies.  Antibodies attach to and inactivate the antigens. T lymphocytes directly attack microbes.

33. Copyright 2010, John Wiley & Sons, Inc. Lymphocytes 14-17

34. Copyright 2010, John Wiley & Sons, Inc. Monocytes Macrophages (“big eaters”)  Largest blood cell Kidney-shaped or oval nuclei 14-16

35. Copyright 2010, John Wiley & Sons, Inc. White Blood Cell Functions Major histocompatibility (MHC) antigens  Proteins on plasma membrane of WBCs (and most other body cells)  Called “self-identity markers” Unique for each person (except for identical twins) Used to “type tissues” to check for compatibility and reduce risk of rejection

36. Copyright 2010, John Wiley & Sons, Inc. WBC Life Span RBCs outnumber WBCs about 700:1 Life span: typically a few hours to days Abnormal WBC counts  Leukocytosis: high WBC count in response to infection, exercise, surgery  Leukopenia: low WBC count Differential WBC count: measures % of WBCs made up of each of the 5 types

37. Copyright 2010, John Wiley & Sons, Inc. Diapadesis Leukocytes squeeze through capillary walls to enter tissue space outside the blood vessel 14-18

38. Copyright 2010, John Wiley & Sons, Inc. Platelets Myeloid stem cells  megakaryocytes  2000–3000 fragments = platelets Normal count: 150,000-400,000/µl blood Functions  Plug damaged blood vessels  Promote blood clotting Life span 5–9 days

39. Copyright 2010, John Wiley & Sons, Inc. Hemostasis: “Blood Standing Still” 1.Vascular spasm - smooth muscle contracts  Response to damage  Triggered by pain receptors, platelet release, or serotonin  Quick reduction of blood loss 2.Platelet plug formation  Platelets become sticky when contact damaged vessel wall  Adhere to rough surface to form a plug  Triggered by exposure of platelets to collagen

40. Copyright 2010, John Wiley & Sons, Inc. Hemostasis: “Blood Standing Still” 3. Blood clotting (coagulation)  Series of chemical reactions involving clotting factors     triggered by cellular damage and blood contact with foreign surfaces

41. Copyright 2010, John Wiley & Sons, Inc. Blood Clotting (Coagulation) Extrinsic pathway  Tissue factor (TF) from damaged cells  Triggered by thromboplastin (not found in blood)  Triggered when blood contacts a foreign surface Intrinsic Pathway  Triggered by Hageman factor  Triggered when blood contacts damaged tissue

42. Copyright 2010, John Wiley & Sons, Inc. Blood Clotting (Coagulation) Common pathway: 3 major steps 1.Prothrombinase  (enzyme) 2.Prothrombin  thrombin 3.Fibrinogen  fibrin  clot Ca ++ plays important

43. Copyright 2010, John Wiley & Sons, Inc. Platelet Plug Formation 14-28

44. Copyright 2010, John Wiley & Sons, Inc. Blood Coagulation 14-29

45. Copyright 2010, John Wiley & Sons, Inc. Clot Retraction and Vessel Repair Clot plugs ruptured area Gradually contracts (retraction)  Pulls sides of wound together Repair  Fibroblasts replace connective tissue  Epithelial cells repair lining

46. Copyright 2010, John Wiley & Sons, Inc. Prevention of Coagulation The smooth lining of blood vessels discourages the accumulation of platelets As a clot forms, fibrin absorbs thrombin and prevents the reaction from spreading Antithrombin interferes with the action of excess thrombin 14-32

47. Copyright 2010, John Wiley & Sons, Inc. Hemostatic Control Mechanisms Fibrinolysis: breakdown of clots by plasmin  Inactivated plasminogen   Activated (by tPA)  plasmin Inappropriate (unneeded) clots  Thrombosis  Loose (on-the-move) clot = Embolism Anticoagulants: decrease clot formation  Heparin  Warfarin (Coumadin)

48. Copyright 2010, John Wiley & Sons, Inc. Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca 2+ Damaged platelets Ca 2+ Platelet phospholipids Activated X Activated platelets Activated X PROTHROMBINASE Ca 2+ V Prothrombin (II) Ca 2+ THROMBIN (c) Common pathway V 1 2 + + Stages of Clotting

49. Copyright 2010, John Wiley & Sons, Inc. Blood Groups and Blood Types RBCs have antigens (agglutinogens) Each blood group consists of two or more different blood types  There are > 24 blood groups Blood types determined by genetics

50. Copyright 2010, John Wiley & Sons, Inc. ABO Group Two types of antigens on RBCs: A or B  Type A has only A antigen  Type B has only B antigen  Type AB has both  Type O has neither Most common types in US: type O and A Typically blood has antibodies in plasma  React with antigens  Two types: anti-A antibody or anti-B  Blood lacks antibodies against own antigens Type A blood has anti-B (not anti-A) Type AB blood has neither anti-A nor anti-B

51. Copyright 2010, John Wiley & Sons, Inc. ABO Group

52. Copyright 2010, John Wiley & Sons, Inc. Rh Blood Group Rh: antigen found in rhesus monkey  If RBCs have Rh antigen: Rh +  If RBCs lack Rh antigen: Rh – Rh + blood type in 85-100% of U.S. population Normally neither Rh + nor Rh – has anti-Rh antibodies Antibodies develop in Rh - persons after first exposure to Rh + blood in transfusion (or pregnancy  hemolytic disease of newborn)

53. Copyright 2010, John Wiley & Sons, Inc. Transfusions If mismatched blood given, antibodies bind to antigens on RBCs  hemolyze RBCs Type AB called “universal recipients” Type O called “universal donors” Misleading because many other blood groups must also be matched

54. Copyright 2010, John Wiley & Sons, Inc. Agglutination 14-34

55. Copyright 2010, John Wiley & Sons, Inc. Clinical Application Leukemia Myeloid Leukemia bone marrow produces too many immature granulocytes leukemic cells crowd out other blood cells anemia bleeding susceptible to infections Lymphoid Leukemia lymphocytes are cancerous symptoms similar to myeloid leukemia Treatments blood transfusions marrow transplants anti-cancer drugs stem cell transplants 14-36