1. The Cardiovascular System: Blood and Sheep’s Heart

2. Blood Liquid connective tissue 3 general functions 1. Transportation Gases, nutrients, hormones, waste products 2. Regulation pH, body temperature, osmotic pressure 3. Protection Clotting, white blood cells, proteins

3. Components of Blood  Blood plasma – water liquid extracellular matrix 91.5% water, 8.5% solutes (primarily proteins) Hepatocytes synthesize most plasma proteins  Albumins, fibrinogen, antibodies Other solutes include electrolytes, nutrients, enzymes, hormones, gases and waste products  Formed elements – cells and cell fragments Red blood cells (RBCs) White blood cells (WBCs) Platelets

5. Formed Elements of Blood

6. Formation of Blood Cells Negative feedback systems regulate the total number of RBCs and platelets in circulation Abundance of WBC types based of response to invading pathogens or foreign antigens Hemopoiesis or hemotopoiesis Red bone marrow primary site Pluripotent stem cells have the ability to develop into many different types of cells

8. Formation of Blood Cells Stem cells in bone marrow  Reproduce themselves  Proliferate and differentiate Cells enter blood stream through sinusoids Formed elements do not divide once they leave red bone marrow  Exception is lymphocytes

9. Formation of Blood Cells Pluripotent stem cells produce  Myeloid stem cells Give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils  Lymphoid stem cells give rise to Lymphocytes Hemopoietic growth factors regulate differentiation and proliferation  Erythropoietin – RBCs  Thrombopoietin – platelets  Colony-stimulating factors (CSFs) and interleukins – WBCs

10. Red Blood Cells/ Erythrocytes Contain oxygen-carrying protein hemoglobin Production = destruction with at least 2 million new RBCs per second Biconcave disc – increases surface area Strong, flexible plasma membrane Glycolipids in plasma membrane responsible for ABO and Rh blood groups Lack nucleus and other organelles  No mitochondria – doesn’t use oxygen

11. Hemoglobin  Globin – 4 polypeptide chains  Heme in each of 4 chains  Iron ion can combine reversibly with one oxygen molecule  Also transports 23% of total carbon dioxide Combines with amino acids of globin  Nitric oxide (NO) binds to hemoglobin Releases NO causing vasodilation to improve blood flow and oxygen delivery

12. Shapes of RBC and Hemoglobin

13. Red Blood Cells RBC life cycle  Live only about 120 days  Cannot synthesize new components – no nucleus  Ruptured red blood cells removed from circulation and destroyed by fixed phagocytic macrophages in spleen and liver  Breakdown products recycled Globin’s amino acids reused Iron reused Non-iron heme ends as yellow pigment urobilin in urine or brown pigment stercobilin in feces

14. Formation and Destruction of RBC’s

15. 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

16. Erythropoiesis  Starts in red bone marrow with proerythroblast  Cell near the end of development ejects nucleus and becomes a reticulocyte  Develop into mature RBC within 1-2 days  Negative feedback balances production with destruction  Controlled condition is amount of oxygen delivery to tissues  Hypoxia stimulates release of erythropoietin

17. White Blood Cells/ Leukocytes Have nuclei Do not contain hemoglobin Granular or agranular based on staining highlighting large conspicuous granules Granular leukocytes  Neutrophils, eosinophils, basophils Agranular leukocytes  Lymphocytes and monocytes

18. Types of White Blood Cells

19. Functions of WBCs  Usually live a few days  Except for lymphocytes – live for months or years  Far less numerous than RBCs  Leukocytosis is a normal protective response to invaders, strenuous exercise, anesthesia and surgery  Leukopenia is never beneficial  General function to combat invaders by phagocytosis or immune responses

20. Emigration of WBCs Many WBCs leave the bloodstream Emigration (formerly diapedesis) Roll along endothelium Stick to and then squeeze between endothelial cells Precise signals vary for different types of WBCs

21. WBCs Neutrophils and macrophages are active phagocytes  Attracted by chemotaxis Neutrophils respond most quickly to tissue damage by bacteria  Uses lysozymes, strong oxidants, defensins Monocytes take longer to arrive but arrive in larger numbers and destroy more microbes  Enlarge and differentiate into macrophages

22. WBCs Basophila leave capillaries and release granules containing heparin, histamine and serotonin, at sites of inflammation  Intensify inflammatory reaction  Involved in hypersensitivity reactions (allergies) Eosinophils leave capillaries and enter tissue fluid  Release histaminase, phagocytize antigen- antibody complexes and effective against certain parasitic worms

23. Lymphocytes Lymphocytes are the major soldiers of the immune system  B cells – destroying bacteria and inactivating their toxins  T cells – attack viruses, fungi, transplanted cells, cancer cells and some bacteria  Natural Killer (NK) cells – attack a wide variety of infectious microbes and certain tumor cells

24. Platelets/ Thrombocytes Myeloid stem cells develop eventually into a megakaryocyte Splinters into 2000-3000 fragments Each fragment enclosed in a piece of plasma membrane Disc-shaped with many vesicles but no nucleus Help stop blood loss by forming platelet plug Granules contain blood clot promoting chemicals Short life span – 5-9 days

25. Stem cell transplants Bone marrow transplant  Recipient's red bone marrow replaced entirely by healthy, noncancerous cells to establish normal blood cell counts  Takes 2-3 weeks to begin producing enough WBCs to fight off infections  Graft-versus-host-disease – transplanted red bone marrow may produce T cells that attack host tissues Cord-blood transplant  Stem cells obtained from umbilical cord shortly before birth  Easily collected and can be stored indefinitely  Less likely to cause graft-versus-host-disease

26. Hemostasis Sequence of responses that stops bleeding 3 mechanisms reduce blood loss 1. Vascular spasm  Smooth muscle in artery or arteriole walls contracts 2. Platelet plug formation  Platelets stick to parts of damaged blood vessel, become activated and accumulate large numbers 3. Blood clotting (coagulation)

27. Platelet Plug Formation

28. 1 Red blood cell Platelet Collagen fibers and damaged endothelium Platelet adhesion 1 1 2 Red blood cell Platelet Collagen fibers and damaged endothelium Liberated ADP, serotonin, and thromboxane A2 Platelet adhesion 1 Platelet release reaction 2 1 2 3 Red blood cell Platelet Collagen fibers and damaged endothelium Liberated ADP, serotonin, and thromboxane A2 Platelet plug Platelet adhesion 1 Platelet release reaction 2 Platelet aggregation 3

29. Blood Clotting 3. Blood clotting  Serum is blood plasma minus clotting proteins  Clotting – series of chemical reactions culminating in formation of fibrin threads  Clotting (coagulation) factors – Ca 2+, several inactive enzymes, various molecules associated with platelets or released by damaged tissues

30. 3 Stages of Clotting 1. Extrinsic or intrinsic pathways lead to formation of prothrombinase 2. Prothrombinase converts prothrombin into thrombin 3. Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot

31. 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 V 1 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 + + 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 Ca 2+ Loose fibrin threads STRENGTHENED FIBRIN THREADS Activated XIII Fibrinogen (I) XIII (c) Common pathway V 1 2 3 + +

32. Blood Clotting Extrinsic pathway  Fewer steps then intrinsic and occurs rapidly  Tissue factor (TF) or thromboplastin leaks into the blood from cells outside (extrinsic to) blood vessels and initiates formation of prothrombinase Intrinsic pathway  More complex and slower than extrinsic  Activators are either in direct contact with blood or contained within (intrinsic to) the blood  Outside tissue damage not needed  Also forms prothrombinase

33. Blood Clotting: Common pathway  Marked by formation of prothrombinase  Prothrombinase with Ca 2+ catalyzes conversion of prothrombin to thrombin  Thrombin with Ca 2+ converts soluble fibrinogen into insoluble fibrin  Thrombin has 2 positive feedback effects Accelerates formation of prothrombinase Thrombin activates platelets Clot formation remains localized because fibrin absorbs thrombin and clotting factor concentrations are low

34. Blood Groups and Blood Types Agglutinogens – surface of RBCs contain genetically determined assortment of antigens Blood group – based on presence or absence of various antigens At least 24 blood groups and more than 100 antigens  ABO and Rh

35. ABO Blood Group  Based on A and B antigens  Type A blood has only antigen A  Type B blood has only antigen B  Type AB blood has antigens A and B Universal recipients – neither anti-A or anti-B antibodies  Type O blood has neither antigen Universal donor  Reason for antibodies presence not clear

36. Antigens and Antibodies of ABO Blood Types

37. Hemolytic Disease Rh blood group  People whose RBCs have the Rh antigen are Rh +  People who lack the Rh antigen are Rh -  Normally, blood plasma does not contain anti-RH antibodies  Hemolytic disease of the newborn (HDN) – if blood from Rh + fetus contacts Rh - mother during birth, anti-Rh antibodies made Affect is on second Rh + baby

38. Typing Blood  Single drops of blood are mixed with different antisera  Agglutination with an antisera indicates the presence of that antigen on the RBC

39. The pump Cat heart showing pericardium

40. Structure of the Heart

41. Internal Anatomy of the Heart

42. Sheep heart external

43. Sheep’s heart internal

44. Features to focus on Be able to trace blood flow through the heart starting with the Superior Vena Cava Aorta Superior Vena Cava Pulmonary Trunk Right Atrium Fossa ovalis Right Ventricle Tricuspid valve Chordae tendineae Trabeculae carneae Pulmonary semilunar valves Left Atrium Mitral (bicuspid) valve Left Ventricle Papilary muscle Interventricular septum Exterior features Auricle Apex Coronary arteries and veins Coronary sinus SA node

45. Sheep’s heart internal cont’