1. The Cardiovascular System: Blood and Heart
Muse 2440
Winter lab #1
1/11/11

2. Blood Liquid connective tissue 3 general functions Transportation
Gases, nutrients, hormones, waste products
Regulation
pH, body temperature, osmotic pressure
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. Amino
acids
Reused for
protein synthesis
Globin
Circulation for about
120 days
Bilirubin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
Ferritin
Heme
Biliverdin 10 9 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
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
Ferritin
Heme
Biliverdin
Bilirubin 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
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
Ferritin
Heme
Biliverdin 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
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Kidney
Macrophage in
spleen, liver, or
Ferritin
Urobilin
Heme
Biliverdin 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
Circulation for about
120 days
Bacteria
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Kidney
Macrophage in
spleen, liver, or
Ferritin
Urobilin
Heme
Biliverdin 14 13 12 11 10 9 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
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
Ferritin
Heme 8 7 6 5 4 3 2 1
Amino
acids
Reused for
protein synthesis
Globin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Liver +
Vitamin B12
Erythopoietin
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme 7 6 5 4 3 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
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
Transferrin
Fe3+
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
Fe3+
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
Fe3+
Liver
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme 6 5 4 3 2 1
Red blood cell
death and
phagocytosis
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow 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. White Blood Cells WBC Disorders Leukopenia Leukocytosis Leukemia
Abnormally low WBC count
Leukocytosis
Abnormally high WBC count
Leukemia
Extremely high WBC count

25. Platelets/ Thrombocytes
Myeloid stem cells develop eventually into a megakaryocyte
Splinters into 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

26. Stem cell transplants Bone marrow transplant Cord-blood 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

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

28. Platelet Plug Formation

29. 1
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
Platelet adhesion 1 2
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
Liberated ADP,
serotonin, and
thromboxane A2
Platelet adhesion
Platelet release reaction 1 2 3
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
Liberated ADP,
serotonin, and
thromboxane A2
Platelet plug
Platelet adhesion
Platelet release reaction
Platelet aggregation

30. Blood Clotting Blood clotting
Serum is blood plasma minus clotting proteins
Clotting – series of chemical reactions culminating in formation of fibrin threads
Clotting (coagulation) factors – Ca2+, several inactive enzymes, various molecules associated with platelets or released by damaged tissues

31. 3 Stages of Clotting
Extrinsic or intrinsic pathways lead to formation of prothrombinase
Prothrombinase converts prothrombin into thrombin
Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot

32. PROTHROMBINASE 1 PROTHROMBINASE THROMBIN 1 2 + PROTHROMBINASE THROMBIN
Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway
(b) Intrinsic pathway
Activated XII
Ca2+
platelets
Platelet
phospholipids
Activated X
Activated
PROTHROMBINASE V 1
Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway
(b) Intrinsic pathway
Activated XII
Ca2+
platelets
Platelet
phospholipids
Activated X
Activated
PROTHROMBINASE V
Prothrombin
(II)
THROMBIN
(c) Common
pathway 1 2 +
Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway
(b) Intrinsic pathway
Activated XII
Ca2+
platelets
Platelet
phospholipids
Activated X
Activated
PROTHROMBINASE V
Prothrombin
(II)
THROMBIN
Loose fibrin
threads
STRENGTHENED
FIBRIN THREADS
Activated XIII
Fibrinogen
(I)
XIII
(c) Common
pathway 1 2 3 +

33. Blood Clotting Extrinsic pathway Intrinsic 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

34. Blood Clotting: Common pathway
Marked by formation of prothrombinase
Prothrombinase with Ca2+ catalyzes conversion of prothrombin to thrombin
Thrombin with Ca2+ 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

35. 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

36. 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

37. Antigens and Antibodies of ABO Blood Types

38. 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

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

40. The pump
Cat heart showing pericardium

41. Structure of the Heart

42. Internal Anatomy of the Heart

43. Sheep heart external

44. Sheep’s heart internal

45. 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

46. Sheep’s heart internal cont’

47. Review - Components of blood - cell types & roles of these
- recognition of wbcs
- blood typing (A,B,O and Rh systems)
- initial clot formation and platelets
- diseases of blood (anemia, leukemia, leukopenia)
- the heart - basic structure and blood flow.

48. White Blood Cells

49. White Blood Cells

50. White Blood Cells

51. White Blood Cells