1. Cardiovascular System
Blood
Cardiovascular System

2. Blood Functions 1. Transports Dissolved gasses Nutrients
Waste products to lungs and kidneys
Enzymes
Hormones from endocrine organs
2. Regulates pH
Electrolyte concentration of body fluids
Body temperature
3. Restricts fluid loss
4. Defends pathogens and toxins

4. Blood Composition 1. Formed elements 2. Plasma Erythrocytes Leukocytes
Platelets
2. Plasma

6. Overview of Blood Circulation
Blood leaves the heart via arteries that branch repeatedly until they become capillaries
• Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues
• Carbon dioxide (CO2) and wastes move from tissues into the blood
• Oxygen-deficient blood leaves the capillaries and flows in veins to the heart
• This blood flows to the lungs where it releases CO2 and picks up O2
•      The oxygen-rich blood returns to the heart

7. Blood Physical Characteristics and Volume
Sticky, opaque fluid with a metallic taste
•  Color varies from scarlet (oxygen-rich) to dark red (oxygen-poor)
•  pH of blood is 7.35–7.45
•  Temperature is 38C, slightly higher than “normal” body temperature
•   Blood accounts for approximately 8% of body weight
•   Average volume of blood is 5–6 L for males, and 4–5 L for females

8. Plasma Plasma accounts for 55 % of the volume of whole blood.
92% of plasma is water, the rest consists of electrolytes and dissolved organic compounds.
Blood plasma contains over 100 solutes, including:
•    Proteins – albumin, globulins, clotting proteins, etc…
•    Non-protein nitrogenous substances – lactic acid, urea, creatinine
•    Organic nutrients – glucose, carbohydrates, amino acids
•    Electrolytes – sodium (Na+), potassium (K+), calcium (Ca++), chloride (Cl-), bicarbonate (HCO3-)
•    Respiratory gases – oxygen and carbon dioxide

9. Plasma Proteins Albumin
1. Contributes to the osmotic pressure of the blood
2. Provides a transport mechanism for specific insoluble or valuable materials in the blood.
Globular proteins
Binding and transporting hormones, lipids (lipoproteins), and metal ions.
The immunoglobulins (antibodies) are proteins that attack foreign proteins and pathogens.
Fibrinogen molecules aggregate to form large insoluble strands of fibrin that establish the basis for a blood clot.

10. Erythrocytes Biconcave discs
RBCs have no nuclei or organelles (anucleate) allow for a huge surface area to volume ratio
Hematocrit – % of RBCs out of the total blood volume. (Ave) 46 adult men & 42 adult women.
There are roughly 5 million RBCs in each microliter of blood
Erythrocytes are unable to perform normal maintenance operations and usually degenerate after about 120 days in the circulation.

12. Hemoglobin
Hemoglobin (Hgb), a globular protein formed from four subunits.
Heme molecules bind to oxygen when plasma concentrations are high; the oxygen is released when plasma concentrations decline.
Carbon dioxide molecules can be bound to the globin portion of the hemoglobin molecule.

14. Hemoglobin Composed of:
•  The protein globin, made up of two alpha and two beta chains, each bound to a heme group
•  Each heme group bears an atom of iron, which can bind one to oxygen molecule
•  Each hemoglobin molecule can transport four molecules of oxygen
Oxyhemoglobin – hemoglobin bound to oxygen
•    Oxygen loading takes place in the lungs
Deoxyhemoglobin- hemoglobin after oxygen diffuses into tissues (reduced Hgb)
Carboxyhemoglobin – hemoglobin bound to carbon dioxide
•    Carbon dioxide loading takes place in the tissues
•  The fetus forms HbF, which has a higher affinity for oxygen than adult hemoglobin

15. What happens to old RBC’S?
Damaged or expired red blood cells are recycled by phagocytes.
Proteins are disassembled into amino acids
Iron gets bound to transferrin for transport to the bone marrow and liver
Heme units are not recycled, but removed from the circulation by the liver

16. Fate and Destruction of Erythrocytes
The life span of an erythrocyte is 100–120 days
Dying erythrocytes are engulfed by macrophages
Heme & globin are separated and the iron is salvaged for reuse
Fate of Hemoglobin
Heme is degraded to a yellow pigment called bilirubin
The liver secretes bilirubin into the intestines as bile
The intestines metabolize it into urobilinogen
This degraded pigment leaves the body in feces, in a pigment called stercobilin or as urobilinogen in urine
Globin is metabolized into amino acids and is released into the circulation

17. Iron transport

18. Blood Types
Agglutinogens A, B, and D (Rh) on the exposed surfaces of the red blood cells determine an individual's blood type.
Anti-Rh agglutinins are only synthesized after an Rh-negative individual becomes sensitized to the Rh agglutinogen. (During pregnancy)
Testing for compatibility involves the determination of blood type and a cross-match test.
Standard blood typing detects the A, B, and D (Rh) agglutinogens. The most common blood type used for transfusion is O-negative (universal donor – NO ANTIGENS). AB-positive (Universal recipient – NO ANTIBODIES)

19. Blood Type
Rh Type
Percent A +
34 % -
6 % B
9 %
2 % AB
3 %
1 % O
38 %
7 %

21. Erythroblastosis Fetalis

22. Hemolytic Disease of the Newborn (Erythroblastosis fetalis)
Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby
Rh– mother become sensitized when Rh+ blood (from a previous pregnancy of an Rh+ baby or a Rh+ transfusion) causes her body to synthesis Rh+ antibodies
The drug RhoGAM can prevent the Rh– mother from becoming sensitized

23. Production of Blood Cells
Hematopoiesis – blood cell formation
Hematopoiesis occurs in the red bone marrow of the:
- Axial skeleton and girdles
- Epiphyses of the humerus and femur
   
Hemocytoblasts give rise to all formed elements
Circulating stem cells give rise to embryonic blood cells which migrate into the liver, spleen, thymus, and bone marrow.

25. Erythropoiesis
Occurs within red marrow of the sternum, vertebrae, skull, scapulae, pelvis, and proximal limb bones.
Red blood cell formation increases under erythropoietin stimulation. This hormone is released from the kidneys when they are not receiving adequate supplies of oxygen.
Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins
Reticulocytes (immature RBC’s) usually account for 0.8 percent of circulating red blood cells.

27. Erythropoietin
Erythropoietin (EPO) release by the kidneys is triggered by: • Hypoxia due to decreased RBCs • Decreased oxygen availability • Increased tissue demand for oxygen Erythropoiesis increases the: • RBC count in circulating blood • Oxygen carrying ability of the blood increases

29. Erythropoiesis requirement
Proteins, lipids, and carbohydrates
Iron, vitamin B12, and folic acid
The body stores iron in Hgb (65%), the liver, spleen, and bone marrow
Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin
Circulating iron is loosely bound to the transport protein transferrin

30. Erythrocyte pathophysiology
Anemia – blood has abnormally low oxygen-carrying capacity
• Blood oxygen levels cannot support normal metabolism
• Signs/symptoms include fatigue, paleness, shortness of breath, increased heartrate, low blood pressure, and chills

31. Anemia: Insufficient Erythrocytes
Hemorrhagic anemia
– result of acute or chronic loss of blood (e.g.Trauma & Menstruation)
Hemolytic anemia
– prematurely ruptured erythrocytes
Aplastic anemia
– destruction or inhibition of red bone marrow
Sickle cell anemia

34. Anemia: Decreased Hemoglobin Content
Iron-deficiency anemia results from:
A secondary result of hemorrhagic anemia
Inadequate intake of iron-containing foods
Impaired iron absorption
Pernicious anemia results from:
Deficiency of vitamin B12
Often caused by lack of intrinsic factor needed for absorption of B12

35. Pernicious Anemia

36. Anemia: Abnormal Hemoglobin
Thalassemias – absent or faulty globin chain in hemoglobin
•    Erythrocytes are thin, delicate, & deficient in hemoglobin
Sickle-cell anemia – results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (HbS)

39. Polycythemia Excess RBCs that increase blood viscosity
Blood doping in athletics

40. Leukocytes
White blood cells are components of the immune system that defends the body against pathogens, toxins, wastes, and abnormal or damaged cells and tissues.
There are 6,000-9,000 white blood cells in each microliter of whole blood

42. Leukocytes Normal response to bacterial or viral invasion
Move through tissue spaces
Granular leukocytes include neutrophils, eosinophils , and basophils.
Neutrophils are abundant, highly mobile phagocytes.
Eosinophils are attracted to foreign compounds coated with antibodies.
Basophils migrate into damaged tissues and release histamine, aiding in the inflammation response.
Monocytes migrating into peripheral tissues become free macrophages.
Lymphocytes, cells of the lymphatic system, include T cells and B cells. T cells migrate to peripheral tissues and attack foreign or abnormal cells; B cells produce antibodies.

44. Leukopoiesis
Granulocytes and monocytes are produced by stem cells in the bone marrow
Lymphocytes are produced in bone marrow, thymus, & spleen

47. Which WBC’s are granulocytes?

48. Neutrophils (Polymorphonuclear)
60-70% of WBC’s
Neutrophils have two types of granules that:
•    Take up both acidic and basic dyes
•    Give the cytoplasm a lilac color
•    Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins)
Neutrophils are our body’s bacterial slayers
Lifespan : 1 day in blood; 1-2 days in tissue

49. Eosinophils 1-4% of WBC’s
Have red-staining, bi-lobed nuclei connected via a broad band of nuclear material
Lead the body’s counterattack against parasitic worms
Lessen the severity of allergies by phagocytizing immune complexes
Lifespan: 1 day in blood; weeks in tissue

50. Basophils
0.5-1% of WBC’s
Have large, purplish-black (basophilic) granules that contain histamine
Histamine – inflammatory chemical that acts as a vasodilator & attracts other WBCs
Lifespan: 1 day in blood; hours in tissue

51. Which WBC’s are agranulocytes?

52. Lymphocytes 20-25% of WBC’s
Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm
Found mostly enmeshed in lymphoid tissue (some circulate in the blood)
There are two types of lymphocytes: T cells and B cells
T cells function in the immune response
B cells give rise to plasma cells, which produce antibodies
Lifespan: Years

53. Monocytes 3-8% of WBC’s They are the largest leukocytes
They have abundant pale-blue cytoplasms
They have purple staining, U- or kidney-shaped nuclei
They leave the circulation, enter tissue, and differentiate into macrophages
Lifespan: Days in blood; years in tissue

54. Leukocyte pathophysiology
Leukemia refer to cancerous conditions involving white blood cells
Immature white blood cells are found in the bloodstream in all leukemias
Bone marrow becomes totally occupied with cancerous leukocytes
The white blood cells produced, though numerous, are not functional
Death is caused by internal hemorrhage and overwhelming infections
Acute leukemia involves blast-type cells and primarily affects children
Chronic leukemia is more prevalent in older people

55. Leukemia Common symptoms of leukemia: Anemia Fever
Weakness and fatigue
Frequent infections
Loss of appetite and/or weight
Swollen or tender lymph nodes, liver, or spleen
Easy bleeding or bruising
Tiny red spots (called petechiae) under the skin
Swollen or bleeding gums
Sweating, especially at night
Bone or joint pain.

56. Thrombocytes Platelets
Megakaryocytes in the bone marrow release packets of cytoplasm, called platelets, into the circulating blood. There are 150, ,000 platelets in each microliter of whole blood.
Platelet granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF)
Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels

58. Blood clotting Cascade

60. Blood clotting
The coagulation process requires calcium ions, and Vitamin K must be available for the synthesis of five of the clotting factors.

61. Hemostasis Pathophysiology
Thromboembolytic Disorders
Thrombus – a clot that develops and persist in an unbroken blood vessel
Embolus – a thrombus freely floating in the blood stream
Thrombocytopenia – condition where the number of circulating platelets is deficient
Hemophilias – hereditary bleeding disorders caused by lack of clotting factors

63. Hemophilia
Hemophilia A – most common type (83% of all cases) due to a deficiency of factor VIII
•    Hemophilia B – results from a deficiency of factor IX
•    Hemophilia C – mild type, caused by a deficiency of factor XI
•   Symptoms include prolonged bleeding and painful and disabled joints
• Treatment is with blood transfusions and the injection of missing factors

64. Hemophilia after injection

66. Prevention of undesirable clots
Substances used to prevent undesirable clots include: • Aspirin • Heparin • Warfarin (Coumadin) • Flavonoids – substances found in tea, red wine, and grape juice that have natural anticoagulant activity

68. Differential Practice
Leukocyte
Differential
Practice

74. Are we done yet?