1. Chapter 19: Blood Primary sources for figures and content:
Marieb, E. N. Human Anatomy & Physiology. 6th ed. San Francisco: Pearson Benjamin Cummings, 2004.
Martini, F. H. Fundamentals of Anatomy & Physiology. 6th ed. San Francisco: Pearson Benjamin Cummings, 2004.

2. The components of the cardiovascular system, and their major functions.

3. The Cardiovascular System
Cardiovascular system = Anatomical division
A circulating transport system:
heart
blood vessels
blood
Circulatory system = Clinical division
Cardiovascular system
Lymphatic system

4. Functions of the Cardiovascular System
To transport materials to and from cells:
oxygen and carbon dioxide
nutrients
hormones
immune system components
waste products

5. The important components and major functions of blood.

6. Blood Is specialized fluid of connective tissue CT = cells in matrix
Functions:
Distribution
Regulation
Protection

7. Functions of Blood Distribution Regulation Protection
Deliver oxygen and nutrients to cells
Remove metabolic waste
Transport hormones to targets
Regulation
Maintain body temp  distribute heat
Maintain pH & fluid volume
Protection
Restrict loss at injury (clotting)
Prevent infection (leukocytes)

8. Characteristics of Blood
pH 7.4
Temperature 38⁰C/100.4⁰F
Total volume 4-6 Liters (9-11 pints)
Estimate your own blood volume:
7% body weight in kg = blood in Liters
1kg = 2.2lb
(weight lb/2.2) x 0.07 = blood in Liters

9. Composition of Blood
Fractionation = Process of separating whole blood into plasma and formed elements
Blood matrix = Plasma
~55% (water + soluble proteins)
Blood cells: formed elements
Erythrocytes: ~45%, transport oxygen
Leukocytes: < 1%, defense
Platelets: < 1%, cell fragments and for clotting

10. Plasma 90% water + dissolved solutes
Nutrients, gasses, hormones, wastes, ions, proteins
Plasma Proteins (~8% of total plasma)
7.6g/100ml of plasma
5x more proteins than interstitial fluid
Proteins remain in plasma, not absorbed by cells for nutrients

11. 3 Classes of Plasma Proteins
Albumins (60%)
Globulins (35%)
Fibrinogen (4%)

12. Plasma Proteins Albumins (60% of plasma proteins)
Produced by the liver
Functions:
Act as pH buffer for blood
Contribute to osmotic pressure of blood
- Keep water in blood
Transport fatty acids
Transport Thyroid hormones
Transport Steroid hormones

13. Plasma Proteins Globulins (35% of plasma proteins)
Gamma globulins / Antibodies / Immunoglobulins:
Produced by plasma cells in the lymphatic system
Function to attack foreign substances
Alpha and Beta globulins/Transport globulins:
Produced by the liver
Function to transport small or insoluble compounds to prevent filtration loss by the kidney

14. Plasma Proteins Clotting Factors (4% plasma proteins)
Produced by the liver
11 total, fibrinogen most abundant
All function to promote or form a clot
Fibrinogen produce long, insoluble strands of fibrin
**Serum = plasma (-) minus fibrinogen

15. Plasma Proteins Other (1% of plasma proteins) From Liver:
Metabolic enzymes and antibacterial proteins
From endocrine organs:
Hormones
*Liver disease = leads to blood disorders b/c plasma proteins are produced by the liver

16. Figure 19–1b

17. Hemopoiesis Process of producing formed elements
Blood cell production
All formed elements arise from the same progenitor cell
The hemocytoblast, located in the red bone marrow

19. KEY CONCEPT
Total blood volume (liters) = 7% of body weight (kilograms)
About 1/2 the volume of whole blood is cells and cell products
Plasma resembles interstitial fluid, but contains a unique mixture of proteins not found in other extracellular fluids

20. What would be the effects of a decrease in the amount of plasma proteins?
Decrease in plasma osmotic pressure
Decrease in ability to fight infection
Decrease in transport and binding of some ions, hormones, and other molecules
All of the above

21. Which plasma protein would you expect to be elevated during a viral infection?
albumin
fibrinogen
immunoglobulins
regulatory proteins

22. What are the characteristics and functions of red blood cells?

23. Erythrocytes: Red Blood Cells
99.9% of blood’s formed elements
1/3 of total body cells
Average human = ~75 trillion cells
Average RBC count = million/µl

24. Measuring RBCs Red blood cell count:
reports the number of RBCs in 1 microliter whole blood
Hematocrit (packed cell volume, PCV):
% of whole blood occupied by formed elements
Mostly erythrocytes: 99.9%
Males have a greater percentage of RBC then females

25. Blood Counts RBC: Normal Blood Counts
male: 4.5–6.3 million
female: 4–5.5 million
Polycythemia = excess erythrocytes but normal blood volume
Usually due to bone marrow cancer
hematocrit = viscosity 
heart strain and stroke

26. Erythrocyte Structure
Small and highly specialized biconcave disc
Thin in middle and thicker at edge
Figure 19–2d

27. Importance of RBC Shape and Size
Large surface area for gas exchange:
quickly absorbs and releases oxygen
Folds and form stacks:
passes through narrow blood vessels
Discs bend and flex entering small capillaries:
7.8 µm diamater passes through capillary

28. Erythrocytes Mature erythrocytes lack all organelles
Lack nuclei, mitochondria, and ribosomes
No division, no repair
Life span < 120 days
Cell is 97% hemoglobin protein (red color)
Hemoglobin transports oxygen and some carbon dioxide

29. The structure and function of hemoglobin.

30. Hemoglobin Structure Complex quaternary structure
2 α chains and 2 β chains
Each chain has one heme group with iron in center: iron binds oxygen
Figure 19–3

31. Hemoglobin (Hb) Oxyhemoglobin = oxygen bound, RED
Deoxyhemoglobin = no oxygen, BURGUNDY
Fetal Hb binds oxygen stronger than adults
Insures transfer of oxygen from mom
Most oxygen is carried in blood bound to Hb, some in plasma
Only 20% carbon dioxide carried by Hb:
Carbaminohemoglobin – carbon dioxide bound to amino acids on α / β chains, not on heme

32. Hemoglobin (Hb)
280 million Hb/RBC, 4 hemes/Hb, each heme binds 1 oxygen = >1 billion oxygen/RBC
25 trillion RBC per person
Normal hemoglobin (adult male):
14–18 g/dl whole blood
When plasma oxygen is low, Hb releases oxygen and binds carbon dioxide
At lungs carbon dioxide exchanged for oxygen by diffusion

33. Anemia Hemoglobin levels are below normal Oxygen starvation, due to:
Insufficient # RBC’s
Low Hb
Abnormal Hb
Thalassemia
Sickle-cell anemia

34. Abnormal Hb Thalassemia = inability to produce α or β chains
slow RBC production
cells fragile and short lived
Sickle-cell anemia = single amino acid mutation in β chain high oxygen
cells normal low oxygen
Hb misfolds
RBC’s deform into crescent shape
RBC’s are fragile, blocks capillaries

35. Components of old or damaged red blood cells are recycled.

36. Figure 19–4

37. Recycling RBCs
Macrophages (phagocytes) of liver, spleen, and bone marrow:
monitor RBCs
engulf old/damaged RBCs
Replaced by new
1% of circulating RBCs replaced per day:
about 3 million RBCs per second

38. Hemoglobin Recycling Phagocytes break cells down:
1. Protein  globulin amino acids, released for use
Heme  hemoglobin into components:
1. Iron is removed:
It is bound to transferrin in blood for recycling back to bone marrow (new RBCs)
2. Pigment  heme to biliverdin (green), Biliverdin  bilirubin (yellow-green)
Bilirubin is released into blood
Filtered by liver
Excreted in bile
In gut, bilirubin  urobilins (yellow),stercobilins (brown)
- urobilins is excreted in urine
- stercobilins remain in feces

39. Blood Disorders Jaundice Hemoglobinuria:
Failure of bilirubin to be excreted in bile, collects in peripheral tissues
Causes yellow skin and eyes
Hemoglobinuria:
Cause  Hemolysis, RBC rupture in blood
Red/brown urine due to kidney filtering intact α and β chains of hemoglobin

40. How would the hematocrit change after an individual suffered a hemorrhage?
The hematocrit would be higher.
The hematocrit would be lower.
The hematocrit would show a larger percent WBC.
No change would be seen.

41. How would the level of bilirubin in the blood be affected by a disease that causes damage to the liver?
The level would decrease.
The level would increase.
The level would fluctuate wildly.
The level would not change.

42. Erythropoiesis: The stages of red blood cell maturation, and red blood cell production.

43. Erythropoiesis Red blood cell formation
Occurs in reticular CT in red bone marrow, in spongy bone
Stem cells mature to become RBCs
2 million/sec (1 oz new blood per day)

44. RBC Maturation
Figure 19–5

45. Hemocytoblasts Stem cells in bone marrow divide to produce:
myeloid stem cells:
become RBCs, some WBCs
lymphoid stem cells:
become lymphocytes

46. Erythropoiesis Hemocytoblast differentiates into myeloid stem cells
Followed by many stages of differentiation, all involve an increase in protein synthesis
Cell fills with Hb
- loses organelles including the nucleus
3-5 days reticulocytes are formed (Hb + some ribosomes), released into blood.
- 1-2% of total blood RBCs
2 days in circulation lose ribosomes = mature erythrocytes
- No more protein synthesis

47. Components Building red blood cells requires: amino acids iron
vitamins B12, B6, and folic acid
Lack B12 = pernicious anemia
Low RBC production

48. Stimulating Hormones Erythropoietin (EPO)
Also called erythropoiesis-stimulating hormone:
secreted by the kidney
Secreted when oxygen in tissues is low (hypoxia = low oxygen level)
due to disease or high altitude
No EPO = Kidney failure b/c low RBCs

49. Erythropoietin (EPO) Stimulate RBC production:
Increase cell division rates (up to 30 million/sec)
Increase Hb synthesis = decrease maturation time
“blood doping” = injection EPO or RBC to enhance athletic performance:
Increase oxygen to tissue
Increase hematocrit/viscosity = clots, stroke, and heart strain

50. RBC Tests
Table 19–1

51. KEY CONCEPT
Red blood cells (RBCs) are the most numerous cells in the body
RBCs circulate for approximately 4 months before recycling
Several million are produced each second
Hemoglobin in RBCs transports:
oxygen from lungs to peripheral tissues
carbon dioxide from tissues to lungs

52. Blood typing. The basis for ABO and Rh incompatibilities.

53. Blood Types All cell membranes have surface antigens
Antigens indicate “self”
Antigen = substance that triggers immune response
Normal cells are ignored and foreign cells attacked

54. Blood Types Are genetically determined
Classified by the presence or absence of RBC surface antigens A, B, or D (Rh)
RBCs have 3 important antigens for transfusion, agglutingens A, B, D (Rh)

55. 4 Basic Blood Types
Figure 19–6a

56. 4 Basic Blood Types A (surface antigen A) = 40%
B (surface antigen B) = 10%
AB (antigens A and B) = 4%
O (neither A nor B) = 46%

57. Agglutinogens Antigens on surface of RBCs Screened by immune system
Plasma antibodies attack (agglutinate) foreign antigens

58. Blood Plasma Antibodies
Type A:
type B antibodies
Type B:
type A antibodies
Type O:
both A and B antibodies
Type AB:
neither A nor B

59. The Rh Factor Also called D antigen
Either Rh positive (Rh+) or Rh negative (Rh—)
Only sensitized Rh— blood has anti-Rh antibodies

60. Cross-Reaction
Figure 19–6b

61. Cross-Reaction Also called transfusion reaction
At birth, blood contains antibodies against A or B antigens that are not present
Plasma antibody meets its specific surface antigen
Antibodies will cause blood agglutination (clumping) of antigen (agglutinogen) and hemolyze
If donor and recipient blood types not compatible

62. Blood Type Test
Determines blood type and compatibility
Figure 19–7

63. Cross-Match Test
Performed on donor and recipient blood for compatibility
Without cross-match, type O— is universal donor
It lacks all agglutinogens (A, B, and D)
No risk of agglutination by antibodies in anyone

64. Erythroblastosis fetalis
Aka Hemolytis disease of the newborn
Antibodies against D antigen only form upon exposure and can cross the placenta
Rh- mom pregnant with Rh+ baby
Gets exposed to D antigen during birth
Makes anti-D antibodies
Pregnant with second Rh+ baby
Antibodies cross placenta
Causes agglutination and lysis of fetal RBCs  anemia and death
Prevention = treat mom with RhoCAM during first birth to prevent antibody formation

65. What are surface antigens on RBCs?
glycoproteins in the cytosol
receptor proteins in the cell membrane
peripheral proteins of the cell membrane
glycolipids in the cell membrane

66. Which blood type(s) can be transfused into a person with Type O blood?
Type A
Type B
Types A and B
Type O

67. Why can’t a person with Type A blood safely receive blood from a person with Type B blood?
Type B blood will break down in the person’s veins.
Type B blood will destroy Type A cells.
Type A blood contains agglutinating agents for Type B.
Type B blood contains agglutinating agents for Type A.

68. The types of white blood cells, and the factors that regulate the production of each type.

69. Leukocytes (WBCs) < 1% of total blood volume Function:
leukocytes/µl blood
Use blood to travel to tissues
Not permanent residents of blood
Most in connective tissue proper and lymphatic system organs
Function:
Defend against pathogens
Remove toxins and wastes
Attack abnormal/damaged cells
All have nuclei & organelles, no hemoglobin

70. Circulating WBCs Migrate out of bloodstream (diapedesis)
Margination = adhere to vessel
Emigration = pass between endothelial cells in vessel walls
Have amoeboid movement in bloodstream
Attracted to chemical stimuli (positive chemotaxis)
Some are phagocytic:
- Engulf pathogens and debris
neutrophils, eosinophils, and monocytes

71. 5 Types of WBCs
Figure 19–9

72. 5 Types of Leukocytes Granulocytes vs. Agranulocytes (on handout)
Neutrophils
Eosinophils
Basophils (in tissues = mast cells)
Monocytes (in tissues = macrophages)
Lymphocytes

73. Neutrophils Also called polymorphonuclear leukocytes (PMNs)
Non-specific defense
Phagocytic
50–70% of circulating WBCs
3-5 lobed nucleus
Pale cytoplasm granules with:
lysosomal enzymes and defensins
bactericides
hydrogen peroxide and superoxide
Very mobile: first at injury
Life span less than 10 hours

74. Neutrophil Function Respiratory burst Degranulation:
- H2O2 and O2- , kills and phagocytize
Degranulation:
- Release defensins (against some bacteria, fungi, and viruses), lyse bacteria
Release prostaglandins
- Induce inflammation to stop the spread of injury
Release leukotrienes
- Attract phagocytes

75. Degranulation Defensins (host defense proteins):
peptides from lysosomes
attack pathogen membranes

76. Eosinophils Also called acidophils Phagocytic 2–4% of circulating WBCs
Bilobed nucleus
12µm diameter
Granules contain toxins
Life span 9 days
Attack large parasites

77. Eosinophil Functions Phagocytosis of antibody covered objects
Defense against parasties:
- Exocytose toxins on large pathogens
Reduce inflammations
- anti-inflammatory chemicals/enzymes that counteract inflammatory effects of neutorphils and mast cell

78. Basophils In Tissues = Mast cells
Non-specific defense
Not phagocytic
Are less than 1% of circulating WBCs
Are small, 8-10µm diameter
Granules contain
Histamine: dilate blood vessels
Heparin: prevents clotting
Accumulate in damaged tissue
Life span 9 days

79. Basophil Functions Inflammation (Histamine)
Allergic response, also via histamine

80. Monocytes In Tissues = Macrophages
Non-specific defense
Phagocytic
2–8% of circulating WBCs
Are large and spherical, kidney shaped nucleus
Circulate 24 hours, exit to tissues = macrophage
Life span several months

81. Macrophage Functions 1. Phagocytosis: virus & bacteria
2. Attract phagocytes
3. Attract fibroblasts for scar formation
4. Activate lymphocytes:
Mount immune response

82. Lymphocytes Immune response 20–30% of circulating WBCs
Large round nucleus
5-17µm diameter, larger than RBCs
Migrate between blood and tissues
Mostly in connective tissues and lymphatic organs
Life span days to lifetime

83. 3 Classes of Lymphocytes
T cells
B cells
Natural killer (NK) cells

84. Lymphocyte Functions B cells: T cells NK cells: Humoral immunity
Differentiate into plasma cells
Synthesize and secrete antibodies
T cells
cell-mediated immunity
attack foreign cells
NK cells:
Immune surveillance
Destroy abnormal tissues

85. KEY CONCEPT RBCs outnumber WBCs 1000:1
WBCs defend against infection, foreign cells, or toxins
WBCs clean up and repair damaged tissues

86. KEY CONCEPT The most numerous WBCs: neutrophils lymphocytes
engulf bacteria
lymphocytes
are responsible for specific defenses of immune response

87. Which type of white blood cell would you find in the greatest numbers in an infected cut?
eosinophils
neutrophils
lymphocytes
monocytes

88. Which type of cell would you find in elevated numbers in a person who is producing large amounts of circulating antibodies to combat a virus?
B lymphocytes
T lymphocytes
neutrophils
basophils

89. How do basophils respond during inflammation?
secrete antibodies
phagocytize foreign particles
release histamine
reduce inflammation

90. Leukopoiesis: WBC Production
Figure 19–10

91. Leukopoiesis
All blood cells originate from hemocytoblasts which produce:
myeloid stem cells and
lymphoid stem cells
Lymphoid stem cells  Lymphocytes
Production involves the immune response
Myeloid stem cells  Basophils, Eosinophiles, Neutrophils, Macrophages as directed by specific colony stimulating factors (CSF)
CSF is produced by Macrophages and T cells
Different CSF results in different cell

92. Myeloid Stem Cells Differentiate into progenitor cells:
which produce all WBCs except lymphocytes

93. Lymphocytes Are produced by lymphoid stem cells Lymphopoiesis:
the production of lymphocytes

94. WBC Development WBCs, except monocytes: Monocytes:
develop fully in bone marrow
Monocytes:
develop into macrophages in peripheral tissues

95. Other Lymphopoiesis
Some lymphoid stem cells migrate to peripheral lymphoid tissues (thymus, spleen, lymph nodes)
Also produce lymphocytes

96. WBC Disorders Leukopenia: Leukocytosis: Leukemia: WBC > 100,000/µl
abnormally low WBC count
Leukocytosis:
abnormally high WBC count in normal blood volume
Normal infection increases WBCs from 7,500 to 11,000/µl
>100,000/µl  leukemia, cancerous stem cells
Leukemia: WBC > 100,000/µl
extremely high WBC count
WBC produced  immature and abnormal

97. Infectious Mononucleosis:
Epstein Bar virus infection causes:
Production of excess agranulocytes that are abnormal, self limiting

98. Table 19–3

99. The structure and function of platelets and how are they produced.

100. Platelets (Thrombocytes)
Cell fragments involved in clotting
Flattened discs, no nucleus
2-4µm diameter, 1µm thick
Constantly replace
9-12 days in circulation
Phagocytosed by cells in spleen
350,000/µl blood
1/3 of total platelets held in reserve in spleen, mobilized for crisis

101. Platelet Counts 150,000 to 500,000 per microliter
Thrombocytopenia: < 80,000/µl
abnormally low platelet count
Results in bleeding
Thrombocytosis: > 1 million/µl
abnormally high platelet count
Due to cancer or infection
Results in a clotting risk

102. 3 Functions of Platelets
Transport clotting chemicals, and release important clotting chemicals when activated
Temporarily form patch (platelet plug) over damaged vessel walls
Actively contract wound after clot formation
- Contain actin and myosin

103. Platelet Production Also called thrombocytopoiesis:
occurs in bone marrow
1. Induced by thrombopoietin from kidney and CSF of leukocytes
2. Megakaryocyte in bone marrow breaks off membrane enclosed cytoplasm to blood
3. Each megakaryocyte can produce ~4,000 platelets

104. Mechanism that controls blood loss after injury, and the reaction sequence in blood clotting.

105. Hemostasis The cessation of bleeding: vascular phase platelet phase
coagulation phase

106. The Vascular Phase A cut triggers vascular spasm 30-minute contraction
Figure 19–11a

107. 3 Steps of the Vascular Phase
Endothelial cells contract:
expose basal lamina to bloodstream
Endothelial cells release:
chemical factors:
ADP, tissue factor, and prostacyclin
local hormones
stimulate smooth muscle contraction and cell division

108. 3 Steps of the Vascular Phase
Endothelial cell membranes become “sticky”:
seal off blood flow

109. The Platelet Phase
Begins within 15 seconds after injury
Figure 19–11b

110. The Platelet Phase Platelet adhesion (attachment):
to sticky endothelial surfaces
to basal laminae
to exposed collagen fibers
Platelet aggregation (stick together):
forms platelet plug
closes small breaks

111. Activated Platelets Release Clotting Compounds
Adenosine diphosphate (ADP)
Thromboxane A2 and serotonin
Clotting factors
Platelet-derived growth factor (PDGF)
Calcium ions

112. The Coagulation Phase Begins 30 seconds or more after the injury
Figure 19–12a

113. The Coagulation Phase Blood clotting (coagulation):
Involves a series of steps
converts circulating fibrinogen into insoluble fibrin

114. Blood Clot Fibrin network Covers platelet plug Traps blood cells
Seals off area

115. The Common Pathway Enzymes activate Factor X
Forms enzyme prothrombinase
Converts prothrombin to thrombin
Thrombin converts fibrinogen to fibrin

116. Functions of Thrombin Stimulates formation of tissue factor
forms positive feedback loop  accelerates clotting

117. KEY CONCEPT
Platelets are involved in coordination of hemostasis (blood clotting)
Platelets, activated by abnormal changes in local environment, release clotting factors and other chemicals
Hemostasis is a complex cascade that builds a fibrous patch that can be remodeled and removed as the damaged area is repaired

118. A sample of bone marrow has unusually few megakaryocytes
A sample of bone marrow has unusually few megakaryocytes. What body process would you expect to be impaired as a result?
hematopoiesis
immune response
clotting
oxygen carrying capacity

119. Vitamin K is fat-soluble, and some dietary fat is required for its absorption. How could a diet of fruit juice and water have an effect on blood clotting?
Clotting time would increase.
Clotting time would decrease.
Clotting protein synthesis would increase.
Vitamin K has no effect on clotting.

120. Bleeding Disorders Thrombosis Clotting in undamaged vessels
Slow or prevent flow
Embolus
Free floating thrombosis
Blocks small vessels  tissue damage, heart attack, stroke
Disseminated intravascular coagulation
Widespread clotting followed by systemic bleeding
Rare: complication of pregnancy or mismatched transfusion

121. Bleeding Disorders Hemophilia:
Inadequate production of clotting factors
Type A  Factor VIII (X linked)
Type B  Factor IX
Type C  Factor XI

122. Plasma Clotting Factors
Table 19–4

123. Blood Disorders 5. Dietary: Calcium required for clotting cascade
Vitamin K required for liver to synthesize clotting factors
Iron required for hemoglobin production
Vitamin B12 required for RBC stem cell division
Organ Health:
Impaired liver =
reduced clotting b/c of reduced clotting factors
Impaired kidney =
reduced RBC b/c of reduced EPO
Reduced platelets b/c reduced thrombopoietin

124. SUMMARY Functions of cardiovascular system 5 functions of blood
Structure of whole blood:
plasma and formed elements
Process of blood cell formation (hemopoiesis)
3 classes of plasma proteins:
Albumins, globulins, and fibrinogen
RBC structure and function
Hemoglobin structure and function

125. SUMMARY RBC production and recycling Blood types: ABO and Rh
WBC structure and function
5 types of WBCs:
Neutrophils, eosinophils, basophils, monocytes, lymphocytes
Differential WBC counts and disease
WBC production
Platelet structure and function
Platelet production