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Chapter 19: Blood Primary sources for figures and content:

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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

18

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


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