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Chapter 14
The Cardiovascular
System: Blood

Copyright 2010, John Wiley & Sons, Inc.
Functions





Transportation: water, gases, nutrients,
hormones, enzymes, electrolytes, wastes,
heat
Regulation: pH, temperature, water balance
Protection: blood clotting, defense:
phagocytic cells, interferons, complement

Copyright 2010, John Wiley & Sons, Inc.
Composition


A connective tissue with components readily
seen when blood is centrifuged:




Plasma(~55%): soluble materials (mostly
water); lighter so at top of tube
Formed elements (~45%): cells (heavier so at
bottom of tube)


Mostly red blood cells (RBCs)
Percent of blood occupied by RBCs = hematocrit (Hct)
 Normal hematocrit value: 42-47%
 Females: 38 to 46%; males: 40 to 54%




Buffy coat: site of white blood cells (WBCs), platelets

Copyright 2010, John Wiley & Sons, Inc.
Composition

Copyright 2010, John Wiley & Sons, Inc.
Composition

Copyright 2010, John Wiley & Sons, Inc.
Plasma: Liquid Portion of Blood



Water: 91.5%
Plasma proteins: 7%






Albumin (54%): function in osmosis; carriers
Globulins (38%): serve as antibodies
Fibrinogen (7%): important in clotting

Other: 1.5%


Electrolytes, nutrients, gases, hormones,
vitamins, waste products

Copyright 2010, John Wiley & Sons, Inc.
Formed Elements
I. Red Blood Cells (RBCs)
II. White blood cells (WBCs)
A. Granular leukocytes
1. Neutrophils
2. Eosinophils
3. Basophils

B. Agranular leukocytes
1. Lymphocytes and natural killer (NK) cells
2. Monocytes

III Platelets

Copyright 2010, John Wiley & Sons, Inc.
Formation of Blood Cells



Called hemopoiesis or hematopoiesis
Occurs throughout life




In response to specific hormones, stem cells
undergo a series of changes to form blood cells

Pluripotent stem cells in red marrow




Lymphoid stem cells  lymphocytes (in lymphatic
tissues)
Myeloid stem cells  all other WBCs, all RBCs,
and platelets (in red bone marrow)

Copyright 2010, John Wiley & Sons, Inc.
Formation of Blood Cells

Copyright 2010, John Wiley & Sons, Inc.
Formation of
Blood Cells

Copyright 2010, John Wiley & Sons, Inc.
Erythrocytes (RBCs)


Hemoglobin (red pigment)




RBC count: about 5 million/µl




Carries 98.5% of O2 and 23% of CO2
Male: 5.4 million cells/µl; female: 4.8 million/µl

Structure of mature RBC



No nucleus/DNA so RBCs live only 3 to 4 mos
Lack of nucleus causes biconcave disc shape
with extensive plasma membrane



Provides for maximal gas exchange
Is flexible for passing through capillaries

Copyright 2010, John Wiley & Sons, Inc.
RBC Recycling



Cleared by macrophages (liver and spleen)
Recycled components



Globin  amino acids recycled to form proteins
Heme broken down into:


Fe
Carried in blood by transferrin (“protein escort” of Fe)
 Recycled in bone marrow for forming synthesis of new
hemoglobin; proteins and vitamin B12 required also




Non-Fe portion of heme biliverdin  bilirubin
Bilirubin to liver  bile  helps absorb fats
 Intestinal bacteria convert bilirubin into other chemicals
that exit in feces (stercobilin) or urine (urobilin)


Copyright 2010, John Wiley & Sons, Inc.
Formation and Destruction of RBC’s
Circulation for about
120 days

7

3
Reused for
protein synthesis

Amino
acids

Globin

4

6

5

Fe3+

Fe3+ Transferrin

2 Heme

Fe3+

Ferritin
Transferrin
Bilirubin

9
1 Red blood cell

Biliverdin

Bilirubin

death and
phagocytosis

11

10

Small
intestine

Kidney

13

12

Urobilin

Macrophage in
spleen, liver, or
red bone marrow

Bilirubin

Urobilinogen
Stercobilin

Urine

Liver

Feces

+
Globin
+
Vitamin B12
+
Erythopoietin

8 Erythropoiesis in
red bone marrow

Bacteria

Key:
in blood

Large 14
intestine

Copyright 2010, John Wiley & Sons, Inc.

in bile
RBC Synthesis: Erythropoiesis




Develop from myeloid stem cells in red
marrow
Cells lose nucleus; are then released into
bloodstream as reticulocytes




These almost-mature RBCs develop into erythrocytes
after 1-2 days in bloodstream
High reticulocyte count (> normal range of 0.5% to
1.5% as more of these circulate in bloodstream)
indicates high rate of RBC formation

Copyright 2010, John Wiley & Sons, Inc.
RBC Synthesis: Erythropoiesis


Production and destruction: normally
balanced





Stimulus for erythropoiesis is low O2 delivery
(hypoxia) in blood passing to kidneys 
Kidneys release erythropoietin release (EPO) 
Stimulates erythropoiesis in red marrow 
increased O2 delivery in blood (negative
feedback mechanism)

Copyright 2010, John Wiley & Sons, Inc.
RBC Synthesis: Erythropoiesis


Signs of lower-than-normal RBC count 
changes in skin, mucous membranes, and
finger nail beds



Cyanosis: bluish color
Anemia: pale color

Copyright 2010, John Wiley & Sons, Inc.
Regulation of
Erythropoiesis

Copyright 2010, John Wiley & Sons, Inc.
White Blood Cells (WBCs or Leukocytes)
Appear white because lack hemoglobin
Normal WBC count: 5,000-10,000/µl





WBC count usually increases in infection

Two major classes based on presence or
absence of granules (vesicles) in them]





Granular: neutrophils, eosinophils, basophils




Neutrophils usually make up 2/3 of all WBCs

Agranular: lymphocytes, monocytes

Major function: defense against





Infection and inflammation
Antigen-antibody (allergic) reactions
Copyright 2010, John Wiley & Sons, Inc.
White Blood Cell Functions


Neutrophils: first responders to infection





Monocytes  macrophages (“big eaters”)




Phagocytosis
Release bacteria-destroying enzyme lysozyme
Known as wandering macrophages

Eosinophils




Phagocytose antibody-antigen complexes
Help suppress inflammation of allergic reactions
Respond to parasitic infections

Copyright 2010, John Wiley & Sons, Inc.
White Blood Cell Functions
Basophils






Intensify inflammatory responses and allergic
reactions
Release chemicals that dilate blood vessels:
histamine and serotonin; also heparin
(anticoagulant)

Copyright 2010, John Wiley & Sons, Inc.
White Blood Cell Functions
Lymphocytes




Three types of lymphocytes






T cells
B cells
Natural killer (NK) cells

Play major roles in immune responses




B lymphocytes respond to foreign substances called
antigens and differentiate into plasma cells that
produce antibodies. Antibodies attach to and
inactivate the antigens.
T lymphocytes directly attack microbes.

Copyright 2010, John Wiley & Sons, Inc.
White Blood Cell Functions


Major histocompatibility (MHC) antigens




Proteins protruding from plasma membrane of
WBCs (and most other body cells)
Called “self-identity markers”





Unique for each person (except for identical twins)
An incompatible tissue or organ transplant is rejected
due to difference in donor and recipient MHC antigens
MHC antigens are used to “type tissues” to check for
compatibility and reduce risk of rejection

Copyright 2010, John Wiley & Sons, Inc.
WBC Life Span





WBCs: 5000-10,000 WBCs/µl blood
RBCs outnumber WBCs about 700:1
Life span: typically a few hours to days
Abnormal WBC counts






Leukocytosis: high WBC count in response to
infection, exercise, surgery
Leukopenia: low WBC count

Differential WBC count: measures % of
WBCs made up of each of the 5 types
Copyright 2010, John Wiley & Sons, Inc.
Platelets





Myeloid stem cells  megakaryocytes 
2000–3000 fragments = platelets
Normal count: 150,000-400,000/µl blood
Functions





Plug damaged blood vessels
Promote blood clotting

Life span 5–9 days

Copyright 2010, John Wiley & Sons, Inc.
Hemostasis: “Blood Standing Still”
Sequence of events to avoid hemorrhage
1.Vascular spasm



Response to damage
Quick reduction of blood loss

1.Platelet plug formation


Platelets become sticky when contact damaged
vessel wall

1.Blood clotting (coagulation)


Series of chemical reactions involving clotting
factors   

Copyright 2010, John Wiley & Sons, Inc.
Blood Clotting (Coagulation)


Extrinsic pathway




Intrinsic Pathway




Tissue factor(TF) from damaged cells 1  2  3
Materials “intrinsic” to blood  1  2  3

Common pathway: 3 major steps
1. Prothrombinase 
2. Prothrombin  thrombin
3. Fibrinogen  fibrin  clot



Ca++ plays important role in many steps
Copyright 2010, John Wiley & Sons, Inc.
Clot Retraction and Vessel Repair



Clot plugs ruptured area
Gradually contracts (retraction)




Pulls sides of wound together

Repair



Fibroblasts replace connective tissue
Epithelial cells repair lining

Copyright 2010, John Wiley & Sons, Inc.
Hemostatic Control Mechanisms


Fibrinolysis: breakdown of clots by plasmin





Inappropriate (unneeded) clots






Inactivated plasminogen 
Activated (by tPA)  plasmin
Clots can be triggered by roughness on vessel
wall = thrombosis
Loose (on-the-move) clot = embolism

Anticoagulants: decrease clot formation



Heparin
Warfarin (Coumadin)
Copyright 2010, John Wiley & Sons, Inc.
(a) Extrinsic pathway

Stages of
Clotting

Tissue trauma

(b) Intrinsic pathway
Blood trauma
Damaged
endothelial cells
expose collagen
fibers

Tissue
factor
(TF)

Damaged
platelets

Activated XII
Activated
platelets

Ca2+

Ca2+

+
Platelet
phospholipids
Activated X Activated X
V

1

Ca2+

Ca2+

V +

PROTHROMBINASE
(c) Common
pathway
Ca2+
Prothrombin
(II)

THROMBIN
Ca

2+

Fibrinogen
(I)
Loose fibrin
threads

2

XIII

Activated XIII

STRENGTHENED 3
FIBRIN THREADS

Copyright 2010, John Wiley & Sons, Inc.
Blood Groups and Blood Types




RBCs have antigens (agglutinogens) on their
surfaces
Each blood group consists of two or more
different blood types



There are > 24 blood groups
Two examples:





ABO group has types A, B, AB, O
Rh group has type Rh positive (Rh+), Rh negative (Rh–)

Blood types in each person are determined
by genetics
Copyright 2010, John Wiley & Sons, Inc.
ABO Group


Two types of antigens on RBCs: A or B





Type A has only A antigen
Type B has only B antigen
Type AB has both A and B antigens
Type O has neither A nor B antigen




Most common types in US: type O and A

Typically blood has antibodies in plasma




These can react with antigens
Two types: anti-A antibody or anti-B antibody
Blood lacks antibodies against own antigens



Type A blood has anti-B antibodies (not anti-A)
Type AB blood has neither anti-A nor anti-B antibodies
Copyright 2010, John Wiley & Sons, Inc.
ABO Group

Copyright 2010, John Wiley & Sons, Inc.
Rh Blood Group



Name Rh: antigen found in rhesus monkey
Rh blood types








If RBCs have Rh antigen: Rh+
If RBCs lack Rh antigen: Rh–

Rh+ blood type in 85-100% of U.S. population
Normally neither Rh+ nor Rh– has anti-Rh
antibodies
Antibodies develop in Rh- persons after first
exposure to Rh+ blood in transfusion (or
pregnancy  hemolytic disease of newborn)
Copyright 2010, John Wiley & Sons, Inc.
Transfusions






If mismatched blood (“wrong blood type”)
given, antibodies bind to antigens on RBCs
 hemolyze RBCs
Type AB called “universal recipients” because
have no anti-A or anti-B antibodies so can
receive any ABO type blood
Type O called “universal donors” because
have neither A nor B antigen on RBCs so can
donate to any ABO type


Misleading because of many other blood groups
that must be matched
Copyright 2010, John Wiley & Sons, Inc.
End of Chapter 14


Copyright 2010 John Wiley & Sons, Inc.
All rights reserved. Reproduction or translation of
this work beyond that permitted in section 117 of the
1976 United States Copyright Act without express
permission of the copyright owner is unlawful.
Request for further information should be addressed
to the Permission Department, John Wiley & Sons,
Inc. The purchaser may make back-up copies for
his/her own use only and not for distribution or
resale. The Publishers assumes no responsibility
for errors, omissions, or damages caused by the
use of theses programs or from the use of the
information herein.
Copyright 2010, John Wiley & Sons, Inc.

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Lecture 6 the cardiovascular system blood

  • 1. Chapter 14 The Cardiovascular System: Blood Copyright 2010, John Wiley & Sons, Inc.
  • 2. Functions    Transportation: water, gases, nutrients, hormones, enzymes, electrolytes, wastes, heat Regulation: pH, temperature, water balance Protection: blood clotting, defense: phagocytic cells, interferons, complement Copyright 2010, John Wiley & Sons, Inc.
  • 3. Composition  A connective tissue with components readily seen when blood is centrifuged:   Plasma(~55%): soluble materials (mostly water); lighter so at top of tube Formed elements (~45%): cells (heavier so at bottom of tube)  Mostly red blood cells (RBCs) Percent of blood occupied by RBCs = hematocrit (Hct)  Normal hematocrit value: 42-47%  Females: 38 to 46%; males: 40 to 54%   Buffy coat: site of white blood cells (WBCs), platelets Copyright 2010, John Wiley & Sons, Inc.
  • 4. Composition Copyright 2010, John Wiley & Sons, Inc.
  • 5. Composition Copyright 2010, John Wiley & Sons, Inc.
  • 6. Plasma: Liquid Portion of Blood   Water: 91.5% Plasma proteins: 7%     Albumin (54%): function in osmosis; carriers Globulins (38%): serve as antibodies Fibrinogen (7%): important in clotting Other: 1.5%  Electrolytes, nutrients, gases, hormones, vitamins, waste products Copyright 2010, John Wiley & Sons, Inc.
  • 7. Formed Elements I. Red Blood Cells (RBCs) II. White blood cells (WBCs) A. Granular leukocytes 1. Neutrophils 2. Eosinophils 3. Basophils B. Agranular leukocytes 1. Lymphocytes and natural killer (NK) cells 2. Monocytes III Platelets Copyright 2010, John Wiley & Sons, Inc.
  • 8. Formation of Blood Cells   Called hemopoiesis or hematopoiesis Occurs throughout life   In response to specific hormones, stem cells undergo a series of changes to form blood cells Pluripotent stem cells in red marrow   Lymphoid stem cells  lymphocytes (in lymphatic tissues) Myeloid stem cells  all other WBCs, all RBCs, and platelets (in red bone marrow) Copyright 2010, John Wiley & Sons, Inc.
  • 9. Formation of Blood Cells Copyright 2010, John Wiley & Sons, Inc.
  • 10. Formation of Blood Cells Copyright 2010, John Wiley & Sons, Inc.
  • 11. Erythrocytes (RBCs)  Hemoglobin (red pigment)   RBC count: about 5 million/µl   Carries 98.5% of O2 and 23% of CO2 Male: 5.4 million cells/µl; female: 4.8 million/µl Structure of mature RBC   No nucleus/DNA so RBCs live only 3 to 4 mos Lack of nucleus causes biconcave disc shape with extensive plasma membrane   Provides for maximal gas exchange Is flexible for passing through capillaries Copyright 2010, John Wiley & Sons, Inc.
  • 12. RBC Recycling   Cleared by macrophages (liver and spleen) Recycled components   Globin  amino acids recycled to form proteins Heme broken down into:  Fe Carried in blood by transferrin (“protein escort” of Fe)  Recycled in bone marrow for forming synthesis of new hemoglobin; proteins and vitamin B12 required also   Non-Fe portion of heme biliverdin  bilirubin Bilirubin to liver  bile  helps absorb fats  Intestinal bacteria convert bilirubin into other chemicals that exit in feces (stercobilin) or urine (urobilin)  Copyright 2010, John Wiley & Sons, Inc.
  • 13. Formation and Destruction of RBC’s Circulation for about 120 days 7 3 Reused for protein synthesis Amino acids Globin 4 6 5 Fe3+ Fe3+ Transferrin 2 Heme Fe3+ Ferritin Transferrin Bilirubin 9 1 Red blood cell Biliverdin Bilirubin death and phagocytosis 11 10 Small intestine Kidney 13 12 Urobilin Macrophage in spleen, liver, or red bone marrow Bilirubin Urobilinogen Stercobilin Urine Liver Feces + Globin + Vitamin B12 + Erythopoietin 8 Erythropoiesis in red bone marrow Bacteria Key: in blood Large 14 intestine Copyright 2010, John Wiley & Sons, Inc. in bile
  • 14. RBC Synthesis: Erythropoiesis   Develop from myeloid stem cells in red marrow Cells lose nucleus; are then released into bloodstream as reticulocytes   These almost-mature RBCs develop into erythrocytes after 1-2 days in bloodstream High reticulocyte count (> normal range of 0.5% to 1.5% as more of these circulate in bloodstream) indicates high rate of RBC formation Copyright 2010, John Wiley & Sons, Inc.
  • 15. RBC Synthesis: Erythropoiesis  Production and destruction: normally balanced    Stimulus for erythropoiesis is low O2 delivery (hypoxia) in blood passing to kidneys  Kidneys release erythropoietin release (EPO)  Stimulates erythropoiesis in red marrow  increased O2 delivery in blood (negative feedback mechanism) Copyright 2010, John Wiley & Sons, Inc.
  • 16. RBC Synthesis: Erythropoiesis  Signs of lower-than-normal RBC count  changes in skin, mucous membranes, and finger nail beds   Cyanosis: bluish color Anemia: pale color Copyright 2010, John Wiley & Sons, Inc.
  • 18. White Blood Cells (WBCs or Leukocytes) Appear white because lack hemoglobin Normal WBC count: 5,000-10,000/µl    WBC count usually increases in infection Two major classes based on presence or absence of granules (vesicles) in them]   Granular: neutrophils, eosinophils, basophils   Neutrophils usually make up 2/3 of all WBCs Agranular: lymphocytes, monocytes Major function: defense against    Infection and inflammation Antigen-antibody (allergic) reactions Copyright 2010, John Wiley & Sons, Inc.
  • 19. White Blood Cell Functions  Neutrophils: first responders to infection    Monocytes  macrophages (“big eaters”)   Phagocytosis Release bacteria-destroying enzyme lysozyme Known as wandering macrophages Eosinophils    Phagocytose antibody-antigen complexes Help suppress inflammation of allergic reactions Respond to parasitic infections Copyright 2010, John Wiley & Sons, Inc.
  • 20. White Blood Cell Functions Basophils    Intensify inflammatory responses and allergic reactions Release chemicals that dilate blood vessels: histamine and serotonin; also heparin (anticoagulant) Copyright 2010, John Wiley & Sons, Inc.
  • 21. White Blood Cell Functions Lymphocytes   Three types of lymphocytes     T cells B cells Natural killer (NK) cells Play major roles in immune responses   B lymphocytes respond to foreign substances called antigens and differentiate into plasma cells that produce antibodies. Antibodies attach to and inactivate the antigens. T lymphocytes directly attack microbes. Copyright 2010, John Wiley & Sons, Inc.
  • 22. White Blood Cell Functions  Major histocompatibility (MHC) antigens   Proteins protruding from plasma membrane of WBCs (and most other body cells) Called “self-identity markers”    Unique for each person (except for identical twins) An incompatible tissue or organ transplant is rejected due to difference in donor and recipient MHC antigens MHC antigens are used to “type tissues” to check for compatibility and reduce risk of rejection Copyright 2010, John Wiley & Sons, Inc.
  • 23. WBC Life Span     WBCs: 5000-10,000 WBCs/µl blood RBCs outnumber WBCs about 700:1 Life span: typically a few hours to days Abnormal WBC counts    Leukocytosis: high WBC count in response to infection, exercise, surgery Leukopenia: low WBC count Differential WBC count: measures % of WBCs made up of each of the 5 types Copyright 2010, John Wiley & Sons, Inc.
  • 24. Platelets    Myeloid stem cells  megakaryocytes  2000–3000 fragments = platelets Normal count: 150,000-400,000/µl blood Functions    Plug damaged blood vessels Promote blood clotting Life span 5–9 days Copyright 2010, John Wiley & Sons, Inc.
  • 25. Hemostasis: “Blood Standing Still” Sequence of events to avoid hemorrhage 1.Vascular spasm   Response to damage Quick reduction of blood loss 1.Platelet plug formation  Platelets become sticky when contact damaged vessel wall 1.Blood clotting (coagulation)  Series of chemical reactions involving clotting factors    Copyright 2010, John Wiley & Sons, Inc.
  • 26. Blood Clotting (Coagulation)  Extrinsic pathway   Intrinsic Pathway   Tissue factor(TF) from damaged cells 1  2  3 Materials “intrinsic” to blood  1  2  3 Common pathway: 3 major steps 1. Prothrombinase  2. Prothrombin  thrombin 3. Fibrinogen  fibrin  clot  Ca++ plays important role in many steps Copyright 2010, John Wiley & Sons, Inc.
  • 27. Clot Retraction and Vessel Repair   Clot plugs ruptured area Gradually contracts (retraction)   Pulls sides of wound together Repair   Fibroblasts replace connective tissue Epithelial cells repair lining Copyright 2010, John Wiley & Sons, Inc.
  • 28. Hemostatic Control Mechanisms  Fibrinolysis: breakdown of clots by plasmin    Inappropriate (unneeded) clots    Inactivated plasminogen  Activated (by tPA)  plasmin Clots can be triggered by roughness on vessel wall = thrombosis Loose (on-the-move) clot = embolism Anticoagulants: decrease clot formation   Heparin Warfarin (Coumadin) Copyright 2010, John Wiley & Sons, Inc.
  • 29. (a) Extrinsic pathway Stages of Clotting Tissue trauma (b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers Tissue factor (TF) Damaged platelets Activated XII Activated platelets Ca2+ Ca2+ + Platelet phospholipids Activated X Activated X V 1 Ca2+ Ca2+ V + PROTHROMBINASE (c) Common pathway Ca2+ Prothrombin (II) THROMBIN Ca 2+ Fibrinogen (I) Loose fibrin threads 2 XIII Activated XIII STRENGTHENED 3 FIBRIN THREADS Copyright 2010, John Wiley & Sons, Inc.
  • 30. Blood Groups and Blood Types   RBCs have antigens (agglutinogens) on their surfaces Each blood group consists of two or more different blood types   There are > 24 blood groups Two examples:    ABO group has types A, B, AB, O Rh group has type Rh positive (Rh+), Rh negative (Rh–) Blood types in each person are determined by genetics Copyright 2010, John Wiley & Sons, Inc.
  • 31. ABO Group  Two types of antigens on RBCs: A or B     Type A has only A antigen Type B has only B antigen Type AB has both A and B antigens Type O has neither A nor B antigen   Most common types in US: type O and A Typically blood has antibodies in plasma    These can react with antigens Two types: anti-A antibody or anti-B antibody Blood lacks antibodies against own antigens   Type A blood has anti-B antibodies (not anti-A) Type AB blood has neither anti-A nor anti-B antibodies Copyright 2010, John Wiley & Sons, Inc.
  • 32. ABO Group Copyright 2010, John Wiley & Sons, Inc.
  • 33. Rh Blood Group   Name Rh: antigen found in rhesus monkey Rh blood types      If RBCs have Rh antigen: Rh+ If RBCs lack Rh antigen: Rh– Rh+ blood type in 85-100% of U.S. population Normally neither Rh+ nor Rh– has anti-Rh antibodies Antibodies develop in Rh- persons after first exposure to Rh+ blood in transfusion (or pregnancy  hemolytic disease of newborn) Copyright 2010, John Wiley & Sons, Inc.
  • 34. Transfusions    If mismatched blood (“wrong blood type”) given, antibodies bind to antigens on RBCs  hemolyze RBCs Type AB called “universal recipients” because have no anti-A or anti-B antibodies so can receive any ABO type blood Type O called “universal donors” because have neither A nor B antigen on RBCs so can donate to any ABO type  Misleading because of many other blood groups that must be matched Copyright 2010, John Wiley & Sons, Inc.
  • 35. End of Chapter 14  Copyright 2010 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein. Copyright 2010, John Wiley & Sons, Inc.