1. Chapter 14 The Cardiovascular System: Blood
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Functions
Transportation: water, gases, nutrients, hormones, enzymes, electrolytes, wastes, heat
Regulation: pH, temperature, water balance
Protection: blood clotting, defense: phagocytic cells, interferons, complement
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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
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Composition
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Composition
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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
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Formed Elements
I. Red Blood Cells (RBCs)
II. White blood cells (WBCs)
Granular leukocytes
Neutrophils
Eosinophils
Basophils
Agranular leukocytes
Lymphocytes and natural killer (NK) cells
Monocytes
III Platelets
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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)
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9. Formation of Blood Cells
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10. Formation of Blood Cells
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Erythrocytes (RBCs)
Hemoglobin (red pigment)
Carries 98.5% of O2 and 23% of CO2
RBC count: about 5 million/µl
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 months
Lack of nucleus causes biconcave disc shape with extensive plasma membrane
Provides for maximal gas exchange
Is flexible for passing through capillaries
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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)
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Formation and Destruction of RBC’s
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
Globin
Red blood cell
death and
phagocytosis
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Heme 2 1
Red blood cell
death and
phagocytosis
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow 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
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 6 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 5 4 3 2 1
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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
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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)
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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
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17. Regulation of Erythropoiesis
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18. Characteristics & functions of blood cells

19. 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
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20. White Blood Cell Functions
Neutrophils: first responders to infection
Phagocytosis
Release bacteria-destroying enzyme lysozyme
Monocytes  macrophages (“big eaters”)
Known as wandering macrophages
Eosinophils
Phagocytose antibody-antigen complexes
Help suppress inflammation of allergic reactions
Respond to parasitic infections
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21. White Blood Cell Functions
Basophils
Intensify inflammatory responses and allergic reactions, e.g. after contact with poison oak.
Release chemicals that strongly dilate blood vessels, such as histamine and serotonin; also release heparin (anticoagulant)
Poison ivy reaction
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22. 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.

23. 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
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WBC Life Span
WBCs: ,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
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Platelets
Myeloid stem cells  megakaryocytes  2000–3000 fragments = platelets
Normal count: 150, ,000/µl blood
Functions
Plug damaged blood vessels
Promote blood clotting
Life span 5–9 days
Copyright 2010, John Wiley & Sons, Inc.

26. Hemostasis: “Blood Standing Still”
Sequence of events to avoid hemorrhage
Vascular spasm
Response to damage
Quick reduction of blood loss
Platelet plug formation
Platelets become sticky when contact damaged vessel wall
Blood clotting (coagulation)
Series of chemical reactions involving clotting factors   
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27. Blood Clotting (Coagulation)
Extrinsic pathway
Tissue factor(TF) from damaged cells 1  2  3
Intrinsic Pathway
Materials “intrinsic” to blood  1  2  3
Common pathway: 3 major steps
Prothrombinase 
Prothrombin  thrombin
Fibrinogen  fibrin  clot
Ca++ plays important role in many steps
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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 +
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 1
Stages of Clotting
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29. Triggering of blood coagulation

30. 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
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31. Hemostatic Control Mechanisms
Fibrinolysis: breakdown of clots by plasmin
Inactivated plasminogen 
Activated (by tPA)  plasmin
Inappropriate (unneeded) clots
Clots can be triggered by roughness or micro-lesions on vessel wall = can cause thrombosis
Loose (on-the-move) clot = embolism
Anticoagulants: decrease clot formation
Heparin
Warfarin (Coumadin)
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32. Anti-blood coagulation drugs
 1. Aspirin (low doses, 80mg "Baby pill")  - inhibits vasoconstriction and platelet aggregation in low concentrations  - blocks formation of vaso-regulatory prostaglandins due to inhibition of the cyclooxygenase enzyme  - synthetic anti-coagulant (acetyl-salicylic acid) - side effects includes he danger of internal bleedings ("hemorrhages") especially in individuals with pre- existing ulcers;      2. Heparin (natural (physiological) anti-coagulant)   - inhibits the conversion of prothrombin into thrombin (Factor IIa) by interferingwith coagulation factors   - produced by mast cells and basophils 

33. 3. Hirudin - traditional medicinal anti-coagulant derived from the saliva of leeches (Hiruda medicinalis)   4. natural or recombinant tissue plasminogen activator (r-tPA; "Actilyse") -  blood clot dissolving body- produced protease enzyme which converts plasminogen into plasmin  - released by endothelial cells  - often used to treat acute stroke or heart attack patients

34. 5. Warfarin ("Coumarin-derivative") - plant-derived antagonist of vitamin K which blocks the synthesis of 4 coagulation factors 6. Streptokinase - thrombolytic protein produced by streptococcal bacteria - first thrombolytic agent approved in 1982 to dissolving blood clots in the   heart arteries of heart attack patients   7. ACD or CPD - calcium ion-chelating, citrate- containing solution routinely used to prevent spontaneous clotting of donated blood in blood banks and laboratories

35. 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
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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
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ABO Group
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38. Blood type distribution

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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 % 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”
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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
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41. Complement & Immune system

42. Blood & Health
There is a connection of life style habits and healthy blood function as well as cardiovascular health:
Following factors are critical: 1. Watch cholesterol (& LDL) levels 2. Quit smoking (Free radicals & mutagens) 3. Exercise regularly & moderately 4. Watch blood pressure 4. Cope effectively with psychological and physical stress 5. Eat a heart-healthy diet rich in anti- oxidants, fibers, and flavonoids  

43. Hematocrit
A simple measure for the percentage of red blood cells (RBCs) in the blood (= blood cell count method).
A normal hematocrit of 40 means that 40% of the volume of blood is composed of RBCs; - hematocrit 40:                normal - hematocrit 35:                mild anemia - hematocrit 15:                severe anemia - hematocrit > 40:            often the case in extreme athletes or                                          in humans living in high altitudes           

44. Induced polycythemia
Abnormal increase of the RBC count in blood over an hematocrit of 55% due to "EPO doping“, the injection of the RBC-differentiating hormone erythropoietin (EPO), usually in its recombinant form ("Epoetin alpha”).
Leads to a vastly increased risk for heart attacks and strokes.

45. Hemophilia X-chromosome-inherited human genetic disorder.
Affected humans. mostly of male gender, show a deficiency or absence of normal blood clotting which leads to continuous bleeding which may occur spontaneously or after traumatic injury.
Caused by mutations of the genes of critical coagulation factors (CF), e.g. the gene for CV VIII.
Disorder is characterized by spontaneous or traumatic subcutaneous and intramuscular hemorrhaging, nosebleeds, blood in the urine, and hemorrhages in the joints that generate pain and tissue damage.
Treatment: transfusions of fresh plasma or of the deficient coagulation factor, e.g. in form of recombinant (= bio-technologically produced) CF versions.