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Blood
17
Blood is a viscous suspension:
pH 7.35-7.45
Temperature 38C
Volume of blood is about 5L (8% body weight)
A Liquid Tissue
Functions of Blood

Distribution:
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Regulation:

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O2, nutrients, metabolic products/wastes, hormones, H2O
Temp, pH, fluid volume
Protection:

Fluid/blood loss prevention, prevention of infection
Components of Whole Blood
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes & platelets
(<1% of whole blood)
Formed
elements
1 Withdraw blood &
2 Centrifuge
place in tube

Composition:
 Plasma: about 55%
 Formed Elements: about 45%
Erythrocytes
(45% of whole blood)
Figure 17.1
Plasma
whole blood
Cells
Plasma
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Mostly H2O, straw-colored
> 100 solutes: electrolytes, gases, hormones,
proteins & metabolic products
Predominate protein: Albumin (responsible for
plasma osmotic pressure)
Formed Elements

Erythrocytes (RBCs), leukocytes (WBCs), &
platelets (PLTs)
 Only WBCs are complete cells
 RBCs have no nuclei or organelles
 Platelets are cell fragments
Blood Cell Production

Hematopoiesis
 Tissue: Red bone marrow
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Flat bones
Epiphysis of femur & humerus
Cell: all blood cells arise from Hematopoietic
Stem Cells (Hemocytoblasts)
Erythrocytes (RBCs)
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Biconcave discs, 7.5 microns
Anucleate, essentially no organelles
Filled with hemoglobin (Hb)
Shape is maintained by a protein framework
(spectrin) & other proteins:
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Figure 17.3
Gives RBCs their shape & flexibility
RBC function is gas transport/exchange
Erythrocyte Function: Hb

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2 a & 2 b chains, each bound to a heme group
Heme:
 Fe containing organic ring structure (porphyrin)
 Reversibly binds O2 ; each Hb can bind 4 O2
 Each RBC has 250 million Hb molecules = 1 billion O2
Hemoglobin

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Oxyhemoglobin: Hb bound to O2
Deoxyhemoglobin: Hb after O2 diffuses into tissues
Carbaminohemoglobin: Hb bound to CO2
 CO2 is bound to the polypeptide not to the heme group
 Carries about 20% of CO2 in the blood
Erythropoiesis (RBC Production):
Hormonal Control

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Erythropoietin (EPO) release by the kidneys is triggered by
hypoxia (decreased [O2])
 Decreased RBC count
 Decreased oxygen availability
 Increased tissue demand for oxygen
Effect: EPO causes maturation of precursor cells that are in
a committed RBC line
Erythropoiesis: RBC Line

Effect: EPO causes maturation of precursor cells that are in
a committed RBC line
Erythropoiesis: Iron (Fe)

65% of Fe stored in Hb:
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Intracellular Fe stored in protein-Fe complexes (ferritin &
hemosiderin) in liver & spleen
Fe is transported on transferrin (transport protein)
Fe obtained in diet; small daily losses
Other dietary requirements: B12 & folate (needed
for DNA synthesis), other nutrients.
Erythrocyte Disorders

Anemia: blood has abnormally low O2 carrying capacity (A
symptom not a disease itself)
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Blood O2 levels cannot support normal metabolism
Signs: fatigue, paleness, shortness of breath, & chills
Anemia
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Decreased RBCs
Decreased Hb
Abnormal Hemoglobin
Anemia: Decreased RBCs

Decreased RBCs: increased destruction/loss or decreased
production
 Hemorrhagic anemia – blood loss
 Hemolytic anemia – RBC destruction (due to abnormal
Hb, infection, trauma etc.)
 Aplastic anemia – destruction or inhibition of red bone
marrow (impacts other formed elements)
Anemia: Decreased Hb
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Iron-deficiency anemia (small pale RBC): decreased HB
 Inadequate Fe intake
 Impaired Fe absorption
 Secondary to hemorrhagic anemia
Pernicious anemia (large pale RBC):
 Deficiency of vitamin B12
 Lack of intrinsic factor (required to absorption B12)
 Treatment - give B12
Anemia: Abnormal Hemoglobin
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Abnormal Hb: due to genetic defect
Thalassemias (Mediterranean ancestry)
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Absent or faulty globin chain in Hb:
Fragile RBCs
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Thin, delicate, & deficient in Hb
Low RBC count
Anemia: Abnormal Hemoglobin
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Sickle-cell anemia: (African ancestry)
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Abnormal Hb called HbS
HbS has a single amino acid substitution in the beta chain
Causes RBCs to become sickle-shaped in low O2 situations
RBC debris clog capillaries
Polycythemia
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Polycythemia: excess RBCs - increased blood
viscosity/sludging
Three main polycythemias are:
 Polycythemia vera
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Secondary polycythemia
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(may be due to marrow cancer)
(due to erythropoesis)
Blood doping
Fate & Destruction of RBCs
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RBCs are anucleate; do not grow, do not make new
protein, do not divide
Old RBCs become rigid & fragile.
The life span of an RBC is 100–120 days
Fate & Destruction of RBCs
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Dying RBCs are engulfed by macrophages in the spleen
Heme & globin are separated & the Fe is recycled to ferritin
or hemosiderin
 Heme is degraded to bilirubin (yellow)
 Bilirubin is secreted by the liver into the intestine as bile
 The intestines metabolize it into urobilinogen (green)
then to stercobilin (brown)
 Globin portion is metabolized into amino acids & is
released into the circulation
Life Cycle of Red Blood Cells
Figure 17.7
Leukocytes (WBCs): Characteristics
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Complete cells: contain nucleus , organelles
Diapedesis: the ability to move out of the bloodstream &
function
 Circulatory system used to get WBC to the vicinity
 Cellular/chemical signals prompt diapedesis
Amoeboid movement – WBCs travel through tissues to the
target area
Positive chemotaxis: WBCs follow a chemical trail to the target
WBC Function & Classification
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Function:
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Phagocytosis, antibody production, waste clean-up, act
as chemical “sharpshooters”
Classification:
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Based upon appearance after staining
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(Wright’s stain)
Granulocytes
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Visible granules on staining – lobed nuclei
Neutrophils, eosinophils, & basophils
 Granules stain specifically (acidic, basic, or both)
 Larger & usually shorter-lived than RBCs
 All are phagocytic cells
Figure 17.10a-c
Neutrophils
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Multi-lobed nucleus;
neutral staining
 Granules take up both
acidic & basic dyes
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Contain peroxidases,
hydrolytic enzymes, &
defensins (antibiotic-like
proteins)
Phagocytize bacteria &
some fungi
Eosinophils
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Large bilobed nucleus
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Red staining (acidophilic)
large, coarse, granules
containing digestive enzymes
Attack parasitic worms by
degranulation
Phagocytize immune
complexes
Basophils
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Large, dark (basophilic)
granules containing
histamine
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inflammatory chemical;
vasodilator, attracts other
WBCs (antihistamines
counter this effect)
Interact with IgE
antibodies (allergies) to
promote degranulation
Agranulocytes
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No visible granules, mononuclear
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Monocytes & lymphocytes
Have spherical (lymphocytes) or kidney-shaped
(monocytes) nuclei
Figure 17.10e,d
Monocytes
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The largest WBCs
Active phagocytes;
attack viruses
Help activate
lymphocytes (immune
response)
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In tissues they
differentiate into
macrophages
Lymphocytes
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Most found in lymphoid
tissue (some circulate in the
blood)
Two types of lymphocytes:
 T cells – immune system
functions
 B cells give rise to plasma
cells, which produce
antibodies
Summary of Formed Elements
Table 17.2
Summary of Formed Elements
Table 17.2
Leukocyte Production
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Leukopoiesis - hormonally stimulated by cytokines:
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Interleukins
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Colony-stimulating factors
Macrophages & T cells are most important sources
of cytokines
Leukocyte (WBC) Formation
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All WBCs originate from
hemocytoblasts
Hemocytoblasts
differentiate into
myeloid stem cells &
lymphoid stem cells
Stem cells mature &
differentiate into specific
WBC lines
Figure 17.11
Leukocytes Disorders:
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Leukopenia: abnormally low WBC count
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some drugs & viruses
Leukocytosis: WBC count greater than 11,000/mm3
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Infection and/or stress
Leukemia
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Leukemia: cancer involving WBCs
Leukemias are named according to the abnormal WBCs
 Myelocytic – involves cells of myeloid lineage
 Lymphocytic – involves cells of lymphoid lineage
Leukocyte (WBC) Formation
Figure 17.11
Leukemia (cont)
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Acute - involves more primitive cells (blasts) & primarily
affects children
Chronic - more prevalent in older people
Leukemia (cont)
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Bone marrow becomes overwhelmed with the clone cell
population.
Cancerous cells crowd out all other cell lines
 Anemia
 Decrease in all other cell populations
 Bleeding problems
The cancerous WBCs are nonfunctional
Death by hemorrhage & overwhelming infections
Treatment - radiation, antileukemic drugs, & bone marrow
transplants
Platelets (PLTs): Characteristics &
Function
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Characteristics:
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Platelets are not true cells they are fragments of megakaryocytes
Small purple spots on Wright’s stain
Function: granules contain a large number of
chemicals involved in clot formation
Platelet Production: regulated by Thrombopoietin
Platelet Production
Figure 17.12
Hemostasis
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A series of reactions designed to stop bleeding
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Three phases:
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Vascular spasm
Platelet plug formation
Coagulation (blood clotting)
Vascular Spasm
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Vascular spasm: vasoconstriction in response to
smooth muscle injury & chemicals from damaged
cells
Platelet Plug Formation
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PLT adhesion: PLTs adhere to collagen exposed by
endothelial damage
PLT activation (degranulation): releases chemicals
 Serotonin – enhances vasospasm
 ADP – attracts more PLTs
 Thromboxane A2 – enhances serotonin & ADP release
(positive feedback)
As PLTs aggregate a plug is formed
PGI2 (prostacyclin) a prostaglandin made by endothelium
limits the extent of the plug
Coagulation
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Thirteen clotting factors (I – XIII) react to transform blood
from a liquid to a gel
Follow the intrinsic & extrinsic pathways yielding
prothrombin activator
Final Common Pathway: Final three steps of this
series of reactions are:
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Prothrombin activator is formed
Prothrombin is converted into thrombin
Thrombin catalyzes the joining of fibrinogen into a fibrin
mesh
Coagulation:
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Procoagulants (clotting factors) act as
enzymes that catalyze the conversion of
other factors
Conversion of fibrinogen (a plasma protein)
to fibrin (insoluble protein strands) forms a
net that traps RBCs & PLTs
Coagulation
Figure 17.13
Coagulation:
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Final Common Pathway: Final three steps of these reactions;
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Prothrombin activator is formed
Prothrombin is converted into thrombin
Thrombin catalyzes the joining of fibrinogen into a fibrin mesh
Clot Retraction & Repair
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Clot retraction: PLTs release actin & myosin which contract
& solidify the clot
Repair: Platelet-derived growth factor (PDGF) stimulates
repair of blood vessel wall
Factors Limiting Clot Growth
or Formation

Two homeostatic mechanisms prevent clots from becoming
large
 Swift removal of clotting factors
 Inhibition of activated clotting factors
Factors Limiting Clot Growth
or Formation
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Fibrinolysis: dissolving the clot
 Plasminogen is activated by tissue plasminogen
activating factor to form;
 Plasmin which digests fibrin
Clot formation must be limited to the area of injury
 Dilution: clotting factors must be present in high enough
concentration to interact
 Antithrombin III: inactivates thrombin that is not in
association with fibrin
Disorders of Hemostasis :
Thromboembolytic Conditions
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Thrombus:
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Embolus:
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a clot that develops & persists in an unbroken blood vessel
a thrombus broken free & moving in the circulation
Embolism:
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an embolus wedged in a vessel
Hemostasis Disorders
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Disseminated Intravascular Coagulation (DIC):
runaway coagulation in intact blood vessels
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Consumes clotting factors - residual blood cannot clot
Untreated: severe hemorrhage
Hemostasis Disorders:
Bleeding Disorders
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Thrombocytopenia: insufficient platelets
Spontaneous bleeding
 Petechiae - small bruises
 Often due to viral infection
 May be due to medication or bone marrow destruction
Liver dysfunction - failure to synthesize procoagulants
May be due to vitamin K deficiency
Hepatitis/cirrhosis
Hemostasis Disorders:
Bleeding Disorders
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Hemophilias: hereditary bleeding disorders
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Hemophilia A (Classic): factor VIII deficiency
Hemophilia B: factor IX deficiency
Both A & B are sex linked recessive
Hemophilia C: factor XI deficiency, a milder form that can
effect both sexes
Definitions: Blood antigens
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Antigen; a substance that is capable of eliciting an immune
response
Antibody; a protein released by the immune system that
binds to a specific antigen
Blood Groups
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Humans have >30 varieties of naturally occurring RBC
surface antigens
M, N, Duffy, Kell, & Lewis are mainly used for legalities
Lansteiner (ABO) group:
 Corresponding antibodies are naturally present & can
cause vigorous transfusion reactions
Rh Blood Groups
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Antibodies to the D (Rh+) antigen are not naturally
present
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If an Rh– individual receives Rh+ blood, anti-Rh
antibodies form
A second exposure to Rh+ blood will result in a typical
transfusion reaction
Hemolytic Disease of the
Newborn
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First pregnancy: Rh– Mom & Rh+ infant yields no reaction
but, antibodies are formed
Second pregnancy: sensitized Rh– mother with Rh+ infant;
antibodies cross the placenta & attack & destroy the RBCs
the baby
The drug RhoGAM can prevent the Rh– mother from
becoming sensitized
Transfusion

Group/type specific blood (i.e. give A+ patient A+ blood):
cross match
Universal donor (O-)
 Neither A nor B nor Rh on cells
 Use only packed cells not O- plasma
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Autologous transfusion: patient receives their own blood
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Transfusion Reaction
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Occurs when recipient plasma has antibodies to donor cells
(antigens)
Can involve antigens other than A, B or Rh
Sx (symptoms): fever, chills, hypotension, tachycardia,
nausea/vomiting, etc. Can result in renal failure.