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Blood
Overview of Blood Circulation
Blood leaves the heart via arteries that
branch repeatedly until they become
capillaries
 Oxygen (O2) and nutrients diffuse across
capillary walls and enter tissues
 Carbon dioxide (CO2) and wastes move
from tissues into the blood

Overview of Blood Circulation
Oxygen-deficient blood leaves the
capillaries and flows in veins to the heart
 This blood flows to the lungs where it
releases CO2 and picks up O2
 The oxygen-rich blood returns to the heart

Composition of Blood
Blood is a connective fluid tissue
 It is composed of liquid plasma and formed
elements
 Formed elements include:

 Erythrocytes,
or red blood cells (RBCs)
 Leukocytes, or white blood cells (WBCs)
 Platelets

Hematocrit – the percentage of RBCs out
of the total blood volume
Components of Whole Blood
Physical Characteristics and
Volume
Blood is a sticky, opaque fluid with a
metallic taste
 Color varies from scarlet to dark red
 The pH of blood is 7.35–7.45
 Temperature is 38C
 Blood accounts for approximately 8% of
body weight
 Average volume: 5–6 L for males, and 4–5
L for females

Functions of Blood

Blood performs a number of functions
dealing with:
 Substance
distribution
 Regulation of blood levels of particular
substances
 Body protection
Distribution

Blood transports:
 Oxygen
from the lungs and nutrients from
the digestive tract
 Metabolic wastes from cells to the lungs and
kidneys for elimination
 Hormones from endocrine glands to target
organs
Regulation

Blood maintains:
 Appropriate
body temperature by absorbing
and distributing heat
 Normal pH in body tissues using buffer
systems
 Adequate fluid volume in the circulatory
system
Protection

Blood prevents blood loss by:
 Activating
plasma proteins and platelets
 Initiating clot formation when a vessel is
broken

Blood prevents infection by:
 Activating
complement proteins
 Activating WBCs to defend the body against
foreign invaders
Blood Plasma

Blood plasma contains over 100 solutes,
including:
– albumin, globulins, clotting
proteins, and others
 Lactic acid, urea, creatinine
 Organic nutrients – glucose, carbohydrates,
amino acids
 Electrolytes – sodium, potassium, calcium,
chloride, bicarbonate
 Respiratory gases – oxygen and carbon
dioxide
 Proteins
Formed Elements

Erythrocytes, leukocytes, and platelets
make up the formed elements
 Only
WBCs are complete cells
 RBCs have no nuclei or organelles, and
platelets are just cell fragments
Most formed elements survive in the
bloodstream for only a few days
 Most blood cells do not divide but are
renewed by cells in bone marrow

Components of Whole Blood
Erythrocytes (RBCs)
Biconcave discs, anucleate, essentially no
organelles
 Filled with hemoglobin (Hb), a protein that
functions in gas transport
 Contain the plasma membrane protein
spectrin and other proteins that:

 Give
erythrocytes their flexibility
 Allow them to change shape as necessary
Erythrocytes (RBCs)
Erythrocytes (RBCs)
Erythrocytes are an example of the
complementarity of structure and function
 Structural characteristics contribute to its
gas transport function

 Biconcave
shape has a huge surface area
relative to volume
 Erythrocytes are more than 97% hemoglobin
 ATP is generated anaerobically, so the
erythrocytes do not consume the oxygen
they transport
Erythrocyte Function





RBCs are dedicated to respiratory gas
transport
Hb reversibly binds with oxygen and most
oxygen in the blood is bound to Hb
Hb is composed of the protein globin, made up
of two alpha and two beta chains, each bound
to a heme group
Each heme group bears an atom of iron, which
can bind to one oxygen molecule
Each Hb molecule can transport four molecules
of oxygen
Structure of Hemoglobin
Hemoglobin (Hb)

Oxyhemoglobin – Hb bound to oxygen
 Oxygen
loading takes place in the lungs
Deoxyhemoglobin – Hb after oxygen
diffuses into tissues (reduced Hb)
 Carbaminohemoglobin – Hb bound to
carbon dioxide

 It
binds to globin’s amino acids
 Carbon dioxide loading takes place in the
tissues
Production of Erythrocytes
Hematopoiesis – blood cell formation
 Hematopoiesis occurs in the red bone
marrow of the:

 Axial
skeleton and girdles
 Epiphyses of the humerus and femur

Hemocytoblasts give rise to all formed
elements
Production of Erythrocytes:
Erythropoiesis
A hemocytoblast is transformed into a
proerythroblast
 Proerythroblasts develop into early
erythroblasts

Production of Erythrocytes:
Erythropoiesis


The developmental pathway consists of three
phases
 1 – ribosome synthesis in early erythroblasts
 2 – Hb accumulation in late erythroblasts and
normoblasts
 3 – ejection of the nucleus from normoblasts
and formation of reticulocytes
Reticulocytes then become mature erythrocytes
 1-2% of RBC in health people
Production of Erythrocytes:
Erythropoiesis
Regulation and Requirements for
Erythropoiesis

Circulating erythrocytes – the number
remains constant and reflects a balance
between RBC production and destruction
 Too
few RBCs leads to tissue hypoxia
 Too many RBCs causes undesirable blood
viscosity

Erythropoiesis is hormonally controlled and
depends on adequate supplies of iron,
amino acids, and B vitamins
Hormonal Control of
Erythropoiesis

Erythropoietin (EPO) release by the
kidneys is triggered by:
 Hypoxia
due to decreased RBCs or
hemoglobin content
 Decreased oxygen availability
 Increased tissue demand for oxygen

Enhanced erythropoiesis increases the:
 RBC
count in circulating blood
 Oxygen carrying ability of the blood
Erythropoietin Mechanism
Start
Homeostasis: Normal blood oxygen levels
Stimulus: Hypoxia due to
decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2
Increases
O2-carrying
ability of blood
Reduces O2 levels
in blood
Enhanced
erythropoiesis
increases
RBC count
Erythropoietin
stimulates red
bone marrow
Kidney (and liver to a smaller
extent) releases erythropoietin
Dietary Requirements of
Erythropoiesis




Erythropoiesis requires:
 Proteins, lipids, and carbohydrates
 Iron, vitamin B12, and folic acid
The body stores iron in Hb (65%), the liver,
spleen, and bone marrow
Intracellular iron is stored in protein-iron
complexes such as ferritin and hemosiderin
Circulating iron is loosely bound to the
transport protein transferrin
Fate and Destruction of
Erythrocytes
The life span of an erythrocyte is 100–120
days
 Old RBCs become rigid and fragile, and
their Hb begins to degenerate
 Dying RBCs are engulfed by macrophages
 Heme and globin are separated and the
iron is salvaged for reuse

Fate and Destruction of
Erythrocytes
Heme is degraded to a green pigment
biliverdin
 Biliverdin is converted to a yellow pigment
called bilirubin
 The bilirubin is picked up by the liver and
secreted into the intestines as bile

Fate and Destruction of
Erythrocytes
The intestines metabolize it into
urobilinogen and stercobilinogen
 These degraded pigments leave the body
in feces and urine, in a pigment called
stercobilin and urobilin

Fate and Destruction of
Erythrocytes
Globin is metabolized into amino acids
and is released into the circulation
 Hb released into the blood is captured by
haptoglobin and phagocytized

Low O2 levels in blood stimulate
kidneys to produce erythropoietin.
1
2
3
Erythropoietin levels
rise in blood.
Erythropoietin and necessary
raw materials in blood promote
erythropoiesis in red bone marrow.
4
5
Aged and damaged red
blood cells are engulfed by
macrophages of liver, spleen,
and bone marrow; the hemoglobin
is broken down.
Hemoglobin
New erythrocytes
enter bloodstream;
function about
120 days.
1 Low O2 levels in blood stimulate
kidneys to produce erythropoietin.
2 Erythropoietin levels
rise in blood.
3 Erythropoietin and necessary
raw materials in blood promote
erythropoiesis in red bone marrow.
4 New erythrocytes
enter bloodstream;
function about
120 days.
5 Aged and damaged red
blood cells are engulfed by
macrophages of liver, spleen,
and bone marrow; the hemoglobin
is broken down.
Hemoglobin
Heme
Globin
Bilirubin
Iron stored
as ferritin,
hemosiderin
Amino
acids
Iron is bound to
transferrin and released
to blood from liver
as needed for
erythropoiesis
Bilirubin is picked up from
blood by liver, secreted into
intestine in bile, metabolized
to stercobilin by bacteria
and excreted in feces
Circulation
Food nutrients,
including amino
acids, Fe, B12,
and folic acid
are absorbed
from intestine
and enter blood
6 Raw materials are
made available in
blood for erythrocyte
synthesis.
Erythrocyte Disorders


Anemia
Low RBC count or Hemoglobin content
 Low oxygen-carrying capacity
 It is a symptom rather than a disease itself
 Blood oxygen levels cannot support normal
metabolism
 Signs/symptoms include fatigue, paleness,
shortness of breath, and chills
Anemia: Insufficient
Erythrocytes
Hemorrhagic anemia – result of acute or
chronic loss of blood
 Hemolytic anemia – prematurely ruptured
RBCs
 Aplastic anemia – destruction or inhibition
of red bone marrow

Anemia: Decreased Hemoglobin
Content



Iron-deficiency anemia results from:
 A secondary result of hemorrhagic anemia
 Inadequate intake of iron-containing foods
 Impaired iron absorption
Pernicious anemia results from:
 Deficiency of vitamin B12
 Lack of intrinsic factor needed for absorption of
B12
Treatment is intramuscular injection of B12
Anemia: Abnormal Hemoglobin

Thalassemias – absent or faulty globin
chain in Hb
 RBCs

are thin, delicate, and deficient in Hb
Sickle-cell anemia – results from a
defective gene coding for an abnormal Hb
called hemoglobin S (HbS)
 HbS
has a single amino acid substitution in
the beta chain
 This defect causes RBCs to become sickleshaped in low oxygen situations
Polycythemia
Polycythemia – excess RBCs that
increase blood viscosity
 Three main polycythemias are:

 Polycythemia
vera
 Secondary polycythemia
 Blood doping
Leukocytes (WBCs)

Leukocytes, the only blood components
that are complete cells:
 Are
less numerous than RBCs
 Make up 1% of the total blood volume
 Can leave capillaries via diapedesis
 Move through tissue spaces
Leukocytes (WBCs)

Leukocytosis – WBC count over 11,000 /
mm3
 Normal
response to bacterial or viral
invasion

Leukopenia – WBC count under
4,000/mm3
Percentages of Leukocytes
Granulocytes

Granulocytes – neutrophils, eosinophils,
and basophils
 Contain
cytoplasmic granules that stain
specifically (acidic, basic, or both) with
Wright’s stain
 Are larger and usually shorter-lived than
RBCs
 Have lobed nuclei
 Are all phagocytic cells
Neutrophils

Neutrophils have two types of granules
that:
 Take
up both acidic and basic dyes
 Give the cytoplasm a lilac color
 Contain peroxidases, hydrolytic enzymes,
and defensins (antibiotic-like proteins)

Neutrophils are our body’s bacteria slayers
burst – by metabolizing oxygen
they produce substances that pierce holes in
the germ’s membrane
 Respiratory
Eosinophils

Eosinophils account for 1–4% of WBCs
 Have
red-staining, bilobed nuclei connected
via a broad band of nuclear material
 Have red to crimson (acidophilic) large,
coarse, lysosome-like granules
 Lead the body’s counterattack against
parasitic worms
 Lessen the severity of allergies by
phagocytizing immune complexes
Basophils

Account for 0.5% of WBCs and:
 Have
U- or S-shaped nuclei with two or
three conspicuous constrictions
 Have large, purplish-black (basophilic)
granules that contain histamine
 Histamine – inflammatory chemical that
acts as a vasodilator and attracts other
WBCs (antihistamines counter this effect)
 Mast cells
 Are functionally similar to basophils
Agranulocytes

Agranulocytes – lymphocytes and
monocytes:
 Lack
visible cytoplasmic granules
 Are similar structurally, but are functionally
distinct and unrelated cell types
 Have spherical (lymphocytes) or kidneyshaped (monocytes) nuclei
Lymphocytes

Account for 25% or more of WBCs and:
 Have
large, dark-purple, circular nuclei with
a thin rim of blue cytoplasm
 Are found mostly enmeshed in lymphoid
tissue (some circulate in the blood)

There are two types of lymphocytes: T
cells and B cells
T
cells function in the immune response
 B cells give rise to plasma cells, which
produce antibodies
Monocytes

Monocytes account for 4–8% of
leukocytes
 They
are the largest leukocytes
 They have abundant pale-blue cytoplasms
 They have purple-staining, U- or kidneyshaped nuclei
 They leave the circulation, enter tissue, and
differentiate into macrophages
Macrophages

Macrophages:
 Are
highly mobile and actively phagocytic
 Activate lymphocytes to mount an immune
response
Leukocytes
Summary of Formed Elements
51
Summary of Formed Elements
52
Production of Leukocytes

Leukopoiesis is stimulated by interleukins
and colony-stimulating factors (CSFs)
 Interleukins
are numbered (e.g., IL-1, IL-2),
whereas CSFs are named for the WBCs
they stimulate (e.g., granulocyte-CSF
stimulates granulocytes)
Macrophages and T cells are the most
important sources of cytokines
 Many hematopoietic hormones are used
clinically to stimulate bone marrow

Formation of Leukocytes
All leukocytes originate from
hemocytoblasts
 Hemocytoblasts differentiate into myeloid
stem cells and lymphoid stem cells
 Myeloid stem cells become eosinophilic,
basophilic and neutrophilic myeloblasts or
monoblasts
 Lymphoid stem cells become lymphoblasts

Formation of Leukocytes
The myeloblasts develop into eosinophils,
neutrophils, and basophils
 Monoblasts develop into monocytes
 Lymphoblasts develop into lymphocytes

56
Leukocytes Disorders: Leukemias




Leukemia refers to cancerous conditions
involving WBCs
Leukemias are named according to the
abnormal WBCs involved
 Myelocytic leukemia – involves myeloblasts
 Lymphocytic leukemia – involves
lymphocytes
Acute leukemia involves blast-type cells and
primarily affects children
Chronic leukemia is more prevalent in older
people
Leukemia





Immature WBCs are found in the bloodstream
in all leukemias
Bone marrow becomes totally occupied with
cancerous leukocytes
The WBCs produced, though numerous, are
not functional
Death is caused by internal hemorrhage and
overwhelming infections
Treatments include irradiation, antileukemic
drugs, and bone marrow transplants
Platelets




Platelets are fragments of megakaryocytes
with a blue-staining outer region and a purple
granular center
Their granules contain serotonin, Ca2+,
enzymes, ADP, and platelet-derived growth
factor (PDGF)
Platelets function in the clotting mechanism by
forming a temporary plug that helps seal
breaks in blood vessels
Platelets not involved in clotting are kept
inactive by NO and prostacyclin
Genesis of Platelets
The stem cell for platelets is the
hemocytoblast
 The sequential developmental pathway is
as shown.

Stem cell
Hemocytoblast
Developmental pathway
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Platelets
Hemostasis
A series of reactions for stoppage of
bleeding
 During hemostasis, three phases occur in
rapid sequence

spasms – immediate
vasoconstriction in response to injury
 Platelet plug formation
 Coagulation (blood clotting)
 Vascular
Hemostasis

Vascular spasms because of:
 Direct
injury to the smooth muscle layer of
the blood vessel
 Chemicals released by the platelet and
endothelial cells
 Reflexes initiated by local pain receptors
Hemostasis



Platelet Plug Formation
Platelets do not stick to each other or to blood
vessels in normal conditions
Upon damage to blood vessel endothelium the
exposed collagen will cause platelets to swell
and become sticky :
 With the help of von Willebrand factor (VWF)
secreted by the endothelial cells .
 Stick to exposed collagen fibers and form a
platelet plug
Hemostasis
 Release

serotonin and ADP, which attract
still more platelets and promote vascular
spam
 Release thromboxane A2 that promotes
further platelet aggregation
The platelet plug is limited to the immediate
area of injury by prostacyclin secreted by
endothelial cells
Hemostasis



Coagulation
A set of reactions in which blood is
transformed from a liquid to a gel
Coagulation follows intrinsic and extrinsic
pathways
Coagulation
67
Detailed Events of Coagulation
Coagulation

May be initiated by either the intrinsic or
extrinsic pathway
 Triggered by tissue-damaging events
 Involves a series of procoagulants
 Each pathway cascades toward factor X
Coagulation
Prothrombin is transformed into thrombin
 Thrombin converts fibrinogen into fibrin
 Fibrin becomes part of the clot


It causes plasma to become a gel-like trap
Clot Retraction and Repair
Clot retraction – stabilization of the clot by
squeezing serum from the fibrin strands
 Restoration of the blood vessel wall

 Platelet
will stimulate
 smooth muscle cells mitosis
 fibroblast multiplication
 endothelial cells division
Fibrinolysis




The process of removal of clots after healing
has occurred
Plasminogen is activated by
 Tissue plasminogen activator (tPA)
released by many tissues
 Thrombin
Plasminogen is converted into plasmin
Plasmin will then digest the clot
Factors Limiting Clot Growth or
Formation

Two homeostatic mechanisms prevent clots
from becoming large
 Blood flow
 Wash away activated clotting factors
 Hinder further grow of forming clot
Factors Limiting Clot Growth or
Formation
 Mechanisms
that prevents thrombin
action
 Fibrin binds thrombin preventing its:
Positive feedback effects of
coagulation
 Fast inactivation of thrombin that escapes
into blood circulation by:
Antithrombin III
Prevention of clotting in the normal
vascular system
The presence of a smooth and intact
endothelial surface
 The presence of circulating antithrombin
factors

 Antithrombin
III
 also inhibits steps of the intrinsic pathway
 Protein C
 inhibits steps of the intrinsic pathway
Prevention of clotting in the
normal vascular system


Heparin
 increases the action of antithrombin III
Vitamin E
 a potent anticoagulant
Hemostasis Disorders:
Thromboembolytic Conditions

Thrombus – a clot that develops and
persists in an unbroken blood vessel
 Thrombi
can block circulation, resulting in
tissue death
 Coronary thrombosis – thrombus in blood
vessel of the heart
Hemostasis Disorders:
Thromboembolytic Conditions

Embolus – a thrombus freely floating in the
blood stream
 Pulmonary
emboli can impair the ability of
the body to obtain oxygen
 Cerebral emboli can cause strokes
Prevention of Undesirable Clots

Substances used to prevent undesirable
clots:
– an antiprostaglandin that inhibits
thromboxane A2
 Heparin – an anticoagulant used clinically
for pre- and postoperative cardiac care
 Warfarin – competes with vitamin K in the
production of some procoagulants
 Aspirin
Hemostasis Disorders
Disseminated Intravascular Coagulation
(DIC): widespread clotting in intact blood
vessels
 Residual blood cannot clot
 Blockage of blood flow and severe
bleeding follows
 Most common as:

A
complication of pregnancy
 A result of septicemia or incompatible blood
transfusions
Hemostasis Disorders: Bleeding
Disorders

Thrombocytopenia – condition where the
number of circulating platelets is deficient
 Patients
show petechiae due to
spontaneous, widespread hemorrhage
 Caused by suppression or destruction of
bone marrow (e.g., malignancy, radiation)
 Platelet counts less than 50,000/mm3 is
diagnostic for this condition
 Treated with whole blood transfusions
Hemostasis Disorders: Bleeding
Disorders




Inability to synthesize procoagulants by the
liver results in severe bleeding disorders
Causes can range from vitamin K deficiency to
hepatitis and cirrhosis
Inability to absorb fat can lead to vitamin K
deficiencies as it is a fat-soluble substance and
is absorbed along with fat
Liver disease can also prevent the liver from
producing bile, which is required for fat and
vitamin K absorption
Hemostasis Disorders: Bleeding
Disorders

Hemophilias – hereditary bleeding
disorders caused by lack of clotting factors
A – most common type (83% of
all cases) due to a deficiency of factor VIII
 Hemophilia B – due to a deficiency of factor
IX
 Hemophilia C – mild type, due to a
deficiency of factor XI
 Hemophilia
Hemostasis Disorders: Bleeding
Disorders
Symptoms include prolonged bleeding and
painful and disabled joints
 Treatment is with blood transfusions and
the injection of missing factors

Blood Transfusions

Whole blood transfusions are used:
 When
blood loss is substantial
 In treating thrombocytopenia

Packed red cells (cells with plasma
removed) are used to treat anemia
Human Blood Groups
RBC membranes have glycoprotein
antigens on their external surfaces
 These antigens are:

 Unique
to the individual
 Recognized as foreign if transfused into
another individual
 Promoters of agglutination and are referred
to as agglutinogens

Presence or absence of these antigens is
used to classify blood groups
Blood Groups
Humans have 30 varieties of naturally
occurring RBC antigens
 The antigens of the ABO and Rh blood
groups cause vigorous transfusion
reactions when they are improperly
transfused
 Other blood groups (M, N, Dufy, Kell, and
Lewis) are mainly used for legalities

ABO Blood Groups

The ABO blood groups consists of:
 Two
antigens (A and B) on the surface of the
RBCs
 Two antibodies in the plasma (anti-A and
anti-B)
ABO blood groups may have various types
of antigens and preformed antibodies
 Agglutinogens and their corresponding
antibodies cannot be mixed without
serious hemolytic reactions

ABO Blood Groups
Rh Blood Groups
There are eight different Rh agglutinogens,
three of which (C, D, and E) are common
 Presence of the Rh agglutinogens on
RBCs is indicated as Rh+
 Anti-Rh antibodies are not spontaneously
formed in Rh– individuals
 However, 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
Hemolytic disease of the newborn – Rh+
antibodies of a sensitized Rh– mother
cross the placenta and attack and destroy
the RBCs of an Rh+ baby
 Rh– mother becomes sensitized when
exposure to Rh+ blood causes her body to
synthesize Rh+ antibodies

Hemolytic Disease of the
Newborn
The drug RhoGAM can prevent the Rh–
mother from becoming sensitized
 Treatment of hemolytic disease of the
newborn involves pre-birth transfusions
and exchange transfusions after birth

Transfusion Reactions
Transfusion reactions occur when
mismatched blood is infused
 Donor’s cells are attacked by the
recipient’s plasma agglutinins causing:

 Diminished
oxygen-carrying capacity
 Clumped cells that impede blood flow
 Ruptured RBCs that release free
hemoglobin into the bloodstream
Transfusion Reactions

Circulating hemoglobin precipitates in the
kidneys and causes renal failure
Blood Typing
When serum containing anti-A or anti-B
agglutinins is added to blood, agglutination
will occur between the agglutinin and the
corresponding agglutinogens
 Positive reactions indicate agglutination

Blood Typing
Blood type being
tested
RBC agglutinogens
Serum Reaction
Anti-A
Anti-B
AB
A and B
+
+
B
B
–
+
A
A
+
–
O
None
–
–
Plasma Volume Expanders
When shock is imminent from low blood
volume, volume must be replaced
 Plasma or plasma expanders can be
administered

Plasma Volume Expanders

Plasma expanders
 Have
osmotic properties that directly
increase fluid volume
 Are used when plasma is not available
 Examples: purified human serum albumin,
plasminate, and dextran

Isotonic saline can also be used to replace
lost blood volume
Diagnostic Blood Tests
Laboratory examination of blood can
assess an individual’s state of health
 Microscopic examination:

in size and shape of RBCs –
predictions of anemias
 Type and number of WBCs – diagnostic of
various diseases
 Variations

Chemical analysis can provide a
comprehensive picture of one’s general
health status in relation to normal values
Developmental Aspects
Before birth, blood cell formation takes
place in the fetal yolk sac, liver, and
spleen
 By the seventh month, red bone marrow is
the primary hematopoietic area
 Blood cells develop from mesenchymal
cells called blood islands
 The fetus forms HbF, which has a higher
affinity for oxygen than adult hemoglobin

Developmental Aspects
Age-related blood problems result from
disorders of the heart, blood vessels, and
the immune system
 Increased leukemias are thought to be due
to the waning deficiency of the immune
system
 Abnormal thrombus and embolus
formation reflects the progress of
atherosclerosis
