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Functions of Blood
Substance distribution
Regulation of blood levels of particular
substances

Blood

Body protection

Blood Functions: Distribution

Blood Functions: Regulation

Oxygen from the lungs and nutrients from

the digestive tract

Appropriate body temperature by absorbing and

distributing heat to other parts of the body

Metabolic wastes from cells to the lungs

and kidneys for elimination

Normal pH in body tissues using buffer systems

Adequate fluid volume in the circulatory system

Hormones from endocrine glands to target

organs

Blood Functions: Protection

Prevents blood loss by:
Activating plasma proteins and platelets
Initiating clot formation when a vessel is
broken

Blood Functions: Protection

Prevents infection by:
Synthesizing and utilizing antibodies
Activating complement proteins
Activating WBCs to defend the body
against foreign invaders

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Physical Characteristics of Blood

Average volume of blood:
56 L for males
45 L for females
Viscosity (thickness) - 4 - 5 (water = 1)
The pH of blood is 7.357.45

Physical Characteristics of Blood

Osmolarity = 300 mOsm or 0.3 Osm (osmole)
This value reflects the concentration of solutes in the plasma
Tap water has an osmolarity of roughly 28 mOsm

Salinity = 0.85%
Reflects the concentration of NaCl in the blood

Temperature is 38C, slightly higher than normal body

temperature (37C)
Blood accounts for approximately 8% of body weight

Composition of Blood

Components of Whole Blood

Blood is the bodys only fluid tissue (a

connective tissue)
Plasma
(55% of whole blood)

2 major components
Liquid = plasma (55%)
Formed elements (45%)
Erythrocytes, or red blood cells (RBCs)
Leukocytes, or white blood cells (WBCs)
Platelets - fragments of megakaryocytes in marrow

Blood Plasma Components

Water=90-92%
Proteins = 6-8%
Albumins; maintain osmotic pressure of the blood
Globulins
Alpha and beta globulins are used for transport
purposes
Gamma globulins are the immunoglobulins
(IgG, IgA, etc)

Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)

1 Withdraw blood

and place in tube

2 Centrifuge

Formed
elements

Erythrocytes
(45% of whole blood)

Hematocrit=Packed cell volume

Males: ~45%
Females: ~40%

Blood Plasma Components

Organic nutrients glucose, carbohydrates,
amino acids
Electrolytes sodium, potassium, calcium,
chloride, bicarbonate
Nonprotein nitrogenous substances lactic
acid, urea, creatinine
Respiratory gases oxygen and carbon dioxide

Fibrinogen; a clotting protein

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Formed Elements
Formed elements comprise ~45% of blood
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

Erythrocytes (RBCs)

Erythrocytes (RBCs)
Biconcave disc
Folding increases surface area (30% more surface area)
Plasma membrane contains cytoskeletal protein spectrin which
give RBCs their flexibility

Anucleate and no organelles

No cell division
No mitochondria means they generate ATP anaerobically
Prevents consumption of O2 being transported

Erythrocytes (RBCs)

Filled with hemoglobin (Hb) - 97% of cell

contents
Hb functions in gas transport
Hb + O2
HbO2 (oxyhemoglobin)
Most numerous of the formed elements
Females: 4.35.2 million cells/cubic millimeter
Males: 5.25.8 million cells/cubic millimeter
40-45% of blood

Figure 17.3

Erythrocyte Function
Erythrocytes are dedicated to respiratory gas
transport

Erythrocyte Function
Composition of hemoglobin
A protein called globin
made up of two alpha and two beta chains

Hemoglobin reversibly binds with oxygen

Most oxygen in the blood is bound to
hemoglobin

A heme molecule
Each heme group bears an atom of iron, which can bind
to one oxygen molecule
Blood is red due to spectral properties of hemic iron ions
Each hemoglobin molecule has 4 heme groups thus can
transport four molecules of oxygen
Each RBC has ~270m Hb

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Structure of Hemoglobin

Hemoglobin
Oxyhemoglobin hemoglobin bound to
oxygen
Oxygen loading takes place in the lungs

Deoxyhemoglobin hemoglobin after

oxygen diffuses into tissues (reduced Hb)
Carbaminohemoglobin hemoglobin bound
to carbon dioxide
Figure 17.4

Carbon dioxide loading takes place in the tissues

Carbon Monoxide Poisoning

Found in combustion fumes from cars, fires, gas
ranges, etc
Odorless and colorless

Life Cycle of
Red Blood Cells

Preferentially binds to RBCs and blocks O2

Can combine with proteins and destroy tissue

Fate and Destruction of

Erythrocytes
The life span of an erythrocyte is 100120 days
Travels ~750 miles in its lifetime (LA to Chihuahua,
Mexico )

Old erythrocytes become rigid and fragile, and

their hemoglobin begins to degenerate

Fate and Destruction of

Erythrocytes
Heme and globin are separated
Iron is removed from the heme and salvaged for reuse
Stored as hemosiderin or ferritin in tissues
Transported in plasma by beta-globulins as transferrin

Dying erythrocytes are engulfed by

macrophages

Iron is critical for many biochemical reactions (redox)

but toxic when not properly contain

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Fate and Destruction of

Erythrocytes
Heme is degraded to a yellow pigment called
bilirubin
Liver secretes bilirubin into the intestines as bile (digests
fats)
Intestines metabolize bilirubin into urobilinogen

Stages of
Differentiation of
Blood Cells

Urobilinogen leaves the body in feces, in a pigment called

stercobilin (can be used as a marker for fecal pollution in
rivers)

Globin is metabolized into amino acids which are

then released into the circulation

Production of Erythrocytes
Hematopoiesis blood cell formation

Figure 17.9

Production of Erythrocytes:
Erythropoiesis
A hemocytoblast is transformed into a committed cell
called the proerythroblast

Occurs in the red bone marrow (myeloid tissue)

Axial skeleton and girdles

Epiphyses of the humerus and femur
Marrow contains immature erythrocytes
Composed of reticular connective tissue

Hemocytoblasts give rise to all formed

elements
Lymphoid stem cells - give rise to lymphocytes
Myeloid stem cells - give rise to all other blood cells

Production of Erythrocytes:
Erythropoiesis

Proerythroblasts develop into early erythroblasts

The developmental pathway consists of three phases
Phase 1 ribosome synthesis in early erythroblasts
Phase 2 hemoglobin accumulation in late erythroblasts and
normoblasts
Phase 3 ejection of the nucleus from normoblasts and formation
of reticulocytes

Reticulocytes then become mature erythrocytes

Reticulocytes make up about 1 -2 % of all circulating
erythrocytes

Regulation and Requirements for

Erythropoiesis
Circulating erythrocytes the number remains constant and
reflects a balance between RBC production and destruction
Too few red blood cells leads to tissue hypoxia
Too many red blood cells causes undesirable blood
viscosity
Erythropoiesis is hormonally controlled and depends on
adequate supplies of iron, amino acids, and B vitamins

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Erythropoietin Mechanism

Hormonal Control of Erythropoiesis

Imb
ala
nce

Erythropoietin (EPO) release by the kidneys is

triggered by:
Hypoxia due to decreased RBCs
Decreased oxygen availability
Increased tissue demand for oxygen
Enhanced erythropoiesis increases the:
RBC count in circulating blood
Oxygen carrying ability of the blood

Start

Normal blood oxygen levels

Imb
ala
nce

Increases
O2-carrying
ability of blood

Stimulus: Hypoxia due to

decreased RBC count,
decreased availability of O2
to blood, or increased
tissue demands for O2

Reduces O2
levels in blood

Erythropoietin
stimulates red
bone marrow

Enhanced
erythropoiesis
increases RBC
count

Kidney (and liver to a

smaller extent) releases
erythropoietin

Figure 17.6

Dietary Requirements of
Erythropoiesis

Blood Doping

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

Erythrocyte Disorders
Polycythemia
Abnormal excess of erythrocytes
Increases viscosity, decreases flow rate of blood

Anemia blood has abnormally low oxygencarrying capacity

It is a symptom rather than a disease itself

Use frozen blood or

drugs

Side effects:
Clots
Kidney damage
Metabolic shock
Etc.

Anemia: Insufficient
Erythrocytes
Hemorrhagic anemia result of acute or
chronic loss of blood
Hemolytic anemia prematurely ruptured
erythrocytes

Blood oxygen levels cannot support normal metabolism

Signs/symptoms include fatigue, paleness, shortness of
breath, and chills

Aplastic anemia destruction or inhibition of

red bone marrow

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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

Sickle Cell Anemia

Valine replaces glutamic acid in each

of 2 beta subunit proteins changing
shape of protein

Anemia: Abnormal Hemoglobin

Thalassemias absent or faulty globin chain in hemoglobin
Erythrocytes are thin, delicate, and deficient in hemoglobin
Sickle-cell anemia results from a defective gene
Codes for an abnormal hemoglobin called hemoglobin S
(HbS)
This defect causes RBCs to become sickle-shaped in low
oxygen situations

Figure A shows normal red blood

cells flowing freely in a blood
vessel. The inset image shows a
cross-section of a normal red
blood cell with normal hemoglobin.
Figure B shows abnormal, sickled
red blood cells blocking blood flow
in a blood vessel. The inset image
shows a cross-section of a sickle
cell with abnormal (sickle)
hemoglobin forming abnormal
strands.

Heterozygous for allele confers

resistance to malaria without disease
No cure

Leukocytes (WBCs)
Leukocytes, the only blood components that are
complete cells:
4,800 - 10,000/cubic millimeter
Protect the body from infectious microorganisms
Can leave intact capillaries to site of infection/injury
Move through tissue spaces (amoeboid motion)
Many are phagocytic (possess numerous lysosomes)

Leukocytes (WBCs)
Two major types of leukocytes
Granulocytes: Neutrophils, Eosinophils,
Basophils
Agranulocytes: Monocytes, Lymphyocytes
Leukocytosis WBC count over 11,000/mm3
Normal response to bacterial or viral invasion
Leukopenia - a decrease in WBC count below 4,800/
mm3
Leukemia - a cancer of WBC

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Granulocytes
Granulocytes neutrophils, eosinophils, and
basophils
Contain cytoplasmic granules that stain
specifically (acidic, basic, or both) with Wrights
stain
Are larger and usually shorter-lived than RBCs
Have lobed nuclei
Are all phagocytic cells

Granulocytes: Eosinophils
Eosinophils account for 14% of WBCs
Have red-staining, bilobed nuclei
Have red to crimson granules

Granulocytes: Neutrophils
(Polymorphonuclear leukocytes)
Account for 65-75% of total WBCs
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)
Critical in first line defense
PMNs (PolyMorphoNuclear) because shape of
nucleus varies

Granulocytes: Basophils
Account for 0.5-1% of all WBCs
Have U- or S-shaped nuclei with two or three
conspicuous constrictions
Are functionally similar to mast cells

Function:
- Lead the bodys counterattack against parasitic infections
like worms
- Generate ROS like superoxide
- Cytotoxic granule proteins
- Fight viruses
- Lessen the severity of allergies by phagocytizing immune
complexes (ending allergic reactions)

Agranulocytes: Lymphocytes

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)

Monocytes

Account for 20-25% or more of WBCs:

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)

Most important cells of the immune system

There are two types of lymphocytes:
T cells - attack foreign cells directly
B cells which produce antibodies

Monocytes account for 37% of leukocytes

They are the largest leukocytes
They have purple-staining, U- or kidney-shaped
nuclei

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Production of Leukocytes

Monocytes
They leave the circulation, enter tissue, and
differentiate into macrophages or dendritic cells
Can move within 8-12 hours to site of tissue
Half are stored in spleen

Leukopoiesis is hormonally stimulated by two

families of cytokines interleukins and colonystimulating factors (CSFs)
Cytokines are a broad category of cell signaling
proteins
Macrophages and T cells are the most important
sources of cytokines
Many hematopoietic hormones are used clinically to
stimulate bone marrow

Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e.g.,
granulocyte-CSF stimulates granulocytes)

Leukocytes Disorders: Leukemias

Leukemia refers to cancerous conditions involving
white blood cells

Formation of
Leukocytes

Leukemias are named according to the abnormal

white blood cells involved:
Myelogenous leukemia involves myeloblasts-WBCs, WBCs,
and platelets
Lymphocytic leukemia involves lymphocytes such as B-cells

Many types: chronic lymphocytic leukemia (CLL),

chronic myelogenous leukemia (CML), etc

Acute Leukemia
Acute leukemia involves blast-type cells
Rapid increase in the number of immature blood cells

Chronic Leukemia
Chronic leukemia is characterized by
excessive buildup or relatively mature and
abnormal WBCs

Needs to be treated ASAP because it will crowd out

normal blood cells and spread to organs

Months to years to progress

Primarily affects children

More prevalent in older people

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Leukemia
Immature white blood cells are found in the
bloodstream in all leukemias
Bone marrow becomes totally occupied with
cancerous leukocytes
Severe anemia ensues due to excess
production of WBCs

Leukemia
The white blood cells produced, though numerous,
are not functional
Displace normal blood cells such as platelets
Anemia, nausea, flu-like symptoms, etc.
Death is caused by internal hemorrhage and
overwhelming infections
AML has a 5 year survival rate of 40%

Leukemia
Treatments include irradiation, chemotherapy, and
bone marrow transplants
Correct diagnosis is critical as treatment and
outcomes differ significantly
Improved used of molecular markers

Markers

Platelets or Thrombocytes
Platelets are fragments of megakaryocytes (large bone marrow
cell)
They release a multitude of growth factors that stimulate
deposition of extracellular matrix (ECM)
Significant role in repair and regeneration of connective tissue
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 Nitric
Oxide (NO) and prostaglandins

Computer vs human

10

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Coagulation
The final thee steps of
this series of reactions
are:

Detailed Reactions of Hemostasis

Prothrombin
activator is formed
Prothrombin is
converted into
thrombin
Thrombin catalyzes
the joining of
fibrinogen into a
fibrin mesh
Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings

platelets

Hemophilia

Hemostasis

Figure 18.13a

Figure 18.13b

Copyright 2003 Pearson Education, Inc. publishing as Benjamin Cummings

Hemostasis Disorders
Thrombus a clot that develops and persist in an unbroken
blood vessel
Thrombi can block circulation, resulting in tissue death
Coronary thrombosis thrombus in blood vessel of the heart
Embolus a thrombus freely floating in the blood stream

Queen Victoria (1819-1901) was a carrier

Mutations are usually bad and recessive

Hemophilia prominent in European royalty in 19th & 20th century
Missing blood clotting factor so bleeding can occur a lot longer

Prevention of Undesirable Clots

Aspirin inhibits thromboxane A2 (which binds platelets
together to form a patch)
Heparin an anticoagulant used clinically for pre- and
postoperative cardiac care
Warfarinin used for those prone to atrial fibrillation (cardiac
arrhythmia)
Flavonoids substances found in tea, red wine, and grape
juice that have natural anticoagulant activity

Pulmonary emboli can impair the ability of the body to obtain

oxygen
Cerebral emboli can cause strokes

French Paradox
French eat 108g of fat/day vs. 72g for Americans
Death from coronary heart disease was 83 per 100k
vs. 115 per 100k in USA in 1999
Red wine, vegetables/fruits, less trans-fat, or
statistical issues

11

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Human Blood Groups

RBC membranes have glycoprotein antigens on
their external surfaces
Antigen=Antibody Generator

Blood Type
4 main blood types: A, B, AB, and O
Rh blood group being 2nd most significant system
Over 50 antigens with Rh D antigen most significant.

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

Antibodies

Most commonly referred to as Rh +/ About 85% people are Rh+ but this can vary in ethnic
groups
Can pose problem in babies when mother has different
Rh factor (erythroblastosis)

ABO Blood Groups

Agglutination

Table 17.4

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