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PowerPoint® Lecture Slides
prepared by Vince Austin,
Bluegrass Technical
and Community College
CHAPTER
Elaine N. Marieb
Katja Hoehn
Human
Anatomy
& Physiology
SEVENTH EDITION
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17
Blood
Body Water Content

Infants: 73% or more water (low body fat, low
bone mass)

Adult males: ~60% water

Adult females: ~50% water (higher fat content,
less skeletal muscle mass)

Water content declines to ~45% in old age
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Fluid Compartments

Total body water = 40 L
1.
Intracellular fluid (ICF) compartment: 2/3 or 25 L in cells
2.
Extracellular fluid (ECF) compartment: 1/3 or 15 L

Plasma: 3 L

Interstitial fluid (IF): 12 L in spaces between cells

Other ECF: lymph, CSF, humors of the eye, synovial
fluid, serous fluid, and gastrointestinal secretions
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Total body water
Volume = 40 L
60% body weight
Extracellular fluid (ECF)
Volume = 15 L
20% body weight
Intracellular fluid (ICF)
Volume = 25 L
40% body weight
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Interstitial fluid (IF)
Volume = 12 L
80% of ECF
Figure 26.1
OBTAIN THE BLOOD

1. Venipuncture

2. Arterial Stick

3. Capillary Stick
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Composition of Blood

Blood is the body’s only fluid tissue

It is composed of (1) liquid plasma and (2) 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
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Components of Whole Blood
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Figure 17.1
Blood Tube Colors

Red Top-This is the red top used for serum
chemistries; your electrolytes, your basic and
complete metabolic panel, your hepatic and your
renal panels, are all done using this red top tube.

Lavender Top

This has an EDTA anticoagulant in it. It is used for
your blood counts — your whole blood counts
(CBC), your Sed rates are all taken using the
lavender top tube.
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Blood Tube Colors

Blue Top -The blue top tube has a different
anticoagulant in it. It’s the citrate-based
anticoagulant, and this one is used for plasma
coagulation tests; your PT, PTT, APTT, the
different prothrombin times, and the activated
partial thromboplastin time; also fibrinogens and
factor essays are all done using the blue top.

Gray Top -Gray top has a fluoride that inhibits
cellular glycolysis, and this is used for making
accurate glucose measurements to diagnose
diabetes patients. This is the gray top.
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Blood Tube Colors
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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 varies – upper end of body temp 100.4

Blood accounts for approximately 8% of body weight

Average volume: 5–6 L for males, and 4–5 L for
females

Hematocrit (Hct.) 30% – 60%

Viscosity 4.5 – 5.5 centipoise per second
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
Temperature classification

Core (rectal, esophageal, etc.)

Hypothermia <35.0 °C (95.0 °F)

Normal 36.5–37.5 °C (97.7–99.5 °F)

Fever >37.5–38.3 °C (99.5–100.9 °F)

Hyperthermia >37.5–38.3 °C (99.5–100.9 °F)

Hyperpyrexia >40.0–41.5 °C (104.0–106.7 °F)

The commonly accepted average core body temperature (taken
internally) is 37.0 °C (98.6 °F). The typical oral (under the
tongue) measurement is slightly cooler, at 36.8° ± 0.4 °C (98.2° ±
0.7 °F), and temperatures taken in other places (such as under the
arm or in the ear) produce different typical numbers.[
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Functions of Blood

Blood performs a number of functions dealing
with:

Transport

Regulation of blood levels of particular substances

Protection
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Transportation

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
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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
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Protection


Blood prevents blood loss by:

Activating plasma proteins and platelets

Initiating clot formation when a vessel is broken
Blood prevents infection by:

Synthesizing and utilizing antibodies

Activating complement proteins

Activating WBCs to defend the body against
foreign invaders
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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
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





Red Blood Cells (Erythrocytes) 4.8 – 5.2 million
per microliter
White Blood Cells (Leukocytes) 5,000 – 10,000
per microliter
Granulocytes
Neutrophils, Eosinophils, Basophils
Agranulocytes
Lymphocytes, Monocytes
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Percentages of Leukocytes
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Figure 17.9
The Formed Elements of Blood
Figure
19.1
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19-21
Components of Whole Blood
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Figure 17.2
Blood Plasma

Blood plasma contains over 100 solutes, including:





Proteins – 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
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Blood Plasma

91% – 92 % Water

7% Plasma Proteins
55% Albumins 38% Globulins 7% Fibrinogen
1.5% Other Solutes
0.9 % Electrolytes – 0.3% Nutrients – 0.1% Gases
0.1% Hormones, Enzymes 0.1% Wastes
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Hematopoiesis

Formation of Blood
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Hematopoiesis


Formation of Blood
1. Conception (Sperm fertilizes egg) – giving first
complete cell (1n + 1n) = 2n

2. Rapid mitosis of first cell to provide many cells
– culminating in a morula (mulberry)

3. Cells begin to migrate
and differentiate –
giving the first germ (germination) layers – (ectoderm,
mesoderm, endoderm)

4. From mesoderm comes the blood
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Figure 28.2
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Figure 28.3
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Figure 28.4
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Figure 28.5
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Figure 28.7a–c
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Figure 28.7d
Week 1–3
5–7 days after fertilization, the blastocyst attaches to the wall
of the uterus (endometrium). When it comes into contact
with the endometrium it performs implantation. Implantation
connections between the mother and the embryo will begin
to form, including the umbilical cord. The embryo's growth
centers around an axis, which will become the spine and
spinal cord. The brain, spinal cord, heart, and gastrointestinal
tract begin to form.
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Week 4–5
Chemicals produced by the embryo stop the woman's
menstrual cycle. Neurogenesis is underway, showing brain
activity at about the 6th week. The heart will begin to beat
around the same time. Limb buds appear where arms and
legs will grow later. Organogenesis begins. The head
represents about one half of the embryo's axial length, and
more than half of the embryo's mass. The brain develops
into five areas. Tissue formation occurs that develops into
the vertebra and some other bones. The heart starts to beat
and blood starts to flow.
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Week 6–8
Myogenesis and neurogenesis have progressed to where the
embryo is capable of motion, and the eyes begin to form.
Organogenesis and growth continue. Hair has started to form
along with all essential organs. Facial features are beginning
to develop. At the end of the 8th week, the embryonic stage
is over, and the fetal stage begins.
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2 Weeks – primitive red blood cells (nucleated) seen in
yolk sac
6 Weeks – primitive red blood cells start development
in primordial liver
6 ½ Weeks – see definitive red blood (non-nucleated)
cells developed in liver
8 weeks – begin to see red blood cell development in
the spleen along with development of granulocytes,
and thrombocytes
4th month – see blood cell development to start in bone
marrow – also start to see development of lymphocytes
5th month – see development of monocytes
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Embryonic Development of
Blood Vessels
• Angiogenesis begins at
13–15 days of gestation
• Mesenchymal cells
differentiate into blood
islands
• Hemoblasts become
blood cells
• Angioblasts become
endothelial cells
Figure 21.34
21-38
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Types of Developmental Cells




Pluripotential Hematopoietic Stem Cells (Hemocytoblast)
– usually amitotic but may undergo bursts of cell division
giving rise to more PHSC
Multipotential Stem Cells – less potentiality – can do
mitosis and further differentiation – CFU-S and CFU – Ly
(Colony Forming Unit) in other classification – Myeloid
Stem Cell and Lymphoid Stem Cell
Progenitor Cell- unipotential- creates a single cell line like
eosinophils mitotic ability and differentiation are controlled
by hematopoietic factors – only limited ability for selfrenewal
Precursor Cell – arise from progenitor cell – no selfrenewal
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Growth Factors for Hematopoiesis


Chemicals or other factors that stimulate the
various type of blood forming cells to proliferate
and/or differentiate
Three types- (1) Cytokines – small protein, peptide
or glycoproteins secreted locally (paracrine) – like
the interleukins and colony stimulating factors (2)
Hormones – like erythropoietin and
Thrombopoietin and (3) Direct cell contact – like
the Steel Factor (Stem Cell Factor) which is
produced by stromal cells and inserted into the
various stem cells to stimulate them.
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Erythrocytes (RBCs)

Biconcave discs, anucleate, essentially few
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
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Erythrocytes (RBCs)
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Figure 17.3
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Figure 3.3
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
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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
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Structure of Hemoglobin
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Figure 17.4
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

PLAY
Carbon dioxide loading takes place in the tissues
InterActive Physiology ®:
Respiratory System: Gas Transport, pages 3–13
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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
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Production of Erythrocytes: Erythropoiesis

A hemocytoblast is transformed into a proerythroblast

Proerythroblasts develop into early erythroblasts

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
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Production of Erythrocytes: Erythropoiesis

A hemocytoblast is transformed into a
proerythroblast

Proerythroblasts develop into early erythroblasts
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
Erythropoiesis Synopsis
RBC produced at 2 million per second

Proerythroblast – all cell components present

Early Erythroblast – loss of nucleolus

Intermediate Erythroblast – start of Hgb. Synthesis

Late Erythroblast – Maximum rate of synthesis of Hgb.


Reticulocyte – nucleus has been extruded – still has
ribosomes and mitochondria
Mature RBC – no ribosomes and no mitochondria
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Production of Erythrocytes: Erythropoiesis
Normoblast – the red blood cell precursor still has a nucleus
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Figure 17.5
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
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Hormonal Control of Erythropoiesis


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
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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
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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
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Fate and Destruction of Erythrocytes

Heme is degraded to a yellow pigment called
bilirubin

The liver secretes bilirubin into the intestines as bile

The intestines metabolize it into urobilinogen

This degraded pigment leaves the body in feces, in a
pigment called stercobilin
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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 phgocytized
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Synopsis of RBC destruction
 When the RBC has loss its ability to bend its cell
membrane – then it must be removed so it does not
cause blood clots

Macrophages in the spleen (main organ) and other
organs like the liver – engulf the RBC

Enzymes in macrophage tear the RBC apart
separating the cell from its hemoglobin

The components of the rest of the cell are
enzymatically degraded into carbohydrate, protein
and lipid. These then are used by the macrophage
or transported to other cells for use or eliminated.
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Synopsis of Fate of Hgb. destruction

Enzymes in the macrophage split hemoglobin into
heme and globin.

The globin, a protein, is broken down into its basic
amino acids by proteolytic enzymes in the
macrophage. The amino acids are either used by
the macrophage or transported to other cells in the
body or eliminated by being converted to urea in
the liver.

The heme is enzymatically split into the iron
portion and the tetrapyrrole rings.
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



Fate of Iron
See Iron PowerPoint
Some iron is maintained in the macrophage and some
iron is transported out of the macrophage and attached to
the protein carrier known as apotransferrin – so as not
to allow the iron to be a free radical in the bloodstream.
Once iron is attached to apotransferrin – the molecule’s
name is changed to transferrin.
The transferrin iron circulates until it is picked up by cell
surface receptors for transferrin- particularly cells in the
bone marrow, liver and spleen . However all cells have
some receptors for iron – in that all cells need some iron.
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

Fate of the Tetrapyrrole rings
In the macrophage the tetrapyrrole rings are
enzymatically converted to biliverdin (green bile
pigment) – they then are further converted to bilirubin
(yellow bile pigment)
Bilirubin is transported out of the macrophage into the
circulation – but since bilirubin is not soluble in the
water of the blood it must hook to a carrier – which is
plasma albumin.
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Fate of Tetrapyrrole rings (2)


Upon the albumin – bilirubin circulating through
the liver – the bilirubin is removed from the
albumin and goes into the liver (hepatic cell) –
where it is “conjugated” with glucuronic acid
(80%) or sulfate (10%) or other substances.
The conjugation process makes the bilirubin very
water soluble and allows it to be placed into a
substance known as bile – which is made in liver
and stored in the gallbladder.
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Bile Composition
Bile is formed in the liver and stored in the gallbladder its function is to
solubilize (emulsify) fats in the small intestines.


Water – when stored in gallbladder considerable water is removed
from the bile so as to make it more concentrated thus easier to store.
Unesterified Cholesterol

Bile pigments (Bilirubin)

Bile salts (glycocholic acid & taurocholic acid)

Bile acids – primary – cholic acid and chenodeoxycholic acid

Bile acids – secondary – deoxycholic acid and lithocholic acid

Phospholipids (mainly lecithin) Dipalmitoyl phosphatidyl choline

Electrolytes

Bicarbonate
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Fate of Tetrapyrrole Rings (3)

Bile gets secreted into the small intestines for the
purpose of emulsifying fat from the diet.

The conjugated bilirubin component of bile in the
intestine is enzymatically converted by bacterial
(normal flora) enzymes in the large intestines into
urobilinogen .

Some urobilinogen is reabsorbed with the bile in
the large intestine (enterohepatic recirculation) and
some that is not reabsorbed is further degraded
through oxidation by bacterial action into
Stercobilin.
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Fate of Tetrapyrrole Rings (4)

Some of the urobilinogen reabsorbed with the bile
is eliminated by the kidneys. After the
urobilinogen is urinated out – air oxidizes it to
urobilin.
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Right and left
hepatic ducts
of liver
Cystic duct
Common hepatic duct
Bile duct and sphincter
Accessory pancreatic duct
Mucosa
with folds
Gallbladder
Major duodenal
papilla
Hepatopancreatic
ampulla and sphincter
Tail of pancreas
Pancreas
Jejunum
Duodenum
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Main pancreatic duct
and sphincter
Head of pancreas
Figure 23.21
Sternum
Nipple
Liver
Bare area
Falciform
ligament
Left lobe of liver
Right lobe
of liver
Gallbladder
(a)
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Round ligament
(ligamentum
teres)
Figure 23.24a
(a)
Lobule
(b)
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Central vein
Connective
tissue septum
Figure 23.25a, b
Interlobular veins
(to hepatic vein)
Central vein
Sinusoids
Bile canaliculi
Plates of
hepatocytes
Bile duct (receives
bile from bile
canaliculi)
Fenestrated
lining (endothelial
cells) of sinusoids
Portal vein
Hepatic
macrophages
in sinusoid walls
Bile duct
Portal venule
Portal arteriole
Portal triad
(c)
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Figure 23.25c
Jaundice Causes

Pre-hepatic – example massive internal
hemorrhage

Hepatic – example hepatitis or cirrhosis

Post-Hepatic – obstruction of bile duct
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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
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Discussion of Blood Typing

Surface markers on cells – MHC versus RBC
markers

ABO – Glycoproteins

Rh - Proteins
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Figure 3.3
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
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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
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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
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Blood Types

Several genetically
determined blood groups
with multiple types

ABO and Rh most common

Red blood cell contains
glycolipid antigens on
membrane

Plasma contains antibodies
that react against foreign
antigens
Figure 19.6
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19-83
ABO Blood Groups
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Table 17.4
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
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Blood Typing
Blood type being tested
RBC agglutinogens
Serum Reaction
Anti-A
Anti-B
AB
A and B
+
+
B
B
–
+
A
A
+
–
O
None
–
–
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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
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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
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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
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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
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Transfusion Reactions

Circulating hemoglobin precipitates in the kidneys
and causes renal failure
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Plasma Volume Expanders

When shock is imminent from low blood volume,
volume must be replaced

Plasma or plasma expanders can be administered
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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
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Erythrocyte Disorders

Anemia – blood has abnormally low oxygencarrying 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
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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
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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;
application of Nascobal
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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 sickle-shaped
in low oxygen situations
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Polycythemia


Polycythemia – excess RBCs that increase blood
viscosity
Three main polycythemias are:

Polycythemia vera

Secondary polycythemia

Blood doping
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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
Leukocytosis – WBC count over 11,000 / mm3

Normal response to bacterial or viral invasion
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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
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Granulocyte Development
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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
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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
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Basophils

Account for 0.5% of WBCs and:

Have U- or S-shaped nuclei with two or three
conspicuous constrictions

Are functionally similar to mast cells

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)
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Agranulocytes

Agranulocytes – lymphocytes and monocytes:

Lack visible cytoplasmic granules

Are similar structurally, but are functionally
distinct and unrelated cell types

Have spherical (lymphocytes) or kidney-shaped
(monocytes) nuclei
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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
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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 kidney-shaped
nuclei

They leave the circulation, enter tissue, and
differentiate into macrophages
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Macrophages

Macrophages:

Are highly mobile and actively phagocytic

Activate lymphocytes to mount an immune
response by producing cytokines

Some act as antigen presenting cells
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Mononuclear phagocyte system

The mononuclear phagocyte system is a part of
the immune system that consists of the phagocytic
cells located primarily in reticular connective
tissue. The cells are primarily monocytes and
macrophages, and they accumulate in lymph
nodes, bone marrow, the spleen and some other
areas. The Kupffer cells of the liver and tissue
histiocytes are also part of the MPS.

Its functions include:

Formation of new red blood cells (RBCs) and
white blood cells (WBCs).
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Mononuclear phagocyte system (Functions)

Formation of new red blood cells (RBCs) and white blood
cells (WBCs).

Destruction of old RBCs and WBCs.

Assist in formation of plasma proteins.

Formation of bile pigments.

"Reticuloendothelial system" is an older term for the
mononuclear phagocyte system, but it is used less
commonly now, as it is understood that most endothelial
cells are not macrophages
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Leukocytes
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Figure 17.10
Summary of Formed Elements
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Table 17.2.1
Summary of Formed Elements
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Table 17.2.2
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
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Formation of Leukocytes

All leukocytes originate from hemocytoblasts

Hemocytoblasts differentiate into myeloid stem cells and
lymphoid stem cells

Myeloid stem cells become myeloblasts or monoblasts

Lymphoid stem cells become lymphoblasts

Myeloblasts develop into eosinophils, neutrophils, and
basophils

Monoblasts develop into monocytes

Lymphoblasts develop into lymphocytes
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Stem cells
Hemocytoblast
Myeloid stem cell
Committed
Myeloblast
cells
Myeloblast
Lymphoid stem cell
Myeloblast
DevelopPromyelocyte Promyelocyte Promyelocyte
mental
pathway
Eosinophilic
myelocyte
Basophilic
myelocyte
Neutrophilic
myelocyte
Eosinophilic
band cells
Basophilic
band cells
Neutrophilic
band cells
Eosinophils
Basophils Neutrophils
(a)
(b)
(c)
Lymphoblast
Promonocyte
Prolymphocyte
Monocytes
Lymphocytes
(e)
(d)
Agranular leukocytes
Granular leukocytes
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Some become
Macrophages (tissues)
Some
become
Plasma cells
Figure 17.11
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
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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
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Platelets

See Platelet PowerPoint
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Hemostasis

A series of reactions for stoppage of bleeding

During hemostasis, three phases occur in rapid
sequence
1.
Vascular spasms – immediate vasoconstriction
in response to injury
2.
Platelet plug formation
3.
Coagulation (blood clotting)
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Vascular Spasm

The first step is immediate constriction of damaged
vessels caused by (1) disturbance of myogenic tone
and (2) vasoconstrictive paracrine secretions
released by the endothelium – like endothelin and
thromboxane. Vasoconstriction temporarily
decreases blood flow and pressure within the
vessel. When you put pressure on a bleeding
wound, you also decrease flow within the damaged
vessel.
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Platelet Plug Formation

Platelets do not stick to each other or to blood vessels

Upon damage to blood vessel endothelium platelets:


With the help of von Willebrand factor (VWF) adhere to
collagen

Are stimulated by thromboxane A2

Stick to exposed collagen fibers and form a platelet plug

Release serotonin and ADP, which attract still more
platelets
The platelet plug is limited to the immediate area of injury
by prostacyclin
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Coagulation

A set of reactions in which blood is transformed
from a liquid to a gel

Coagulation follows intrinsic (new name contact
activation pathway) and extrinsic pathways (new
name tissue factor pathway)

The final three steps of this series of reactions are:

Prothrombin activator is formed

Prothrombin is converted into thrombin

Thrombin catalyzes the joining of fibrinogen into a
fibrin mesh
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Classes of Clotting Factors

Thrombin sensitive – Factors I, V, VIII and XIII

Vitamin K Dependent – II, VII, IX, X
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Coagulation
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Figure 17.13a
Detailed Events of Coagulation
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Figure 17.13b
Coagulation Phase 1: Two Pathways to
Prothrombin Activator
 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
Once factor X has been activated, it complexes
with calcium ions, PF3, and factor V to form
prothrombin activator
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Coagulation Phase 2: Pathway to Thrombin

Prothrombin activator catalyzes the transformation
of prothrombin to the active enzyme thrombin
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Coagulation Phase 3: Common Pathways to
the Fibrin Mesh
 Thrombin catalyzes the polymerization of
fibrinogen into fibrin

Insoluble fibrin strands form the structural basis of
a clot

Fibrin causes plasma to become a gel-like trap

Fibrin in the presence of calcium ions activates
factor XIII that:

Cross-links fibrin

Strengthens and stabilizes the clot
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Factor XIII action
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Clot Retraction and Repair


Clot retraction – stabilization of the clot by
squeezing serum from the fibrin strands
Repair

Platelet-derived growth factor (PDGF) stimulates
rebuilding of blood vessel wall

Fibroblasts form a connective tissue patch

Stimulated by vascular endothelial growth factor
(VEGF), endothelial cells multiply and restore the
endothelial lining
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Factors Limiting Clot Growth or Formation

Two homeostatic mechanisms prevent clots from becoming
large

Swift removal of clotting factors

Inhibition of activated clotting factors



Protein C – glycoprotein produced in the liver and is the
major inhibitor of coagulation. It degrades factors V and
VIII. It needs Protein S to work.
Protein S – Produced in liver and acts as a cofactor for
Protein C.
Thrombomodulin – binds to thrombin and activates and
activates Protein C
Antithrombin III – produced in liver and is major inhibitor
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
Heparin

Produced by mast cells, basophils and endothelial
cells.

Complexes with Antithrombin III to inhibit
Thrombin – but also inhibits XII, XI, X, IX
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Plasminogen
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Inhibition of Clotting Factors

Thrombin not absorbed to fibrin is inactivated by
antithrombin III

Heparin, another anticoagulant, also inhibits
thrombin activity
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Inhibition of Clotting Factors

Fibrin acts as an anticoagulant by binding
thrombin and preventing its:

Positive feedback effects of coagulation

Ability to speed up the production of prothrombin
activator via factor V

Acceleration of the intrinsic pathway by activating
platelets
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Factors Preventing Undesirable Clotting

Unnecessary clotting is prevented by endothelial
lining the blood vessels

Platelet adhesion is prevented by:

The smooth endothelial lining of blood vessels

Heparin and PGI2 secreted by endothelial cells

Vitamin E quinone, a potent anticoagulant
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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
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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
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Prevention of Undesirable Clots

Substances used to prevent undesirable clots:



Aspirin – an antiprostaglandin that inhibits
thromboxane A2
Heparin – an anticoagulant used clinically for preand postoperative cardiac care
Warfarin – used for those prone to atrial fibrillation
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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
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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
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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
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Hemostasis Disorders: Bleeding Disorders

Hemophilias – hereditary bleeding disorders
caused by lack of clotting factors



Hemophilia 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
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Hemostasis Disorders: Bleeding Disorders

Symptoms include prolonged bleeding and painful
and disabled joints

Treatment is with blood transfusions and the
injection of missing factors

PT (Prothrombin Time)

PTT (Partial Thromboplastin Time)

INR (International Normalized Ratio)
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Diagnostic Blood Tests

Laboratory examination of blood can assess an
individual’s state of health

Microscopic examination:



Variations in size and shape of RBCs – predictions
of anemias
Type and number of WBCs – diagnostic of various
diseases
Chemical analysis can provide a comprehensive
picture of one’s general health status in relation to
normal values
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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
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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
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