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Overview of the
Cardiovascular System
• Cardiovascular system
– Heart and blood vessels
• Circulatory system
– Heart, blood vessels, and the blood
19-1
The Pulmonary and Systemic Circuits
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CO2display.O
2
• Left side of heart
Pulmonary circuit
O2-poor,
CO2-rich
blood
O2-rich,
CO2-poor
blood
Systemic circuit
CO2
O2
Figure 19.1
– Fully oxygenated blood
arrives from lungs via
pulmonary veins
– Blood sent to all organs of
the body via aorta
• Right side of heart
– Oxygen-poor blood arrives
from inferior and superior
venae cavae
– Blood sent to lungs via
pulmonary trunk
19-2
Position, Size, and Shape
of the Heart
• Heart located in
mediastinum, between
lungs
• Base—wide, superior portion
of heart, large vessels attach
here
• Apex—tapered inferior end,
tilts to the left
• In adult: weighs 10
ounces, 3.5 in. wide at
base, 5 in. from base to
apex
• At any age, heart is size of
fist
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Aorta
Pulmonary
trunk
Superior
vena cava
Right lung
Base of
heart
Parietal
pleura (cut)
Pericardial
sac (cut)
Apex
of heart
Diaphragm
(c)
Figure 19.2c
19-3
The Pericardium
• Pericardium—double-walled sac that encloses the heart
– Allows heart to beat without friction, provides room to
expand, yet resists excessive expansion
– Anchored to diaphragm inferiorly and sternum anteriorly
• Parietal pericardium—pericardial sac
– Superficial fibrous layer of connective tissue
– Deep, thin serous layer
• Visceral pericardium (epicardium)
– Serous membrane covering heart
• Pericardial cavity—space inside the pericardial sac filled
with 5 to 30 mL of pericardial fluid
• Pericarditis—painful inflammation of the membranes
19-4
The Pericardium
Figure 19.3
19-5
The Heart Wall
• Heart wall has three layers: epicardium,
myocardium and endocardium
• Epicardium (visceral pericardium)
– Serous membrane covering heart
– Adipose in thick layer in some places
– Coronary blood vessels travel through this layer
• Endocardium
– Smooth inner lining of heart and blood vessels
– Covers the valve surfaces and is continuous with
endothelium of blood vessels
19-6
The Heart Wall
• Myocardium
– Layer of cardiac muscle proportional to work load
• Muscle spirals around heart which produces wringing
motion
– Fibrous skeleton of the heart: framework of
collagenous and elastic fibers
• Provides structural support and attachment for cardiac
muscle and anchor for valve tissue
• Electrical insulation between atria and ventricles; important
in timing and coordination of contractile activity
19-7
The Chambers
• Four chambers
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– Right and left atria
• Two superior chambers
• Receive blood returning
to heart
• Auricles (seen on
surface) enlarge
chamber
Aorta
Right pulmonary
artery
Left pulmonary artery
Superior vena cava
Pulmonary trunk
Right pulmonary
veins
Left pulmonary veins
Pulmonary valve
Interatrial
septum
Right atrium
Left atrium
Aortic valve
Left AV (bicuspid)
valve
Left ventricle
Fossa ovalis
Pectinate muscles
Right AV
(tricuspid) valve
Papillary muscle
Interventricular septum
Tendinous cords
Endocardium
Trabeculae carneae
Right ventricle
Inferior vena cava
Myocardium
Epicardium
– Right and left ventricles
• Two inferior chambers
• Pump blood into arteries
Figure 19.7
19-8
The Chambers
Figure 19.7
19-9
The Valves
• Valves ensure one-way flow of blood through heart
• Atrioventricular (AV) valves—control blood flow
between atria and ventricles
– Right AV valve has three cusps (tricuspid valve)
– Left AV valve has two cusps (mitral valve, formerly
‘bicuspid’)
– Chordae tendineae: cords connect AV valves to papillary
muscles on floor of ventricles
• Prevent AV valves from flipping or bulging into atria when
ventricles contract
• Each papillary muscle has 2-3 attachments to heart floor (like
Eiffel Tower) to distribute physical stress, coordinate timing of
electrical conduction, and provide redundancy
19-10
The Valves
• Semilunar valves—control flow into great
arteries; open and close because of blood flow
and pressure
– Pulmonary semilunar valve: in opening between
right ventricle and pulmonary trunk
– Aortic semilunar valve: in opening between left
ventricle and aorta
19-11
The Valves
Figure 19.8a
19-12
Aortic Valve
Figure 19.8b
19-13
Blood Flow Through the Chambers
• Ventricles relax
– Pressure drops inside the ventricles
– Semilunar valves close as blood attempts to back up
into the ventricles from the vessels
– AV valves open
– Blood flows from atria to ventricles
19-14
Blood Flow Through the Chambers
• Ventricles contract
– AV valves close as blood attempts to back up into the
atria
– Pressure rises inside of the ventricles
– Semilunar valves open and blood flows into great
vessels
19-15
Blood Flow Through the Chambers
Figure 19.9
• Blood pathway travels from the right atrium through the pulmonary
circuit, then systemic circuit (through the body) and back to the starting
point
19-16
The Coronary Circulation
• 5% of blood pumped by heart is pumped to
the heart itself through the coronary
circulation to sustain its strenuous workload
– 250 mL of blood per minute
– Needs abundant O2 and nutrients
19-17
Arterial Supply
• Myocardial infarction (MI)—heart attack
– Interruption of blood supply to the heart from a blood
clot or fatty deposit (atheroma) can cause death of
cardiac cells within minutes
– Some protection from MI is provided by arterial
anastomoses which provide alternative routes of blood
flow (collateral circulation) within the myocardium
19-18
Arterial Supply
• Flow through coronary arteries is greatest
when heart relaxes
– Contraction of the myocardium compresses the
coronary arteries and obstructs blood flow
– Opening of the aortic valve flap during ventricular
systole covers the openings to the coronary arteries
blocking blood flow into them
– During ventricular diastole, blood in the aorta surges
back toward the heart and into the openings of the
coronary arteries
19-19
Angina and Heart Attack
• Angina pectoris—chest pain from partial
obstruction of coronary blood flow
– Pain caused by ischemia of cardiac muscle
– Obstruction partially blocks blood flow
– Myocardium shifts to anaerobic fermentation,
producing lactic acid and thus stimulating pain
19-20
Angina and Heart Attack
• Myocardial infarction (MI)—sudden death of a
patch of myocardium resulting from long-term
obstruction of coronary circulation
– Atheroma (blood clot or fatty deposit) often obstructs
coronary arteries
– Cardiac muscle downstream of the blockage dies
– Heavy pressure or squeezing pain radiating into the left
arm
– Some painless heart attacks may disrupt electrical
conduction pathways, leading to fibrillation and cardiac
arrest
• Silent heart attacks occur in diabetics and the elderly
– MI responsible for about 27% of all deaths in the U.S.
19-21
Structure of Cardiac Muscle
Striated myofibril Glycogen Nucleus Mitochondria Intercalated discs
(b)
Intercellular space
Desmosomes
Gap junctions
Figure 19.11a–c
(c)
(a): © Ed Reschke
19-22
The Conduction System
• Coordinates the heartbeat
– Composed of an internal pacemaker and nerve-like
conduction pathways through myocardium
• Generates and conducts rhythmic electrical
signals in the following order:
– Sinoatrial (SA) node: modified cardiocytes
• Pacemaker initiates each heartbeat and determines
heart rate
• Pacemaker in right atrium near base of superior vena
cava
– Signals spread throughout atria
19-23
The Conduction System
(Continued)
– Atrioventricular (AV) node
• Located near the right AV valve at lower end of interatrial septum
• Electrical gateway to the ventricles
• Fibrous skeleton—insulator prevents currents from getting to
ventricles by any other route
– Atrioventricular (AV) bundle (bundle of His)
• Bundle forks into right and left bundle branches
• Branches pass through interventricular septum toward apex
– Purkinje fibers
• Nerve-like processes spread throughout ventricular myocardium
• Cardiocytes then pass signal from cell to cell through gap
junctions
19-24
The Conduction System
Figure 19.12
19-25
Nerve Supply to the Heart
• Sympathetic nerves increase heart rate and
contraction strength
– Sympathetic pathway to heart originates in the lower
cervical to upper thoracic segments of the spinal cord
– Continues to adjacent sympathetic chain ganglia and
some ascend to cervical ganglia
– Postganglionic fibers pass through cardiac plexus in
mediastinum and continue as cardiac nerves to the
heart
– Fibers terminate in SA and AV nodes, in atrial and
ventricular myocardium (also aorta, pulmonary trunk,
and coronary arteries)
19-26
Nerve Supply to the Heart
• Parasympathetic nerves slow heart rate
– Pathway begins with nuclei of the vagus nerves in
the medulla oblongata
– Extend to cardiac plexus and continue to the heart by
way of the cardiac nerves
– Fibers of right vagus nerve lead to the SA node
– Fibers of left vagus nerve lead to the AV node
– Little or no vagal stimulation of the myocardium
19-27
Electrical and Contractile
Activity of the Heart
• Cycle of events in heart
– Systole: contraction
– Diastole: relaxation
• Although “systole” and “diastole” can refer
to contraction and relaxation of either type
of chamber, they usually refer to the action
of the ventricles
19-28
The Cardiac Rhythm
• Sinus rhythm—normal heartbeat triggered by
the SA node
– Adult at rest is typically 70 to 80 bpm (vagal tone)
• Ectopic focus—a region of spontaneous firing
other than the SA node
– May govern heart rhythm if SA node is damaged
– Nodal rhythm—if SA node is damaged, heart rate is set
by AV node, 40 to 50 bpm
• Other ectopic focal rhythms are 20 to 40 bpm and too
slow to sustain life
19-29
Pacemaker Physiology
• SA node does not have a stable resting
membrane potential
– Starts at −60 mV and drifts upward due to slow Na+
inflow
• Gradual depolarization is called pacemaker potential
– When it reaches threshold of −40 mV, voltage-gated
fast Ca2+ and Na+ channels open
• Faster depolarization occurs peaking at 0 mV
– K+ channels then open and K+ leaves the cell
• Causing repolarization
• Once K+ channels close, pacemaker potential starts over
• When SA node fires it sets off heartbeat
– As the internal pacemaker, it typically fires every 0.8
seconds, setting the resting rate at 75 bpm
19-30
Pacemaker Physiology
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Membrane potential (mV)
+10
0
–10
Fast K+
outflow
Fast
Ca2+–Na+
inflow
–20
–30
Action
potential
Threshold
–40
Pacemaker
potential
–50
–60
Slow Na+
inflow
–70
0
.4
.8
1.2
1.6
Time (sec)
Figure 19.13
19-31
Impulse Conduction to the
Myocardium
• Signal from SA node stimulates two atria to
contract almost simultaneously
– Reaches AV node in 50 ms
• Signal slows down through AV node
– Thin cardiocytes with fewer gap junctions
– Delays signal 100 ms which allows the ventricles
time to fill
19-32
Impulse Conduction to the
Myocardium
• Signals travel very quickly through AV bundle and
Purkinje fibers
– Entire ventricular myocardium depolarizes and contracts
in near unison
• Signals reach papillary muscles slightly later than rest of
myocardium
• Ventricular systole progresses up from the
apex of the heart
– Spiral arrangement of myocardium twists ventricles
slightly; like someone wringing out a towel
19-33
Electrical Behavior of the Myocardium
• Cardiocytes have a stable resting potential of −90
mV, and depolarize only when stimulated
• Three phases to cardiocyte action potential:
depolarization, plateau, repolarization
– Depolarization phase (very brief)
• Stimulus opens voltage-regulated Na+ gates (Na+ rushes in),
membrane depolarizes rapidly
• Action potential peaks at +30 mV
• Na+ gates close quickly
– Plateau phase lasts 200 to 250 ms, sustains contraction
for expulsion of blood from heart
• Voltage-gated slow Ca2+ channels open admitting Ca2+ which
triggers opening of Ca2+ channels on sarcoplasmic reticulum (SR)
• Ca2+ (mostly from the SR) binds to troponin triggering contraction
19-34
Electrical Behavior of the Myocardium
• Cardiocyte action potential (Continued)
– Repolarization phase: Ca2+ channels close, K+
channels open, rapid diffusion of K+ out of cell returns it
to resting potential
– Has a long absolute refractory period of 250 ms
(compared to 1 to 2 ms in skeletal muscle)
• Prevents wave summation and tetanus which would stop
the pumping action of the heart
19-35
Electrical Behavior of the Myocardium
1. Na+ gates open
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3
Plateau
3. Na+ gates close
4
0
Membrane potential (mV)
2. Rapid
depolarization
+20
4. Slow Ca2+ channels
open
2
Na+ inflow depolarizes the membrane
and triggers the opening of still more Na+
channels, creating a positive feedback
cycle and a rapidly rising membrane voltage.
3
Na+ channels close when the cell
depolarizes, and the voltage peaks at
nearly +30 mV.
4
Ca2+ entering through slow Ca2+
channels prolongs depolarization of
membrane, creating a plateau. Plateau falls
slightly because of some K+ leakage, but most
K+ channels remain closed until end of
plateau.
5
Ca2+ channels close and Ca2+ is transported
out of cell. K+ channels open, and rapid K+
outflow returns membrane to its resting
potential.
Myocardial
relaxation
2
Myocardial
contraction
–60
–80
Voltage-gated Na+ channels open.
5
Action
potential
–20
–40
1
Absolute
refractory
period
1
0
.15
Time (sec)
.30
Figure 19.14
5. Ca2+ channels close,
K+ channels open
(repolarization)
19-36
The Electrocardiogram
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0.8 second
R
R
Millivolts
+1
PQ
ST
segment segment
T wave
P wave
0
PR
Q
interval
S
QT
interval
QRS interval
• Electrocardiogram
(ECG or EKG)
– Composite of all
action potentials of
nodal and
myocardial cells
detected, amplified
and recorded by
electrodes on arms,
legs, and chest
–1
Atria
contract
Ventricles
contract
Atria
contract
Ventricles
contract
Figure 19.15
19-37
The Electrocardiogram
• P wave
– SA node fires, atria depolarize and contract
– Atrial systole begins 100 ms after SA signal
• QRS complex
– Ventricular depolarization
– Complex shape of spike due to different thickness
and shape of the two ventricles
• ST segment—ventricular systole
– Corresponds to plateau in myocardial action potential
• T wave
– Ventricular repolarization and relaxation
19-38
The Electrocardiogram
1.
2.
Atrial depolarization
begins
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Key
Atrial depolarization
complete (atria
contracted)
Wave of
depolarization
Wave of
repolarization
R
P
P
Q
S
4 Ventricular depolarization complete.
1 Atria begin depolarizing.
3.
4.
5.
6.
Ventricles begin to
depolarize at apex; atria
repolarize (atria relaxed)
Ventricular
depolarization complete
(ventricles contracted)
Ventricles begin to
repolarize at apex
Ventricular
repolarization complete
(ventricles relaxed)
R
T
P
P
Q
S
2 Atrial depolarization complete.
5 Ventricular repolarization begins at apex
and progresses superiorly.
R
R
T
P
P
Q
3 Ventricular depolarization begins at apex
and progresses superiorly as atria repolarize.
Q
S
6 Ventricular repolarization complete; heart
is ready for the next cycle.
Figure 19.16
19-39
Blood Flow, Heart Sounds,
and the Cardiac Cycle
• Cardiac cycle—one complete contraction and
relaxation of all four chambers of the heart
• Questions to consider: How does pressure
affect blood flow? How are heart sounds
produced?
19-40
Phases of the Cardiac Cycle
• Ventricular filling (during diastole)
• Isovolumetric contraction (during systole)
• Ventricular ejection (during systole)
• Isovolumetric relaxation (during diastole)
• The entire cardiac cycle (all four of these
phases) are completed in less than 1 second
19-41
Phases of the Cardiac Cycle
• In a resting person
– Atrial systole lasts about 0.1 second
– Ventricular systole lasts about 0.3 second
– Quiescent period, when all four chambers are in
diastole, lasts about 0.4 second
• Total duration of the cardiac cycle is therefore
0.8 second in a heart beating 75 bpm
19-42
Overview of Volume Changes
• Normally, right and left sides of heart eject
the same volume of blood even though they
are under different pressure
• Congestive heart failure (CHF)—results from
the failure of either ventricle to eject blood
effectively
– Usually due to a heart weakened by myocardial
infarction, chronic hypertension, valvular
insufficiency, or congenital defects in heart
structure
19-43
Overview of Volume Changes
• Left ventricular failure—blood backs up into the
lungs causing pulmonary edema
– Shortness of breath or sense of suffocation
• Right ventricular failure—blood backs up in the
vena cava causing systemic or generalized
edema
– Enlargement of the liver, ascites (pooling of fluid in
abdominal cavity), distension of jugular veins, swelling
of the fingers, ankles, and feet
• Eventually leads to total heart failure
19-44
Overview of Volume Changes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1 Right ventricular
output exceeds left
Ventricular output.
2 Pressure backs up.
3 Fluid accumulates in
pulmonary tissue.
1
2
3
• If the left ventricle
pumps less blood
than the right, the
blood pressure
backs up into the
lungs and causes
pulmonary edema
(a) Pulmonary edema
Figure 19.21a
19-45
Overview of Volume Changes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1 Left ventricular
output exceeds right
ventricular output.
2 Pressure backs up.
3 Fluid accumulates in
systemic tissue.
• If the right ventricle
pumps less blood than
the left, pressure
backs up in the
systemic circulation
and causes systemic
edema
1
2
(b) Systemic edema
3
Figure 19.21b
19-46
Heart Rate
• Pulse—surge of pressure produced by heart beat
that can be felt by palpating a superficial artery
–
–
–
–
Infants have HR of 120 bpm or more
Young adult females average 72 to 80 bpm
Young adult males average 64 to 72 bpm
Heart rate rises again in the elderly
19-47
Heart Rate
• Tachycardia—resting adult heart rate above
100 bpm
– Stress, anxiety, drugs, heart disease, or fever
– Loss of blood or damage to myocardium
• Bradycardia—resting adult heart rate of less
than 60 bpm
– In sleep, low body temperature, and endurancetrained athletes
• Positive chronotropic agents—factors that
raise the heart rate
• Negative chronotropic agents—factors that
lower the heart rate
19-48
Coronary Artery Disease
• Coronary artery disease (CAD)—a constriction
of the coronary arteries
– Usually the result of atherosclerosis: an
accumulation of lipid deposits that degrade the arterial
wall and obstruct the lumen
– Begins when endothelium damaged by hypertension,
diabetes, or other causes
19-49
Coronary Artery Disease
(Continued)
– Monocytes penetrate walls of damaged vessels and
transform into macrophages
• Absorb cholesterol and fats to be called foam cells
– Can grow into atherosclerotic plaques (atheromas)
– Platelets adhere to damaged areas and secrete plateletderived growth factor
• Attracting immune cells and promoting mitosis of muscle
and fibroblasts, and the deposition of collagen
• Bulging mass grows to obstruct arterial lumen
19-50
Coronary Artery Disease
• Causes angina pectoris, intermittent chest pain,
by obstructing 75% or more of the blood flow
• Immune cells of atheroma stimulate
inflammation
– May rupture, resulting in traveling clots or fatty emboli
• Cause coronary artery spasms due to lack of
secretion of nitric oxide (vasodilator)
• Inflammation transforms atheroma into a
hardened complicated plaque
– One cause of arteriosclerosis
19-51
Coronary Artery Disease
• Major risk factor for CAD is excess of lowdensity lipoprotein (LDL) in the blood
combined with defective LDL receptors in
arterial walls
– LDLs—protein-coated droplets of cholesterol, neutral
fats, free fatty acids, and phospholipids
– Dysfunctional receptors in arterial cells cause them to
accumulate excess cholesterol
19-52
Coronary Artery Disease
• Unavoidable risk factors: heredity, aging,
being male
• Preventable risk factors: obesity, smoking,
lack of exercise, anxious personality, stress,
aggression, and diet
• Treatment
– Coronary bypass surgery
• Uses great saphenous vein from leg or small thoracic
arteries
– Balloon or laser angioplasty
– Insertion of a stent to prevent restenosis
19-53
Blood Pressure
• Blood pressure (BP)—the force that blood exerts
against a vessel wall
• Measured at brachial artery of arm using
sphygmomanometer
– A close approximation of pressure at exit of left ventricle
• Two pressures are recorded
– Systolic pressure: peak arterial BP taken during
ventricular contraction (ventricular systole)
– Diastolic pressure: minimum arterial BP taken during
ventricular relaxation (diastole) between heart beats
• Normal value, young adult: 120/75 mm Hg
20-54
Blood Pressure
• Hypertension—high blood pressure
– Chronic resting BP > 140/90
– Consequences
• Can weaken arteries, cause aneurysms, promote
atherosclerosis
• Hypotension—chronic low resting BP
– Caused by blood loss, dehydration, anemia
20-55
Capillary Exchange
• The most important blood in the body is in the
capillaries
• Only through capillary walls are exchanges
made between the blood and surrounding
tissues
• Capillary exchange—two-way movement of fluid
across capillary walls
– Water, oxygen, glucose, amino acids, lipids, minerals,
antibodies, hormones, wastes, carbon dioxide,
ammonia
20-56
The Major Systemic Arteries
Figure 20.21
• Arteries supply oxygen and nutrients to all organs
20-57
The Aorta and Its Major Branches
• Ascending aorta
– Right and left coronary arteries supply heart
• Aortic arch
– Brachiocephalic
• Right common carotid supplying right side of head
• Right subclavian supplying right shoulder and upper limb
– Left common carotid supplying left side of head
– Left subclavian supplying shoulder and upper limb
• Descending aorta: differently named in chest and
abdomen
– Thoracic aorta above diaphragm
– Abdominal aorta below diaphragm
20-58
The Major Systemic Veins
Figure 20.22
• Deep veins run parallel to arteries while
superficial veins have many anastomoses
20-59
Arterial Pressure Points
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Superficial temporal a.
Facial a.
Common carotid a.
Anterior superior iliac spine
Inguinal ligament
Pubic
tubercle
Femoral n.
Femoral a.
Radial a.
Brachial a.
Adductor
longus m.
Femoral v.
Sartorius m.
Gracilis m.
Rectus femoris m.
Femoral a.
Great saphenous v.
Vastus lateralis m.
(b)
Inguinal ligament
Popliteal a.
Sartorius
Adductor longus
Posterior tibial a.
Dorsal pedal a.
(c)
Figure 20.41a–c
(a)
• Some major arteries close to surface allow for palpation of
pulse and serve as pressure points to reduce arterial
bleeding
20-60
Hypertension—The “Silent Killer”
• Hypertension—most common cardiovascular
disease affecting about 30% of Americans over 50
• “The silent killer”
– Major cause of heart failure, stroke, and kidney failure
• Damages heart by increasing afterload
– Myocardium enlarges until overstretched and inefficient
• Renal arterioles thicken in response to stress
– Drop in renal BP leads to salt retention (aldosterone) and
worsens the overall hypertension
20-61
Hypertension—The “Silent Killer”
• Primary hypertension
– Obesity, sedentary behavior, diet, nicotine
– 90% of cases
• Secondary hypertension—secondary to other
disease
– Kidney disease, atherosclerosis, hyperthyroidism,
Cushing syndrome
– 10% of cases
20-62
Components and General
Properties of Blood
• Hematology: Study of blood
• A liquid connective tissue consisting of cells
and extracellular matrix
– Plasma: matrix of blood
• Clear, light yellow fluid
– Formed elements: blood cells and cell
fragments
• Red blood cells, white blood cells, and platelets
18-63
Components and General
Properties of Blood
• Seven kinds of formed elements
– 1)Erythrocytes: red blood cells (RBCs)
– 2)Platelets
• Cell fragments from special cell in bone marrow
– Leukocytes: white blood cells (WBCs)
• Five leukocyte types divided into two categories
• Granulocytes (with granules)
– 3)Neutrophils
– 4)Eosinophils
– 5)Basophils
• Agranulocytes (without granules)
– 6)Lymphocytes
– 7)Monocytes
18-64
Components and General
Properties of Blood
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Monocyte
Small
lymphocyte
Neutrophil
Platelets
Eosinophil
Small
lymphocyte
Erythrocyte
Young (band)
neutrophil
Neutrophil
Monocyte
Large
lymphocyte
Neutrophil
Basophil
Figure 18.1
18-65
Components and General
Properties of Blood
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Withdraw
blood
Centrifuge
Plasma
(55% of whole blood)
Buffy coat: leukocytes
and platelets
(<1% of whole blood)
Erythrocytes
(45% of whole blood)
Figure 18.2
Formed
elements
• Hematocrit—centrifuge blood to
separate components
– Erythrocytes are heaviest and
settle first
• 37% to 52% total volume
– White blood cells and platelets
• 1% total volume
• Buffy coat
– Plasma
• The remainder of volume
• 47% to 63%
• Complex mixture of water,
proteins, nutrients,
electrolytes, nitrogenous
wastes, hormones, and gases
18-66
Blood Plasma
• Plasma—liquid portion of blood
– Serum: remaining fluid when blood clots and solids are removed
• Identical to plasma except for the absence of fibrinogen
• Three major categories of plasma proteins
– Albumins: smallest and most abundant
• Contribute to viscosity and osmolarity; influence blood pressure,
flow, and fluid balance
– Globulins (antibodies)
• Provide immune system functions
• Alpha, beta, and gamma globulins
– Fibrinogen
• Precursor of fibrin threads that help form blood clots
• Plasma proteins are formed by liver
– Except globulins (produced by plasma cells)
18-67
Blood Plasma
• Nitrogenous compounds
– Free amino acids from dietary protein or tissue breakdown
– Nitrogenous wastes (urea)
• Toxic end products of catabolism
• Normally removed by the kidneys
• Nutrients
– Glucose, vitamins, fats, cholesterol, phospholipids, and
minerals
• Dissolved O2, CO2, and nitrogen
• Electrolytes
– Na+ makes up 90% of plasma cations
18-68
Blood Viscosity and Osmolarity
• Viscosity—resistance of a fluid to flow, resulting
from the cohesion of its particles
– Whole blood 4.5 to 5.5 times as viscous as water
– Plasma is 2.0 times as viscous as water
• Important in circulatory function
18-69
Blood Viscosity and Osmolarity
• Osmolarity of blood—the total molarity of those
dissolved particles that cannot pass through the
blood vessel wall
– If too high, blood absorbs too much water, increasing
the blood pressure
– If too low, too much water stays in tissue, blood
pressure drops, and edema occurs
– Optimum osmolarity is achieved by the body’s
regulation of sodium ions, proteins, and red blood cells
18-70
Starvation and Plasma Protein
Deficiency
• Hypoproteinemia
– Deficiency of plasma proteins
• Extreme starvation
• Liver or kidney disease
• Severe burns
• Kwashiorkor
– Children with severe protein deficiency
• Fed on cereals once weaned
– Thin arms and legs
– Swollen abdomen
18-71
How Blood is Produced
• Adult production of 400 billion platelets, 100-200
billion RBCs, and 10 billion WBCs every day
• Hemopoiesis—production of blood, especially its
formed elements
• Hemopoietic tissues produce blood cells
– Yolk sac produces stem cells for first blood cells
• Colonize fetal bone marrow, liver, spleen, and thymus
– Liver stops producing blood cells at birth
– Spleen remains involved with lymphocyte production
18-72
How Blood is Produced
– Red bone marrow produces all seven formed
elements
• Pluripotent stem cells (PPSC)
– Formerly called hemocytoblasts or hemopoietic
stem cells
• Colony-forming unit—specialized stem cells only
producing one class of formed element of blood
• Myeloid hemopoiesis—blood formation in the
bone marrow
• Lymphoid hemopoiesis—blood formation in the
lymphatic organs (beyond infancy this only
involves lymphocytes)
18-73
Erythrocytes
Figure 18.4c
• Two principal functions
– Carry oxygen from lungs to cell tissues
– Pick up CO2 from tissues and bring to lungs
• Insufficient RBCs can cause death in minutes due to
lack of oxygen to tissues
18-74
Form and Function
• Disc-shaped cell with thick
rim
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or
display.
Surface view
– 7.5 m diameter and 2.0 m
thick at rim
– Lose nearly all organelles
during development
• Lack mitochondria
– Anaerobic fermentation to
produce ATP
• Lack of nucleus and DNA
– No protein synthesis or
mitosis
7.5 µm
2.0 µm
(a)
Sectional view
Figure 18.4a
18-75
Form and Function
– Blood type determined by surface glycoproteins
and glycolipids
– Cytoskeletal proteins (spectrin and actin) give
membrane durability and resilience
• Stretch and bend as squeezed through small
capillaries
18-76
Form and Function
• Gas transport—major function
– Increased surface area/volume ratio
• Due to loss of organelles during maturation
• Increases diffusion rate of substances
– 33% of cytoplasm is hemoglobin (Hb)
• 280 million hemoglobin molecules on one RBC
• O2 delivery to tissue and CO2 transport to lungs
• Carbonic anhydrase (CAH) in cytoplasm
– Produces carbonic acid from CO2 and water
– Important role in gas transport and pH balance
18-77
Hemoglobin
• Each Hb molecule consists of:
– Four protein chains—globins
• Adult HB has two alpha and two
beta chains
• Fetal Hb contains two alpha and
two gamma chains
• Globins bind CO2 (5% of CO2 in
blood)
– Four heme groups
• Heme groups
– Nonprotein moiety that binds O2
to ferrous ion (Fe) at its center
Figure 18.5a,b
18-78
Quantities of Erythrocytes
and Hemoglobin
• RBC count and hemoglobin concentration
indicate amount of O2 blood can carry
– Hematocrit (packed cell volume): percentage of
whole blood volume composed of RBCs
• Men 42% to 52% cells; women 37% to 48% cells
– Hemoglobin concentration of whole blood
• Men 13 to 18 g/dL; women 12 to 16 g/dL
– RBC count
• Men 4.6 to 6.2 million/L; women 4.2 to 5.4
million/L
18-79
Quantities of Erythrocytes
and Hemoglobin
• Values are lower in women
– Androgens stimulate RBC production
– Women have periodic menstrual losses
– Hematocrit is inversely proportional to percentage of
body fat
18-80
Erythrocyte Production
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Pluripotent
stem cell
Colony-forming
unit (CFU)
Erythrocyte CFU
Precursor
cells
Erythroblast
Mature
cell
Reticulocyte
Erythrocyte
Figure 18.6
•
•
•
•
Erythroopoiesis—RBC production
1 million RBCs are produced per second
Average lifespan of about 120 days
Development takes 3 to 5 days
– Reduction in cell size, increase in cell number, synthesis of
hemoglobin, and loss of nucleus
18-81
Erythrocyte Production
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Pluripotent
stem cell
Colony-forming
unit (CFU)
Erythrocyte CFU
Precursor
cells
Erythroblast
Mature
cell
Reticulocyte
Erythrocyte
Figure 18.6
• First committed cell—erythrocyte colony-forming unit
– Has receptors for erythropoietin (EPO) from kidneys
• Erythroblasts (normoblast) multiply and synthesize
hemoglobin
• Nucleus discarded to form a reticulocyte
– Named for fine network of endoplasmic reticulum
– 0.5% to 1.5% of circulating RBCs are reticulocytes
18-82
Iron Metabolism
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
leaves
8 Remaining transferrin is distributed
to other organs where Fe2+ is used
to make hemoglobin, myoglobin, etc.
7 Fe2+ binds to
apoferritin
to be stored
as ferritin
1 Mixture of Fe2+ and
Fe3+ is ingested
Fe3+
Ferritin
2 Stomach acid
converts Fe3+
to Fe2+
Fe2+
Apoferritin
Gastroferritin
6 In liver, some transferrin
releases Fe2+ for storage
Blood plasma
5 In blood plasma,
Fe2+ binds to transferrin
Transferrin
3 Fe2+ binds to
gastroferritin
4 Gastroferritin transports
Fe2+ to small intestine and
releases it for absorption
Figure 18.7
18-83
Iron Metabolism
• Iron—key nutritional requirement
– Lost daily through urine, feces, and bleeding
• Men 0.9 mg/day and women 1.7 mg/day
– Low absorption rate of iron requires consumption
of 5 to 20 mg/day
18-84
Iron Metabolism
• Dietary iron: ferric (Fe3+) and ferrous (Fe2+)
– Stomach acid converts Fe3+ to absorbable Fe2+
– Gastroferritin binds Fe2+ and transports it to small
intestine
– Absorbed into blood and binds to transferrin for
transport to bone marrow, liver, and other tissues
- Bone marrow for hemoglobin, muscle for myoglobin,
and all cells use for cytochromes in mitochondria
• Liver apoferritin binds to create ferritin for
storage
18-85
Iron Metabolism
• Vitamin B12 and folic acid
– Rapid cell division and DNA synthesis that occurs in
erythropoiesis
• Vitamin C and copper
– Cofactors for enzymes synthesizing hemoglobin
• Copper is transported in the blood by an alpha globulin called
ceruloplasmin
18-86
Erythrocyte Homeostasis
• Negative feedback control
– Drop in RBC count causes
hypoxemia detected by kidney
– Kidney production of
erythropoietin stimulates bone
marrow
– RBC count increases in 3 to 4
days
• Stimuli for increasing
erythropoiesis
–
–
–
–
Low levels O2 (hypoxemia)
High altitude
Increase in exercise
Loss of lung tissue in emphysema
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or
display.
Hypoxemia
(inadequate O2 transport)
Increased
O2 transport
Sensed by liver and kidneys
leaves
Increased
RBC count
Accelerated
erythropoiesis
Secretion of
erythropoietin
Stimulation of
red bone marrow
Figure 18.8
18-87
Erythrocyte Death and Disposal
• RBCs rupture (hemolysis) in narrow channels of
spleen and liver
• Macrophages in spleen
– Digest membrane bits
– Separate heme from globin
• Globins hydrolyzed into amino acids
• Iron removed from heme
– Heme pigment converted to biliverdin (green)
– Biliverdin converted to bilirubin (yellow)
– Released into blood plasma (kidneys—yellow urine)
– Liver removes bilirubin and secretes into bile
- Concentrated in gallbladder: released into small
intestine; bacteria create urobilinogen (brown feces)
18-88
Erythrocyte Death and Disposal
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or
display.
Amino acids
Iron
Folic acid
Vitamin B12
Erythropoiesis in
red bone marrow
Nutrient
absorption
Erythrocytes
circulate for
120 days
Small intestine
Expired erythrocytes
break up in liver and spleen
Cell fragments
phagocytized
Hemoglobin
degraded
Figure 18.9
Globin
Heme
Biliverdin
Bilirubin
Bile
Feces
Iron
Storage
Reuse
Hydrolyzed to free
amino acids
Loss by
menstruation,
injury, etc.
18-89
Anemia
• Causes of anemia fall into three categories
– Inadequate erythropoiesis or hemoglobin synthesis
• Kidney failure and insufficient erythropoietin
• Iron-deficiency anemia
• Pernicious anemia—autoimmune attack of stomach tissue
leads to inadequate vitamin B12 absorption
• Hypoplastic anemia—slowing of erythropoiesis
• Aplastic anemia—complete cessation of erythropoiesis
– Hemorrhagic anemias from bleeding
– Hemolytic anemias from RBC destruction
18-90
Anemia
• Anemia has three potential consequences
– Tissue hypoxia and necrosis
• Patient is lethargic
• Shortness of breath upon exertion
• Life-threatening necrosis of brain, heart, or kidney
– Blood osmolarity is reduced, producing tissue edema
– Blood viscosity is low
• Heart races and pressure drops
• Cardiac failure may ensue
18-91
Sickle-Cell Disease
• Hereditary defects that occur mostly
among people of African descent
• Caused by recessive allele that
modifies structure of Hb (makes
HbS)
– Differs only on the sixth amino acid
of the beta chain
– HbS does not bind oxygen well
– RBCs become rigid, sticky, pointed
at ends
– Clump together and block small
blood vessels
– Can lead to kidney or heart failure,
stroke, joint pain, or paralysis
– Heterozygotes (only one sickle cell
allele) are resistant to malaria
Figure 18.10
18-92
Blood Types
• Blood types and transfusion compatibility are a
matter of interactions between plasma proteins
and erythrocytes
• Karl Landsteiner discovered blood types A, B,
and O in 1900
– He won a Nobel Prize in 1930
• Blood types are based on interactions between
antigens and antibodies
18-93
Blood Types
• Antigens
– Complex molecules on surface of cell membrane
that activate an immune response
•
•
•
•
They are genetically unique to the individual
Used to distinguish self from foreign matter
Foreign antigens generate an immune response
Agglutinogens—antigens on the surface of the
RBC that are the basis for blood typing
18-94
Blood Types
• Antibodies
– Proteins (gamma globulins) secreted by plasma
cells
•
•
•
•
Part of immune response to foreign matter
Bind to antigens and mark them for destruction
Forms antigen–antibody complexes
Agglutinins—antibodies in the plasma that bring
about transfusion mismatch
• Agglutination
– Antibody molecule binding to antigens
– Causes clumping of red blood cells
18-95
Blood Types
• RBC antigens called
agglutinogens
– Called antigen A and B
– Determined by
glycolipids on RBC
surface
• Antibodies called
agglutinins
– Found in plasma
– Anti-A and anti-B
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Type O
Type B
leaves
Type A
Type AB
Key
Galactose
Fucose
N-acetylgalactosamine
Figure 18.12
18-96
The ABO Group
• Your ABO blood type is determined by
presence or absence of antigens
(agglutinogens) on RBCs
–
–
–
–
Blood type A person has A antigens
Blood type B person has B antigens
Blood type AB has both A and B antigens
Blood type O person has neither antigen
• Most common: type O
• Rarest: type AB
18-97
ABO Blood Typing
Figure 18.14
18-98
The ABO Group
• Antibodies (agglutinins); anti-A and anti-B
• Appear 2 to 8 months after birth; maximum
concentration by 10 years of age
– Antibody-A or antibody-B (or both or neither) are
found in plasma
• You do not form antibodies against your antigens
18-99
The ABO Group
• Agglutination
– Each antibody can attach to several foreign antigens
on several different RBCs at the same time
• Responsible for mismatched transfusion reaction
– Agglutinated RBCs block small blood vessels,
hemolyze, and release their hemoglobin over the
next few hours or days
– Hb blocks kidney tubules and causes acute renal
failure
18-100
The ABO Group
• Universal donor
– Type O: most common blood type
– Lacks RBC antigens
– Donor’s plasma may have both antibodies
against recipient’s RBCs (anti-A and anti-B)
• May give packed cells (minimal plasma)
• Universal recipient
– Type AB: rarest blood type
– Lacks plasma antibodies; no anti-A or anti-B
18-101
The Rh Group
• Rh (C, D, E) agglutinogens discovered in rhesus
monkey in 1940
– Rh D is the most reactive and a patient is considered
blood type Rh+ if having D antigen (agglutinogens) on
RBCs
– Rh frequencies vary among ethnic groups
18-102
The Rh Group
• Anti-D agglutinins not normally present
– Form in Rh- individuals exposed to Rh+ blood
• Rh- woman with an Rh+ fetus or transfusion of Rh+
blood
• No problems with first transfusion or pregnancy
• Hemolytic disease of the newborn (HDN) can occur
if Rh- mother has formed antibodies and is pregnant
with second Rh+ child
– Anti-D antibodies can cross placenta
• Prevention
– RhoGAM given to pregnant Rh- women
• Binds fetal agglutinogens in her blood so she will not
form anti-D antibodies
18-103
Hemolytic Disease of the Newborn
Figure 18.16
• Rh antibodies attack fetal blood causing
severe anemia and toxic brain syndrome
18-104
Form and Function
• Least abundant formed element
» 5,000 to 10,000 WBCs/L
• Protect against infectious microorganisms and
other pathogens
• Conspicuous nucleus
• Spend only a few hours in the bloodstream before
migrating to connective tissue
• Retain their organelles for protein synthesis
• Granules
– All WBCs have lysosomes called nonspecific (azurophilic)
granules
– Granulocytes (some WBCs) have specific granules that
contain enzymes and other chemicals employed in defense
against pathogens
18-105
Types of Leukocytes
• Granulocytes
– Neutrophils (60% to 70%): polymorphonuclear leukocytes
• Barely visible granules in cytoplasm; three- to five-lobed nucleus
– Eosinophils (2% to 4%)
• Large rosy-orange granules; bilobed nucleus
– Basophils (less than 1%)
• Large, abundant, violet granules (obscure a large S-shaped
nucleus)
• Agranulocytes
– Lymphocytes (25% to 33%)
• Variable amounts of bluish cytoplasm (scanty to abundant);
ovoid/round, uniform dark violet nucleus
– Monocytes (3% to 8%)
• Usually largest WBC; ovoid, kidney-, or horseshoe-shaped
nucleus
18-106
Granulocytes
• Neutrophils—aggressively antibacterial
– Neutrophilia—rise in number of neutrophils in response to bacterial
infection
• Eosinophils—increased numbers in parasitic infections,
collagen diseases, allergies, diseases of spleen and CNS
– Phagocytosis of antigen–antibody complexes,
allergens, and inflammatory chemicals
– Release enzymes to destroy large parasites
• Basophils—increased numbers in chickenpox, sinusitis,
diabetes
– Secrete histamine (vasodilator): speeds flow of blood to an
injured area
– Secrete heparin (anticoagulant): promotes the mobility of other
WBCs in the area
18-107
Agranulocytes
• Lymphocytes—increased numbers in diverse
infections and immune responses
– Destroy cells (cancer, foreign, and virally infected
cells)
– “Present” antigens to activate other immune cells
– Coordinate actions of other immune cells
– Secrete antibodies and provide immune memory
18-108
Agranulocytes
• Monocytes—increased numbers in viral
infections and inflammation
– Leave bloodstream and transform into macrophages
• Phagocytize pathogens and debris
• “Present” antigens to activate other immune cells—
antigen-presenting cells (APCs)
18-109
The Leukocyte Life History
• Leukopoiesis—production of white blood cells
– Hemopoietic stem cells (HSCs) differentiate into:
• Myeloblasts—form neutrophils, eosinophils,
basophils
• Monoblasts—form monocytes
• Lymphoblasts give rise to all forms of lymphocytes
– T lymphocytes complete development in thymus
• Red bone marrow stores and releases
granulocytes and monocytes
18-110
The Leukocyte Life Cycle
• Circulating WBCs do not stay in bloodstream
– Granulocytes leave in 8 hours and live 5 days longer
– Monocytes leave in 20 hours, transform into
macrophages, and live for several years
– Lymphocytes provide long-term immunity (decades),
being continuously recycled from blood to tissue fluid
to lymph and back to the blood
18-111
Leukopoiesis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Pluripotent
stem cell
Colony-forming
units (CFUs)
Mature
cells
Precursor
cells
leaves
Eosinophilic
CFU
Eosinophilic
myeloblast
Eosinophilic
promyelocyte
Eosinophilic
myelocyte
Eosinophil
Basophilic
CFU
Basophilic
myeloblast
Basophilic
promyelocyte
Basophilic
myelocyte
Basophil
Neutrophilic
CFU
Neutrophilic
myeloblast
Neutrophilic
promyelocyte
Neutrophilic
myelocyte
Neutrophil
Monocytic
CFU
Monoblast
Promonocyte
Monocyte
B lymphocyte
B prolymphocyte
Figure 18.18
Lymphocytic
CFU
T prolymphocyte
T lymphocyte
NK prolymphocyte
NK cell
Lymphoblast
18-112
Leukocyte Disorders
• Leukopenia—low WBC count: below 5,000
WBCs/L
– Causes: radiation, poisons, infectious disease
– Effects: elevated risk of infection
• Leukocytosis—high WBC count: above 10,000
WBCs/L
– Causes: infection, allergy, disease
– Differential WBC count: identifies what percentage
of the total WBC count consist of each type of
leukocyte
18-113
Leukocyte Disorders
• Leukemia—cancer of hemopoietic tissue usually
producing a very high number of circulating leukocytes
– Myeloid leukemia: uncontrolled granulocyte production
– Lymphoid leukemia: uncontrolled lymphocyte or
monocyte production
– Acute leukemia: appears suddenly, progresses rapidly,
death within months
– Chronic leukemia: undetected for months, survival time
3 years
– Effects: normal cell percentages disrupted; impaired
clotting; opportunistic infections
18-114
Normal and Leukemic Blood
Figure 18.19a,b
18-115
The Complete Blood Count
• Includes several values
– Hematocrit
– Hemoglobin concentration
– Total count for RBCs, reticulocytes, WBCs, and
platelets
– Differential WBC count
– RBC size and hemoglobin concentration per RBC
18-116
Platelets and Hemostasis—
The Control of Bleeding
• Hemostasis—the cessation of bleeding
– Stopping potentially fatal leaks
– Hemorrhage: excessive bleeding
• Three hemostatic mechanisms
– Vascular spasm
– Platelet plug formation
– Blood clotting (coagulation)
• Platelets play an important role in all three
18-117
Platelet Form and Function
• Platelets—small fragments of
megakaryocyte cells
– 2 to 4 m diameter; contain “granules”
– Platelet contains a complex internal structure
and an open canalicular system
– Amoeboid movement and phagocytosis
• Normal platelet count—130,000 to 400,000
platelets/L
18-118
Platelet Form and Function
• Platelet functions
– Secrete vasoconstrictors that help reduce blood loss
– Stick together to form platelet plugs to seal small
breaks
– Secrete procoagulants or clotting factors to promote
clotting
– Initiate formation of clot-dissolving enzyme
– Chemically attract neutrophils and monocytes to sites
of inflammation
– Phagocytize and destroy bacteria
– Secrete growth factors that stimulate mitosis to
repair blood vessels
18-119
Hemostasis
• Vascular spasm—prompt constriction of a broken
vessel
– Most immediate protection against blood loss
• Causes
– Pain receptors
• Some directly innervate blood vessels to constrict
– Smooth muscle injury
– Platelets release serotonin (vasoconstrictor)
• Effects
– Prompt constriction of a broken vessel
• Pain receptors—short duration (minutes)
• Smooth muscle injury—longer duration
– Provides time for other two clotting pathways
18-120
Hemostasis
• Platelet plug formation
– Intact vessels have a smooth endothelium coated with
prostacyclin—a platelet repellant
– Broken vessel exposes collagen
– Platelet pseudopods stick to damaged vessel and other platelets
– Pseudopods contract - draw together a platelet plug
– Platelets degranulate releasing a variety of substances
• Serotonin is a vasoconstrictor
• ADP attracts and degranulates more platelets
• Thromboxane A2, an eicosanoid, promotes platelet
aggregation, degranulation, and vasoconstriction
– Positive feedback cycle is active until break in small vessel is
sealed
18-121
Hemostasis
• Coagulation (clotting)—last and most effective defense
against bleeding
– Conversion of plasma protein fibrinogen into insoluble fibrin
threads to form framework of clot
– Procoagulants (clotting factors)—usually produced by the
liver; are present in plasma
• Activate one factor and it will activate the next to form a
reaction cascade
– Extrinsic pathway
• Factors released by damaged tissues begin cascade
– Intrinsic pathway
• Factors found in blood begin cascade (platelet degranulation)
18-122
Coagulation
18-123
Figure 18.22
Coagulation
• Extrinsic pathway
– Initiated by release of tissue thromboplastin
(factor III) from damaged tissue
– Cascade to factor VII, V, and X (fewer steps)
• Intrinsic pathway
– Initiated by platelets releasing Hageman factor
(factor XII)
– Cascade to factor XI to IX to VIII to X
• Calcium required for either pathway
18-124
Reaction Cascade in Clotting
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Factor
XII
Factor
IX
Factor
VIII
Factor
X
Figure 18.23
Prothrombin
activator
Reaction cascade (time)
Factor
XI
Thrombin
Fibrin
• Rapid clotting—each activated cofactor activates many
more molecules in next step of sequence
18-125
Completion of Coagulation
• Activation of factor X
– Leads to production of prothrombin activator
• Prothrombin activator
– Converts prothrombin to thrombin
• Thrombin
– Converts fibrinogen into fibrin monomers
– Monomers covalently bind to form fibrin polymer
– Factor XIII cross links fibrin polymer strands
• Positive feedback—thrombin speeds up formation of
prothrombin activator
• Overall efficiency in coagulation can be measured with
bleeding time after a 1 mm deep incision
18-126
The Fate of Blood Clots
• Clot retraction occurs within 30 minutes
• Platelet-derived growth factor secreted by
platelets and endothelial cells
– Mitotic stimulant for fibroblasts and smooth muscle to
multiply and repair damaged vessel
• Fibrinolysis—dissolution of a clot
– Factor XII speeds up formation of kallikrein enzyme
– Kallikrein converts plasminogen into plasmin, a fibrindissolving enzyme that breaks up the clot
18-127
Clotting Disorders
• Deficiency of any clotting factor can shut down
the coagulation cascade
• Hemophilia—family of hereditary diseases
characterized by deficiencies of one factor or another
• Sex-linked recessive (on X chromosome)
– Hemophilia A missing factor VIII (83% of cases)
– Hemophilia B missing factor IX (15% of cases)
• Hemophilia C missing factor XI (autosomal)
18-128
Clotting Disorders
• Physical exertion causes bleeding and
excruciating pain
– Transfusion of plasma or purified clotting
factors
– Factor VIII produced by transgenic bacteria
• Hematomas—masses of clotted blood in the
tissues
18-129
Clotting Disorders
• Thrombosis—abnormal clotting in unbroken vessel
– Thrombus: clot
• Most likely to occur in leg veins of inactive people
– Pulmonary embolism: clot may break free, travel
from veins to lungs
• Embolus—anything that can travel in the blood and
block blood vessels
• Infarction (tissue death) may occur if clot blocks
blood supply to an organ (MI or stroke)
– 650,000 Americans die annually of thromboembolism
(traveling blood clots)
18-130
Clinical Management of Blood Clotting
• Goal—prevent formation of clots or dissolve existing
clots
• Preventing clots
– Vitamin K is required for formation of clotting factors
• Coumarin, warfarin (Coumadin)—vitamin K
antagonists
– Aspirin suppresses thromboxane A2
– Other anticoagulants discovered in animal research
• Medicinal leeches used since 1884 (hirudin)
• Snake venom from vipers (arvin)
18-131
Clinical Management of Blood Clotting
• Dissolving clots that have already formed
– Streptokinase: enzyme made by streptococci bacteria
• Used to dissolve clots in coronary vessels
• Digests almost any protein
– Tissue plasminogen activator (TPA): works faster, is
more specific, and now made by transgenic bacteria
– Hementin: produced by giant Amazon leech
18-132