Heart
Functions
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William Harvey was an English physician in the 1600s that was the first to
explain the heart and says it pumps blood
Anatomy
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The heart is about the size of a large fist and is located in the mediastenum
between the lungs. It is displaced 65% to the left of the mediastenum.
It is in the shape of an inverted cone
The Parietal Pericardium completely encloses the heart and has two layers.
o Serous Coat
 This is the innermost layer, consisting of two smooth serous layers.
This continues at the base of the heart and around large vessels in
the area of the epicardium. The serous layers are separated by a
fluid material that serves as lubrication to minimize friction as the
heart beats.
o Fibrous Coat
 This is the outer layer that attaches to the large vessels at the base
of the heart. It serves as a tough, protective later for the heart.
 Other attachments include a central tendon of the diaphragm,
interior of the sternal wall of the thoracic cavity, and mediastinal
parietal pleurae.
The all of the heart has three layers
o Endocardium (Tunica intima)
 This is the innermost layer, lining the myocardium. It consists of
simple epithelial tissue that lines all of the heart chambers, valve
surfaces, and continues into the blood vessels of the heart. It is
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supported by fibrous tissue, especially at valve cusps where it is
the thickest. The subendothelial connective tissue becomes
continuous with the perimysium of the cardiac muscle. It supports
deep blood vessels and nerve conduction tissue of the heart.
o Myocardium (Tunica media)
 This is the middle and thickest layer. It consists of cardiac muscle,
forming an irregular pattern of ridges, folds, and bridges at the
ventricles called trabeculae carneae. It contains extensive elastic
fibers in the atria, but elastic fibers are sparse in the myocardium
of the ventricles. It is thickest at the ventricles and thinnest at the
atria, with the left ventricle being the thickest. This is due to the
great workload of this area. The papillary muscles of the ventricles
are etensions of the myocardium which, by the chordae tendineae,
stabilize the cusps of the mitral and tricuspid valves.
o Epicardium (Tunica adventitia)
 This is the visceral, outermost layer. It is thin and transparent,
made of fibrous tissue. The outer connective tissue is of the
fibroelastic type, while the deeper connective tissue is largely
adipose tissue. It is composed of an outer medothelial secretory
layer of flat epithelial cells overlying a connective tissue layer. The
mesothelial cells secrete serous fluid which lubricates the
movement of the epicardium on the parietal pericardium. It
contains blood vessels, lymphatics, and fat tissue. Branches of the
coronary vessels and the nerves pass through the epicardium to
supply the myocardium.
Cardiac Skeleton
o It consists of dense connective tissue, forming the central support of the
heart, and as origin and insertion of the cardiac muscles. Specifically, it
consists of the annuli fibrosa, trigona fibrosa, septum membranaceum, and
chrodae tendineae (Geneser).
o Fibrous rings surround the atrioventricular canals and the origins of the
aorta and pulmonary trunks.
o These rings prevent the valve-containing outlets from becoming dilated
when the chambers of the heart contract and force blood through them.
o The various fibrous structures of the cardiac skeleton, together with the
membranous part of the interventricular septum, also provide insertion for
the fibers of the cardiac musculature.
Chambers
o Right Atrium
 This receives the deoxygenated blood. It contains mostly smooth
muscle, and it contains parallel folds called the musculi pectinati.
 Compared to the left atrium, the cavity is larger, and the wall is
thinner.
 Structures that enter
 Superior vena cava
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o This enters on the superior and posterior side. It
drains areas of the head, thorax, and upper
extremities. It does not have a valve.
 Inferior vena cava
o This enters on the inferior, posterior side. It drains
the trunk and lower extremities. A valve is used to
direct blood flow. This is a fetal remnant with no
significant functional important in the adult heart.
o Right Ventricle
 Structures here include
 Papillary muscles
o These are located at the ends of the chordae
tendineae. They are cone-shaped muscles that
project from the ventricular wall, attaching to the
tricuspid valve. The purpose is to maintain its
integrity during ventricular contraction by
tightening and preventing the valves from being
pushed up on the aorta.
 Trabeculae Carnea
o This is located in the inner wall of the ventricle.
They are irregular ridges and bridges.
 Conus Arteriosus
o This is the smooth and narrowing superior portion
of the ventricle. Trabeculae carnae are absent from
this area.
o Left Atrium
 This receives four pulmonary veins, two from each lung.
 The lining is smooth, except for the area of the auricle, which has
parallel fibers called musculi pentinati.
o Left Ventricle
 This has the same capacity as the right ventricle, but the walls are
three times thicker.
Heart Valves
o These are mechanical devices to prevent backflow, permitting blood flow
in only one direction. They are passive, working on pressure gradients.
Blood flows in and closes the valve.
o They are formed by overlapping folds of the endocardium with a desnse
connective tissue core.
o Atrioventricular Valves (AV)
 On the right, this is called the tricuspid
 This has three triangular, serrated cusps composed of
strong fibrous tissue.
 On the left, this is called the bicuspid (mitral) valve.
 This has two cusps, instead of three.
o Semilunar Valves (3 cusps)
 Pulmonic Semilunar Valve
 This is between the right ventricle and pulmonary artery,
passing deoxygenated blood to the lungs to be oxygenated.
It holds blood in the relaxed ventricle during diastole.
 It contains three semilunar cusps and is made from the
endocardial layer of the heart. It is reinforced by fibrous
tissue.
 Aortic semilunar valve
 This is between the left ventricle and aorta, passing
oxygenated blood for systemic circulation.
 These cusps are larger and stronger. They contain dilated
areas from which the coronary arteries arise.
Thickness
AV Valve
Thin and Filmy
Pressure
Opening
Velocity
Lower
Larger
Slower
Semilunar Valves
Thick and Leathery due to increased
abrasion.
High, especially when closed
Smaller, therefore higher pressure
Increased, due to smaller valve. There
is greater ventricular force than in the
atria.
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Cardiac Muscle
o This is striated with actin and myosin arranged in sarcomeres. These
sarcomeres are joined by gap junctions which electrically join the muscle
cells. The heart contracts in an all-or-none fashion.
Coronary Circulation
o Arteries of the Heart Wall
 The right and left coronary arteries supply the heart wall. They
originate in the area of the aortic valve and are the only branches
of the ascending aorta. Both coronary arteries have two main
branches with few anastomoses between the large branches. The
right coronary artery follows the sulcus of the heart closely,
forming an almost complete crown around the heart.
o Veins of the Heart Wall
 The venous channel of the heart is the coronary sinus, which
collects all of the cardiac veins. It is located near the inferior vena
cava. The cardiac veins return the blood to the heart. These drain
almost all the veins of the heart, with a few draining directly into
the right atrium.
Main Blood Vessels
o Aorta
 This is the largest of the arteries and is the outlet of the left
ventricle.
 The first portion, the ascending aorta, appears anteriorly,
leading upward and to the left. This is what pumps blood to
the head. The right and left coronary arteries are the only
branches of the ascending aorta.
 The second portion, the arch of the aorta, curves to the left.
This has three branches: the brachiocephalic, left common
carotid artery, and the left subclavian artery.
o The brachiocephalic branches off to the right
common carotid and the right subclavian arteries.
 The right subclavian arches slightly from its
origin at the brachiocephalic artery, and
crossing over the first rib, at the outer border
of which it becomes the axillary artery. Its
principal branches are the vertebral artery
and internal thoracic artery.
 Vertebral artery
o This is the first branch of the
subclavian. It ascends, giving
off muscular branches to the
deep muscles of the neck and
the suboccipital muscles and
ultimately enters the cranial
cavity to supply the brain.
 Thyrocervical Trunk
o Arises from the subclavian to
supply the muscles in the
anterior part of the neck. The
deep cervical arteries supply
the posterior muscles of the
neck.
o The common carotids course with the internal
jugular vein of the neck deep into the head. These
bifurcate into the external and internal carotids.
 The external carotids supply the face, scalp,
and neck with branches to the thyroid gland,
tongue, angle between the eye and the nose,
occipital region, and the superficial and deep
areas of the temporal region. It is more
superficially placed. Their branches include
the
 Facial artery
o This courses beneath the
digastric and stylohyoid
muscles, crosses the
submandibular gland, and
curves over the body of the
mandible. It proceeds upward
and forward to the angle of
the mouth.
o The facial artery has a
cervical branch and branches
that also go to the lips.
 Infraorbital artery
 Superficial temporal artery
o This ascends in the parotid
gland and crosses the
zygomatic process above
which it terminates in the
frontal and parietal branches.
o Transverse facial artery
o Orbital artery
o Frontal artery
 Maxillary artery
o This is the larger terminal
branch of the external
carotid. This artery runs
rostrally in the parotid gland
then crosses the external
pterygoid muscle and enters
the pterygopalatine fossa.
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o There are five branches for
each part of the maximllary
artery (15 in all). The first 5
reach their destinations by
entering formaine, the middle
five supply soft tissues and
use the foramina, and the last
five also use foramina. The
infraorbital artery can be
considered as the termination
of the artery.
Occipital Artery
o Posteriorly-directed branch
off of the external carotid.
Goes to the occipital region.
Lingual Artery
o Principally goes to the tongue
Superior Thyroid
Transverse Facial
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The internal carotids supply the orbit and
skull. It ascends in the neck in association
with CN X and the internal jugular vein in a
common sheath. It has no branches in the
neck but enters the cranium to carry blood to
the brain. Their branches include the
 Ophthalmic artery
 Posterior communicating artery
 Anterior cerebral artery
 Middle cerebral artery
The third part, the descending aorta, continues through the
thorax and the abdomen. This goes to the thoracic and
abdominal arteries
o Thoracic
 This leads to the bronchial, esophageal,
mediastinal, and superior intercostals.
o Abdominal
 This goes to the inferior phrenic, celiac,
superior mesenteric, renals, inferior
mesenteric, testicular, ovarian, and common
iliacs.
o Pulmonary Artery
 This is the outlet of the right ventricle. It passes to the left in front
of the aorta and divides into the right and left pulmonary arteries.
The right branch disappears behind the arch of the aorta and the
left branch passes in front of the descending aorta.
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The ligamentum arteriosum is a fibrous cord joining the
aortic arch and the left pulmonary artery. In the fetus, this
is a patent vessel, the ductus arteriosus.
Main Veins
o Superior Vena Cava
 This drains the head, neck, upper extremeties, and parts of the
thoracic and abdominal walls into the right atrium.
o Subclavian Vein
 The principle deep vein draining the upper extremity. Untion of the
subclavian vein with the internal jugular forms the brachiocephalic
vein, which is joined by its fellow from the opposite side of the
neck to form the superior vena cava.
o Supratrochlear Vein
 From the middle scalp and forehead, this vein descends to the
medial angle of the eye.
o Supraorbital Vein
 From the scalp and forehead this vein sends a branch through the
supraorbital notch and continues to join the frontal vein forming
the angular vein.
o Angular Vein
 This runs at the side of the nose to the level of the lower orbit.
o Facial Vein
 A continuation of the angular vein and runs beneath the facial
muscles to join the posterior facial vein.
o Superficial Temporal Vein
 Located on the side of the head and scalp.
o Pterygoid Plexus
 A network located between the pterygoid and temporalis muscles.
o Maxillary Vein
 A short vein that drains the pterygoid plexus.
o External Jugular Vein
 This is outside the skull. The superficial temporal and maxillary
veins form the retromandibular vein which eventually forms the
external jugular vein. The external jugular joins the subclavian
vein. It drains the face.
o Internal Jugular Vein
 Within the skull. Meningeal, cerebral, cerebellar, and ophthalmic
veins drain into the venous sinuses which ultimately form right and
left internal jugular veins.
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Main Misc Vessels
o Superior and Inferior Vena Cava
 These are the great veins that lie to the right and behind and lead
into the right atrium.
o Pulmonary Veins- lead to the left atrium
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Common carotid- supplies blood to the brain
Subclavian- supplies blood to the arms.
Iliac- supplies blood to the legs.
Circle of Willis
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This makes up the arterial circulation in the base of the brain and
consists of
 Internal carotid arteries
 Cerebral arteries
 Communicating arteries
o Arteries of the Head and Neck
Physiology
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Histology
o The heart is made up of a latticework of interconnected fibers.
 Striated myocardial heart muscle is present with myofibrils
containing actin and myosin.
o This histology allows the heart to act as a syncytium, or one cell.
 The entire heart will react if one point is stimulated. The stimulus
spreads to all parts and the entire heart contracts at once.
 The cells are separated by intercalated disks, meaning that there is
decreased energy resistance. Ion movement is faster through discs
than a membrane.
 There are two separate syncytiums.
 Both atrium and both ventricles constrict at once.
 The AV valves separate the syncytiums via a fibrous
connective tissue.
Cardiogenesis
o The cardiovascular system is the first system to develop to a functional
state in the developing embryo. The heart begins to beat at 3.5 weeks.
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o Isolated masses of medenchymal cells, often called angioblasts, organize
to form the endothelium. The endothelium, by budding develops vessels in
adjacent areas and there is a joining of these vessels with other vessels.
o In order to maintain blood flow and adequate pressure, a pump must be
provided within the system of developing vessels, the heart. The heart
starts as blood vessels do, but in an area in the ventral anterior end of the
embryo known as the cardiogenic plate. Here, a pair of longitudinal heart
tubes develop. A cavity which will become the pericardial cavity forms
around the plate and tubes. These all join with other vessels of the embryo
to form a primitive cardiovascular system.
o The now single heart tube has slight constrictions and dilatations to form a
heart of five parts. These parts are the truncus arteriosus, bulbus cardis,
ventricle, atrium, and sinus venosus. The oval foramen forms by division
of the atrium. The ventricles divide into left and right, and the bulbus
cardis and truncus arteriosus become divided into two vessles, the aorta
from the left ventricle and the pulmonary artery from the right ventricle,
respectively. Until birth, these two vessels maintain a connection, the
ductuis arteriosus. The three layers of the heart wall develop from the
mesenchyme.
o Cardiac muscle develops from myoblasts, derived from the splanchnic
mesoderm. After birth, the foramen ovale connecting the left and right
atria closes (within about a year, about 20% of individuals do not attain
complete closure). The ductus arteriosus connecting the aorta and
pulmonary artery closes and becomes the ligamentum arteriosum.
Heart Rhythm
o Autorythmicity is a property of cardiac muscle. Each cell contracts on its
own with different rates when separate, not joined. The fastest takes over
when joined. The heart of a vertebrate will continue to beat and contract
even if all nerve connections are severed.
o The heart beats about 72 times per minute, which is about 100,000 times a
day.
o Conducting System- takes the depolarized signals to ventricles
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SA Node  AV Node (via internodal path)  AV Bundle  L &
R Bundle Branch  Walls
 These structures generally have more glycogen and less
myofibril content that regular cardiac muscle fibers. They
are capable of much faster impulse conduction than
ordinary fibers.
This moves at a speed of about 0.3 m/s.
 The time span from the SA to the Atria is about 0.07s.
o SA  AV (0.045)  Bundle (0.16)  Apex (0.20)
 Wall (0.22)
 The span is longer on the left.
Sinoatrial (SA) Node
 This is where the rhythm originates. It is called the
pacemaker of the heart and is located in the right atria, in
the endocardium of the posterior wall, medial/inferior to
the opening of the vena cava. This initiates the electrical
impulse of the heartbeat.
 Histologically, it is a patch of tissue. The fibers have a
smaller diameter (3-5 microns), but are similar in all other
aspects. It is continuous with the rest of the atria.
 The resting membrane potential at SA node is ~55mV,
which is higher and closer to 0 than the other (~90). The
fibers are leaky to sodium, accounting for rhythmic
discharge.
 Electrical impulses spread from the SA node into the
myocardium of the atrial walls. This creates contraction of
the right and left atria, causing blood to be emptied into the
right and left ventricles.
The internodal path has a velocity of 0.45-0.6m/s. This conducts
impulses from the SA Node to the AV node.
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AV node
 This is a mass of tissue on the posterior wall at the inferior
portion of the interatrial septum. Its purpose it to slow the
impulse to 0.10 sec, so the ventricles can fill and the atria
can contract. There is no joint contraction.
 The junctional fibers are smaller, causing the slowdown to
~0.02m/s.
 The entire node conduction is about 0.05m/s.
 AV Bundle (aka Bundle of His)
 This carries the impulse from the atria to the
interventricular septa. From here, the impulse is carried in
the endocardium of the right and left ventricles.
 Purkinje fibers
 These are in the endocardium of the ventricles and are
continuous with the right and left branches of the AV
bundle. It conducts the cardiac impulse to all parts of the
ventricles, causing simultaneous contraction of both
ventricles.
 They are modified cardiac muscle fibers that terminate in
the myocardium of the ventricles.
 Its conduction is 1.5-4m/s.
Action Potential in Cardiac Muscle
o Action potentials occur around 105mV
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The resting membrane potential is about -85 to -95 mV, similar to
skeletal muscles and nerves. It rises to a positive 20 mV.
 This is a unique action potential. A plateau is seen at about 0.2s in
atrium/ and 0.3s in the ventricles. The plateau causes the
contraction to last 3-15x longer, causing a “squeezing” action vs.
quick spurts to move blood.
 The rate of diastolic depolarization determines the rate at which the
heart beats.
o Conduction
 0.3-0.5 m/s in atrium and ventricles. This is 1/10 the speed of
skeletal muscle and 1/250 the speed of large nerves.
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In conducting system, it varies between 0.02-4 m/s due to the
coordination of the two syncytiums.
 Conduction is performed by the AV bundles that take signals from
the atrium to the ventricle.
o Refractory Period
 Ventricles- 0.25-0.3s
 Atria- 0.15s
 Because the absolute refractory period is as long as the muscle
twitch, tetanus is not possible in cardiac muscle. This limits the
heart rate. It is not faster due to the refractory period.
 15 year olds have an average of 210 beat/min. It can be as
high as 250 if the sympathetic muscles are stimulated.
Blood Flow
o Superior (from upper body) / Inferior Vena Cava (from lower body) 
Right Atrium  Tricuspid  Right Ventricle  Pulmonary Artery 
Lungs  Pulmonary Veins  Left Atrium  Mitral Valves  Left
Ventricle  Aorta  Upper Body
Cardiac Cycle
o Systole
 This is an active ejection phase. The heart contracts and pushes
fluid out of the atria at the same time.
 Ventricular Events
 Isometric contraction (aka isovolumic)
o This is a muscle contraction with no movement.
The muscles start to tense. Blood does not move,
but the pressure increases.
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 80mmHg in left ventricle
 8mmHg in right ventricle
o This opens the AV valve.
Ejection
o This occurs when the semilunar valves open. The
volume decreases when the semilunar valves open,
but the pressure still peaks due to contracting
muscles.
o 70% flows out in the first quarter, then the
semilunar valves close due to pressure.
o Contraction of the ventricles raises the
intraventricular pressure causing the AV valves to
close, so no blood goes to the atria.
o Diastole
 This is a passive filling phase. The heart relaxes and fills.
 Systole of the atria is the diastole of the ventricles
 Ventricular Events
 Isometric relaxation causes decreased pressure.
 The AV valve opens, causing a rapid inflow of blood.
 Diastasis occurs in the mid 1/3 where blood flow tapers.
 Atrial Systole causes a “topping off of the ventricles,”
contributing to 30% of the ventricular volume.
 As the ventricles relax during diastole, the semilunar valves
close and the AV valves open.
o Summary
AV Valves
Semilunar Valves
Diastole
Open
Closed
Systole
Closed
Open
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Heart Sounds (Auscultation)
o Phonocardiogram- heart sounds. These are caused by the closing of the
valves at the beginning and end of systole.
o 1st sound “Lub” represents the closure of the AV valves.
o 2nd sound “Dub” represents the semilunar valves closing.
o We cannot hear the third sound, which represents the chordae tendinae
vibrating.
o Murmurs are abnormal heart sounds. They can be due to multiple reasons.
 Insufficient “leaky” valves
 These are from minor amounts of blood squirting back up
the AV valves. It can be congenital or acquired.
 Stenosis
 This is a congential very small opening, causing increased
velocity.
 Mitral valve prolapse
 The congenital condition is where the valve is a little loose.
When the ventricle contracts, the valve “clicks” into the
atria. It occurs more in women.
 Aorta
 Some men only have two cusps congenitally.
 Scarring of heart valves from rheumatic fever
 This can cause some scarring of the heart valves from
acquired “crossreactivity.” The valves, usually the
bicuspids, no longer seal.
Control of Heart
o Blood-borne
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The heart is controlled by epinephrine and norepinephrine from the
adrenal glands. These are the same chemically, but epinephrine has
extra CH3.
 These compounds increase heart rate and stroke volume, as
well as increasing the influx of calcium across the
membrane.
 This control is not very fast. It is slow, because the compounds
need to be made, secreted, travel, etc. Yet, it has a longer effect,
since it lasts longer because stays in blood.
o Nervous System
 This is a quicker control of the heart. It increases only the heart
rate.
 Autonomic Nervous System
 Sympathetic (aka Cardiac Nerves)
o These cardiac nerves arise from the first five
thoracic spinal nerves (T1-T5) to innervate the SA
and AV nodes. These are called the accelerator
nerves.
o These control the fight or flight response.
Stimulation of the sympathetic nerves speed up the
heart.
 Parasympathetic
o This comes from the CNS and is controlled via the
vagus nerve. This synapses at the cardiac plexus,
which is an area of interjoining nerves in the aortic
arch. The postsynaptic nerves go to the heart and
stimulate the SA node, AV node, and atrial muscle.
o This keeps the heart going on a constant basis by
decreasing the heart rate.
o These are cardio-inhibitory nerves. Stimulation of
vagus slows the heart. Cutting the vagus doubles the
heart rate.
 Medulla
 Centers in the medulla serve as the coordination center,
coordinating nerves, receiving input, and passing it on. This
is not spontaneous.
 Cardioinhibitory Center
o This stimulates the vagus. Stimulating this can
cause fainting or Vasovagal Syncope.
 This is caused by strong parasympathetic
input, such as fear, strong emotions, etc. The
heart slows, causing less oxygen to be
transferred to the brain. Fainting is a selfremedy, because the body lays flat.
 This can occur with tonometry.
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If the patient is nauseous, put head
below the heart to restore oxygen.
Cardiovascular Center
o This is the sympathetic or excitatory center.
Afferent- sensory input
o Sensory receptors
o Baroreceptors
 These are located in the carotid sinuses of
the neck and aortic arch.
 These respond to stretch and send responses
to the cardioinhibitory center.
 Pressure on the carotid sinus can create
artificial high blood pressure, slows heart
rate causing fainting. This is called Carotid
Sinus Syncope. This can occur when
applying too much pressure when taking a
pulse on the carotid artery or atherosclerotic
plaque.
o Chemoreceptors
 These respond to decreases in oxygen, as
well as increases in carbon dioxide and H+.
 These are in the blood, and if oxygen drops,
signals are sent to the cardioaccelatory
center.
Cardiac Testing
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EKG/ECG- Electrocardiogram
o This is generally measured through electrodes placed on the skin,
recording extracellular potentials of 1-2mV. The EKG reflects electrical
activity seen externally across the entire heart muscle at any given time.
o When the heart depolarizes (contracts), a wave is spread throughout the
body. It is recorded at the wrist and ankles. “V” electrodes also run across
the chest, which is closer to the heart.
o The EKG is only a record of voltage and time. Only the electrical events
that involved large amounts of muscle show up in the EKG record.
o It is amplified to:
o Three leads, with one ground. In leads the difference is in amplitude.
o Einthoven’s Triangle
 I: RA & LA
 II: RA & LL
 III: LA & LL
o Einthoven’s Law: I + III = II
 This is because the heart is dipolar and II is parallel to the dipole.
 An electrical vector tells of a mass or an enlargement.
o The Reading
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The P wave represents the depolarization of the atria.
The QRS Complex is the depolarization of the ventricle.
 This covers artial repolarization. It is a larger electric event
due to the larger mass.
The T Wave represents the repolarization of the ventricles.
When the entire heart is either depolarized or is resting, there is no
potential difference to set up a current flow, and there is no
delfection seen in the EKG. The line of no deflections is called the
isoelectric line.
o Pathology
 Only P wave- conduction blocked between the atria and ventricles
 This is due to infections, ischemia, infarction, or
compression.
 Broad QRS- later activation of ventricles. This implies a defect in
the ventricular conducting system.
 Delay between P and QRS- AV conduction more decremental.
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 Reversed T wave- PVC
 Dissociated P to QRS- tertiary blockage
Atrial Pressure Change
o The a wave represents the atrial contraction.
 This occurs directly after the p wave of the EKG.
 There is about a 7mmHg peak, then it falls as the blood goes to the
ventricles.
o The c wave represents the ventrical contraction.
 This is due to the pushing AV valve into the atria and pulling on
the atrial walls.
o The v wave represents the blood returned to the atria until the AV valve
opens.
Cardiac Output
o This is the quantity of how much blood moves through the heart in a given
time. Algebraically, the Cardiac Output = Stroke volume x Rate
o This rate changes with certain activities, such as exercise, etc.
o Stroke volume, or how much blood is passed, also changes.
 Under normal conditions, the end diastolic volume is about 120130ml, and the end systolic volume is about 50-60ml.
 The difference, ~70ml, is the stroke volume.
 With stronger contractions, due to exercise for example, there is a
decreased end systolic pressure of about 10-30ml, and an increased
end diastolic pressure of about 200-250ml. The difference can be
up to 210ml, which is 3x the normal value.
Summary
Pathology
No mechanical pump has the efficiency, durability, and reliability of the human heart.
Basic to this function is the near-indefatigable cardiac muscle. The myocardium
compromises a syncytium of branching and anastomosing fibers divided into individual
cells by modified, closely-apposed cell membranes creating the intercalated disks. The
apposition provides in essence a continuous “tight junction” with free passage of ions and
action potentials such as an excitatory stimulus from cell to cell and throughout the
syncytium. In addition, the cardiac muscle has specialized excitatory and conducting
Purkinje fibers (the SA node, AV bundle, AV node, and the bundle of His), which
contain only few contractile myofilaments and conduct action potentials faster than
contractile fibers. Lesions involving these specialized structures underlie many of the
disturbances in cardiac rate or rhythm.
Abnormal Rhythms
 Terminology
o Tachycardia is a faster than normal heart rate, generally that over 100bpm.
o Bradycardia is a slower than normal heart rate, generally that under 60
bpm.
o Flutter is 200-300 bpm in a coordinated fashion.
 Causes
o Abnormal rhythmicity of the pacemaker itself
o Block in transmission (can result in needing pacemaker)
o Shift of the pacemaker
 This is a discharge from another tissue instead of the SA node. It is
also known as an ectopic pacemaker. The most common cause is
ischemia and a reduction of blood flow to the tissues due to
atherosclerosis.
 Another part is irritated and charged faster than the pacemaker.
Under normal conditions these tissues do not take over due to their
rates.
 AV node- 40-60bpm
 Purkinje Fibers- 15-40bpm
 SA node- 70-80bpm
 Most frequently it is the AV node or the Purkinje Fibers. Rarely it
is the atrial/ventricular myocardial muscles.
o Abnormal pathways of impulse transmission through the heart.
Abnormal Impulse from excitable areas
 These are sporadic impulses from excitable areas. The timing is upset due to the
randomness
 Premature Atrial Contractions
o This is also known as ectopic focus or “flutter.”
o It is different than a pacemaker, because it does not take over the pace.
o Causes
 Decreased blood flow (ischemia)
 Stimulants (i.e., caffeine)
 Lack of sleep
 Anxiety
 Plaque causing pressure
o This is best observed with a EKG. Timing changes are seen.
 Premature Ventricle Contractions (PVCs)
o Unlike premature atrial contractions, this is an indication of serious
cardiac problems. Some can be benign, but it generally means that an area
of the heart is infracted. A scar throws off the stimulus, possibly leading to
a myocardial infarction.
o On the EKG, this is seen as the T wave is reversed
Blockage in conducting system
 Common blockages include AV Block and blockage of the Bundle Branches.
 Causes
o Infections including diphtheria and rheumatic fever can lead to
myocarditis. The inflammation interferes with the conducting system,
causing blockage.
o Infarct
o Compression cause by plaque building up pressure, as seen with
atherosclerosis.

o Ischemia
Types
o 1st degree
 Conduction slows down. P  QRS, which is normally 0.2s, goes
to about 0.25s.
nd
o 2 degree
 This blockage is worse, but sometimes the impulse is strong
enough to go through, so the P  QRS can be doubled or
sometimes the QRS is missed.
o 3rd degree
 This is a complete blockage. The P wave is dissociated from the
QRS. Periodically these patients faint due to the low blood
pressure.
 This is a serious problem, and these patients are good candidates
for pacemakers.
Fibrillations
 Fibrillation
o These are serious abnormal cardiac rhythms located either in the atria or
ventricules. Instead of acting as a synctium, all the cells go on their own
with no rhythm or coordination. The rate of flutter is anywhere from 200300x/min. In contrast to flutter, this is in an uncoordinated fasioh. This can
be devastating.
o Treatment
 Drugs like quinidine, a depressant, can slow down the quivering
allowing the SA node to take over.
 If drugs do not work, a defibrillator can be implanted.
 Atrial Fibrillation (not too rare)
o This is common. It is not life threatening, because the job of the atria are
only to “top off” the ventricles. 70% of blood flows through without atrial
help.
o During fibrillation, no blood is pumped through the atria. This can cause a
blood clot, which could be a serious problem.
o This can be caused by coronary disease or a congenital problem.
o This is demonstrated on the EKG with a missing P wave, because of the
lack of atrial depolarization.
 Ventricular Fibrillation
o Unlike atrial fibrillations, ventricular fibrillations is fatal. A patient has 5-6
minutes to live without the ventricles moving blood to the lungs, body,
heart, etc. This is actual coronary blockage (MI). The blood begins to
clot, and the tissue is denied blood and fibrillates.
o Treatment
 Electrical currents in the form of several thousand volts for a few
milliseconds via electrodes must be utilized. This produces a
myocardium refractor in which the muscle fibers enter a refractory
period allowing the SA node to send signals to take over.


This defibrillation is also known as cardioversion. It is
performed in hospitals with an AED (Automated External
Defibrillator). It relies on a computer and is easy to use.
One needs certification to be covered by the good
sumaritan law.
Cardiac Massage circulates oxygenated blood.
Congestive Heart Failure
 This is where the heart loses its ability to pump blood forward. Congestion in the
tissue occurs, and nutrients cannot be delivered. It is an outcome of hypertension.
 It occurs equally in males and females, in 1/100 greater than 65 years, or about 5
million Americans. It is characterized by increased heart rate, increased heart
volume, ventricular hypertrophy, and an enlarged heart.
 Forms of Heart Failure
o Systolic
 This is a contractile failure of the myocardium, leading to a
reduced left ventricular ejection fraction.
 The ejection fraction is the percentage of blood ejected out of the
heart with each squeeze. Normal is 60-65%. Here it is 10-40%..
o Diastolic
 Here, a higher filling pressure is required to maintain cardiac
output, but the ejection fraction is normal.
o Left-sided
 This is an inadequate output by the left ventricle, the workhouse of
the heart.
o Right-sided
 This is a dysfunction of the right ventricle secondary to left-sided
heart failure or pulmonary disease.
 A clinical sign is swollen legs.
o Left Ventricular Hypertrophy (LVH)
 This is a diastolic dysfunction, because this area cannot fill nor
squeeze well, because it is stiff. This is generally due to
hypertension.
 Clinical features
o Dyspnea- shortness of breath
 Exertional
 Orthopnea- shortness of breath from laying down
 Paroxysmal nocturnal dyspnea- sudden lose of breath when
sleeping due to increased blood volume.
o Systemic venous congestion in the liver, gut (bloated), neck veins, and
lower extremity edema.
o Cardiomegaly- enlarged heart
 Diagnosis
o EKG
 This determines the ejection fraction, heart squeezing, and muscle
thickness.
Cor Pulmonale
 This is isolated right-sided heart failure, usually due to left-side failure.
 Multiple causes include
o Pulmonary hypertension, due to increase blood pressure in the lung and
pulmonary artery.
o Lung disease, such as emphysema
o Diseases of the pulmonary vessels
o Disorders affecting chest movement
o Disorders inducing pulmonary arteriolar constriction
 The primary symptom is leg swelling.
Ischemic Heart Disease
 This is left-sided heart disease.
 Angina Pectoris
o This is a pain in the chest or pressure due to decreased blood to the
muscles caused by stenosis, blockage, or spasm.
o It is atypical if there are no symptoms.
o Types
 Typical or atherosclerotic angina represents typical symptoms of
pressure and squeezing. This is angina of effort.
 Prinzmetal’s or variant angina is angina due to vasospasms, not
atherosclerosis.
 Unstable angina is not predictable. It changes in magnitude,
severity, etc. it is generally a precursor to infarction.
o Treat with nitroglycerine to dilate the coronary arteries.
 Myocardial Infarction/ Heart Attack/ Coronary Artery Disease
o This is a full, acute obstruction of the coronary blood vessel leading to the
heart. This causes a sudden onset of anoxia of a duration sufficient to
cause irreversible cell damage.
 This causes ischemia of heart muscle. The extent of damage
depends on location and size of blockage and extent of collateral
circulation.
o About 1 million occur per year.
o Pathogenesis
 Coronary artery thrombosis
 Ischemia  injury  infarction
o Causes include coronary atherosclerosis, arterial thrombi, spasm, and
coronary emboli.
o Risk factors include hypercholesterolemia, DM, elderly, male, family
history, smoking, obesity, alcohol, HTN, stress, and lack of exercise.
o Clinical features
 Symptoms include chest pain/discomfort/heaviness/squeezing,
even at rest. It feels like a “band around the chest or squeezing
sensation.” The pain is variable and located at the center of the
chest beneath the sternum. Referred pain can also be felt in the
shoulder, neck, or arm via nerve endings and brain connections.
Usually it is felt more on the left side. The pain lasts longer than
two minutes.
 Other signs
 Sweating, nausea, shortness of breath
 Levine’s sign- grabbing of the chest
 EKG changes
 Cardiac enzyme markers in the blood are elevated with dying
muscles.
o Complications of Acute MI
 Arrhythmia, i.e., Ventricular tachycardia, within minutes
 Pericarditis, cardiac arrest, aneurysms, congestive heart failure,
pulmonary edema, rupture of chamber walls, and death due to any
of these.
 Cardiogenic shock
 Infarction and decreased squeezing causes a decrease in
blood, leading to decreased blood pressure and acute CHF
due
o Large infarction
o Papillary muscle infarction and MR
o Myocardial rupture- regurgitation of blood flow
o Ventricular wall aneurism
o Treatment
 Time is critical in a heart attack. Bloodflow needs to be
reestablished to the muscle to prevent injury.
 One way a heart attack can begin is when plaque in a
coronary artery suddenly breaks apart. A blood clot begins
to form at the site of the fragmented plaque. As the artery
becomes blocked, less oxygen reaches the heart, resulting
in chest pain. If the artery becomes completely blocked
(usually within 3-4 hours) irreversible damage to the heart
muscle can occur.
 1st time problem, previously unknown
 Have the patient stop activity and lie down. Wait about 2
minutes, then contact EMS (911) and have the patient go to
the emergency room.
 Known to have heart disease
 Stop activity and lie down.
 Administer 3 nitroglycerine tablets in 10 minutes
 If signs persist after 10 minutes, activate EMS and go to the
emergency room.
 In the office, ODs must legally administer CPR. Decreased fatality
occurs due to intervention.
o Angioplasty



This is a balloon that pushes the plaque out. This can also be
performed with laser, etc. Stints, wire coils, are later placed in the
arteries.
 For chronic stable angina or acute MI.
Chronic Ischemic Heart Disease
o Ischemic Cardiomyopathy
 Multiple MIs
o Enlarged heart, dilated chambers, and CHF
 Due to IC
o Progressive heart failure
o Arrythmias common
o Treat with heart transplant or bypass surgery.
Sudden cardiac death, non-MI
o This is the most common symptom of atherosclerosis. There are no
symptoms of the condition except death.
o Causes
 Coronary artery diseases
 Myocardial diseases and infections
 Valvular diseases are less common
 Conduction system abnormalities, as seen in athletes
Hypertensive Heart Disease
 Causes
o Increased peripheral resistance causes an excessive work load for the
heart.
 Risk factors
o Stress, obesity, female, black
 Complications
o Compensation is by left ventricular hypertrophy, however, this extra tissue
requires more blood, and ischemia can develop. Ischemia leads to greater
necrosis and scarring of the heart with eventual left ventricular failure.
Left-sided heart failure may also lead to right-sided heart failure. The
distant effects of left-sided failure are manifested most prominently in the
lungs, although the function of the kidneys and brain may also be
markedly impaired.
Valvular Heart Disease
 Here the valves in the heart are damaged due to varying reasons including
o Rheumatic fever and heart disease
o Calcific aortic stenosis
o Mitral valve prolapse
 The valve does not shut completely or just prolapses (pushes up)
o Infective endocarditis
 Prosthetic cardiac valves
o These replace damaged valves.
o They can be natural, where the donor is usually a pig. These wear out
quickly, in about 5 years. They can also be mechanical, which last forever,
but clots may form in them. Anticoagulants are required. Another problem
is that the old ball and chamber valves break with time.
Primary Myocardial Diseases
 Myocarditis
o This is an infection of the heart muscle.
 Cardiomyopathies
o These are problems with the heart itself. It is dilated and hypertrophic
(thickened), especially the septum. This restricts blood flow.
o It can be due to a virus, like coxsaxie B, as well as alcohol, toxins, etc.
Streptococcal Infections
 Rheumatic Heart Disease
o This is an acute, recurrent, inflammatory disease, principally in children,
that follows a pharyngeal infection with group A streptococci. The
evidence strongly suggests that it is the result of an autoimmune response
to tissue antigens principally in the heart of an autoimmune reaction to
tissue antigens.
o Causes
 Fibrinoid degeneration of collagen in heart muscle. Cause is
delayed sequel to Strep A infection. Strep Abs also attack cardiac
tissue (autoimmune disease).
o The acute disease is characterized principally by fever, migratory
polyarthritis of the large joints, carditis, subcutaneous nodules, erythema
marginatum of the skin, and Sydenham’s chorea, a neurologic disorder
with involuntary purposeless rapid movements.
o Although the acute may induce arthritis and sometimes myocarditis, both
resolve.
o In contrast, chronic rheumatic heart disease is characterized principally by
deforming fibrotic valvular disease (particularly mitral stenosis), which
produces permanent dysfunction and severe, sometimes fatal, cardiac
failure decades later.
o Mitral valve and aortic valve functional impairment. Mitral stenosis occurs
in 40% of patients with rheumatic heart disease (2/3 are female).
Symptoms include dyspnea, cough, orthopnea, pulmonary edema, and
arrythmias, emboli from left atrium. Death in 2-5 years after seriously
symptomatic.
o 95% of patients have elevated liters of antistreptolysin 0,
antistreptokinase, antistreptodomase, or antistreptohyaluronidase.
 Endocarditis
o This is one of the most serious of all infections. It is characterized by
colonization or invasion of the heart valves or the mural endocardium by a
microbiologic agent, leading to the formation of friable vegetations laden
with organisms.
o The condition may be acute (with highly virulent microorganisms) or
subacute.
o Streptococci are the dominant cause of the subacute disease and account
for 65% of all cases. These invasive spreading organisms of relatively low
virulence are able to gain a foothold only in hearts having some
underlying disease or predisposition.
o Causes
 Microbial infection of heart valves on endocardium. Bacteria
adhere to platelets and fibrin forming vegetative growths. May be
initiated by transient bacteremias (S. aureus, Strep, E. Coli) from
dental work, food, gum infection.
o Clinical Features
 Abrupt or indisidious onset. Symptoms include nonspecific
malaise, weight loss, flulike symptoms, fever, cardiac murmurs,
anemia, and emboli. Emboli complications are less frequent than
with the acute form. Infiltration of blood may infect other organs
(CNS, eyes, kidneys, spleen, skin). This is fatal if not treated.
 The disease seems to have a protracted course, even without
treatment, and is less often fatal than acute infective endocarditis.
The 5-year survival rate is 80-90% with subacute and 50% with
acute.
 Clinical consequences involve direct injury to valves, embolic
phenomena to the spleen, kidneys, and brain, and splenomegaly.
o Pathological Features
 Valve destruction may cause mitral or aortic regurgitation.
Congenital Heart Disease
 Malformations causing
o Left-to-right shunts include atrial septal defects, ventricular septal defects,
and patent ductus arteriosis.
o A right-to-left shunt is known as Tetrology of Fallot. This patient is
cyanotic due to the transposition of the great arteries.
o Obstruction lesions such as a coarctation of the aorta can lead to
differences in the blood presure between the two sides. This is due to
secondary causes, such as hypertension.
Pericardial Disease
 These are problems with the sac around the heart.
 Pericarditis is an inflammation of the sac itself.
 Pericardial Effusion is fluid inside the sac.
 Pericardial Temponade is a decreased ability to fill with blood in ventricles
because the sac is filled with fluids
Cardiomyopathies (CMP)
 Primary
o Heart muscle disease of unknown origin

o Classifications
 Congestive or dilated CMP
 Dilatation and hypertrophy of both ventricular cavities and
poor systolic function.
 Gradual four-chamber dilatation
 Linked with alcohol toxicity, peripartum state, genetic
defect, or postviral myocarditis.
 Hypertrophic
 Massive increase in ventricular muscle mass, small
ventricular cavities, hypercontracting left ventricle.
 Heavy, poor-compliant heart
 AD inheritance
 Restrictive and obliterative
 Restriction of ventricular filling and reduced cardiac
output. There are diverse associations.
Secondary
o Myocardial disease of known cause or associated with a disease of another
organ.
o Causes
 Alcohol abuse, viral infections, hypersensitivity and connective
tissue disease, neuromuscular disease, metabolic disorders,
pregnancy, and drugs.
 Catecholamines. Cocaine, doxorubicin, and daunorubicin (cancer
chemotherapeutic agents), and common morphologic changes
(myofiber swelling, fatty change).
Cardiac Tumors
 These are very rare.
 Metatstatic Neoplasms
 Primary Neoplasms are almost never seen. Metastasis from other cancers is more
common.
 Rhabdomyosarcoma is a primary tumor of the heart seen in kids.
 Atrial Myxoma is benign, but can get in way of blood flow.
Circulatory System- Systemic Circulation
Function

To maintain a constant, homeostatic pressure at the capillaries
Anatomy

Hierarchy

o Heart  aorta  artery  arterioles  capillary  capillary bed 
venous system  venule  vein  heart
o The lymphatic system serves as a detour.
Arteries
o Layers of Tunics
 Tunica Intima is the innermost consisting of endothelial cells. It
also contains a basement membrane.
 Tunica media is concentrically around the tunica intima. It contains
smooth muscle, giving arterioles their elastic nature.
 Tunica Adventitia is the most external. It offers longitudinal
collagen fibers for protection.
 An Internal Elastic Lamina separates the tunica intima and tunica
media, serving an important role in the development of
atherosclerosis.
o The arteries are highly elastic. They need to be due to the pulsatile nature
of the heart. Energy is stored, and a pressure is maintained between pulses
or pressure waves. Rigid tubing would not work. This maintained pressure
is the “80” in the reading “120/80.”
o The arteries are conduits for high pressure.
o Elastic Arteries
 Examples- common carotid, aorta, pulmonary arteries
 TI- a thick, collagenous layer with relatively few elastic fibers.
 TM- broad layer composed of sheets of elastin and smooth muscle.
 TA- collagenous connective tissue, including the vasa vasorum.
o Muscular Arteries
 TI- thin
 TM- broad muscular layer with few elastic fibers
 TA- nerves, vessels, and the external elastic lamina.
o Superficial and Deep Arteries

Arterioles
o The arterioles are made of more smooth muscle. They are of variable
sizes, ranging from the small with only a single layer of muscle cells, to
the large with several layers of smooth muscle cells. There is no external
elastic lamina associated with the tunica adventitia. The internal elastic
lamina is thin or absent in smaller vessels.
o These function to control peripheral resistance, playing a large role in
blood pressure. This is accomplished via a decreased diameter that
increases the blood pressure.
o They can also shunt blood via sphincters, which are bands of muscles that
can shut off the vessel. Precapillary sphincters shunt blood so that it closes


capillaries that do not need oxygen and open those that do. This is done
based on CO2 levels.
 There are arterioles, veins, and arteries in the back of the eye, so
this is all seen there.
Capillaries
o These are primary exchange sites between blood and tissue and have
structural variations permitting different levels of metabolic exchange
between blood and surrounding tissues. In general, a capillary consists of
an inner endothelial layer and an outer basal lamina layer. The connect
arterioles and venules.
o Specialized vessels
 Purpose- exchange of O2, CO2, waste, food, etc.
 Distance- cells can only be 20-30 microns from capillaries
 O2 and nutrients to cell/ CO2 and waste from cell
o One cell layer thick (due to exchange)
 2 tunics lost. Only endothelium left.
 Some pericytes are found along capillaries. These are
remnants of the media.
 Diffusion allowed
 Slits between cells = intercellular clefts- allows small
molecules/water to pass
o Continuous capillaries
 These are non-fenestrated capillaries in which the endothelial cells
form complete rings around the lumen. Pericytes (flattened
endothelial cells) are occasionally seen.
o Fenestrated Capillaries
 These are porous endothelial cells with a continuous basement
membrane. Pericytes are rarely present. Common in the kidneys
and small intestine.
o Discontinuous Capillaries (Sinusoids)
 These have a discontinuous endothelium and a wide lumen. Found
in the liver and spleen.
Veins
o These are “capacitance” vessels, because >70% of total blood volume is in
this portion of the cardiovascular system at any one time. Compared to
arteries, veins have a very thin tunica intima and a relatively thin tunica
media. The tunica adventitia is usually the thickest later. Veins usually
have a large lumen in relation to the thickness of the vessel wall.
o Return low pressure blood to the heart.
o Low pressure, therefore low resistance
o Venules- small veins
 Very little smooth muscle, yet you can still contract a lot due to
low pressure
 Size- little larger than arterioles

These consist of a very thin tunica intima, tunica media, and tunica
adventitia that may be continuous with surrounding connective
tissue.
o Veins
 Diameter- larger than arteries, tend to be flattened (less elasticity)
 Contain less elastic tissue and smooth muscle than arteries.
 Tunica intima and media are thin or absent. Tunica adventitia is the
thickest.
 Contains one-way valves (towards the heart)
 These are made of connective tissue membrane covered
with endothelium.
 This is a strategy to move blood with low pressure
 Found in legs and arms
 Pumping via skeletal muscles when contracts
 Blood reservoirs- how a vein acts (ex. Superior sagittal sinus- in
the head)
 Purpose: can contract and push blood into system to
maintain pressure in acute blood loss.
o Venous blood drains the head region into the heart via the superior vena
cava.
o Superficial and Deep Veins
 The right and left brachiocephalic veins drain into the superior
vena cava.
 The union of the internal jugular and subclavian veins forms the
brachiocephalic veins.
 The head region is primarily drained by the external and internal
jugular veins.
 The external jugular drains the face and its branches
include the
o Superficial temporal vein
o Infraorbital vein
o Anterior facial vein
 The internal jugular drains the orbit and head, and its
branches include the
o Anterior facial vein
o Pterygoid plexus
o Venous sinuses
Physiology

Hemodynamics
o Microcirculation
 Metarterioles provide a path of least resistance between arterioles
and venules. The precapillary sphincter will regulate the flow of
blood through the capillaries.
o Flow
 The entire cardiac output flows through the aorta to the arteries,
which distribute blood to the various tissues in the body.
 Cardiac output (CO) = Stroke Volume (SV) X Heart Rate (HR)
 Stroke volume is about 70mL
 The elastic arteries serve to convert the pulsatile flow of blood
from the heart into a more continuous blood to the tissues. A
relatively high blood pressure is required to overcome the

resistance of blood flow through the blood vessels. Blood flow can
be calculated as follows
 Blood Flow = Arterial Pressure / Resistance
o Pressure
 The greatest pressure drop occurs at the level of the arterioles due
to the relatively large resistance to flow at this point in the
circulation. The pulsatile pressure in the arteries is calculated as
the systolic pressure minus the diastolic pressure. The amplitude of
the pulse pressure is affected by both the stroke volume and the
distensibility of the arteries. The mean arterial pressure (MAP) is
calculated as 1/3 pulse pressure + diastolic pressure. The flow of
blood through the vascular system is directly related to the MAP.
o Resistance
 Peripheral resistance is determined mainly by blood viscosity and
arterial diameter. in general, the less the blood viscosity, the less
the peripheral resistance. The smaller the diameter of the arterioles,
the greater the peripheral resistance. Vasoconstrictor control
mechanisms play an important role in control of changes in the
diameter of the arterioles.
Total Area
o Area increases from aorta (2.5cm2) to capillaries (2500cm2)
o Area decreases from capillaries to vena cava
o Cauterization
 Catheter- tubes in vessels to measure pressure
 Vessel  heart
 Use
 Take blood gas samples and pressure
 Diagnosis by injecting radiodetectives to find blockage
 Angioplasty- put in balloon and blow up near blockage.
 Danger
 Can knock clots loose and they go into circulation and
cause heart attacks, shock, etc.
o Pulse Pressure
 Can diagnose systemic disease
 Pulse pressure = systolic – diastolic pulses
 Curve
 Ex. 120/80 = 120 – 80 = 40
 Palpation- grabbing/feeling wrist
o Can diagnose atherosclerosis
 Electronically- use pressure clip on fingers
 Diagram
o Normal
 Pattern (Abnormal)
 Aortic Valve Insufficiency- “leaky”
o Diastole at 50 (low)




o Tries to compensate for leaky valve, therefore goes
to 140.
Aortic stenosis (small opening)
o Cant build up pressure (high resistance)
o Can only get blood through so fast.
Arteriosclerosis- loss of elasticity (no energy stored)
o Diastole: 80-90mmHg (norm)
o Goes to 165 due to maintaining diastole pressure
o Big difference between diastole and systole due to
pulse pressure.
o “Water hammer” pulse
Factors
 Stroke volume
o Epinephrine increases stroke volume
o Intrinsic mechanism increases stroke volume
(Starling’s Law)
 Change in elasticity
o Increased elasticity- decrease pulse pressure (and
vice versa)
o Arteriosclerosis- decreased elasticity
o DM- can develop arteriosclerosis
o Starling’s Law
 If more blood flows back to the heart, it compensates and increases
stroke volume
 Intrinsic control of stroke volume
 Increased diastole = increased stroke volume
 Decreased peripheral resistance during exercise
 Ventricles compensate and pump more.
 Stretch muscles (mechanism for Starling)
 Actin and myosin line up = stronger contraction
 Increase number crossbridges
o Overstretched = reduced number of crossbridges
(lose strength)
 Can occur in left ventricle in CHF
 Important because there are 2 circuits (pulmonary and systemic)
and amount of blood must be equal.
 Ex. Breathing (inspiration) causes a decrease in lungs and
increase flow back to left ventricle.
 Diagram
 As blood builds up in the pulmonary system, it pushes fluid
into the lungs, therefore we need Starling’s Law (left
ventricle needs to pump more).
Blood Flow and Permeability of Capillaries
o Blood flows intermittently in capillaries. This is due to vasomotion, which
means intermittent contraction of the metarterioles and precapillary
sphincters.




o The most important means by which substances are transferred between
the plasma and interstitial fluids is by diffusion.
Blood Barriers
o Peripheral resistance is determined mainly by blood viscosity and arteriole
diameter. in general, the less the blood viscosity, the less the peripheral
resistance. The smaller the diameter of the arterioles, the greater the
peripheral resistance.
o Vasoconstrictor control mechanisms play an important role in control of
changes in the diameter of arterioles.
Fluid Exchange at Capillaries
o Three forces
 Hydrostatic capillary pressure (blood pressure)
 35mmHg at arterials
 15mmHg at venules
 Average about 25mmHh
 Osmotic (aka Oncotic) Pressure
 Caused by blood albumin
 Hydrostatic pressure of interstitial fluid
 Tissue exerts pressure on fluid and fluid goes into capillary.
 The filtration pressure is the difference between the two
hydrostatic pressures
 Diagram
 90% is reabsorbed
 10% is left and the lymphatic system takes care of this.
o Rate of filtration
 Filter pressure
 Osmotic
 Example
Pressure and Flow in Veins
o Problem
 Decreased pressure (1/10 of normal)
 No pump
o Factors aiding
 Skeletal muscle acts as a venous pump
 One way valves
 Varicose veins are a pooling of blood due to a failure of
these valves. This is genetic.
 Breathing movements
 Ventricle relaxation- opening chamber creates suction
Control of Vessels
o 2 stimuli (nervous and blood-borne)
o Nervous- Vasomotor nerves
 Stimuli cause constriction
 Relaxation causes dilation
 Vasoconstrictor- from sympathetic system
 Adrenergic- secretes norepinephrine at nerve endings

Distribution- widely distributed
o More innervating than dilators
 Constriction causes an increase in blood pressure
 Tone- a normal component (constant constriction)
o Maintains blood pressure
o Decreased tone can lead to shock (fatal)
o Anaphylactic or neurogenic shock can damage the
medulla center. Smooth muscle relaxes due to
trauma, overdose on anesthesia, etc.
 Vasodilator- from parasympathetic
 Cholinergic- nerve endings secrete acetylcholine, which
inhibits contraction
 Increased diameter = decreased blood pressure
 Vasomotor Nerves
 Centers in medulla
 Afferent impulse from baroreceptors
o Separate centers for dilation and constriction
o Blood-borne Control
 Epinephrine and norepinephrine from adrenal gland
 Response different between tissues
 Vasoconstriction is skin, kidney, and spleen (less blood)
 Vasodilation in lungs, skeletal muscle, and heart
o Gets more blood
 There is a difference due to different receptors
 Renin-angiotensin-aldosterone system
 Based in kidneys
o In glomerule of nephron (Juxtaglomerulus
Apparatus)- senses blood pressure.
 Decreased blood pressure causes secretion of rennin into
the blood by the juxtaglomerulus apparatus
o This causes changes
 Renin goes to angiotensin II
 Action: very potent vasoconstrictor
o 4-8x more potent than norepinephrine
o promotes release of aldosterone, reabsorbs sodium,
and brings water
o Increases secretion of renin.
 CO2 Excess- dilates vessels
 CRAO
o If occluded, vision is gone (due to blood clot)
o Need to increase CO2 in the blood (breathe into a
bag)
 Migraines (genetic)
o Vessels are unstable, they narrow and cut blood
o Leads to visual aura- flashing lights/sensations
o When muscles lax (no tone), they stretch and touch
pain receptors during systole
o When vessels begin to narrow, breath into a paper
bag, which skips the lax phase.

Regulation of Blood Flow
o The arterioles are vessels that branch off the arteries as they enter the
various tissue beds in the body. The resistance to blood flow through the
arterioles is large because of their small diameter. the arterioles contain
smooth muscle, which allows them to change diameter (vasodilation and
vasoconstriction) and thus the resistance they provide. Altering the
resistance to blood flow through the various tissue beds in the body is a
way of decreasing blood flow to some tissues while increasing flow to
others.
 One local factor affecting blood flow is myogenic activity, a
strength-induced contraction of vascular smooth muscle that
allows for autoregulation of blood flow so that flow remains
relatively constant in the face of changing arterial pressure.
 Chemical factors such as the concentrations of oxygen, carbon
dioxide, adenosine, and hydrogen ions can also affect local blood
flow and contribute to the overall autoregulation of flow. Reactive
hyperemia represents an extreme example in which massive
vasodilation follows occlusion of blood flow to a tissue. This is the
result of the local depletion of oxygen and accumulation of
metabolites during the absence of blood flow.
 Cells can release other vasoactive substances such as histamine
and prostaglandins to produce a local change in blood flow.
 Extrinsic regulation of blood flow provides for the coordinated
distribution of the limited blood flow available from the heart to
the various tissue beds. Blood vessels are innervated primarily by
the sympathetic division of the ANS. Sympathetic nerve fibers
release norepinephrine, which binds to alpha receptors in the
membrane of the vascular smooth muscle cells resulting in
vasoconstriction. Resting vascular tone is maintained by
continuous sympathetic nerve activity originating from vasomotor
centers in the medulla.
 Hormones also play an important role in regulation of the
vasculature.
 Epinephrine binds predominantly to beta receptors. The
blood vessels of the heart, skeletal muscle, and liver
contain the greatest numbers of beta receptors and are
therefore most sensitive to the vasodilator activity of
circulating epinephrine.
 Angiotensin is a very potent vasoconstrictor agent that
plays a role in the regulation of arterial blood pressure.
 Atrial natriuretic peptide, secreted from cells in a number
of tissues, including the heart, is a potent vasodilator


substance and also causes excretion of salt and water by the
kidneys.
Regulation of Blood Pressure
o The arterial baroreceptors are stretch receptors located in the walls of the
aortic arch and carotid sinuses that respond to the changes in arterial
pressure. An increase in pressure leads to stretching of the nerve endings,
which initiates an increase in action potential firing.
o Baroreceptor nerve activity is transmitted to the cardiovascular control
centers in the medulla. These integrate sensory information from
baroreceptors and other control centers in the brain and then initiate a
change in the level of efferent parasympathetic and sympathetic nerve
activity to the heart and vasculature such that arterial pressure is kept
relatively constant.
o An increase in blood pressure results in increase baroreceptor nerve
activity, which leads to decreased sympathetic nerve activity to the
cardiovascular system. This in turn decreases heart rate and cardiac
contractibility, leading to a reduction in cardiac output. The changes in
autonomic nerve activity also result in a decrease in total peripheral
resistance owing to vasodilation. The combined reduction of both cardiac
output and total peripheral resistance leads to a reduction of MAP. A
reduction of arterial pressure results in the opposite changes, with the end
result being an increase in blood pressure back toward normal.
Contraction of venous smooth muscle also occurs in response to reduced
baroreceptor stimulation, as a result of an increase in sympathetic nerve
activity to the veins. This causes a shift of blood volume to the heart, with
a resultant increase in end diastolic volume and subsequently an increase
in cardiac output. Regulation of circulating blood volume is one of the
more important aspects of long-term blood pressure regulation. Blood
volume regulation is controlled primarily by the kidneys and
gastrointestinal system, which mediate the secretion and absorption of salt
and water.
Extrinsic Control of vascular resistance and blood flow

Intrinsic Control of vascular resistance and blood flow
Pathology
Arterial Disorders

Atherosclerosis
o This is the formation of plaque/deposits in the inner layer (intima) of the
arteries, resulting in fibrotic and calcification changes, principally in the
large arteries. Cholesterol plaques are the most common. The causes
decreased compliance and increased pulse pressure. Central core is rich in
lipids. Protrude in arteries and weakens the media. As the deposits
increase in size, there will be development of lumen stenosis, lumen
occlusion, embolism, weakened vessel wall, or rupture.
o Epidemiology
 Mainly in the US
o Risk factors
 Age- increased age
 Gender- men more than women (premenopausal)
 Family predisposition
 Hyperlipidemia, hypercholesterolemia, high cholesterol intake
 HTN
 Smoking
 DM
 Thyroid, kidney, and liver disease
 Alcohol abuse
o Pathogenesis
 Response to injury hypothesis
 Endothelial injury
 Caused by risk factors, other toxins (homocysteine, etc), stress
 Caused by LDL cholesterol causing inflammation
 We are concerned with oxidized LDL, which is increased
with smoking. It is protected by HDL.
 Seen at bifurcations
o Atherosclerosis is asymptomatic for decades until it causes disease (and
often death) by narrowing vascular lamina (e.g., gangrene), sudden
occlusion of the lumen by superimposed thrombus (e.g., MI), providing a
site for thrombosis and then embolism (e.g. renal infarction), or
weakening the wall of a vessel followed by aneurysm formation and
possibly rupture (e.g., an abdominal aortic aneurysm).
o Lesion Classification
 Intimal lesion
 Isolated macrophage foam cells induce injury
 Fatty streaks
 Mainly intracellular lipid accumulation
 This is the first notable sign. It is a precursor lesion.
 Intermediate Lesion
 Also has small extracellular lipid pools
 Atheromatous Plaque
 Now has core of extracellular lipid
 Fibroatheroma
 Lipid core and fibrotic layer, may be multiple.


These can calcify (seen with CT scan and heart screening),
but not as threatening as “vulnerable plaques” that can
rupture.
 Complicated lesion
 Surface defect, hematoma-hemorrhage, thrombus
o Complicated plaque- What can happen?
 The surface of the plaque becomes damaged, resulting in thrombus
formation (MI)
 The fibrous cap cracks, discharging grumous debris into the lumen
(obstruction)
 One of the weak little arteries that develops in the plaque
(“neovascularization”) bursts, ballooning the roof of the plaque
against the opposite wall of a small artery.
 The plaque deprives the inner media of its nutrients, causing it to
weaken and balloon out (“Aneurysm”)
 Progressive sclerosis, thrombus formation, emboli, hemorrhage
(MI or stroke), aortic aneurysm, and atherosclerotic heart disease
(ASHD) kills half of all humans.
o Good news: It’s reversible with medical therapy
 Treatment not only helps prevent progression, actually can provide
regression
 Confirmed by cardiac catherization studies.
 Decrease smoking, treat blood pressure, decrease cholesterol, etc.
 Just takes time.
Hyperlipidemia
o Routine screening recommendations
 8 hour fasting lipoprotein profile (total cholesterol, LDL
cholesterol, HDL cholesterol, triglycerides) every 5 years in all
adults over 20.
 If nonfasting test is done and total cholesterol >200mg/dl or HDL
cholesterol <40mg/dl, fasting lipoprotein profile is recommended.
 Can only check the LDL with a fasting panel.
o LDL Cholesterol Goals
 NCEP Adult Treatment Panel III
 <100 mg/dl is optimal
 If coronary heart disease, other forms of atherosclerotic
disease (peripheral arterial disease, abdominal aortic
aneurysm, symptomatic carotid artery disease), DM, TIAs,
MI, or multiple risk factors conferring 10-year risk of
coronary heart disease >20%
o DM is the atherotic equivalent of someone that has
had an MI.
 This allows the regression of plaque.
 <130mg/dl if 2 or more risk factors
 Cigarette smoking
 Blood pressure >140/90 or on medication


HDL cholesterol <40mg/dl
Family history of coronary heart disease in male firstdegree relative <55 or female first-degree relative <65
 Age >45 in men or >55 in women
 Subtract 1 risk factor if HDL cholesterol >60mg/dl
 <160mg/dl if 0 or 1 risk factor
o Therapeutic recommendations
 Therapeutic lifestyle changes for all with LDL above target
 Reduced intake of saturated fats (<7% total calories) and
cholesterol (<200mg/day)
 Plant stanols/sterols (2g/day) fruit and veggies
 Increased soluble fiber
 Weight reduction
 Increased physical activity (increases HDL)- Niacin also
helps.
 Can be intensified after 6 weeks if goals not achieved
 Medications considered if
 Failure to achieve target LDL levels after 12 weeks of
lifestyle changes
 LDL cholesterol level >30mg/dl above target LDL
cholesterol level
 LDL cholesterol >130mg/dl and 10-year risk 10-20%
 Monitor responses 6 and 12 weeks after initiating or
changing therapy, and every 4-6 months on long-term
therapy,.
 Treatment triglyceride level >150mg/dl.
o This is not a problem with atherosclerosis, but a
marker for other problems (hyperinsulinemia,
insulin resistance and high LDL, etc)
 Drugs that impair intestinal absorption of cholesterol
 Cholestyramine, Colestipol, Neomycin
 Binds bile acids in the intesting.
 Drugs that impair cholesterol and VLDL synthesis
 Lovastatin (Mevacor, Mevinolin)
o It specifically inhibits HMG-coenzyme A reductase,
an enzyme that is necessary to convert HMGcoenzyme to mevalonate (an early step in the
biosynthesis of cholesterol). The levels of VLDL,
LDL, and plasma triglycerides are all reduced while
plasma concentration of HDL is increased.
o Side effects include blurred vision, cramps,
diarrhea, headaches, and lenticular opacities.
 Simvastatin- same mechanism
 Nicotinic Acid: inhibits VLDL synthesis.
 Drugs that increase lipoprotein lipase activity



Clofibrate
Gemfibrozil (Lopid)
o Decreases VLDL and LDL fractions resulting in
decreased serum triglycerides and possibly total
serum cholesterol. The levels of VLDL, LDL, and
plasma triglycerides are all reduced while the
plasma concentration of HDL are increased.
 Dextrothyroxine: increases LDL clearance
 Probucol: increases synthesis of Apo-E messenger RNA
Systemic Hypertension
o “Optometrists can screen for high blood pressure and cardiovascular risk
factors, as well as deliver messages to patients about awareness, treatment,
and control of HTN and heart disease”
o Definitions
 Elevated blood pressure (systolic or diastolic), generally a systolic
blood pressure of over 140mmHg or diastolic pressure over
90mmHg.
o Epidemiology
 Very common
 Increases with age.
 Greater incidence in females, blacks, and the middle-aged.
o Essential vs. Secondary
 Essential (primary)- not reversible. No single cause.
 90% of people with HTN
 This is HTN of unknown origin due to increased peripheral
vascular resistance.
 Seen more in blacks than whites.
 Secondary- caused from something else. Reversible.
 10% of people with HTN.
 This is due to an underlying cause
o Adrenal Hyperplasia (Cushing’s corticosteroid
excess and Conn’s aldosterone excess).
o Adrenal tumor (pheochromocytoma) causes an
increase in adrenaline
o Hypoperfusion of kidney causes sodium and fluid
retention.
o Just not increased blood pressure
 Systemic affecting all cardiovascular system
 Usually asymptomatic
o Pathogenesis
 Blood pressure regulation
 Multifactorial pathophysiology
 BP = CO x SVR (Cardiac output x systemic vascular
resistance)
o Blood volume
o Humeral factors
o
o
o
o
o Cardiac factors
o Neural factors
o Local factors
Public Health Challenges for the National High Blood Pressure Education
Program
 Prevent blood pressure rise with age.
 Decrease prevalence
 Increase awareness and detection
 Improve control
 Reduce cardiovascular risks
Complications
 Eye
 Retinal exudates, papilledema, flame hemorrhages
 Heart
 Left ventricular hypertrophy, left ventricular ischemia,
coronary arteriosclerosis, heart disease
 Brain
 Cerebral hemorrhage, stroke
 Kidney
 Hemorrhage, renal disease
Blood pressure measurement
 Patients should be seated with back supported and arm bared and
supported.
 Patients should refrain from smoking or ingesting caffeine for 30
minutes prior to measurement
 Measurement should begin after at least 5 minutes of rest.
 Appropriate cuff size and calibrated equipment should be used.
 If too small, the blood pressure appears increased.
 Both SBP and DBP should be recorded.
 Two or more reading should be averaged.
Classification of BP
Category
SBP (mmHg)
F/U
< 120
<130
130-139
DBP
(mmHg)
<80
<85
85-89
Optimal
Normal
High Normal
HTN
Stage 1
140-159
90-99
Stage 2
160-179
100-109
Stage 3
>180
>110
Confirm within 2
mo, give lifestyle
advice
Evaluate to care
within 1 mo.
Evaluate to care
Recheck in 2 yr
Recheck in 1 yr
Give lifestyle
advice
within 7 days.
 With organ damage (i.e. decreased VA) refer immediately.
o Components of Cardiovascular Risk in patients with HTN
 Major risks
 Smoking
 Dyslipidemia
 DM
 Age older than 60 years
 Sex (men or postmenopausal women)
 Family history of cardiovascular disease
 Stress
 Obesity
o Clinical Factors for Stratification of Patients with HTN (Clinical
Cardiovascular Disease- CCD/ Target Organ Damage- TOD)
 These all need increased aggressive treatment
 Heart disease
 Stroke or TIA
 Nephropathy
 Peripheral artery disease
 Retinopathy
 Group A
 No risk factors
 No target organ disease/CCD
 Group B
 Males
 At least one risk factor, not including DM
 No TOD/CCD
 Group C
 TOD/CCD and/or DM (DM = HD)
 With or without other risk factors
o Treatment Strategies and Risk Stratification
BP Stages
Group A
Group B
Group C
High-Normal
Lifestyle
Lifestyle
Drug therapy/
modification
modification
lifestyle
modification
Stage 1
Lifestyle
Lifestyle
Drug therapy/
modification (up to
modification (up to
Lifestyle
12 mo.)
6 mo.)
modification
Stages 2 and 3
Drug Therapy/
Drug Therapy/
Drug Therapy/
Lifestyle
Lifestyle
Lifestyle
modification
modification
modification
o Goal of HTN Prevention and Management
 To reduce morbidity and mortality by the least intrusive means
possible. This may be accomplished by achieving and maintaining





SBP <140mmHg
DBP <90mmHg
Controlling other cardiovascular risk factors
Note: Lower goals for those with CCD/TOD, including
DM.
o Algorithm for treatment of HTN
 Step 1: Begin or continue Lifestyle Modifications
 Lose weight
 Limit alcohol
 Increase physical activity
 Reduce sodium intake
 Maintain potassium, calcium, and magnesium
 Stop smoking
 Reduced saturated fat and cholesterol
 Step 2
 Uncomplicated drug choices
o Diuretics- increase the loss of fluids
o Beta blockers- decrease the blood to the heart and
increased cardiac squeezing. Increase blood vessel
dilation and decreased oxygen consumption
 Specific Indications
o A low dose of initial drug should be used, slowly
titrating upward.
o Optimal formulation should provide 24 hour
efficacy with once-daily does with at least 50% of
peak effect remaining at end of 24 hours.
o Combination therapies may provide additional
efficacy with fewer adverse effects.
 Classes of antihypertensive drugs
 ACE Inhibitors
 Adrenergic inhibitors
o Alpha blockers- vasodilation
o Beta blockers- decrease cardiac output
 Angiotensin II receptor blockers
o No recommended for HTN. No prevention of MI.
 Calcium antiagonists
 Direct vasodilators
 Diuretics- decrease sodium and water reabsorption
o OD’s role in HTN
 ODs have the opportunity to look into the eyes and detect possible
target organ disease. Most importantly, they can also measure
blood pressure and help in the detection and monitoring the control
of HTN.
Vasculitis
o Inflammation of blood vessels, e.g., aortitis
o Immune complexes
o ANCAs (Anti Neutrophil Cytoplasmic Antibodies
o Classification
 Size
 Histology of biopsy
 Presence and number related to disease/ activity.
o Due to viruses, antigens (immune), Hep B and C
o Types
 Polyarteritis Nodosa
 This is easy to diagnose and treat, if you think of it. It is
very rare. Not easily diagnosed because it starts with vague
symptoms.
 At least 2 types:
o Hepatitis immune vasculitis
o Anti-neutrophil antibodies
 Signs
o Medium-small arteries (multiple)
o Granulomas/nodules produced
o Transmural inflammation with necrosis (all layers
of the artery)
o Middle aged adults.
 Symptoms
o Migraines
o Vague aches and pains
o Stroke
o MI
o Bowel infarcts
o Nephritis/ kidney failure
o Gangrene
o Peripheral nerve damage
 Positive ANCA test
 Three layer patchy vasculitis
 Wegner’s Granulomatosis
 This is a problem with the blood from the kidneys and
lungs.
 Triad
o Necrotizing granulomas of respiratory ract
o Vasculitis of small arteries and veins, especially the
lung.
o Glomerulonephritis
 Morphoplogy- like polyarteritis nodosa, but in the lungs.
 Clinical features
o Hemoptysis- blood when coughing
o Hemoturia- blood in the urine
o ANCAs in 90%
o Granulomas on mucosal surfaces.





Microscopic Polyangitis (Hypersensitivity Vasculitis)
 Multiple blood vessels inflamed
 Smaller blood vessels
 Immunological reaction to a disease or medication
o Ex. Henoch Schoenlien purpura, complications to
PCN, seen in kids a lot, palpable red spots on the
skin, also bloody bowels.
Temporal Arteritis
 Most common
 Easy to diagnose and treat, if you think about it
 Granulomatous thickening of the inner portions of the
branches of the external carotid arteries
 Acute and chronic
 Ophthalmic artery can become occluded, leading to a
sudden LOV.
 Females more than males
 Symptoms
o Tender temporal arteries.
o Jaw gets tired chewing
o Physical exam and labs are otherwise nonrevealing
o Easily mistaken for “tension headaches”, until one
or both eyes suddenly goes blind.
o Most patients also have polymyalgia rhuematica,
muscle aches easily, mistaken for rheumatism.
o These patients have high sed rates (>100, normal is
0-30)
 Treat with systemic cortisone
Takayasu’s Arteritis
 Rare
 Primarily in Asians
 In aorta and coronary arteries
 Fibrosis in all layers (especially the intima) means
occlusion/obstruction/inflammation, leading to an MI.
Kawasaki’s Disease
 More common
 In kids. They look red (often Asian)
 Mucocutanteous Lymph Node Syndrome
 Epidemiology
 Morphology
 Clinical features
 Seen in the conj.
 Fever related
 Vasculitis, fevers, nonpurulent, swelling, skin can peel.
 Treat with aspirin
Buerger’s Thromboangiitis Obliterans



Pathologists look for
o Inflamed/ scarred neurovascular bundles
o Neutrophils adjacent to epithelioid giant cells deep
inside thrombi
 Males
 Smokers
Raynoud’s Phenomenon
 Usually beingn
 Related to inflammation of blood vessels
 Circulation decreased due to vasospasm (fingers appear
blue, then white with occlusion due to ischemia, then red
with re-openning)
 In medium arteries, especially tibial (leg) and radial (arm)
 Can get gangrene
Aneurysms
o Dilated blood vessels or blood-filled outpouchings, mostly in the arteries,
due to weakening of the vessel walls.
o Development
 Atherosclerosis may result in an abdominal aortic aneurysm and
syphilis may cause a thoracic aortic aneurysm.
o Complications
 Pressure on surrounding structures, major vessel rupture and death,
occlusion of proximate vessels by either extrinsic pressure or
superimposed thrombosis, embolism from mural thrombosis, and
rupture into pericardium can cause heart failure by cardiac
tamponade.
o Etiologies
 From inflammation and disease, etc.
 Atherosclerosis, cystic medial necrosis, syphilis, trauma,
congenital defects, polyarteritis nodosa, and infections.
o Classification- by gross appearance
 Berry aneurysms- small, spherical dilatations rarely exceeding 11.5cm, typically in the Circle of Willis.
 Saccular aneurysms- large, spherical dilitations up to 20cm in
diameter, often at least partially filled with thrombus
 Fusiform aneurysms- generate a spindle-shaped lesion up to 20cm,
and up to the full length of the aorta.
 Dissecting aneurysm- characterized by blood entering the arterial
wall though the tear, usually in the aortic arch, and dissecting the
layers of the artery.
o Types
 Atherosclerotic abdominal aortic aneurysms (AAA)- worst
 Dilation of the artery, below the renal and above the
bifurcation
o Above belly button
 Can rupture (fatal if not treated now)


 In males over 50 years with HTN
 Detected with ultrasound.
Syphilitic aortitis and aneurysm
 Have had syphilis (dormant), causing inflammation
 Affecting the lining of the artery
o Destroys the media, decreasing elasticity, causing
dilation
 In the chest
Aortic Dissection
 Epidemiology
o Related to HTN, Marfan’s Syndrome, etc.
 Pathogenesis
o This is a tear in the lining of the aorta. Allows blood
to penetrate.
 Morphology
 Clinical features
Venous Disorder
 Varicose Veins
o Superficial vessels in the lower legs
o Swelling due to incompetent valves
o Increased pressure with standing
o Increase with pregnancy.
 Thrombophlebitis
o Venal inflammation
o Superficial- palpebra;, tender, reddened
o Deep Venous Thrombosis (DVT)
 Unilateral
 Painful- bloodflow obstruction (cannot walk)
 In legs, swollen
 Propogates (if higher than knee, can embolyze). If it breaks off, it
goes to the iliac vein  inferior vena cava  heart  pulmonary
artery  lungs and is caught.
 Pulmonary emboli cause infarction. No blood means permanent
dead tissue.
 Treat with aspirin and hot compresses
 Obstructive Phenomena
Lymphatic Disorders- problems with the drainage channels
 Lymphangitis
o Inflammation. “Red streaking” aka blood poisoning
o Treat with antibiotics
 Lymphedema
o Disruption of flow from a tumopr, surgery, etc.
o Tissue thickens, making it have an “orange peel” appearance
o Seen more in females in the upper body.
Vascular Tumors
 These are not common
 Hemangiomas
o Small conglomeration of blood vessels.
o Red, can bleed, superficial (most common)
o Cavernous hemangioma in the brain
 Glomangioma
o Under nails
 Hemangioendotherlioma and angiosarcoma
o Malignant and rare.
 Kaposi’s Sarcoma
o Associated with HIV
o Red/purple lesions on extremeties
o Related to HV-8
Blood
Function
 Maintain a constant diffusion gradient at the cellular level (aka homeostasis)
o Homeostasis is the maintenance of a stable internal environment. Some
important homeostatic mechanisms are osmoregulation, excretion of waste
products, blood glucose level regulation, and thermoregulation. The
blood’s role in homeostasis is that of transporting hormones secreted by
the hypothalamus, anterior pituitary, thyroid gland, adrenal cortex, and
gonads. Homeostasis is maintained by use of negative feedback inhibition
systems used by the hormones. Blood is also involved in
thermoregulation. Superficial blood vessel dilation releases heat and
constriction does the opposite.
 Blood is a major transport media for exchange of important elements with the
interstitial fluid. Blood volume is 7-9% of the lean body weight (5-6L). It is
composed of formed elements and inorganic substances which contribute to gas
transport, excretion, homeostasis, and body protection.
 Gas exchange and Nutrient transport
o This delivers oxygen and nutrients, while removing carbon dioxide and
waste materials.
 Excretion
o Transport waste away from cells to the organs of excretion
 Water balance
o Maintains homeostasis of water
 pH (acid/base balance)
o Blood has buffers to resist pH change



o Blood circulates through the lungs and kidneys that play in acid/base
balance.
Temperature
o There is a core temperature present
o This can be regulated with dilation/ constriction of the capillaries
 Dilation radiates heat away from the core.
 Constriction conserves heat due to loss of air.
Protection
o Against pathogens, toxins, and parasites via the immune system which is
based in the blood.
CSF is formed from blood from the choroid plexi. It protects the brain from
trauma and provides nourishment for the cranial nerves.
Anatomy
 Composition
o Mostly water, electrolytes, gases, plasma proteins, and blood cells.
 Blood Volumes
o Men- 5-6L, Women 4.5-5.5L
o It has a specific gravity of about 1.055, and the whole blood is about 3-4
times more viscous than water.
o Where is blood?
 Heart (7%) and Lung/Pulmonary (9%) = 16%
 Capillaries (5%) Arterioles (2%) and Arteries (13%)= 20%
 Small and large veins (64%)
 Due to large blood reservoirs and diameter
 3X rest of the body
 Plasma
o Composes 55% of total blood volume. This is a yellowish fluid that acts as
a medium for circulating cells and metabolic substances.
o Acts as a solvent, moving easily under pressure and acting as a transport
and temperature regulation medium.
o Water
 Main constituent- 93%. This is for solubility and temperature
control.
o Protein
 Major constituent- 22 types
 Most abundant- Albumin (60%)
 Involved with osmotic pressure (water balance)
o This is so that the blood does not lose an excess of
fluid to the connective tissues at the capillary level.
 Binds and withholds excretion of water.
 Globulins
 Protection- antibodies
 Several types
 Clotting factors- Fibrinogen
 With a cut, this is changed to fibrin (strands)

 When plasma clots, serum is produced (no fibrinogen)
 Hormones (i.e., insulin), enzymes, and nitrogenous wastes.
o Organic nutrients, like glucose, amino acids, fatty acids, and lactic acid.
o Inorganic Compounds- Electrolytes (0.9%)
 4 main electrolytes
 Na+, K+, Phosphate, Chloride, calcium, bicarbonate.
o Also contains gases and waste products.
 Gases include nitrogen, carbon dioxide, and oxygen.
Red Blood Cells (Erythrocytes)
o A normal RBC count is about 5 million cells per mm3 of blood. This is
slightly higher in males. These make up 95% of the formed elements.
o Function: respiratory. They transport oxygen and CO2 between the cells
and lungs utilizing the protein hemoglobin. (30-40% of cell).
o Structure
 Composition
 Water- 60%
 Hemoglobin- 33%
 Others- 7%
o Proteins, lipids, carbohydrates
 Annuclear- no mature nuclei
 The only metabolic process it carries out is glycolysis
 There are also no organelles or ribosomes.
 The cytoplasm includes hemoglobin, which is responsible
for the color, shape, and binding of oxygen.
 The RBCs generate their own ATP via glycoloysis.
 Shape
 Cross-section: looks like a dumbbell. Biconcave disc.
 Front: looks like a doughnut
 Diameter- 7.5 microns
 Area
o Large surface area, small path to the interior of the
cell.
o The cell membrane determines and maintains the
cell’s shape
o The cells are flexible and can conform to enter
small passages.
 Flexible , so they can fit into capillaries.
 Network
 Filled with stroma- a fibrous network skeleton
 Surface
 Contains antigens (antigenic markers), which are proteins
that allow the immune system to recognize foreign
proteins.
 Markers- Blood Types
o A and B
o So can be A, B, AB (both), or O (neither)
o Rh can also be present




Interior
 Hemoglobin makes up the cell fluid, which transports
oxygen and carbon dioxide.
 Carbonic anhydrase is also present which aids in carbon
dioxide transport
 There is no organelles, but a cytoplasm rich in hemoglobin.
Formation
 Fetal (Embryonic)- pre-birth
o Produced in the liver, spleen, lymph nodes, and
bone marrow.
o The hemoglobin is also different, because the
embryo is not exposed to air, therefore cannot get
oxygen.
 Adult
o Produced by the flat bones (vertebrae, ribs, and
sternum) and long bones (humorous, femur, etc)
 Lifespan of 3-4 months.
Death
 These are removed by phagocytosis in the spleen or bone
marrow.
 Older less flexible cells are broken up in the
reticuloendothelial system and excreted via the GI tract
through the liver in the form of bilirubin. About 1% of
circulating cells are lost and replenished daily.
Hemoglobin
o Involved with gas transport (oxygen and carbon dioxide)
o Normal Hb concentration in blood is 13-17g/100ml.
o Globular
o 4 subunnits- composed of Heme and Globin
 Heme- a chemical cage
 Fe2+ (Ferrous)- in the center of Heme
o It is this iron that oxygen binds.
 Globin
 4 polypeptide chains (2 alpha, 2 beta)
o Oxygen Binding
 Reversible depending on the oxygen gradients.
 Each subunit has one oxygen molecule, therefore each Hb has 8
atoms of oxygen. Oxygen bound to Hb does not contribute directly
to the PO2 of the blood.
 The chain can exist in one of two forms
 Deoxyhemoglobin (Hb)
 Oxyhemoglobin (HbO2)
 Oxygen-Hemoglobin Dissociation Curve





After the first oxygen attachment, it is easier for the other
3. This is a called cooperative binding or a positive
allosteric effect.
There is a sigmoid-shaped upsweep. It is not linear.
o It is relatively steep between 10-60mmHg and
flatter between 70-100mmHg.
o The plateau is good, because it protects those
situations in which there is a decreased arterial PO2,
such as higher altitudes or cardiopulmonary disease.
Near 100%, it gets harder again to bind.
A shift to the right indicates Hb has less affinity for
oxygen.
Changes
o PCO2
 An increase in this shifts the curve to the
right.
o Temperature
 Increased temperature shifts to right
 Exercise
 Generates heat and higher demand
for oxygen, because more is
released.
 Oxygen release
 Blood travels near the lungs, which
cools it down (due to inspired air), so
it shifts back to the left and picks up
more oxygen.
o pH/ H+
 Decrease in pH (increase in H+) shifts to
right (more oxygen released)
 This is called the Bohr Effect
 Decreases oxygen affinity (decrease in pH)
 Increases carbon dioxide for metabolism
o 2,3 DPG (Diphosphoglycerate)
 This is a substance in the erythrocytes. It is
present in only trace amounts in mammalian
cells. It is produced in glycolysis. It binds
reversibly with Hb, causing it to have a
lower affinity for oxygen.
 Shift to right
 Rarer
 A production from glycolysis
 Caused by low oxygen tension
o Carbonic Anhydrase
 Increase causes a shift to the right.

CO2 + H2O  H+ + HCO3-, because
decreases pH (increased H+)
o Carbon Monoxide (CO)
 Better competitor for Hb than O2 (250X
better)
 Once attached, hard to dissociate. One
suffocates due to the lack of oxygen
 To dissociate, flood the patient with oxygen.
 Shifts to right (decreased O2).
 Mechanism
o Carbon dioxide and hydrogen ions combine with
hemoglobin and alter its molecular configuration.
Thus, these effects are a form of allosteric
modulation.
 Oxygen Transfer in Lung and Tissue
o Transport of Oxygen
 Hemoglobin carries 95%
 Plasma carries the remaining 5% in the dissolved state.
o Transport of Carbon Dioxide
 CO2 is much more soluble in water than oxygen.
 Some of the CO2 molecules, after dissolving, can react reversibly
with amino group of proteins, particularly HB, to form carbamino
compounds
 RNH2 + CO2 ↔ RNHCOOH (HbCO2)
 But, most of the CO2 molecules, after dissolving in the blood, are
converted to bicarbonate.
 CO2 + H20 ↔ H2CO3 ↔ HCO3- + H+
 The first reaction is catalyzed by the enzyme carbonic
anhydrase, which is present in the erythrocytes but not in
the plasma.
 This is called the Hamburger Shift. It is similar to the Bohr
effect with CO2.
 The reaction is not fast enough without the enzyme.
 The enzyme is located in the RBCs.
 Bicarbonate in the plasma- 70% (HCO3-)
 Deoxygenated hemoglobin carries 23%, forming HbCO2.
 Plasma has 7% in the dissolved state.
o H+ Transport
 Deoxyhemoglobin has a much greater affinity for H+ than does
oxyhemoglobin, and so it binds (buffers) most of the hydrogen
ions, denoted as HbH. Due to this, only a small number of H+
generated in the blood remain free. The pH of arterial blood is
about 7.4, and 7.36 for venous blood.
 As the blood passes through the lungs, deoxyhemoglobin becomes
oxyhemoglobin, releasing hydrogen ions. The H+ react with
bicarbonate to give CO2 and H2O.


Increased arterial H+ concentration due to CO2 retention is called
respiratory acidosis. Conversely, hyperventilation would lower the
arterial values of both PCO2 and H+ concentrations and is called
respiratory alkalosis.
White Blood Cells
o This makes up 5% of the formed elements. Their principal function is
body defense.
o Combine WBC count- Numbers range between 5 and 10,000 cells per
mm3. This is versus the differential WBC count in which the cells are
counted according to type. It is diagnostically useful. Leukocytes are
commonly expressed as a percentage of the combines WBC count.
Normal values for the differentia; percentage are
 Neutrophils- 50-70%
 Eosinophils- 1-4%
 Basophils- 0.4%
 Monocytes- 2-8%
 Lumphocytes- 20-40%
o The lifespan varies according to the function of the type, ranging from
neutropihile which generally survive from a few hours to a few days, to
the lymphocytes which may survive over a year.
o Granulocytes are formed in the bone marrow of the adult, while the
lymphocytes are formed in lymphatic tissues of the spleen, thymus, and
lymph glands.
o Protection- main function (crucial in immunity)
 Against pathogens, toxins, etc.
 Mobile
 Can leave the bloodstream
 This is called diapedesis
 Formed (2 locations)
 Bone Marrow (same as RBC)
 Lymph Nodes
o Two Types
 Determined by the Wright Stain
 Determines type of WBC by staining it into granular or
agranular categories
 Granular (70%)


WBC with little grains of sand in the cytoplasm (packets of
hydrolytic enzymes). There are also multi-lobed nuclei.
They protect the body against pathogens.
 Named based on color of nucleus
 Neutrophiles- most predominant (40-70%)
o Aka PMNs. These become microphages.
o Granules contain lysosomes enzymes. Phagocyticingests other particles (microphages)
o Nucleus does not stain. It has 3-5 lobes.
o This is the major response to tissue damage.
 Eosinophile (1-4%)
o Nucleus stains red, and it is bi-lobed. The granules
contain lysosome enzymes and peroxides. The
granules are acidophilic.
o Involved with allergies
 Basophils- rarest (0.4%)
o Nucleus stains dark blue. It is in a U-shape. The
granules contain histamine, heparin, serotonin, but
not lysosome enzymes.
o Involved with simulation inflammation
Agranular



Contains clear cytoplasm. They do not contain cytoplasmic
granules.
Monocytes (2-8%)
o Contains a “lobed” or indented nucleus
o Largest WBC- 3-8x size of RBC with a large,
centrally displaced nucleus.
o Can cause mononucleosis- high counts of
monocytes
o Phagocytosis- they can do this, but only after they
leave the capillaries
 Become macrophages which bind and
process antigens.
Lymphocytes (20-40%)
o Round cells, about the size of RBCs. This has a
densely staining nucleus and a small rim of
cytoplasm. This is the smallest WBC.
o Involved with the production of antibodies
o T-Cells
 Involved with cell-mediated immunity
 Antibodies are at the surface of the
cell and are involved with the
reactions of the antigens.
o B-Cells
 Involved with humoral immunity (blood)
 Release antibodies into the blood
stream.

Platelets (Thrombocytes)
o These are small biconvex discs with no nucleus.
o These are produced from megakaryocytes in the bone marrow and stored
in the spleen.
o Involved with clotting and hemostasis.
o They stick in the nets of fibrin and swell to form a clot.
o Clots can cause problems if they plug things they’re not supposed to.
o If you had a heart attack or stroke, take aspirin because it inhibits
prostaglandins, which make platelets sticky.
o There is a danger with no clotting at all.
o It also releases thromboplastin, acting on prothrombin to form thrombin,
which converts fibrinogen to fibrin.
o These have a lifespan of about 10 days.
Physiology
Hematopoiesis
 This is the process of formation of blood corpuscles. It involves several stages of
developmental cells which may be described differently by various authors.
Intermediate cells may differ from certain other sources, but the general scheme is
somewhat the same. New blood cells are generated in the bone marrow from
pluripotent stem cells.
 Red blood cells
o Derived from a cell known as hemocytoblast which comes from
primordial stem cells in the bone marrow. The hemocytoblast first forms
the basophil erythroblast which begins the synthesis of hemoglobin. The
erythroblast then becomes a polychromatophil erythroblast, a mixture of
basophilic material and red hemoglobin. The nucleus of the cell shrinks as
more hemoglobin is formed and the cells becomes a normoblast. No
further cell division occurs beyond this stage. The nucleus is extruded, the
endoplasmic reticulum is reabsorbed, and the cell becomes a reticulocyte
containing a small amount of endoplasmic reticulum and hemoglobin. The


reticulocyte passes into the blood capillaries by squeezing through the
pores of the membrane (diapedesis). The endoplasmic reticulum is them
completely absorbed and the cell becomes a mature erythrocyte.
o This entire process takes about one week.
White blood cells
o PMNs monocytes are normally formed only in the bone marrow, but are
also capable of proliferation in the various immune tissues throughout the
body (spleen, lymph glands, thymus, tonsils, etc.). Some white blood cells,
especially granulocytes, are stored in the bone marrow until needed in the
circulatory system, i.e. inflammatory response, etc. They are released in a
mature form.
Platelets
o A platelet or thrombocyte is a cell fragment split from a large multinuclear
cell called a megakaryocyte. Most megakaryocytes remain in the marrow.
Other may enter the blood and travel to other organs where they contribute
to produce platelets. Platelets are not cells in the strict sense, since they are
not produced by a mitotic division of a parent cell, and do not reproduce
themselves. Following injury, platelets release chemicals which stimulate
contraction of the injured blood vessel to minimize blood loss. Platelets
also create a physical barrier by clumping together at the site of damage,
plugging the wound. Platelets also participate in the formation of factors
that initiate blood coagulation, and promote repair of injured tissue by
releasing plated-derived growth factor (PDGF).
Blood Testing
Blood Typing
 OAB
o Blood is grouped according to the presence of certain antigens in its
serum. Type A blood contains A antigen; B blood, B antigen, Type AB
blood contains both A and B antigens while Type O has neither antigen
present.
o Agglutinins are the antibodies that can cause an antibody-antigen reaction.
Type A blood develops B antibodies, called B agglutinins. This probably
occurs due to the ingestion of food with Type B blood containing the B
antigen, or by certain bacteria. Therefore, if a person with Type A blood is
transfused with a patient with Type B blood, a transfusion reaction will
occur; that is, the B agglutinins in Type A’s blood will attach and B
antigens in Type B’s blood causing agglutination and clogging of the
vascular beds with resultant infarction, ischemia, and death. The
importance of blood typing preceding transfusion is thus appreciated.
o Certain Type A and B individuals have strong titers of anti-A and anti-B
agglutinins; their serum is used for the typing of blood. To be typed, a
patient has 2 drops of blood placed on a slide. A drop of the anti-A is
placed on the first drop, anti-B on the second. If there is no agglutination,
the patient is Type O; agglutination with anti-A, the patient is Type A;

agglutination by anti-B, the patient is Type B. If both drops agglutinate, he
is Type AB.
Rh (Rhesus Factor)- Antigen D
o An individual who is Rh positive has antigen on the erythrocyte and no
plasma antibody. If Rh negative, there is not erythrocyte antigen or plasma
antibody. However, if Rh positive cells enter the blood antibody is
produced. This can occur in blood transfusion or in cases of pregnancy
with an Rh positive child and an Rh negative mother. During childbirth,
the baby’s RBC may be forced through the placenta into the mothers
bloodstream. If so, she develops antibody which could endanger future Rh
positive children with the condition erythroblastosis fetalis. The antigen
occurs in 85% of the population.
 Erythroblastosis fetalis- a hemolytic disease in which the RBCs are
attacked.
 Today mothers are given RhoGAM- an antibody that suppresses
antibodies during pregnancy.
The Hemtocrit
 The usual technique for determining hematocrit utilizes a small glass capillary
tube, internally coated with an anticoagulant (heparin). This tube is partially filled
with blood obtained from a finger-puncture. One end of the tube is sealed with
plastic clay. The capillary tube is placed in a special centrifuge, where it is rotated
at high speed for about 5 minutes. After centrifugation, the blood sample appears
separated into two fractions- a column of packed red cells and a column of clear
plasma. The hematocrit is defined as the ratio of the volume of packed red cells to
the volume of the original blood sample, multiplied by 11 or, the percent of the
blood that is cells. Normal male subjects average 42%, females 38%
 The normal adult sedimentation is about 2-10mm/hr.
Pathology
Hemodynamic Disorders, Thrombosis, and Shock


The health and well-being of cells and tissue depend not only on an intact
circulation for delivery of oxygen, food, and nutrition, but also on normal fluid
homeostasis.
All cells and tissues of the body are critically dependent on a normal fluid
environment and on adequate blood supply. Either or both of these supporting
systems may be deranged in a wide variety of clinical settings, and therefore fluid
imbalances and hemodynamic disturbances are not only commonplace, but also
life-threatening. Normal hemostasis requires fluidity of the blood in the vascular
system yet rapid formation of a solid plug of blood to close holes made by
ruptures or other forms of injury to blood vessels.
Abnormalities
Edema
 This is an accumulation of interstitial fluid (swelling) caused by leakage of
plasma from the vessels into tissue until saturation is reached. Etiologies include
inflammation, increased blood pressure, sodium/water retention due to kidney,
liver, or heart disease, and decreased osmotic pressure due to low albumen
protein.
 The body is 60% water. 2/3 is intracellular, inside the cell, and 1/3 is extracellular,
outside the cell in tissues, fatty spaces, etc. As far as the extracellular, 95% is
interstitial and 5% is in the blood plasma. Edema is the abnormal accumulation of
fluid in the interstitial spaces. This is compared to accumulation of fluid in a body
cavity which is denoted by the use of “hydro,” such as hydrothorax,
hydropericardium, hydroperitonium, and hydrocephalus.
 This impairs circulation, wound healing, and infection clearing. In the lungs it can
cause pneumonia and death. In the brain, it causes herniation of vitals organs if
pushed through the foramen magnum.
 Normal fluid transit
o Maintained when the outflow of fluid from the arteriolar end is balanced
with the inflow at the venular end. In other words, the vascular hydrostatic
pressure equals the plasma colloid osmotic pressure. This is aided by
lymphatic drainage
 Abnormal increase in interstitial fluid
o Occurs with increased capillary pressure or diminished colloid osmotic
pressure.
o Altered vascular permeability due to inflammation
o Blood vessels dilate and become “leakey” causing swelling of the
interstitial space.
 Pathophysiology
o Increased hydrostatic pressure caused by:
 Deep venous thrombosis (plug/clot)
 Local, impaired venous outflow
 With a clot, the opposite end needs increased blood, but
they are not getting it.
 Congestive Heart Failure
 Generalized, systemic edema
 This is due to the right ventricle not pumping enough
blood, leading to decreased blood circulation.
o Reduced Plasma Osmotic Pressure because
 Excessive loss of albumin
 Test for albumin with a blood test or check bcc.
 Reduced synthesis of albumin
 Liver and kidney disease
 Protein malnutrition
 Nephrotic syndrome
 Net movement of fluid into interstitial space.
o Lymphatic obstruction

Impaired lymphatic drainage
 Lymph nodes swell, aka lympedema
 Treat by wearing a brace so that muscles contract and
swelling does not occur.
 Inflammatory source
 Filariasis infection, aka elephantiasis (caused by the
parasite Lincuri bencofri)
 Neoplastic (tumors)
o Sodium and Water Retention
 Increased salt intake
 Obligate water retention
 Increased hydrostatic pressure by increasing the volume of
fluid in the blood system.
 Reduced vascular colloid osmotic pressure
 Seen with renal dysfunction
Hyperemia and Congestion
 Both of these terms indicate local increase in volume of blood in a particular
tissue or in the vessel.
 Hyperemia
o Active process
o Arteriolar dilation
o Augmentation of arterial inflow
o Very red tissue, red because it is rich with oxygen.
o Examples include skeletal muscle during exercise, site of inflammation,
and conjunctivitis.
 Congestion
o This is an accumulation of blood and lymph in one area due to decrease in
blood pressure or blood supply.
o Passive process
o Impaired venous outflow so that blood remains
o Blue-red tissue due to deoxygenated blood
o Examples include CHF and venous obstruction where cardiac output is
below the demands of the body. Effects include reduced cardiac output,
increased systemic venous pressure, renal retention of fluid, peripheral and
pulmonary edema, excessive stretching of cardiac muscle (making it less
effective, creating a vicious cycle), and increased heart size.
o Causes: decreased contractibility of the myocardium due to diminished
coronary blood flow (ischemic heart disease), damage to heart valves, etc.
o Treatment
 Digitalis (raises cardiac output) and diuretics/diuresis (decrease
sodium and water reabsorption) and reduce sodium intake.
 Chronic Passive Congestion
o Chronic hypoxia due to decreased nutrients, oxygen, etc.
o Parenchymal cell degeneration and death
o Capillary rupture.
o Response is seen as red spots indicating vascular rupture and accumulation
of proteolytic enzymes and phagocytic materials.
Hemorrhage
 This is the loss of blood from the intravascular space due to rupture of a vessel
(artery, capillaries, or vein). This is compared to an accumulation of blood
specifically in a body cavity, which is indicated by the prefix “hemo.” Examples
include hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis.
 Etiology
o Trauma
o Atherosclerosis
o Inflammatory erosion, i.e. ulcers
o Neoplastic erosion
o Congenital, i.e. hemophilia
 Acute vs. Chronic
o Acute is due to trauma, ulceration, or a bleeding disorder.
o Chronic is usually due to a bleeding disorder associated with aspirin use,
cancer, etc. Iron is usually the limiting factor and often very slow bleeding
like from colon cancer or aspirin use the anemia does not manifest until
the iron stores are depleted.
 The clinical significance of hemorrhage depends on the volume, rate, and site of
blood loss.
o Volume and rate
 Little impact with slow loss or loss of up to 20% of the blood
volume (i.e. aspirin use). For slow loss, use a turnicate, elevation,
etc to stop the bleeding.
 Large, rapid loss may lead to hemorrhagic (hypovolemic) shock.
o Site
 Subcutaneous tissue, i.e. bruise on the knee, is insignificant
 Brain stem can lead to death.
o Hemorrhage loss and iron availability
 Permanent loss if External Hemorrhage, to the body. The blood is
totally lost for any further use. Iron deficiency, anemia may
develop. (i.e. peptic ulcer, menstrual bleeding)
 Retained if Internal Hemorrhage within the body. But not where it
should be in circulation, instead into body cavities or tissues. Red
blood cells re-utilize for hemoglobin synthesis (i.e. bruising)
 If the bleeding stops, the bone marrow will replace the loss in time if the building
blocks are present.
 Characteristic color changes
o Due to erythrocyte degradation and phagocytosis by macrophages
o Hemoglobin- red/blue
o Bilirubin- blue/green
o Hemosiderin- golden brown (iron)
o Jaundice- yellow
 Hematoma



o This is a bruise. It is an accumulation of blood externally or enclosed
within a tissue. Diffuse in the tissue or even separates the cells to form a
pocket of blood within the tissue.
Petechiae
o Minute hemorrhages in the skin, mucous membranes, and serosal surfaces.
Purpura
o Slightly larger hemorrhages than petechiae.
Ecchymosis
o Greater than 1-2cm subcutaneous hematoma.
Hemostasis
 This results from a set of well-regulated processes that maintain blood in a fluid,
clot-free state in normal vessels, while inducing the rapid formation of a localized
hemostatic plug at the site of vascular injury.
 The maintenance of homeostasis is life saving
o Vasoconstriction
 Arteriolar vasoconstriction in response to injury
 Reflex neurogenic mechanisms, local
 Release of endothelin, a vasoconstrictor
 Secretion of extracellular matrix (ECM) to give it bulk. It
attracts platelets and coagulating factors which do not last
long.
o Highly thrombogenic
o Collagen-like
o Primary hemostasis
 Platelet adhesion
 Shape change to mold into the site of injury
 Activation and degranulation
 Recruitment of other platelets
 Hemostatic plug developed via platelet adhesion.
o Secondary hemostasis
 Secretion of tissue factors
 Activation of coagulation cascade
 Phospholipid complex expression
 Fibrin deposition and polymerization.
 Thrombin release and activated.
 Further platelet recruitment and degranulation.
o Antithrombotic counter-regulation
 This is important, because if it keeps going, the clot would go until
the blood vessel lumen is occluded.
 Solid, permanent plug made up of polymerized fibrin and platelet
aggregation. This plug is very strong and secure.
 Counter- regulatory mechanisms
 Blocks coagulation cascade
 Things in the clot break it down and allow the endothelium
to regenerate.
Thrombosis
 This represents the formation of a blood clot (thrombus) within the noninterrupted
vascular system, and can be understood as inappropriate activation of normal
hemostatic processes.
 It is, to a considerable extent, a pathologic extension of the normal hemostatic
mechanism which involves the combined activities of endothelial cells, platelets,
and the coagulation sequence.
 This is significant because it is life threatening.
o Partial or total obstruction of arteries and veins, i.e. pulmonary, coronary,
cerebral emboli
o Source of emboli
 These are classified based on their location: arterial, venous, mural (in heart).
 Predisposition to thrombus formation
o Virchow’s triad
 Endothelial injury
 This is the most dominant factor.
 Sustained from
o Hemodynamic stress (HTN)
o Turbulent flow over scarred valves, i.e. scab
o Bacterial endotoxins
o Others
 Hypercholesteremia, radiation, smoking
 Alterations in normal blood flow
 Normal flow: laminar flow
Blood
*This does not occur with
Nonmoving plasma
thrombus/stasis
Endothelium
 Turbulence (Harsh flow)
o Cause endothelial injury in arterial and cardiac
thrombosis
 Stasis (Blood just sits around)
o Form venous thrombosis
o Blood sticks due to stagnancy.
 This is concurrent with a bend in a flow, which can also
cause endothelial damage.
 In combination
o Disrupt laminar flow- blood sticks
o Prevent dilution of activated clotting factors. They
settle.
o Retard the inflow of clotting factor inhibitors
o Permit the build-up of thrombi
o Promoter endothelial cell effects
 Hypercoagulability, leading to increased viscosity
 Any alteration in the coagulation pathways
 Primary (genetic); cant change





Secondary (acquired)
Causes
o A toughened endothelial surface of a vessel due to atherosclerosis,
infection, and trauma.
o Slow flowing blood can initiate clots, i.e., blood stasis in bedridden
patients.
Conditions associated with an increased risk of thrombosis
o Primary- mutations in Factor V, antithrombin III deficiency, Protein C and
S deficiency, and fibrinolysis defects- all cause coagulation.
o Secondary High Risk
 Prolonged bed rest, myocardial infection, tissue damage, cancer,
prosthetic cardiac valves, lupus
o Secondary Low Risk
 Arterial defibrillation, cardiomyopathy, nephrotic syndrome,
hyperestrogenic states, oral contraceptive use, sickle cell anemia,
smoking.
Fate of a thrombus
o Propagation- it continues to build with platelets and fibrin.
o Embolization- movement of the clot until it blocks something else. This is
the worst fate.
o Dissolution- this is the breakdown of a clot. This is the best fate.
o Organization and recanalization. New capillary channels are formed and
the clot is made a part of the cell wall.
Types of thrombi
o Venous thrombosis (Phlebothrombosis)
 Superficial
 Occurs in the saphenous system
 Varicosities; varicose veins
 Cause local congestion, swelling, pain, and tenderness
 Rarely embolize, but can predispose area to infection and
development of varicose ulcers.
 Deep
 Affecting larger leg veins at or above the knee joint (to
hip), i.e. popliteal, femoral, iliac veins
 Cause edema, pain, and tenderness of the foot, ankle, and
lower leg. 50% asymptomatic
 Capacity to embolize to the vena cava, clotting the heart or
lung, leading to death.
 Increased risk
o Advanced age
o Bed rest
o Immobilization due to trauma, surgery, burns, long
journeys
o Pregnancy and postpartum states, because the blood
is thicker

o Disseminated cancers (Trousseau’s syndrome),
because cancer cells can sometimes secrete procoagulating factors.
o Cardiac and Arterial Thrombosis (arterial more severe than venous)
 Myocardial infarction
 Rheumatic heart disease- affects the left atrium, weakening it
 Atherosclerosis- due to damaged endothelium
Treatment
o Anticoagulants, i.e., Heparin
Embolism
 An embolus is a detached intravascular solid, liquid, or gaseous mass (thrombus)
that is carried by the blood to a site distance from its point of origin. This is how
they are classified.
 Forms
o Dislodges thrombus- 99% (thromboembolism)
o Droplets of fat
 Broken bones can produce fat emboli.
o Bubbles of air or nitrogen from injections or scuba divers ascending too
fast
o Atherosclerotic debris
o Tumor fragments
o Bits of bone marrow = fat
o Foreign bodies i.e. bullets
 Those originating in the large arteries or in the left side of the heart, eventually
plug smaller systemic arteries. Those from the right side of the heart cause
pulmonary obstructions.
 Pulmonary Thromboembolism
o Cause of death in 10-15% of hospitalized patients, resulting in 500,000
deaths in the US.
o 95% originate from deep veins above the level of the knee.
o Large pulmonary embolus from a deep venous thrombosis. This is then
carried through progressively larger channels of the venous system. It
passes through the right heart to lodge in the pulmonary vasculature.
o Sites of occlusion
 Main pulmonary artery- highest mortality rate
 Across a bifurcation (saddle embolus)- may have some leakage
 Smaller, branching arterioles.
 The larger the branch, the more devastating.
o Clinical consequences
 60-80% of pulmonary emboli are clinically silent.
 Sudden death, right heart failure (cor pulmonale or cardiovascular
collapse occur when 60% or more of the pulmonary circulation is
obstructed).
 Obstruction of medium sized arteries or small end-arteriole
branches does not cause infarction.

Systemic Thromboembolism
o Traveling within the arterial circulation, not venous.
o 80% originate from intracardiac mural thrombi, from the carotid artery
and heart. 20% arise from ulcerated atherosclerotic plaques, aortic
aneurysms, and valvular vegetation.
o Sites of occlusion
 Lower extremities- 75%
 Brain- 10%
 Intestines, kidneys, and spleen.
o Clinical Consequences
 Depends on point of origin and volume blood flow.
 Extend of collateral vascular supply
 Tissue’s vulnerability to ischemia
 Caliber of occluded vessel.
 Arterial: causes infarction (ischemic necrosis) in the heart (MI),
brain (stroke), etc.
 Venous: causes pulmonary emboli
Infarction
 An infarct is an area of ischemic necrosis caused by occlusion of either the arterial
supply or the venous drainage in a particular tissue.
 Types
o Myocardial- heart attack
o Cerebral- stroke
o Pulmonary
o Bowel
o Extremities (gangrene)
o Eye (CRAO, CRVO)
 Causes
o Thrombus or embolus- 99%
o Local vasospasm
o Swelling of an atheroma- “balloon”
o Twisting of a vessel
o Compression of a vessel: extrinsic, edema, entrapment
o Traumatic rupture
 Factors that influence the development of an infarct
o Nature of the vascular supply
 Dual arterial blood supply. If one shuts down, the other takes over.
 i.e. lungs, liver, hands, forearm
 End-arterial. One blood supply
 i.e. kidney, spleen
 Collaterals- smaller vessels, which are alternative routes. They are
not new. Don’t confuse this with neovascularization.
o Rate of development of occlusion: slow vs. fast
 Slow allows new channels to be formed. Fast does not.
o Vulnerability to hypoxia
 Neurons 3-4 minutes
 Myocardial cells 20-30 minutes
 Fibroblasts with myocardium- many hours.
o Oxygen content of blood
 The determinant factor is the partial pressure of oxygen in the
blood.
 CHF, Emphysema, Asthma, COPD, Anemia
Shock
 This is characterized by a marked loss of blood pressure and depression vital
processes.
 This constitutes systemic hypoperfusion (inadequate blood flow) due to reduction
either in cardiac output or in the effective circulating blood volume. This causes
tissue damage. It is usually due to low cardiac output.
 The hypoxic and metabolic effects of hypoperfusion initially cause only reversible
cellular injury, persistence of the shock eventually causes irreversible tissue injury
and can culminate in the death of the patient.
 Causes
o Blood loss is the most common cause, pump failure (myocardial
infarction), anaphylaxis/antigen-antibody reaction (histamine-like
substances released causing vasodilation), sepsis.
o Disseminated infection and trauma cause vasodilation and decreased
venous return.
 The initial threats of the life of the patient in shock arise from the medical,
surgical, or obstetric catastrophe that initiated the shock state. However, the
cerebral and cardiac changes worsen the early crisis. If these hazards are survived,
metabolic acidosis, shifts in electrolyte levels, respiratory difficulties, renal
dysfunction, and reduced immunologic competence may occur.
 Types
o Cardiogenic
 This is due to no output at the heart. It results from myocardial
pump failure due to intrinsic myocardial damage or extrinsic
pressure or obstruction to outflow, including myocardial infarction,
arrhythmia (Atrial fibrillation, pulse out of sync, etc), or
pulmonary embolism.
 The problem is the loss of the ability to pump the required amount
of blood to the tissues and especially the vital organs
o Hypovolemic
 Results from loss of blood or plasma volume due to hemorrhage,
burns, trauma (GSW), fluid loss (vomiting or diarrhea).
o Septic
 This is peripheral vasodilation and pooling of blood, cell
membrane injury, endothelial cell injury with disseminated
intravascular coagulation (e.g., overwhelming bacterial infection)
 This is caused by systemic microbial infection.





Gram negative (endotoxic shock), gram positive, or fungal
infection
It is usually due to uncontrolled infection due to gram
negative bacteria and the infection is spread to the
bloodstream (septicemia)
o Neurogenic
 This is encountered in patients receiving general anesthesia or in
spinal cord injury cases. There is an interruption of normal
vascular tone maintenance leading to peripheral vasodilation and a
pooling of blood.
 Fainting (vasovagal syncope) can be considered a mild form. The
pooling of blood means that it is not going to the head.
o Anaphylactic
 This is due to an allergic (IgE mediated) hypersensitivity reaction
to insect stings, medications, food, etc.
 Triggering a widespread, systemic vasodilation and increased
vascular permeability.
o Irreversible
 This may follow any form of shock
 Even of the shock is reversed, death will still ensue due to damage
to a vital organ (at the cellular and tissue level) which cannot be
repaired.
Patient profile
o Cardiogenic and hypovolemic shock
 Hypotension, cool, clammy, cyanotic (blue/green due to no
oxygen) skin, weak, rapid pulse, tachypnea (rapid breath), and
ashen gray color.
o Neurogenic shock
 Slow pulse and the above
o Septic shock
 Warm and flushed skin
Complications
o Decreased cellular metabolism, ischemia, lactic acidosis, renal impairment
(tubular necrosis), and death.
Treatment
o Blood or plasma transfusion and sympathomimetic drugs.
Hematopoietic and Lymphoid System
Introduction
There are a number of diseases in this area. In RBCs, we are usually discussing a
lack of, and in WBCs, there is usually an over abundance (malignancies). The number
one reason for this is infection and pathological response. The entire
hematopoietic/lymphoid system is considered to be the circulating blood, bone marrow,
spleen, lymph nodes, and RE system.
The bone marrow, lymph nodes, and spleen are all involved in hemtopoiesis.
Traditionally, these organs and tissues have been divided into myeloid tissue, which
includes the bone marrow and the cells derived from it (e.g., erythrocytes, platelets,
granulocytes, and monocytes), and lymphoid tissue, consisting of the thymus, lymph
nodes, and spleen. This subdivision is somewhat artificial, as it is not possible to draw
neat lines between diseases involving the myeloid and lymphoid tissues.
RBC Disorders.
The function is to transfer oxygen from the lung to the tissues. Oxygen is
especially important for nervous tissue.
Anemia
 This is defined as a reduction in the normal circulating levels of hemoglobin and
RBC mass. One could be anemic with an increase in RBC mass, but there is just
no hemoglobin.
 This obviously results in an impairment of oxygen delivery to the cells of the
body if significant enough. Therefore, the problem is decreased oxygen carrying
capacity of the blood to the tissues. This results from losing them, destroying
them, or stoppage of making them.
 Mostly women are anemia due to menstruation. Men normally do not have this. If
they do, it may be a symptom of cancer, such as colon cancer. Almost everyone
that takes aspirin on a daily basis has GI blood loss, not visible in the stool. The
stool appears “tarlike” if there is a lot of blood loss. Another symptom is fatigue.
 An eye sign is a pale conjunctiva, especially on the palpebral side.
Hemolytic Anemias
 This is defined as increased RBC destruction resulting in a shortened life span for
the RBCs of less than the normal 120 days. Here the iron stays in the body.
 This has a positive Coombs test, which means that a plasma protein, usually either
IgG or complement has become fixed abnormally and relatively irreversibly to the
red cell surface.
 Symptoms include fatigue, malaise, pallor, and jaundice. Splenomegaly, anemia,
and reticulocytosis also occurs.
 Acute Hemolytic Anemia is induced by drugs or infection. Symptoms include
chills, fever, nausea, vomiting, pallor, back and abdominal pain, jaundice, and
splenomegaly.
 Paroxysmal Nocturnal Hemoglobinuria
o Acquired and characterized by chronic hemolytic anemia,
hemoglobinemia, and hemoglobinuria.
o Also chills, fever, pain and decreased white blood cells and platelets.
 Those due to inherent RBC defects, i.e. the problem is with the RBC itself. These
are usually inherited
o Sickle cell disease- Here the hemoglobin is a problem and sickles in low
oxygen states which leads to hemolysis (RBC destruction). Abnormal red
blood cells may clog capillary system causing necrosis. This is a recessive



disorder. The disease is manifested if it is double recessive. This is due to
a valine being substituted from glutamic acid on the beta chain.
 There are recurrent attacks of fever, and pain in the arms, legs, or
abdomen.
 Carriers of sickle cell anemia are said to have sickle cell trait.
These individuals inherited only one of the two abnormal beta
chains and are usually asymptomatic.
 This is seen more in African-Americans.
o Hereditary Spherocytosis- this is congenital hemolytic anemia or jaundice.
A defect in the cell membrane leads to the cells being spherical instead of
a biconcave disc. This is due to them being abnormally permeable to
sodium. This makes them fragile, they lyse easily and live a shorter period
of time. This appears to be transmitted by a dominant trait.
 Symptoms include malaise, abdominal discomfort, jaundice,
anemia, and splenomegaly.
 There is spherocytosis and negative Coombs test.
o Ovalocytosis
 Characterized by having 25-90% of the red blood cells oval.
 12% of patients have anemia, palpable spleen, jaundice, and
elevated reticulocyte.
 RBC survival is often shortened.
o Hereditary Nonspherocytic Hemolytic Anemia
 Caused by intrinsic red cell deficiencies, moderate anemia, spleen
slightly enlarged, no and high reticulocyte count.
Those due to external influences on the cell, i.e. the cell is normal but is destroyed
by some external influence
o Autoimmune hemolytic anemia- An autoantibody creates an immune
mediated destruction of the RBCs, like in lupus, etc.
o Drugs and chemicals may destroy RBCs due to toxic effects and many
antibiotics will do this, such as cephalosporins.
o Physical Agents- Radiation, bad heart valves due to rheumatic fever, etc.
may physically damage and destroy the cells.
o Malaria is a protozoal infection which infects normal cells and hemolyzes
them as part of the life cycle.
Glucose 6-phosphate dehydrogenase deficiency
o Either hereditary or infection induced.
o Prone to hemolysis
Microangiopathic Hemolytic Anemia
o Refers to a group of acquired hemolytic anemias due to various causes that
are characterized by fragmented or helmet-shaped red cells, burr cells, or
microspherocytes.
Nutritional Anemias
 Here the problem is failure to make adequate or normal RBCs due to a lack of
proper building blocks.
o #1 is due to inadequate iron. Due to diet, chronic slow blood loss, etc.
results in microcytic (cells are too small), hypochronic (decreased
hemoglobin) anemia. Occurs in 10-20% of females in this country related
to inadequate iron intake and menstrual cycles. Symptoms include fatigue,
headache, lack of energy, and even pagophagia (craving of ice).
 This is almost always due to blood loss. Chronic bleeding of as
little as 2-4ml of blood per day may lead to a negative iron balance
and iron deficiency anemia.
 Symptoms are pallor and lassitude. Fatigue, shortness of breath,
exercise intolerance, headache.
 Serum ferritin is low and there is also hypochromia and
microcytosis.
o #2 is due to inadequate Folic Acid. Usually dietary (green, leafy
vegetables), but often associated with pregnancy and alcohol abuse. This
leads to macrocytic (cells are too large) anemia.
 This produces the same hematologic finding as pernicious anemia,
but occurs sooner because folate storage lasts only 1-2 months.
 Most common cause is malnutrition, especially in association with
alcoholism.
o #3 is due to inadequate Vitamin B12 and also causes a macrocytic anemia.
Requires intrinsic factor, which is released from the GI tract to absorb
vitamin B12, for absorption and this is termed pernicious anemia when it
is lacking. Can see in dietary problems but it is more common in
association with gastric atrophy and lack of intrinsic factor so isn’t
absorbed in the small bowel. This is more common in the elderly, due to
decreased GI mucosa.
 Pernicious Anemia (Addisonian Anemia)
 A conditioned vitamin B12 deficiency due to an absorption
defect, not dietary lack.
 Intrinsic factor secreted by the gastric mucosa is absent.
 Symptoms are anorexia, dyspepsia, smooth/sore tongue,
pallor, jaundice, and tingling/numbness of the feet.
 Also involved oral mucocytes, pancytopenia,
hypersegmented neutrophils, and megaloblastic bone
marrow.
Aplastic Anemia
 The bone marrow is a very busy, active, and dynamic place and is very
susceptible to suppression.
 Here the primary line suppressed is the RBC line, however, the other 2 usually are
also down somewhat. Chloramphenicol (chloromycetin) is famous for this.
 Characterized by pancytopenia or a selective depression of red cells, white cells,
or platelets.
 History of exposure to an offending drug or x-ray radiation.
 Symptoms are lassitude, pallor, purpura, and bleeding.
 Agranulocytosis


o WBCs only
Thrombocytopenia
o Platelets only. This can cause spontaneous bleeding.
Pancytopenia
o All 3 cells lines are suppressed, that is RBC (main), WBC, and
megakaryocytes. May be due to radiation, drugs, chemicals, major organ
failure (liver, kidney, etc), chronic diseases of an inflammatory nature
(autoimmune, infections, malignancies, etc).
Anemia of Lead Poisoning
 Coarse basophilic stippling
 Red cell indices in lead poisoning are usually normal but may show some
hypochromia.
 Mark stippling with normal hemoglobin levels.
Anemia of Myxedema
 In some patients with very low thyroid function.
 They have moderately severe anemia either primary or secondary to
hypopituitarism.
 Anemia tends to be macrocytic and normochromic.
Pure Red Cell Aplasia
 Characterized by severe normocytic, normochromic anemia, very low reticulocyte
counts, normal white blood cells and platelets, normal looking red cells, and
isolated erythroblastopenia of the bone marrow.
 Can be present either as a primary hematologic disorder or secondary in several
other clinical conditions.
Polycythemia
 This is defined as having too much circulating hemoglobin or an abnormal
increase in red blood cells. This increases the viscosity and increases the chance
of headaches, thrombosis, or hemorrhage. There is also an increase in white blood
cells and platelets. An ocular manifestation is dilated, engorged, and tortuous
retinal veins and arteries. It is very difficult to tell the difference between arteries
and veins. Also the blood tends to be very vicious, sludgy, etc. and tends to clot
easily leading to thrombotic problems.
 2 distinct forms
o Polycythemia vera- This is true polycythemia due to marked uncontrolled
overproduction of RBCs and is often considered a malignancy. It often
preceded another bone marrow malignancy like leukemia. With no
underlying cause, the hemoglobin will be 20-25 or more and rising.
Normal is 12-16 in males and 11-15 in females.
o Secondary polycythemia- This is due to chronic hypoxia like from severe
lung diseases such as emphysema. The hypoxia increases the
erythropoietin and leads to chronic oversupply of RBCs to help increase
the oxygen carrying capacity of the blood.
Hereditary Hemoglobinopathies
 Sickel Cell Anemia
o Recurrent attacks of fever, and pain in the arms, legs or abdomen since
early childhood in black patients.
o Anemia, jaundice, reticulocytosis, positive sickle cell test, and
demonstration of abnormal hemoglobin.
 S/C Hemoglobin Disease
o Same racial incidence and mode of inheritance as sickle cell anemia.
o Recurrent attacks of abdominal, joint or bone pain, enlarged spleen,
minimal anemia, and positive sickle cell test.
 Sickle Thalassemia
o Frequent episodes of jaundice, enlargement of liveer and spleen, bouts of
fever, joint and abdominal pain.
 Thalassemia Minor
o Insufficient amount of hemoglobin is made to fill the red cells.
o In beta thalaassemia, the beta chains are defective.
o In alpha thalassemia, it is the opposite.
o Mild but persistent anemia.
o Usually black, southern Chinese, or Meditteranean race are more
susceptible.
 Thalassemia Major
o Homozygous form.
o Severe anemia starting in infancy.
o Very large liver and spleen, hypochromic, microcystic red cells with many
erythroblasts.
o Greatly elevated fetal hemoglobin.
White Blood Cell Disorders and Bleeding Disorders
Introduction
 Primarily we are discussing malignancies, and this accounts for about 10% of
cancer deaths.
 WBCs function to fight infection
Nonneoplastic Conditions
 Neutropenia/Leukopenia
o This means a marked decrease in WBC numbers, but not agranulocytosis.
Due to bone marrow suppression, via medication, etc.
 Reactive Leukocytosis
o This is an increased number of leukocytes due to some underlying reason,
i.e. infection due to viral, bacterial, etc. disease.
Neoplastic Disorders of Lymph Nodes
Non-Hodgkins Lymphoma
 This is a misnomer, because it is malignant and should be lymphosarcoma. The
cells do not help fight off infection as they are malignant and do not function
properly. It is characterized by malignant proliferation of lymphoid cells.
 These are primarily B cell malignancies and arise anywhere in the body there is
lymphatic tissue. These usually do not take over the bone marrow so are not seen
circulating in the peripheral blood, so not seen in blood tests. Seen most
commonly in the 50-70 age group but can occur at any age.
 Etiology is thought to be polygenic
 This is generally painless. Signs and symptoms could include nontender
enlargement of any lymph node or group of nodes with the neck (cervical region)
being the single most common area. It is relatively painless. Requires a biopsy to
diagnose as no good blood, etc. markers. Advanced disease usually leads to night
sweats, fever, weight loss, weakness, anemia, and spread of malignancy around
the body.
 Prognosis depends on degree of malignancy and stage detected for treatment.
Early detection is better prognosis.
Hodgkins Lymphoma
 Primarily affects the T cells and is a distinct form lymphoma. It is characterized
by abnormal proliferation, in one or several lymph nodes of lymphocytes,
histiocytes, eosinophils, and preserved of Reed-Sternberg giant cells.
 It has distinct cell on biopsy termed Reed-Sternberg cell which is a multinucleated
giant cell. This is absolutely diagnostic. Otherwise, it is similar to lymphomas
except the peak age of onset is 20-40 and males are affected 3:1 over females.
 Regional lymph nodes are enlarged. They are firm, non-tender, and painless.
 Symptoms include fever, weight loss, excessive sweating, pruritis, and fatigue.
 Possibly polygenic
 This is seen in all races, predominantly in young adults (15-34) and again after
age 50.
Lymphosarcoma
 This has symptoms of fatigue, anorexia, weight loss, and skeletal pain and
tenderness. Enlarged, firm nodes usually arise in the mediastinum or para-aortic
region in individuals 60-80 years old.
Immunoblastic Lymphadenopathy
 Resembles Hodgkin’s disease.
 Fever, sweats, weight loss, rash and lymphadenopathy.
 No Reed-Sternberg cells
 Fatal within a year
Nonneoplastic Disorders of Lymph Nodes
 Acute nonspecific reaction hyperplasis (nonspecific acute lymphadenitis)



o This occurs in nodes draining an area of acute inflammation. Lymph nodes
undergo reactive changes whenever challenged by microscopic agents and
foreign matter introduced into wounds or into circulation. They are
enlarged because of cellular infiltration and edema.
o Acutely inflamed nodes are most commonly caused by direct microscopic
drainage from acute infections.
o Generalized acute lymphadenopathy is characteristic of viral infectious
and bacteremic or exotoxic disease.
o Nodes with acute lymphadenitis are enlarged because of cellular
infiltration and edema.
o Scarring follows the more severe destructive diseases and the nodes
become firm to palpation instead of resolving.
Chronic Nonspecific Reactive Hyperplasia (Chronic Lymphadenitis)
o Chronic reactions assume one of three patterns depending on their
causation.
o Most chronic infections caused by organisms that represent B-cell
antigens induce follicular hyperplasia.
o Microbiologic agents or antigens that stimulate T-cells produce a pattern
of paracortical lymphoid hyperplasia.
o Referred to sinus histiocytosis which is encountered in regional nodes of
draining a site of cancer.
o Characteristically lymph nodes are not tender, because they are not under
pressure.
Acute infectious lymphocytosis
o This is usually present in children and has a possible viral etiology. It may
be asymptomatic or present with a cutaneous rash, vomiting, and
abdominal discomfort. There is an elevation of WBCs with a high
percentage of small lymphocytes.
Infectious Mononucleosis
o This presents with fever, sore throat, malaise, lymphadenopathy,
splenomegaly, and occasionally maculopapular rash. Initially there is a
decrease in WBCs, followed by an increase. While the etiology is
uncomfirmed, it is probably caused by a viral infection. Complications
may include hepatitis, myocarditis, and encephalitis.
Neoplastic Disorders of WBC
Leukemia
 These are bone marrow malignancies and flood the peripheral blood with the
malignant cells. This is diagnosed with CBC. It is an increase of WBC in the
blood.
 Acute forms are disorders of the blood-forming tissue characterized by
proliferation of abnormal white cells. It is characterized by weakness, malaise,
anorexia, bone and joint pain, pallor, fever, petechiae, lymph node swelling,
splenomegaly, anemia, palpitations, dyspnea, easy bruising, and
thrombocytopenia.


Lymphocytic leukemia
o Acute- Explosive onset (within 3 days) of very high lymphocyte counts,
very immature, malignant cells. The cells maturation stops at early “blast”
stage. It starts in the lymph node, spreads to the liver, spleen, bone
marrow, and other sites. Null cells 65% and T-cells 15-20%. Very ill,
high fever, profound weakness, often hemorrhaging from bone marrow
crowding out megakarocytes and anemic from RBC being crowded out.
Often die in acute onset of this malignancy. Invade tissues everywhere.
Generally more in young children.
 In the eye one sees a white spot with blood around it.
o Chronic- Slow insidious onset and often not diagnosed for months or
years. It rarely occurs under the age of 30. There is a progressive
accumulation of small lymphocytes that have lost the capacity to divide.
Lifespan of metabolically active cells may be lengthened. The total body
lymphocyte mass expands considerably. The cells, which originate in
lymph nodes, spleen, blood and marrow. Finally have weakness, fatigue,
anemia, and is often diagnosed even by accident (and too late) at a routine
blood test. Usually have extremely high lymphocyte counts which are
often much higher than the acute, but the cells are much less malignant in
characteristics. There is also pallor, superficial lymph node enlargement,
absolute lymphocytosis in adults.
Myelogenous Leukemia
o Acute- Like acute lymphocytic except the cells are malignant PMNs.
 It is seen more in adults. It starts in the bone marriw before
spreading to other sites.
o Chronic- Like chronic lymphocytic except the cells are malignant PMNs.
The only major difference is that chronic myelogenous leukemia has a
marker called the Philadelphia chromosome which is a translocation (long
arm of chromosome 22 to usually the long arm of 9). This is genetic, so
have the family checked. It can be diagnosed early.
 Characterized by proliferation of abnormal white cells which
invade the bloodstream, and may infiltrate any part of the body to
cause local symptoms. This is fatal. Life expectancy of affected
patients is 3-4 years.
 It is primarily a disease of young adults.
 Symptoms include weakness, lassitude, fever, abdominal
discomfort, enlargement of spleen, immature white blood cells in
peripheral blood and bone marrow and anemia.
Plasma Cell Dyscrasias
 there are several and all are derived from malignant plasma cells (B cells). These
cells secrete some antibody components or a single antibody. Does no good as
one immune globulin only hits one antigen. The most common is marked
secretion of light chain which are secreted in the urine and is called Bence Jones
Protein, not detected by normal urinalysis. Even when an entire immunoglobin is
produced these light chains are often oversecreted.

Ex: multiple myeloma is the most common by far of these malignancies and is a
malignant clone of neoplastic plasma cells in the bone marrow that is usually
associated with lytic lesions throughout the skeletal system. The dentists often
diagnose it due to lytic lesions near teeth making them loose. It erodes holes in
bones (skull, teeth, etc.) It has been estimated that these patients often have the
disease an average of 10-20 years or more before symptoms lead to a diagnosis
and then the prognosis is poor due to such advanced disease. Peak age of onset is
50-70 and usually presents with bone pain and even fractures from minor trauma,
fatigue, hemorrhage, infection, etc.
Bleeding Disorders
 These are characterized by spontaneous, excessive bleeding following trauma.
 Etiology
o Increased fragility of blood vessels such as in Vitamin C deficiency,
vasculitis, aging, etc.
 Women have more fragile blood vessels.
o Inadequate hemostatic response
 Thrombocytopenia or platelet dysfunction from aspirin use which
interferes with adhesiveness and aggregation.
 Derangement of clotting mechanisms which is usually hereditary,
liver disease so can’t produce factors, etc.
Hemophilia
 Tx: need to administer factor 8, which helps with clotting. Can’t use sutures,
cauterizing, etc.
Pulse Assessment
 Definition
o A pulse is produced by the force imparted to the arterial blood each time
the left ventricle contracts and expels into the aorta.
o The pulse depends on the quantity of blood expelled (stroke volume), the
force of expulsion, and the rigidity of the blood vessels.
o Common sites of pulse assessment include
 Radial (wrist)
 Brachial (upper arm)
 Carotid (neck)
 Temporal (temples)
 Femoral (groin)
 Posterior tibial (ankle)
 Note that clinically, we generally assess radial, brachial, and
carotid.
 Indications for pulse assessment in an optometric practice
o Radial and brachial pulse location is part of the blood pressure assessment
technique.



o Carotid pulse assessment is part of a cerebrovascular work-up
o Pulse assessment is indicated prior to prescribing and/or in evaluating
systemic responses to certain medications, such as beta blockers used to
treat glaucoma.
o Pulse assessment is useful in the differential diagnosis of certain systemic
conditions which affect the eyes (such as hyperthyroidism) and in
appropriate management of systemic emergencies which may occur in
your office.
Techniques
o Radial pulse
 Patient’s hand should be held palm upward
 Place your middle 3 fingers over the artery which is located on the
lateral side of the patient’s wrist below the thumb.
 Press firmly until the pulse is felt.
o Brachial pulse
 Patient’s arm should rest with hand palm up
 Palpate brachial pulse with fingers at the bend of the elbow
(antecubital fossa) medial to the bicepts tendon.
o Carotid pulse
 Patient should be looking straight ahead.
 Starting at the angle of the jaw, slide fingers down the medial
aspect of the sternocleidomastoid muscle.
 Lightly press in at the level of the cricoid cartilage (bottom of the
Adam’s apple)
 Avoid putting pressure on the carotid sinus (even with the top of
the Adam’s apple) or putting pressure on both carotids
simultaneously.
Recording
o The following characteristics of the pulse are typically evaluated.
 Rate
 If rate seems basically normal, count the beats for 15
seconds then multiply by 4 and record beats per minute
(bpm). If the rate is unusual, count for a full minute.
 Rhythm
 Note whether the beats are in a regular or irregular rhythm
 Strength
 By pressing the index finger against the vessel (radial
pulse) a determination of whether the pulse volume is
normal, full, or weak (thready) can be made.
Interpretation
o The average pulse rate in adults is 60-80 bpm and is 90-140 in children.
o There is a very slight increase in rate with inhalation and a slight decease
with exhalation.
o High pulse rate (tachycardia) may be normal after eating, exercise, or
during emotional excitement. It can also occur in response to anemia,
o
o
o
o
o
severe hemorrhage, febrile disease, thyrotoxicosis, certain types of heart
disease, and certain medications.
Low pulse rate (bradycardia) may be normal in well-conditioned athletes
or may be associated with myxedema, some infections, and certain
medications
An abnormally “full” pulse volume may occur after exercise, during
fevers, and in certain emotional states.
An abnormally “weak” or “thready” pulse volume may be associated with
syncope, severe hemorrhage, or other types of shock.
A firm, palpable radial artery particularly in an older person may indicate
arteriosclerotic changes.
A humming vibrations (feels like the throat of a purring cat) in the carotid
pulse is called a “thrill” and may indicate arterial narrowing.
Blood Pressure Assessment
 Definitions
o Between each contraction of the heart, blood pressure varies between a
maximal level (systolic) and a minimal level (diastolic).
o The difference between the 2 levels is called the “pulse pressure.”
o Blood pressure is determined by
 Left ventricular stroke volume
 Distensibility of the aorta and other large arteries
 Peripheral vascular resistance regulated by the autonomic nervous
system
 Volume of blood in the arterial system
 Viscosity of the blood
o Blood pressure fluctuates somewhat during the day and is influenced by a
number of environmental factors including
 Physical activity
 Emotional state
 Pain
 Noise
 Environmental temperature
 Use of tobacco, caffeine, and other drugs
o Elevated bp is termed hypertension. “Essential” HTN (no known etiology)
is the most common type.
 Indications for bp assessment (sphygmomanometry) in an optometric practice
o Screening for undetected HTN
 Approximately 20-25 millioon Americans have untreated HTN
 Between 50-85% of people with HTN are not aware that they have
it because it has few or no symptoms. HTN is thus termed “the
silent killer” because if untreated, it increased the patients risk of
death to heart disease, atherosclerotic vascular disease, and stroke.
 The optometrist is an ideal person to screen for HTN for several
reasons.




Many OD patients are over 40 (higher risk group for HTN).
Many patients don’t go to their PCP until they are
symptomatic, so OD may be more likely to detect HTN in a
routine exam.
 Patients tend to be less anxious during an eye exam than
during a medical or dental exam, so results of HTN
screening may be more accurate.
 ODs can compare sphygmomanometry results with fundus
signs
 Routine HTN screenings as part of a PCE are simple,
inexpensive, accurate, and provide an important service to
the patient. It also enhances optometry’s role as part of the
health delivery system.
 Bp assessment can also be used by the OD to help evaluate
effectiveness and compliance with therapy in known
hypertensives.
 BP assessment can be used to aid in the differential
diagnosis of retinopathies, ONH anomalies, and HAs.
 Bp assessment may be useful in the evaluation and
management of ocular hypertensives, glaucoma suspects,
and confirmed glaucoma patients.
 BP assessment may be helpful in determining whether or
not to use certain diagnostic and therapeutic
pharmaceuticals.
 BP assessment may be significant in the management of
certain ocular conditions such as vertical imbalances.
Detection and Confirmation
o HTN detection begins with proper bp measurements, which should be
obtained at each health encounter. Repeated blood pressure measurements
will determine whether initial elevations persist and require prompt
attention or have returned to normal and need only periodic surveillance.
BP should be measured in a standardized fashion using equipment that
meets certification criteria.
Techniques for BP assessment (Sphygmomanometry)
o Patients should be seated in a chair with their backs supported and their
arm, free of constricted clothing, supported palm up, on the arm of the
chair or other firm surface, at heart level. Patients should refrain from
smoking or ingesting caffeine during the 30 minutes preceding the BP
measurement. Measurement should begin after at least 5 minutes of rest.
o Geriatric patient population
 Because older patients are more likely than younger patients to
exhibit an orthostatic fall in bp and hypotension, measure bp in
older patients in the seated position in office AND in the standing
position, if indicated. Record both measurements.

o
o
o
o
o
o
o
o
BP must be measured in older persons with special care because
some older persons have pseudohypertension (falsely high
sphygmomanometer readings) due to excessive vascular stiffness.
 Older persons with HTN, especially women, may have “white coat
HTN” and excessive variability in SBP.
 In the absence of TOD, clinicians should consider
pseudohypertension or white coat HTN and should obtain readins
outside the office.
Select appropriate sphygmomanometer
 Measurements should be taken preferably with a mercury
sphygmomanometer; otherwise calibrated aneroid manometer or a
validated electronic device can be used. All 3 are accurate when
properly used. Mercury sphygmomanometers do not need to be
calibrated as often. Aneroid manometers are more flexible and are
more commonly used in optometric offices.
 The appropriate cuff size must be used to ensure accurate
measurement.
 The width of the bag should be approximately 50% of the
circumference of the patient’s arm.
 The length of the bladder should encircle at least 80% of
the arm.
 A cuff that is too short (tight when deflated) will give false
high readings and one that is too long (loose when deflated)
will give false low readings.
Try to take measurements when the patient is as relaxed as possible.
Toward the end of the case history after the patient has been sitting quietly
in the exam chair for a few minutes is a good time during an optometric
exam. Having the patient take a couple of deep breaths and then fixating a
distant point (rather than the sphygmomanometer) prior to measurement
will also aid relaxation.
Locate the brachial artery at the antecubital fossa.
Center the bag of the cuff over the artery. The lower edge of the bag
should be approximately one inch (2.5cm) above the crease of the elbow.
The arm must be positioned so the cuff is at heart level.
Locate the radial pulse.
Inflate the cuff to about 20-30mmHg above the level at which the pulse
disappears (the brachial pulse can be used instead of the radial pulse but is
usually harder to detect). Can just go up to 200, but sometimes hurts the
patient.
Place the stethoscope over the brachial artery. Korotkov sounds are noises
produced by blood moving through a partially occluded vessel. These
sounds are easier to hear with the bell, but the diaphragm is usually easier
to hold against the arm. Be sure that the ear pieces of the stethoscope are
curving forward to conform to your auditory canals.
Slowly deflate the cuff at about 2-3mmHg per second.


o Note the level at which you first hear the soft regular taping sounds (Phase
I) for at least 2 consecutive beats. This is the SBP.
o Continue to deflate the cuff slowly (about 3mmHg per second) until the
Korotkov sounds become muffled and then disappear (PhaseV). The
disappearance point is the DBP.
o After the DBP has been established, rapidly deflate the cuff to zero.
o Both SBP and DBP should be recorded. Once again, the first appearance
of sound is used to define the SBP. The disappearance of sound (Phase V)
is used to define DBP.
o Noises
 Phase I- Systolic
 First appearance of soft regular tapping sounds.
 Phase II
 Murmur of swishing sound is heard.
 Phase III
 Sounds are crisper and increasing in intensity.
 Phase IV
 Distinct, abrupt muffling of sounds so that a soft blowing
sound is heard
 Phase V- Diastolic
 Sounds disappear completely
o Clinicians should explain to patients the meaning of their bp readings and
advise them of the need for periodic remeasurement.
o One properly performed accurate measurement of normal bp is sufficient
for screening purposes. If the patient demonstrates high-normal or stages
1,2,3 HTN, then 2 or more readings separated by 2 minutes (cuff
loosened) should be averaged when considering recommendations for
referral. If the first two readings differ by more than 5mmHg, additional
readings should be obtained and averaged.
Recording
o BP should be recorded as systolic over diastolic pressure, in mmHg. Also
include which arm was used, patient’s posture (seated, standing, supine),
time of day, and any other pertinent information. The readings should be
rounded off to the nearest even number
o Example
 132/86mmHg, right arm sitting, 11:15am.
Interpretations
o Diagnostic bp levels and referral guidelines are somewhat arbitrary and
vary in literature.
o Goal blood pressure
 Children- <125/<85mmHg
 Adults- Ideally <140/<90mmHg
 Clinically, if the DBP is <90, then 100 plus the patient’s
age up to 60 can be used as a rough estimate for the upper
limit of normal SBP.
 Diabetics; renal failure; heart failure- <130/<85mmHg
 Renal failure with proteinuria >1g/24hr- <125/<75mmHg.
 JNC VI Guidelines
o Sixth report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure provides guidelines
busy clinicians can use to identify high-risk individuals and make
recommendations for follow-up and treatment.
o The objective of identifying and treating HBP is to reduce the risk of
morbidity and mortality associated with major risk factors and target organ
(TOD)/ Clinical Cardiovascular Disease (CCD)
Category
SBP
DBP
F/U
Normal
<130
<85
Recheck 2 years.
Refer patients with unusually low pulse or bp to
their PCP.
High-Normal 130-139
85-89
Recheck in 1 year.
Refer to PCP for advice about lifestyle
modification (and drug therapy?)
Stage 1 HTN 140-159
90-99
Refer to PCP to confirm in 2 months
Stage 2 HTN 160-179
100-109 Refer to PCP within 1 month
Stage 3 HTN >180
>110
Refer to PCP within 1 week or to PCP/ER
immediately depending on the clinical situation.
o When referring a patient to PCP or ER, two or more readings separated by
2 minutes (loosen cuff between measurements) should be averaged. If the
first two readings differ by more than 5 mmHg, additional readings should
be obtained and averaged.
o If systolic and diastolic categories are different, the higher category is
selected and a recommendation is made for a shorter follow-up time.
o Isolated systolic HTN is defined as SBP of 140mmHg or greater and DBP
below 90mmHg
 Example: 170/82…refer to PCP within 1month.
o The DASH Diet
 It should be noted that PCP encouragement to make healthy
lifestyle choices includes choices in diet. The Dietary Approaches
to Stop HTN (DASH) trial confirmed that bp is lowered
substantially when a diet rich in fruits and vegetables and low in
saturated fat is substituted for the Standard American Diet (SAD).
o Age 17 or younger
 Identifiable causes of HTN exist in children and adolescents.
Definitions of HTN take into account age and height by sex.
o Finally, a definitive diagnosis is made by a PCP who can legally treat
HTN. The PCP definitely classifies the patient based on average of 2 or
more readings taken at each of 2 or more visits after the initial screening
measurements. HTN is defined as SBP of 140mmHg or great, DBP of
90mmHg or greater, or taking HTN medication.
 Sources of Error in taking bp measurements
o Patient is wearing constricting clothing on arm
o Improper cuff selection (obese or skinny patients)

o Cuff inflation is too slow. This causes venous congestion and gives false
readings. Repeated measurements can also cause venous congestion. Be
sure to remove the cuff and wait a few minutes between readings.
o Korotkov sounds cannot be heard. Be sure that stethoscope head is
properly adjusted. Having patient raise arm during inflation or clenching
fist at the point of maximal inflation can enhance the sounds.
o Taking pressures without assessing pulse disappearance. Some patients
have an “auscultatory gap” which is a silent interval between the SBP and
DBP. If pulse disappearance is not assessed, you might take measurements
in the gap leading to an under-estimation of SBP or overestimation of
DBP.
o Deflating the cuff too rapidly. This causes both systolic and diastolic
measurements to be too low.
o Poor viewing angle to read the scale. Parallax can cause errors. This is
primarily a problem with the mercury-gravity type. Be sure to be eyelevel
with the meniscus of the mercury.
HTN Risk Factors
o If you do not intend to evaluate bp on every patient that comes into your
office, you should know risk factors for HTN so that you can target higher
risk patients for bp screening.
o Age
 Older patients are at higher risk than younger patients, although
younger patients may gain more benefit from early detection and
control than older patients.
o Sex
 Men have 2x the risk of morbidity and mortality from HTN as
women. The risk for women in the work force is increasing,
however.
o Race
 HTN is twice as prevalent in blacks as in whites and blacks have
between 2-7x the risk of having HTN-related heart disease as
whites.
o Family History
 People who have one or more family members with essential HTN
have an increased risk of having HTN.
o Associated Systemic Conditions
 Patients who are obese or have DM, hyperlipidemia, or
hypercholesteremia are at risk for having HTN.
o Associated Life Style Factors
 Other possible risk factors for developing HTN include high
dietary salt intake, cigarette smoking, type A personality, high
stress lifestyle, and lack of exercise.
Carotid Bruit Assessment
 Definitions

o Cerebrovascular arterial system- the blood supply to the head has two
basic components: the vertebro-basilar complex (back) and the carotid
complex (front). The complexes anastomose at the Circle of Willis.
o Cerebrovascular Disease- characterized by a decrease in blood flow
through the cerebrovascular system and is usually secondary to
atherosclerotic disease, HTN, or both. Some of the consequences of
cerebrovascular disease include transient ischemic attacks (TIAs),
reversible ischemic neurologic deficits (RINDs), and cerebral vascular
accidents (CVAs, cerebral ischemia, “stroke”). All of these may have
ocular or visual signs and symptoms.
o Bruit- a rushing sound heard over large and medium-sized arteries as a
result of vibration in the vessel wall caused by turbulent blood flow.
 Turbulent flow is usually caused by atherosclerotic plaque or
thrombus formation in the vessel wall. Frequent sites for plaque
formation in the neck include the origins of the internal carotids
and the origins of the vertebrals.
 Bruits are not usually heard until the vessel is 50% occluded. The
pitch tends to increase as the lumen narrows to a critical size. With
further narrowing the blood flow becomes so reduced
(approximately 90%) that the bruit can no longer be heard.
Indications for carotid bruit assessment in an optometric practice
o Bruit assessment is not typically part of the PCE. However, it may be
indicated if the patient has a history of cerebrovascular disease if:
 There is a difference between the two carotid pulses
 A “thrill” is palpated.
 The IOP is significantly different between the 2 eyes.
 Hollenhorst plaques or signs of occlusive vascular disease are
noted in the fundus
 The patient has transient vision losses or any of the visual changes
listed below
 VF loss including
o Total losses
o Sector losses
o Central losses
o Periperhal losses
o Congruous and incongruous, homonymous defects
o Altitudinal losses
 Diplopia due to the non-comitancy of the binocular
alignment
 Nystagmus
 Lagophthalmos
 Visual hallucinations
o Formed variety (trees)
o Unformed variety (stars, bolts)
 Anisocoria
 Frequent Has








Loss of fixation
CI
Accommodative problems
Reading difficulties (usually the earliest sign)
Visual perceptual losses including
o Disturbances in body images
o Disturbances of spatial relationships
o Agnosia (difficulty in object recognition)
o Apraxis (difficulty in manipulation of objects)
o Right-left discrimination problems
 Memory losses
o Other cerebrovascular tests which an optometrist may perform are bp
measurements comparing the two arms, DO, ophthalmodynamometry,
perimetry, and CN testing.
Technique
o The patient should be seated comfortably and should be as relaxed as
possible.
o Have the patient look straight ahead and extend the neck slightly.
o Gently locate and palpate the carotid pulse.
o Place the stethoscope over the carotid (Use the diaphragm (large) or bell
(small) depending upon how easily the sounds are heard).
o Have the patient take a deep breath and then hold it so that breath sounds
wont interfere with your detection of bruits. Do not make the patient hold
their breath too long- especially important in elderly patients.
o Listen for “swishing” or “blowing” sounds indicating a bruit in the high,
middle, and lower portions of the neck. Repeat with the other carotid.
Recording
o Record whether bruits sound is present or absent. It can also be graded 04+
Interpretation
o Presence of a bruits sound is suggestive (but not diagnostic) of
cerebrovascular disease. Heart murmurs may radiate to the carotid
simulating a bruit.
o Patients in whom cerebrovascular disease is suspected based on bruits
and/or other findings should be referred to an internist of neurovascular
specialist for further testing as soon as possible.
Antihypertensive Agents

Physiology and Pathology
o Definition: excessively high blood pressure (especially excessive diastolic
pressure)
o Blood pressure is dependent upon cardiac output and total peripheral
resistance (vessel dilation and constriction). Reduce either one, and blood
pressure generally falls.


o Renin from the kidney converts angiotensinogen from the liver to
angiotensin I. Angiotensin Converting Enzyme (ACE) converts
angiotensin I to angiotensin II. Angiotensin II elevates and maintains the
blood pressure via constricting the blood vessels. There are receptors in all
vessels. There is also an AT III and IV, but they are inactive. Renin is
produced in response to ischemia and/or constriction of afferent renal
arterioles.
o A decrease in blood pressure sometimes results in reflex mechanisms
which tend to restore pressure to an elevated level.
 Increased sympathetic activity
 Increased secretion of vasopressin (aka ADH). This increases
water retention, therefore increasing pressure.
 Increased retention of fluids.
Diuretics
o Cause loss of fluid, which reduces blood pressure. It depletes the body of
sodium, increasing the urinary flow and decreasing the blood volume.
o Loop diuretics do not initially raise blood pressure.
o Usually use the thiazide family that is used in conjunction with a beta
blocker or alpha blocker. Thiazides exercise their hypotensive effect
through salt depletion.
o Chlorothiazide
 Hydrochlorothizaide is probably the most commonly prescribed
thiazide diuretic for control of hypertension. Others include
furosemide (Lasix), which is very strong, and spirolactone.
 Adverse effects: hypokalemia, hyperuricemia, aggravation of
diabetes.
Beta Blockers
o These are widely used in the treatment of HTN. It produces fewer side
effects than other antihypertensives. They are used in combination with
diuretics.
o Agents
 Propranolol
 Blocks beta-1 and beta-2 receptors.
 Blocks release of renin from the kidney.
 Reduces cardiac output.
 Alone controlled blood pressure in 52% of patients.
Combined with a diuretic, will control 81%. Add
hydrazaline to increase results to 92%.
 Best used as combination drug because it counteracts some
of the other antihypertensive agents adverse effects.
 Asthmatic attack in susceptible patients
 Bradycardia
 Masks hypoglycemia in insulin-dependent diabetics.
 Metoprolol (Lopressor)
 Beta-1 blocker preferentially
 Effective antihypertensive


Atenolol (Tenormin)
 Beta-1 blocker
 Labetalol (Normodyne, Trandate)
 Nadolol (Corgard)
 Beta blockade
 Effective antihypertensive
 Long lasting (1dose/day)
o Probable Mechanisms
 Decrease contractile force of the heart, reducing the cardiac output.
However, beta blockers reduce cardiac output in all subjects, but
only a portion will respond with a chronic hypotensive effect.
 Decrease renin output from juxtaglomerular apparatus (Decrease
AT). Reductions in blood pressure can occur even when plasma
levels of renin do not fall.
 CNS effects- Not all beta blockers reach the brain, but may have to
only affect a small area of the brain to achieve the desired effect.
o Adverse Effects
 Bradycardia
 Bronchoconstriction
Centrally Acting Sympatholytics
o This is the largest subgroup of antihypertensives. They act at the CNS
level, at the ganglionic level, or at the receptor level (alpha or beta
blockers). They reduce blood pressure by reducing contractability, cardiac
output, venous tone, and peripheral vascular resistance.
o Agents
 Methyldopa (Aldomet)
 Metabolized to alpha-methylnorepinephrine
 The mode of action is not well understood.
 Appears to lower pressure due to stimulation of alpha-2
receptors by being metabolized to alphamethylnorepinephrine.
 Adverse reactions: marked drowsiness, depression, and
nightmares.
 Absorbed well from the GI tract.
 Clonidine (Catapres)
 Stimulates alpha-2 in CNS to lower blood pressure
 Used in combination with a diuretic.
 Some effect on cardiovascular centers in medulla (i.e., may
act on baroreceptor in the cisterna magna, which is part of
the central baroreceptor pathway.
 Guanfacine (Tenex)
 Guanabenz (Wytensin)
o Mechanism
 Decrease sympathetic output from the CNS by stimulating central
alpha-2 receptors.
o Adverse Effects



 Drowsiness
 Dizziness
 Dry mouth
Peripherally-acting Sympatholytics (Adrenergic Neuronal Blocking Drugs)
o Reserpine
 This is the prototype of several alkaloids in rauwolfa serpentine.
 Mechanism: blocks absorption of dopamine and NE into storage
granules
 It causes a depletion of catecholamines in the central and
peripheral nerves. Depletion is from amino release and
prevented re-acumulation.
 Also prevents storage of norepineprhine and dopamine in
granules.
 Parasympathetic effects are a result of decreased sympathetic
activity (e.g., bradycardia, peptic ulcer, increased gastric motility,
miosis).
 CNS effects are its greatest disadvantage (e.g., profound
depression, lethargy, enhances effect of other CNS depressants).
 Several derivatives include Raudixin, Syrosingopine (Singoserp).
 Adverse effects
 Emotional depression
 Weight gain
o Guanethidine (Ismelin) and Guanadrel (Hylorel)
 Mechanisms
 Blocks release of catecholamine by first depleting terminus
of transmitter then blocking further release (i.e., transmitter
feedback system completely shuts down).
 This does not cross the blood-brain barrier, therefore it does
not cause sedation or depression. It also does not inhibit
parasympathetic ganglia.
 Long duration of action (5-7 days)
 Displaces NE in vesicles
 Acutely: stimulation of NE release
 Chronically: depletion of NE from nerve terminal
o Prazosin (Minipress)
 Blocks peripheral alpha-1 receptors
Calcium Channel Blockers
o Agents
 Verapamil (Calan)
 Nifedipine (Adalat)
 Nicardipine
 Diltiazem
o Prevents vasoconstriction by blocking calcium entry into vascular smooth
muscle cells. Normally, calcium binds with calmodulin, activating myosin,
leading to contraction
Direct-acting Vasodilators


o These act on the vascular smooth muscle and are used primarily in
hypertensive crisis
o Types
 Hydrazaline (Apresoline)
 Often provides cardiac stimulation through reflex
mechanism.
 Minoxidil (Loniten, Rogaine)
 This is a powerful vasodilator used only for those that
respond to no other treatment.
 Mechanisms
o Open potassium channels, causing
hyperpolarization, and the muscle cannot contract.
o This causes considerable sodium retention.
 Adverse effects
o Hair growth
o Edema
 Nitroprusside (Nitrate)
 Activates guanalyte cyclase (converts GTP  cGMP),
inhibiting calcium.
 Most nitrates decrease blood pressure.
 Used mainly for hypertensive crisis
 Diazoxide (Hyperstat)
 Injectable used only for emergency lowering of blood
pressure.
 Short duration (12 hours)
 Inhibits insulin release.
o Adverse Effects
 HA, nausea, sweating, reflex tachycardia, arrythmias and
hypotension.
 Palpitations
 GI disturbance
Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)
o Agents
 Captopril (Capoten)
 Enalapril (Vasotec)
o Mechanism
 These reduce peripheral resistance and blood volume by interfering
with the action of angiotensin II.
 Blocks the conversion of AT I  ATII.
Angiotensin II Receptor Blockers
o Agents
 Losartan (Cozaar)
 Saralasin has some agonistic activity
 This inhibits converting enzyme that converts angiotensin
II to III.
o Mechanism


Blockade of AT1 receptors. The AT can still attach, but nothing
will happen.
Ganglionic Blockers
o Used on in emergencies
o Trimethaphan (Arfonad)
o Adverse effects
 Mydriasis
 Cycloplegia
 Constipation
 Urinary retention
Cardiac (Anti-arrhythmic) Drugs
 General Principles
o These act by correcting abnormalities in the rate, regularity, or site of
these impulses. They may also modify, bloc or impair conductions.
o Membrane Potentials- Normal Cardiac Electrophysiology
 All relatively electronegative inside compared to the outside.
 Gradient from due to Na-K-ATPase (Na-K pump) that moves
sodium ions out of cell and potassium ions into cell.
 Rapid influx of sodium through the membrane channel has four
phases.
 Phase 0: rapid depolarization of the ventricular myocardium
 Due to sodium coming into the cell
 This corresponds to familiar QRS segment of EKG.
 Phase 1: initial repolarization, i.e., becomes more negative.
 Sodium influx decreases.
 Due to calcium (fast) channels opening
 Phase 2: action potential plateau
 Due to slow calcium channel opening.
 There is a second inward flux from movement of calcium
ions. Influx means depolarization.
 Phase 3: final repolarization
 Inward sodium and calcium flux decline.
 Rapid repolarization from influx of potassium ions.
 Phase 4: return to stable diastolic potential
 These are for the prevention and treatment of disorders of cardiac rhythm, since
these have a high morbidity and mortality.
 Class I Agents (Blockers of Fast Na Channels)
o Class IA
 These act by depressing the fast inward sodium current in cardiac
muscle, resulting in prolongation of the effective refractory period
(ERP) of depolarized cells and depression of phase 4
depolarization. Since they have a greater effect on rapid
depolarizing cells, this reduces arrythmias by selectively reducing
automaticity in ectopic pacemakers.
 All have anesthetic effects

Quinidine (Quinidex, Quinaglute)
 Given via IV
 The d-isomer of quinine (which is twice as potent)
 A very old drug
 Reduces Vmax of AP depolarization
 Increases excitability threshold, depresses conduction
velocity, depresses spontaneous diastolic depolarization
(i.e., decreases automaticity).
 Depresses all smooth muscle activity which can lead to
peripheral vasodilation and profound hypotension.
 Slows pacemaker activity
 Some anticholinergic activity
 Acts in atria, ventricles, and His-Purkinje system
 Blocks activated more than inactivated Na+ channels.
 May cause tachycardia initially, then slowing because the
vagal receptors are blocked initially.
 Uses
o Atrial flutter (250-350 bpm)
o Atrial fibrillation (>400 bpm)
o Re-entry arrhythmias (reenters and provides extra
systoles)
o Premature ventricular contractions (PVCs)
o Ventricular tachycardia (140-240 bpm)
 Adverse Effects
o Cinchonism: headache, dizziness, tinnitus
o Syncope
 Procainamide (Pronestyl-po) and Disopyramide (Norpace-IV)
 Similar to quinidine
 Derivative of common local anesthetic.
 Metabolized in the liver
 Elevates threshold to electrical stimulation.
 Depress automaticity in SA node and in ectopic foci.
 Disopyramide: initial tachycardia like quinidine
 Uses
o Atrial flutter
o Atrial fibrillation
o Ventricular arrhythmias
 Disopyramide (Norpace)
 Action like procainamide
o Class IB
 Lidocaine (Xylocaine)
 Similar to quinidine
 Differs from class I antiarrhythmic drugs in that it does not
slow conduction and has little effct on atrial function.
 Acts on both activated and inactivated Na+ channels


Acts in the ventricular myocardium and the His-Purkinje
system
 Most widely used drug for treatment of ectopic ventricular
activity associated with MI.
 Can be deadly with an overdose.
 Also used as a common local anesthetic.
 Depresses automaticity of ectopic foci and Purkinje fibers.
 Use: ventricular arrythmias
 Adverse effects: overdose can cause asystole
 Tocainide (Tonocard) and Mexiletine (Mexitil)
 Similar but orally active.
 Phenytoin (Dilantin)
 Similar to lidocaine, but may also block calcium channels.
 Depresses automaticity of SA node and ectopic foci.
 Uses
o Ventricular arrythmias
o Treat digitalis toxicity
o Epilepsy (tonic clonic seizures)
 Adverse Effects
o Drowsiness
o Nystagmus
o Slurred speech
o Class IC
 Flecainide (Tambocor)
 Propafenone (Rhythmol): also blocks calcium channels
 Conduction velocity is slowed
 Use: refractory ventricular arrhythmias (when nothing else works)
o Adverse effects
 Hypotyension, diarrhea, nausea, and (at higher doses) drowsiness
and respiratory arrest.
Class II Agents
o Beta-Adrenergic Blockers (Autonomic)
 Propanolol
 Metoprolol, Nadolol, Timolol, Atenolol
o Mechanisms
 Blockade of beta-1 receptors
 Reduce sympathetic excitation to the heart. Inhibits phase 4
depolarization.
 Membrane effects (blockade of sodium channels)
 Increase ERP and ventricular response to them by decreasing
conduction through the AV node.
 Depresses automatcity, prolongs AV conduction, reduces heart
rate, decreases contractibility, very effective in tachyarrhythmias
secondary to sympathetic activity, prevents reflex tachycardia from
vasodilating antihypertensive drugs
o Uses


 Supraventricular arrhythmias (atrial/nodes)
 Prevent recurrence of MI
o Adverse effects
 Bronchospasm (from beta-2 blockade which contracts bronchial
smooth muscle), hypotension, can worsen CHF, and can cause
cardiac arrest.
Class III Agents- control phase 3
o Prolong the action potential and refractory period.
o Bretylium (Bretylol)
 Mechanism: interference with catecholamine release (NE)
 This increases the ERP of the atria, ventricle, and AV node.
 Adrenergic neuronal blocker, prolongs AP, prolongs effective
refractory period
 Use: ventricular fibrillation/ tachyarrhythmias that are
unresponsive to other drugs.
 It is used to control life threatening ventricular arrythmias
in intensive care units.
 Adverse effects
 Hypotension (postural)
 GI upset (NVD)
o Amiodarone (Cordarone)
 Prolongs AP by blocking potassium channels
 Blocks inactivated sodium channels
 May also block calcium channels, alpha receptors, and beta
receptors.
 Uses: all arrhythmias
 Adverse effects
 Bradycardia
 Anorexia
 NV
o Sotalol (Betapace)
 Similar to class II agents
 Prolongs AP
 Prolongs refractory period
 Uses: all arrhythmias
Class IV Agents- Calcium Channel Blockers
o These are useful in supraventricular arrythmias where they act by
depressing AV node conduction, reducing ventricular response.
o Verapamil (Calan)
 Papaverine derivative
 This is the sole member used for use in arrythmias.
 Used primarily for atrial arrhythmioas and angina pectoris
 Inhibits calcium transmission which then slows the channel for
propagation of AP in pacer cells (i.e., acts at SA and AV nodes)


Very useful in treatment of atrial fibrillation by slowing the AV
conduction and decreasing the ventricular response by slowing SA
conduction.
 Side effects
 Peripheral vasodilation, constipation, nervousness, and
edema.
o Diltiazem (Cardizem)
o Use: supraventricular arrhythmias, which involve reentry
o Negative chrono and ionotropic forces.
Drugs that Increase the Cardiac Contractile Force (+ Ionotropic Force)
o Digitalis glycosides (Cardenolides)
 From the foxglove plant. Was used as a diuretic because the edema
was secondary to CHF
 Digitalis helps relieve the condition by exerting a positive
ionotropic effect on the cardiac muscle, meaning that they increase
the force of contraction.
 Mechanisms: Inhibition of sodium potassium ATPase in
myocardial cells.
 In the absence of digitalis, ATP → ADP + P + energy
 In the presence of digitalis,
o ATPase is inhibited, stopping the sodium potassium
pump
o Intracellular sodium increases
o Sodium calcium exchange increases
o Sarcoplasmic calcium increases
o Contractile force increases
 Direct action at the SA node causes the AV conduction to
be slowed, diuresis, PR interval is prolonged.
 This is used to increase AV ERP, preventing ventricular
tachycardia in atrial arrythmias.
 Types
 Digoxin (Lanoxin)
o Other preparations mainly differ in speed of onset,
duration of action, GI absorption, and suitability for
IV injection.
o All digitalis glycosides exert the same qualitative
effect effect on the heart.
o Has intermediate action with biological half-life of
36 hours.
o Excreted in the glomerular filtration.
 Digitoxin
o Highly bound to plasma protein
o 5-7 day biological half-life
 Ouabain
o Obtained for S. gratus
o Highly polar




o IV use only
Digitalizing (loading) dose necessary for digitoxin; usually not for
digoxin
Adverse effects (TI = 1.5-3, very toxic). These have a low margin
of safety, and must be carefully monitored.
 NV
 Anorexia
 HA
 Green-yellow vision; haloes, because it affects the sodium
in the cones
 Scotomas
 Confusion, dizziness, fatigue, abnormal dreams
 PVC
 Ventricular tachycardia
 Ventricular fibrillation
 Other arrhythmias
Treatment of overdose
 Potassium
 Digoxin immune Fab (Digibind)- specific for digoxin
 Lidocaine
Uses
 CHF
o The heart becomes weak and does not pump blood
out as forcefully as it used to and you’ve got blood
trying to get into the heart from the venous system.
Since the ventricles are not emptying completely
each time, there is a bit of unpumped blood left over
in the heart and then you cannot get enough blood
out of the venous system to fill the heart. This
causes an increase of fluid in the venous system.
Pressure in the venous system is higher, and you get
edema. This puts added pressure on the entire
vascular system. At the capillaries, the blood is
trying to get through and the pressure is higher and
the heart has to beat more forcefully. But it cannot
because the heart is already weak. This weakens the
heart further, causing more fluid to collect out of the
tissues, increasing the pressure. All the excess fluid
causes a congestion of the body, causing CHF. This
can only be overcome by increasing the contractile
force.
 Arrhythmias
 Atrial fibrillation
 Atrial flutter
 Paroxysmal atrial tachycardia
 Cor pulmonale
o Catecholamines
 Dobutamine (Dobutrex)
 This is a synthetic derivative of isoproterenol.
 Stimulates beta-1 and beta-2 receptors
 (+) enantiomer stimulates alpha receptors and (-)
enantiomer blocks alpha receptors. A mixture containing
50% of both will have no alpha interference.
 Increases calcium uptake into sarcoplasmic reticulum.
 Increases myocardial contractility, decreased tachycardia,
and peripheral arterial effects.
 Dopamine (Inotropin)
 May exert a positive chronotropic effect
o Phosphodiesterase Inhibitors (Last resort)
 Agents
 Amrinone (Inocor)
o Bipyridine derivative
o Shown to exert a positive inotropic effect.
 Milrinone (Corotrope)
 Mechanism: Inhibition of cAMP phosphodiesterase
 Concentration of cAMP increases
 Promotes cAMP-dependent protein kinase phosphorylation
of calcium channels in myocardial cells
 Intracellular calcium increases
 Use: advanced heart failure (minimally effective)
 Adverse effects
 Syncope
 Cardiac arrhythmias
Potasium Channel Blockers
 Act by prolonging cardiac action potentials
 The potassium ion
o Hyperkalemia preferentially inhibits automaticity of ectopic pacemakers.
The SA node is less affected. Hypokalemia may induce arrythmias.
Drugs to treat CHF
 Digitalis Glycosides
 Dobutamine
 Vasodilators
Drugs to treat Angina
 Been known for many years that amyl nitrates (1867) and nitroglycerin (1879)
relieve the pain of angina pectoris. Since nitrates and nitrites dilate blood vessels
(including coronary arteries), the role of coronary vasodilation is generally
assumed.



Antianginal drugs work primarily by reducing demand for oxygen in
myocardium, and partly by increasing supply of oxygen.
Most evidence supports that nitrates and nitrites work by reducing demand by
acting on peripheral circulation.
Types
o Nitroglycerin
 This lowers the cardiac demand by vasodilation, which lowers
blood pressure and decreases the preload and afterload. Note the
nitroglycerin acts by decreasing the oxygen demand, not by
increasing the oxygen supply.
o Beta adrenergic blocking agents
 These reduce angina by decreasing work load of heart. They
reduce the myocardial oxygen demand by reducing the heart rate.
 They also block the catecholamine-induced increments in heart
rate and blood pressure.
 They reduce the frequency and severity of exerice-induced angina
in atherosclerotic patients, but are not effective in (and may
aggravate) vasospastic angina. Can cause bronchospasm,
bradycardia, and hypotension.
o Calcium channel blockers
 These dilate the coronary arteries
 These reduce oxygen demand in both types of angina by
vasodilation and by decreasing contractibility. Calcium blockade
also inhibits coronary artery spasm, and restores oxygen supply in
patients with vasospastic angina. May cause orthostatic
hypotension, AB block, CHF, and asystole.
Vasodilators
 Treat HTN. Also prevents attacks of angina pectoris (heart pain with decreased
oxygen)
 Calcium Channel Blockers
o Mechanism: cause closure of L type, voltage-dependent calcium channels
o Verapamil (Calan)
 Dilates the arteries and veins
 Negative ionotropic and chronotropic effect of the heart
 Use: essential HTN, arrhytmias
 Adverse effects: cardiodepression, edema, constipation due to
decreased peristalsis
o Nifedipine (Adalat, Procardia)
 Selective for arterial resistance vessels (small arteries)
 May cause reflex increase in heart rate
 Uses
 HTN
 Raynaud’s phenomenon

o Vascular spasms with severe vasoconstriction,
causing increased sensitivity and decreased
coloration
 Adverse Effects
 HA, edema
o Diltiazem (Cardizem)
 Negative ionotropic and chronotropic effect on the heart
 Uses
 HTN, Raynauds
 Adverse effects: cardiodepression, edema
o Others
 Nicardipine (Cardene)
 Isradipine (DinaCirc)
 Felodipine (Plendil)
 Amlodipine (Norvasc)
Organic Nitrates
o Mechanism
 Possibly converted to NO (which is EDRF)- endothelium derived
relaxing factor
 NO activates a soluble guanylate cyclase, which increases cGMP,
which activates a protein kinase, which causes relaxation by an
unknown process
o Adverse Effects
 Tachycardia
 HA, Monday Fever (seen with increased nitroglycerine inhalation.
Vasodilation. Tolerance developed in a few hours, but lost over the
weekend. Monday, all have HAs)
 Methemoglobinemia
 Fe2+ (Hb) is converted to Fe3+ (Met Hb), which does not
carry oxygen as well.
o Nitroglycerin
 Routes of administration
 Sublingual (Nitrobid): to abort an attack of angina in 30-60
sec. This is the most rapid.
 Transdermal (Nitro-Dur 5, 10, 15, 16, Nitrol): patches to
prevent attacks of angina. Acts in one hour. Change every
24 hours. Lasts the longest.
o Transderm Nitro-5
 5mg nitroglycerine/24 hours
o Transderm Nitro-10
 10mg nitroglycerine/24 hours
 Oral: to prevent attacks of angina
 Transmucosal (Buccal): to prevent or abort an attack of
angina
 IV: in emergency/hospital settings
 Other uses (Nitrol): Raynauds



Mechanism
 Dilates coronary arteries, decrasing the venous tone and
return.
 Peripheral arterial dilation
 Skin vessels of face and neck very susceptible to dilation.
 Usually taken sublingually in actue attacks.
 Multiple time released capsule, ointments, etc, prolong the
action.
 Metabolized to nitrites in the liver.
 Adverse effects
 Decrease blood pressure with syncope
 headaches
o Isosorbide dinitrate (Isordil)
 Routes of administration: sublingual, oral
 Chronic use can lead to methemoglobinemia
o Nitroprusside (Nitropress/ Nitropride)
 Uses
 Hypertensive emergencies
 Treat CHF
o Amyl Nitrate
 Administered by inhalation (volatile liquid)
 To abort an attack of angina
 “Poppers”- smell bad. Decrease blood pressure, prolongs sexual
intercourse, no real high.
Minoxidil (Loniten, Rogaine)
o Mechanism: activation (opening) of potassium channels, which increases
intracellular potassium, which hyperpolarizes the muscle cell membrane,
which relaxes it.
o Use: treat HTN
o Adverse effect: edema, hypertrichosis
Alpha Adrenergic Blockers
o Types
 Prazosin (Minipress)
 This blocks the post-synaptic alpha-2 receptors in blood
vessels, preventing peripheral vasoconstriction. There is no
effect on presynaptic alpha-1 receptors. Blockade of alpha1 receptors increases the release of catecholamines.
 This dilates both the arterial and venous systems.
 Uses
o Treat CHF
o Treat peripheral vascular disease
 First dose phenomenon
 Terazosin (Hytrin)- alpha-1 blocker
 Phentolamine and Phenoxybenzamine







This blocks presynaptic (alpha-2) and post-synaptic (alpha1) receptors. This is not helpful in hypertensive
management because of presynaptic blockade.
o Adverse Effects- these can produce reflex tachycardia
 Weakness, occasional syncope, postural hypertension, may
aggrevate angina.
Beta Adrenergic Agonists (e.g. Isoproterenol)
o Mechanism: stimulation activates adenylate cyclase, which converts ATP
to cAMP, which activates a protein kinase, which causes relaxation by an
unknown process
o Use: treat peripheral vascular disease
Hydrazaline (Apresoline)- dilates bvs
o This relaxes arterial smooth muscles.
o Uses
 CHF
 Peripheral vascular disease
o Adverse effects
 HA, precipitate attacks of angina
Diazoxide
o Adverse effects
 Reflex tachycardia, edema
ACE Inhibitors
AT1 Receptor Blockers
HI Blockers
Diuretics- aka Water Pills
 These increase water excretion. Regulation of extracellular fluid volume is a very
important medical maneuver for controlling blood pressure. It is the first line of
treatment.
 Osmotic diuretics
o Mechanism: Inhibition of reabsorption of water
 These are molecules that are administered that are not reabsorbed.
As they pass through the tubule, they will increase the osmolarity
of the filtrate in the collecting duct, creating less of a difference
between the filtrate and the interstitial tissue. This causes less of a
tendency for water to move out of the filtrate, increasing the
volume of urine.
o Agents
 Mannitol (Osmitrol)- IV
 Most common
 Mannitol is not metabolized, decreasing extracellular fluid
volume.
o Osmotic pressure of the blood is increased. It then is
freely filtered, but not reabsorbed, increasing the
osmolarity of the filtrate.




This is not prescribed for chronic treatment, because it has
to be infused directly into a vein. It is used when a patient
is in emergency and they need to lower the blood pressure
fairly quickly.
 It is safe with no crazy side effects.
Glycerol- Oral
 Very sweet (a carbohydrate, so don’t give to those with
DM)
Urea- IV
Isosorbide (Isordil)- Oral


o Uses
 Edema
 Glycerol and isosorbide- Reduce IOP
o Adverse effects
 Initial hypertension
 Mannitol- Hyponatremia or hypernatremia (unpredictable)
Carbonic Anhydrase Inhibitors
o Mechanism- Inhibition of carbonic acid formation
 Carbonic anhydrase is important as a role in the reabsorption of
bicarbonate, so inhibiting carbonic anhydrase would reduce the
reabsorption of bicarbonate. Bicarbonate is osmotically active, so it
increases the osmolarity of the filtrate.
o Agents
 Acetazolamide (Diamox)
 Methazolamide (Neptazane)
o Uses
 Prevent/treat altitude sickness
 Treat POAG
 Alkalinize the urine (increases HCO3- in urine, making the diuretic
work longer)
o Adverse effects
 Metabolic acidosis (increased HCO3- in urine)
 CNS depression
 Hypokalemia
Thiazide diuretics
o Mechanism- Inhibition of sodium reabsorption in the thick ascending
portion of the Loop of Henle and in the early distal tubule
o Agents
 Chlorothiazide (Diuril)
 Hydrochlorothiazide (Hydrodiuril, Esidrix)
 Chlorthalidone (Hygroton)
o Uses
 Treat edema
 Treat HTN and CHF
 Treat DI
 Increases water put out through the kidneys



Prevents urine dilution and decreased urine output by 50%
(paradoxical)
o Adverse effects
 Increased plasma uric acid (gout)
 Potassium depletion (hypokalemia)
 Metabolic alkalosis- neutralize with CA Inhibitor
Loop Diuretics
o “High ceiling effect.” Most effective.
o Mechanism- Inhibition of sodium (and chloride?) reabsorption in the thick
ascending portion of the loop of henle
 The problem here is keeping the sodium in the filtrate tends to
result in potassium excretion because sodium kept in causes
aldosterone secretion, increasing sodium reabsorption in the distal
tubule, leading to excess secretion of potassium. So, potassium
supplements must be taken.
 Loop diuretics decrease medullary hypertonicity which increases
the volume of the urine.
o Agents
 Furosemide (Lasix)- lasts 6 hours
 Ethacrynic acid (Edecrin)
 Bumetanide (Bumex)
o Uses
 Treat edema, especially in patients with low GFR (glomerular
filtration rate)
 Treat HTN
 Treat pulmonary edema
o Adverse effects
 Increased plasma uric acid
 Dehydration
 Potassium depletion
 Metabolic alkalosis
Sodium Channel Blockers
o Aka Potassium Sparing Diuretics, because they do not have the effect of
increasing potassium secretion.
o Mechanism: blockade of aldosterone receptors and sodium channels in
distal tubule and collecting ducts.
o The problem with these is that they are not that powerful, so they are
given with small amounts of loop diuretics.
o Types
 Spironolactone (Aldactone)
 Uses
o Treat hyperaldosteronism
o Counteract potassium loss induced by other
diuretics
o Treat edema
 Triamterene (Dyrenium) and Amiloride (Midamore)

Probable mechanism: inhibition of renal epithelial sodium
channels
 Use: counteract potassium loss induced by other diuretics
o Adverse effect: hyperkalemia
Anticoagulants and Antianemia Drugs
 Coagulants: Starch
 Anticoagulants
o Decrease blood clots. These prevent or reduce venous clotting by blocking
the conversion of fibrinogen to fibrin.
o Multiple mechanisms to prevent excessive bleeding after injury.
o Blood clots are a multi-staged sequence that involves
 Vascular endothelial cells
 Thrombocytes (platelets)
 Coagulation cascade
 Fibrinolytic system
o Normal coagulation
 Fundamental component of a clot is fibrin.
 Insoluble protein from soluble plasma precursor
(fibrinogen) by the action of thrombin.
 Thrombin produced by two convergent series of reactions
 Intrinsic
o Triggered when plasma comes in contact with
certain substances that have a negative surface
charge.
o Sets off series of reactions. Uncertain what activates
factor XII (Hageman factor) but damage to
endothelial cells. May serve as a stimulus at sites of
vascular injury.
 Extrinsic
o Bypasses several of the steps of the intrinsic
pathway.
o Initiated when plasma comes in contact with tissue
thromboplastin.
o Three methods to attack unwanted clotting
 Anticoagulant
 Thrombolytic
 Antiplatelet
o Heparin
 A sulfated mucopolysaccharide
 Increased MW (3000-30000)
 Mechanism: binds to plasma antithrombin III, activating it,
accelerating its inhibition of factor Xa, thrombin, and other clotting
factors.
 Not pure: hog intestine/beef lung
 Only works on serine proteases

Half-life of 1-2 hours
 Used primarily for in-hospital controlled anticoagulation
and especially for intraoperative anticoagulation.
 Anticoagulation properties are instantaneous.
 Some lipemia-clearance has been shown with heparin.
 This is not important clinically.
 Onset time: immediate
 Route of administration: IV or subcutaneous
 Use: treat acute or prevent thrombosis
 Adverse effects
 Hemorrhage (treat with protamine sulfate. This reverses
heparin instantaneously milligram for milligram)
 Thrombocytopenia
 Osteoporosis
o Low Molecular-weight Heparin (MW- 4000-6000)
 This is more effective than heparin.
 Agent: Enoxaparin (Lovenox)
 Prevents coagulation immediately upon injection
 Mechanism: binds to plasma antithrombin III, accelerating its
inhibition of factor Xa
 Route of administration: subcutaneous
 Use: treat or prevent thrombosis
 Adverse effect: hemorrhage (treat with protamine sulfate)
o Indanedione Anticoagulants
 These all have the same mechanism
 Coumarins (e.g. warfarin)
 This is the most commonly prescribed anticoagulant for
long-term maintenance.
 Molecular structure resembles that of vitamin K
 Mechanism: reduced vitamin K is necessary for the
synthesis of several clotting factors (which becomes
activated when they are reduced by vitamin K); warfarin,
rather than vitamin K epoxide, becomes reduced; thus
clotting factor synthesis is inhibited. Vitamin K is not
regenerated.
 Block carboxylation of various clotting factors by
competing with vitamin K epoxide for reduction by vitamin
K epoxide reductase, thus depleting the supply of reduced
vitamin K, which is necessary for the carboxylation of
several clotting factors.
 Onset time: 1-2 days (delayed onset and action)
o Normal prothrombin content must decline before
delayed clotting is noted.
o Given with heparin at first for an immediate
reaction.
 Route of administration: oral

Use: prevent thrombosis
o Prevention of deep vein thrombosis, pulmonary
embolus in high risk patients, mitral stenosis, etc.
o Usually give heparin first because rapid action and
short half-life followed by coumadin which has
slower onset, longer action and can be administered
orally for long periods of time.
 Adverse effect: hemorrhage
 Antidote
o Fresh whole blood transfusion
o Vitamin K infusion
 Phytonadione (aquamephyton, vitamin K-1)
 Water soluble and can be administered IV
(slowly)
 Has no reversing effect on anticoagulant
properties of heparin.
 Drug interactions- many drugs cause an increase or
decrease in pharmacokinetics of coumadin
o Drugs that increase the effect of coumadin
 Antibiotics that affect intestinal flora
 Salicylates (large doses)
 Chloral hydrate
 Disulfiram
 Adrogrenic anabolic steroids
 Methylphenidate
 Propylthiouracil
 D-thyroxin
o Drugs that decrease effect of coumadin
 Barbiturates
 Ethylchlorvynol
 Glutethimide
o Coumadin potentiation of other drugs
 Tolbutamide
 Phenytoin
 Dicumarol
 First oral anticoagulant synthesized
 Acenocoumon (Sintrom)
 Phenprocoumon (Liquamar)
 Indaneione Derivatives
 Phenindione (Hedulin)
 Anisindine (Meradon)
o Inhibitors of platelet aggregation (Antithrombotics)
 These prevent or reduce arterial platelet aggregation by blocking
the action of cyclooxygenase, reducing the production of
thromboxane.


Platelet activation caused by synthesis of thromboxane A2 (TXA2,
an autocoid non-hormonal neurotransmitter) and ADP; these work
together to bring about platelet adhesion (aka clotting)
 Platelet activation is inhibited by decreased TXA2 synthesis
caused by:
 Aspirin
o Irreversible. With injury, arachadonic acid is
released. This goes to prostaglandin E1 (PGE1),
PGE2, PGI, PGI2, TXA2
o Inhibit platelet function by blocking the
cyclooxygenase enzyme, which converts
arachidonic acid to endoperoxide, which is then
converted to thromboxane A-2 (TXA-2)
o Aspirin irreversibly acetylates the platelet
cyclooxygenase.
o Effects last for the lifetime of the platelet.
o Other NSAIDs are reversible.
 Ibuprofen
 Indomethacin
 Sulfinpyrazone
o Reversible cyclooxygenase inhibitor
o Unlike aspirin, it does not prolong the bleeding time
or affect platelet aggregation in normal individuals.
 Dipryidamole
o Increase platelet cAMP which inhibits platelet
aggregation.
o Inhibits platelet phosphodiesterase, the enzyme that
breaks down cAMP.
o Inhibits adhesion ofplatelets to damaged
endothelium and to artificial surfaces, therefore
used in prosthetic valve surgery patients.
 Dextran
 Anticoagulants interfere with enzymes cyclooxygenase 1 & 2
(COX-1, COX-2). Therefore, it decreases synthesis of TXA2.
 Platelet activation is also inhibited by elevated platelet cAMP, e.g.
by prostacyclin (PGI2)
 Use: prevent thrombosis
 Adverse effect: hemorrhage
Fibrinolytic Agents
o Blood has the inherent ability to dissolve clots by means of the fibrinolytic
system. These function to remove minute fibrin deposition in small
vessels.
o Fibrinolysin (plasmin) is a proteolytic enzyme that attacks a variety of
proteins but has great affinity for fibrinogen or fibrin.
o Streptokinase and urokinase are plasminogen activators.
o Agents


Urokinase
Streptokinase (Streptase)
 An enzyme produced by certain strains of beta streptococci
 Antigenic and can only be used every 6-12 months.
 Used for treatment of acute MI, acute deep vein
thrombosis, acute pulmonary embolus.
 (IV) dissolves blood clots after formation
 Can cause systemic bleeding, but is minimized by
threading a catheter to the site of the thrombus and
injecting the drug directly.
 Tissue plasminogen activator. Like urokinase
 This acts by activating fibrin-bound (rather than
circulating) plasminogen. TPA appears to be somewhat
more effective than Streptokinase at dissolving clots, and
has fewer side effects.
 Tenectoplase
o Mechanism: conversion (“activation”) of circulating plasminogen to
plasmin, an enzyme which attacks fibrin (dissolving the fibrin network
within a clot, reducing its size), fibrinogen, factor V, and factor VIII.
Drugs used to treat anemias
o Iron deficiency anemia
 Treats the symptoms, not the disease
 Need 1-6 mg Fe/day. Females need more due to menstruation.
 Preparations
 Ferrous sulfate
o Most effective form of iron. Ferric is absorbed in
the intestine.
 Ferrous gluconate
 Toxicity: poisoning, especially in kids.
o Megaloblastic anemia (immature RBCs)
 Folic Acid
 Sources: green, leafy vegetables (foliage)
 Deficiency syndrome: megaloblastic anemia, spina bifida,
etc.
 Enterohepatic circulation is important
 Routes of administration: oral, IV (cant overdose)
 Vitamin B12
 Only need a few mg every day. We store a 6 months supply
 Sources: animal products, legumes, fortified cereals, some
water supplies, eggs.
 Deficiency prevents synthesis of folic acid (THF) from
methyl THF
 Deficiency rarely due to dietary insufficiency
 Deficiency symptoms
o Megaloblastic anemia
o Paresthesia
o Demyelination
o Loss of kinesthetic sense
o Memory loss
o Spastic ataxia
 Enterohepatic circulation is important
 Route of administration: im
o End-stage Renal Disease: Erythropoietin (forms RBC)
 Occurs naturally as a factor necessary for development of
erythrocytes
 Routes of administration: iv, sc