CARDIOVASCULAR EMBRYOLOGY

Suyash Sharma
PRIMITIVE VASCULAR SYSTEM

 Blood islands: During the 3rd week of

development, mesenchymal cells associated
with the yolk sac, chorion, and connecting stalk
form clusters called blood islands, which acquire
lumina and fuse to form endothelium-lined
capillary plexuses.
 Peripheral cells of the islands become
angioblasts that give rise to the endothelial
cells of the vessels, whereas centrally located
cells become embryonic hemoblasts that give
rise to primitive blood cells.
 Certain capillaries enlarge to form the major
blood vessels: vitelline vessels are formed
in the yolk sac wall and umbilical vessels
are formed in the vascular chorion.
 Extraembryonic blood vessels join with
intraembryonic blood vessels formed from
splanchnic mesoderm and the primitive
vascular system is established.
HEART
 1st system to function in the embryo, and blood
circulation begins by the 3rd week.
 The blood vessels are derived from angioblastic
tissue that arises in the mesenchyme.
 Two strands of splanchnic mesenchymal cells
organize to form  cardiogenic cordsform
endothelial tubes (endocardial heart tubes) that
fuse and thicken.
 The inner endocardial tube becomes the
endocardium.
 The myoepicardial mantle becomes the
myocardium and epicardium.
 As the tubular heart elongates, dilatations and
constrictions develop that become the chambers.
 As the heart tubes fuse, the mesenchyme around
them thickens into the myoepicardial mantle, which
differentiates into three layers—outer (epicardium),
middle (myocardium), and inner (endocardium).
A.
 Thesemilunar valves of the aorta and
pulmonary arteries develop following the
formation of the aorticopulmonary septum.
Primitive atrium
 1.At the end of the fourth week, the septum
primum grows from the roof of the primitive
atrium towards two mesenchymal cushions,
the endocardial (atrioventricular; AV)
cushions, which appear in the ventral and
dorsal walls of the AV canal.
 In the fetus, the pulmonary and systemic
circulations run in parallel, and the fetus can
survive despite severe cardiac or pulmonary
abnormalities.
 Blood is oxygenated in the placenta and enters
the portal venous system. The transition from fetal
to neonatal circulation occurs as the lungs take
over the function of oxygenation for the placenta
a. The transient opening between the septum primum
and endocardial cushions is known as the interatrial
foramen primum.
b. The endocardial cushions gradually extend along the
edge of the primum, thereby obliterating the foramen
primum.
 The lower edge of the septum secundum encloses the
foramen secundum in the septum primum but does
not extend fully towards the endocardial cushions.
 The opening it leaves between the right and left
primitive atria is known as the foramen ovale.
Hematopoiesis first occurs within the islands of the
yolk sac. Later, blood cells are formed in the liver
(1-7 months), spleen and lymphatic organs (2-4
months), and bone marrow (after 4 months).
Aortic arch derivatives:
 1st Arch= Maxillary artery
 2nd Arch= Hyoid artery, Stapedial artery
 3rd Arch= Common carotid artery, Proximal internal
carotid artery,
 4th Arch= Aortic arch, Proximal right subclavian artery
 6th Arch= Prox pulmonary artery, Ductus arteriosus
MEDIASTINUM :Located between the pleural cavities,
the mediastinum is divided into inferior and superior
parts by a plane passing from the sternal angle
anteriorly, to the intervertebral disc between T4 and
T5 posteriorly.
Content of Superior mediastinum:
 Thymus (remains)

 SVC

 Aortic arch

 Vagus nerves

 Trachea

 esophagus

 Thoracic duct
 INFERIOR MEDIASTINUM:
Middle mediastinum pericardium, phrenic nerves,
and heart.

Anterior mediastinum. This section contains fat and

areolar tissue.

Posterior mediastinum. Thoracic (descending) aorta,

Esophagus, Thoracic duct,
Azygous system of veins,
Sympathetic trunks
PERICARDIUM
outer fibrous sac; it is lined by a double-layered
serous membrane that encloses the pericardial
cavity between its parietal and visceral
layers.
a. Transverse pericardial sinus is a space
posterior to the ascending aorta and
pulmonary trunk and anterior to the superior
vena cava.
b. Oblique pericardial sinus is a blind, inverted,
U-shaped space posterior to the heart and
bounded by reflection of serous pericardium
around the eight vessels entering and leaving
the heart.
2. PHRENIC NERVES

a. Phrenic nerves arise from the ventral

primary rami of cervical nerves 3, 4, and
5.
b. sole motor supply of the diaphragm and
convey sensory information from the
central portion of both the superior and
inferior portions of the diaphragm.
c. Both phrenic nerves pass through the
middle mediastinum lateral to fibrous
pericardium and anterior to the root of the
lung.
MNEMONIC

The four birds in the thoracic case:

Va-goose

Azy-goose

Esopha-goose

Thoracic duck
HEART
Surfaces of the heart:
1. Anterior: Right ventricle
2. Posterior: Left atrium
3. Inferior: Left ventricle

Borders of the heart:

1. Left: Left atrium and ventricle and aorta
2. Right: Superior vena cava(SVC)and right atrium
3. Superior: Aortic arch and pulmonary trunk
4. Inferior: Right ventricle and the apex of left
ventricle.
 ARTERIAL SUPPLY:

Left coronary artery, which gives off the following

branches:
 Left anterior descending artery: Supplies
anterior wall of left ventricle.
 Circumflex artery: Supplies lateral and posterior
walls of left ventricle, ant. interventricular septum.

Right coronary artery: Supplies everything

else, including sinoatrial (SA) and atrioventricu-
lar (AV) nodes, the right atrium, the right ventricle,
 Pic
 In the majority of cases, the SA and AV nodes
are supplied by the RCA.
 80% of the time, the RCA supplies the inferior
portion of the left ventricle via the PD Artery.(=
right dominant).
 20% of the time, the PD arises from the CFX.

 Coronary artery occlusion most commonly

occurs in the LAD, which supplies the anterior
interventricular septum.
 Posterior descending/ interventricular artery
(PD)—supplies posterior interventricular septum.
 Coronary arteries fill during diastole.
 The most posterior part of the heart is the left
atrium;
 Mitral Valve insufficiency can cause Lt. atrial
enlargement, later can cause dysphagia due to
compression of the esophagus or hoarseness
(due to compression of the recurrent laryngeal
nerve, a branch of the vagus).
 Hoarseness as a result of compromise of the
left recurrent laryngeal nerve may also indicate
pressure from an aortic aneurysm.
VENOUS DRAINAGE:
1. Great, middle, and small cardiac veins:
Drain into the coronary sinus. Note that
the middle cardiac vein runs in the
posterior interventricular sulcus.
2. Anterior cardiac veins from right ventricle :
Drain inside right atrium.
3. Venae cordis minimae (thebesian veins)
and anterior cardiac veins open directly to
the chambers of the heart.
NERVE SUPPLY:

1. Parasympathetic: Nucleus ambiguus and

dorsal nucleus of vagus nerve
(Pneumonic=AV node)
2. Sympathetic: Intermediolateral column of
spinal Cord
Valves:
All valves are formed of three cusps, except
mitral, which has only two cusps. Cusps are
connected into papillary muscles of
ventricles via chordae tendineae.
C. CHAMBERS OF THE HEART

1. Right atrium: receives venous blood from

the entire body with the exception of blood
from the pulmonary veins.
a. Auricle is derived from the fetal atrium; it has
rough myocardium known as musculi pectinati.
b. Sinus venarum is the smooth-walled portion
of the atrium, which receives blood from the
superior and inferior venae cavae.
c. Crista terminalis, is the vertical ridge that
separates the smooth from the rough portion of
the right atrium
2. RIGHT VENTRICLE
receives blood from the right atrium via the tricuspid
valve; outflow is to the pulmonary trunk via the
pulmonary semilunar valve.
a. Trabeculae carneae are ridges of myocardium in
the ventricular wall.
b. Papillary muscles project into the cavity of the
ventricle and attach to cusps of the AV valve by
strands of chordae tendineae.
c. Chordae tendineae pull cusps of the valve
together during contraction of the ventricle.
d. Infundibulum is the smooth area of the right
ventricle leading to the pulmonary valve.
3. LEFT ATRIUM
receives oxygenated blood from the lungs via
the pulmonary veins.
a. There are 4 openings for the upper right
and left and the lower right and left
pulmonary veins.
b. The left AV orifice is guarded by the mitral
(bicuspid) valve; it allows oxygenated
blood to pass from the left atrium to the
left ventricle.
 4. LEFT VENTRICLE
Blood enters from the left atrium through the mitral
valve and is pumped out to the aorta through the
aortic semilunar valve.
a. Trabeculae carneae: The myocardium is normally 3
times thicker than that of the right ventricle.
b. Papillary muscles: usually two large ones, are
each attached by chordae tendineae to both cusps
of the bicuspid valve.
c. Aortic vestibule: leads to the aortic semilunar valve
and ascending aorta; right and left coronary arteries
originate from the right and left aortic sinuses at the
root of the ascending aorta.
CONDUCTING SYSTEM OF THE HEART
1. SA node(Pacemaker): It initiates the impulse for
contraction of heart muscle. It is located at the
superior end of the crista terminalis, where the
superior vena cava enters the right atrium.
2. AV node receives impulses from the SA node. The
AV node is located in the interatrial septum near the
opening of the coronary sinus.
3. Bundle of His originates in the AV node. It
distributes to the right and left ventricles. Impulses
pass from the right and left bundle branches to the
papillary muscles and ventricular myocardium.
Innervation:
 The cardiac plexus is a combination
of sympathetic and parasympathetic
(vagal) fibers.
 Sympathetic stimulation increases
the heart rate; parasympathetic
stimulation slows the heart rate.
 BRANCHES OF THE ABDOMINAI AORTA AND
INFERIOR VENA CAVA
1. Three visceral unpaired a. Celiac trunk
branches b. Superior mesenteric
artery
c. Inferior mesenteric artery

2. Three visceral paired a. Renal arteries

branches b. Suprarenal arteries
c. Gonadal arteries

3. Five paired parietal branches a. Inferior phrenic arteries

b. Four pairs of lumbar arteries
c. A fifth pair of lumbar arteries
arise from the median sacral
artery.
 B. The inferior vena cava begins at
vertebral level L5 from the joining of the two
common iliac veins.
 It terminates in the right atrium after
passing through the caval orifice of the
diaphragm at vertebral level T8.
 1. The azygos vein interconnects the
superior and inferior venae cavae. It drains
the posterior intercostal veins of the
thoracic wall and the posterior abdominal
wall.
2. The renal veins lie superficial to the
corresponding arteries. The left renal is longer
because it must cross the aorta and vertebral
column to reach the inferior vena cava.
3. Right gonadal vein is a direct tributary of the
inferior vena cava. (The left gonadal drains to
the left renal vein.)
4. Right suprarenal vein is a direct tributary of
the inferior vena cava. (The left suprarenal
drains to the left renal vein.)
5. The lumbar veins drain the posterior
abdominal wall.
6. The inferior phrenic veins drain the
diaphragm.
7. The hepatic veins open into the inferior
vena cava just before it passes through
the diaphragm. They return blood from the
liver to the systemic circulation.
 C. Azygos vein arises in the abdomen,
usually from the inferior vena cava or
ascending lumbar vein. It ascends to the
posterior mediastinum and terminates in the
superior vena cava just before the superior
vena cava enters the pericardium.
1. The hemiazygos vein drains the lower left
inferior posterior intercostal veins (T9-T12). It
joins the azygos vein.
2. The accessory hemiazygos vein receives
blood from the left posterior intercostal veins
from T5 to T8. It joins the azygos vein.
 The right primary bronchus is straighter and
wider than the left; aspirated object there for
lodge more frequently in the right bronchus
than in the left.
 Right recurrent laryngeal nerve "recurs" around
the derivative of the Fourth aortic arch
(proximal portion of subclavian artery); left
recurrent laryngeal nerve recurs around the
derivative of the Sixth aortic arch (Ligamentum
arteriosum),
CARDIOVASCULAR
PHYSIOLOGY
CARDIAC MYOCYTES PHYSIOLOGY
 Cardiac muscle contraction is dependent on
extracellular calcium, which enters the cell during
plateau of action potential and stimulates calcium
release (calcium induced calcium release).
In contrast to skeletal muscles:
 1. Cardiac muscle action potential has a plateau,
which is due to calcium influx.
 2. A Cardiac Nodal cells spontaneously depolarize,
resulting in automaticity.
 3. Cardiac myocytes are electrically coupled to
each other by gap junctions.
B. ELECTROPHYSIOLOGICAL CATEGORIES OF
CARDIAC CELLS

 1.Cardiac cells can be divided into two

electrophysiologic categories:

 a. Fast fibers: atrial and ventricular

muscle cells, Purkinje cells of the His-
Purkinje system
 b. Slow fibers: SA node, AV node
C. BASIC CELLULAR ELECTROPHYSIOLOGY

 1. The phospholipids bilayer of the

myocardial cell membrane, particularly
its hydrophobic core' serves as an
insulator that allows the cell to
maintain a potential difference
between its interior and its exterior.
 This potential difference is generated
by following events.
 a. Net movement of ions (i.e., electrical current)
across the cell membrane through transmembrane
protein "openings" in the phospholipid bilayer,
called channels. Channels are usually selective for
a specific ion (Na, K, Ca, or Cl).
 b. Exchange of ions along their concentration
gradients via protein transmembrane transport
systems.
 c. Active transport of ions against their
electrochemical energy gradients by special
transmembrane pumps, which may be electrogenic
(i.e., effect net charge movement across the
membrane)
 2. Adjacent myocardial cells are connected end-
to-end by a thickened portion of the cell membrane,
called the intercalated disk. The nexus, or gap
junction, is a region in the intercalated disk that
provides a low-resistance electrical connection and
allows movement of ions between adjacent cells.
 RESTING MEMBRANE POTENTIAL (RMP)
 The RMP is -90 mV in fast fibers (atrial and ventricular
muscle cells, Purkinje cells) and -60 to-70 mV in slow
fibers (SA node, AV node), with the inside of the cell
being negative with respect to the outside.

Two characteristics of resting cardiac cells are

important for establishing the RMP:

 a. Differences in composition between the extracellular

fluid and intracellular fluid. most importantly [K+]i >>
[K+]o and [Na]o >> [Na]i,.
 b. The selective permeability of the cell membrane:
most importantly, the K+ permeability (PK) >> Na+
permeability (PNA).
 Given these two characteristics the RMP
originates as follows:
 (1) Due to the high PK, K+ moves from ICF
to ECF along its concentration gradient,
leaving an excess of anions (many of which
are too large to diffuse out of the cell along
with K +) in the ICF and creating a negative
transmembrane potential (TMP). This
negative TMP tends to slow the further
efflux of K +.
(2) However, due to the small PNA, Na+ moves
from ECF to ICF along its concentration and
electrical gradients, making the actual RMP
less negative than VK (K+ equilibrium
Potential)and allowing for a continued small
K + efflux. Thus, at the RMP there is a small
outward K + current balanced by a small
inward Na + current.
 3) Slow fibers have a somewhat greater
PNA/PK ratio than fast fibers and therefore a
less negative RMP.
THE RMP CAN BE CHANGED BY:

a. Changes in the K+ concentration

gradient.
 For example, a decrease in the K +
concentration gradient decreases the
tendency of K + to leave the cell along its
concentration gradient, resulting in a less
negative RMP.
 (1) Hyperkalemia (increased [K +]o) reduces
the magnitude of the gradient.
 (2) Myocardial injury or ischemia can result
in a local decrease in the magnitude of the
gradient.
b. Changes in the ionic permeabilities.

 For example, an increase in K + permeability

increases the tendency of K + to leave the cell
along its concentration gradient, resulting in a
more negative RMP. Acetylcholine
hyperpolarizes cardiac cells by this
mechanism.
CARDIAC ACTION POTENTIALS (APS).

 When a resting cardiac cell is depolarized to

a certain critical potential, the threshold
potential, an AP is initiated. The APs in fast
fibers (fast response APs) differ from the
APs in slow fibers (slow response APs)
 Also occurs in bundle of his and Purkinje
fibers
 Phase 0 = rapid upstroke- voltage gated
sodium channels open
 Phase 1 = initial repolarization-inactivation
voltage gated Na+ channels. Voltage
gated K+ channels begin to open.
 Phase 2 = Plateau- Ca++ influx through
voltage gated Ca++ channels balances K+
effluxes. Calcium influx triggers calcium
release from sarcoplasmic reliculum and
myocyte contraction.
 Phase 3 = rapid repolarization —massive
K' efflux due to opening of voltage-gated
slow K+ channels and closure of voltage-
gated Ca++ channels.
 Phase 4 = resting potential —high K+
permeability through K+ channels.
 PACEMAKER ACTION POT.
 Occurs in the SA and AV nodes. Key
differences from the ventricular action potential
include:
Phase 0 = upstroke-opening of voltage-gated
Ca++ channels. These cells lack fast voltage-
gated Na+ channels. Results in a slow
conduction velocity that is used by the AV node
to prolong transmission from the atria to
ventricles.
Phase 2 = plateau is absent.
Phase 3 = inactivation of the Ca 2+ channels
and increases activation of K channels 
increases K+ efflux.
Phase 4 = slow diastolic depolarization—
membrane potential spontaneously
depolarizes as Na conductance increases .
Accounts for automaticity of SA and AV
nodes.
The slope of phase 4 in the SA node
determines heart rate.
 Ach decreases the rate of diastolic
depolarization and therefore decrease the
heart rate
 Catecholamines increases the
depolarization and increase heart rate.
Pacemaker action pot.
P WAVE

 P wave represents the depolarization of the atria.

Normal P waves are:
 > 2.5 mm

 > 0.10 sec in duration.

 Upright in leads I, II, aVF, and V4 through V6

 Inverted (negative) in lead aVR

 PR segment is measured between the end of the P

wave and the beginning of the QRS complex. It
reflects the depolarization of the AV node, the
bundle of His, bundle branches, and Purkinje fibers
and is normally isoelectric.
PR INTERVAL
 PR interval is measured from the beginning
of the P wave to the beginning of the QRS
complex, i.e., it includes the P wave plus the
PR segment. It reflects the time it takes for
the depolarizing impulse to travel from the
SA node to the ventricles.
 Is 0.12s 0.20s duration.

 PR interval decreases( due to more rapid

conduction through the-Av node) at faster
rates.
QRS COMPLEX:

 represents the spread of depolarization

through the ventricles.
 deflections in the QRS complex are labeled
according to the following rules:
 (1) If the first deflection is downward
(negative),it is a Qwave.
 (2) The first upward (positive) deflection is
an R wave, regard less of whether it is
preceded by a Q wave.
 (3) A downward deflection following an R
wave is an S wave.
QRS COMPLEX CONT.
 The normal width of the QRS complex, the
QRS interval (or QRS duration), is less than
0.10 seconds. A QRS interval of 0.12
seconds or longer is clearly abnormal and
can be caused by:
 ( 1) Marked slowing of action potential
conduction through ventricular muscle, e.g.,
due to severe hyperkalemia or quinidine or
procainamide toxicity.
 (2)
Asynchrony of ventricular depolarization,
so that the ventricles no longer
depolarization, almost simultaneously, e.g.,
due to bundle branch block or ectopic beats
that originate in the ventricles, such as
premature ventricular contractions.
ST SEGMENT
 The ST segment is measured from the end
of the QRS complex to the beginning of the
T wave.
 a. The ST segment is normally isoelectric,
corresponding to the part of the cardiac
cycle
 when all of the ventricle muscle cells are
depolarized (phase 2 of the action
potential), so that the potential difference
between any two points on the surface of
the body is zero.
 ST segment elevation or depression can be
seen in numerous pathologic conditions,
including myocardial infarction and
ischemia, ventricular hypertrophy, bundle
branch block, and electrolyte abnormalities.
T WAVE
 The T wave represents the electrical recovery,
or repolarization, of the ventricles.
 Unusually tall T waves ("tented T waves") can
be seen in myocardial ischaemia, myocardial
infarction, hyperkalemia, and cerebrovascular
accidents.
 Inverted (negative) T waves can be seen in
numerous pathologic conditions, including
myocardial infarction and ischemia, ventricular
hypertrophy, bundle branch block, and
electrolyte abnormalities.
QT INTERVAL
 The QT interval is measured from the
beginning of the QRS complex to the end of
the T wave; f.e.,li includes the QRS
complex, ST segment, and T wave. The QT
interval:
 a. Varies with heart rate. Normal QT interval
is 0.35 to 0.44 second in duration.
 b. Varies with age and sex of the patient
 c. Is prolonged in congestive heart failure
(CHF), myocardial infarction, and
hypocalcemia, and by quinidine,
procainamide, and tricyclic antidepressant.
Prolongation is
 Congenital in some patients, who are then
at higher risk for ventricular tachyarrythmias
and sudden death.
 d. Is shortened in hypercalcemia and by
digitalis
 TORSADES DES POINTES

 Ventricular tachycardia characterized by shifting

sinusoidal waveforms on ECG.
 Can progress to V-fib. Anything that prolongs the QT
interval can predispose to torsades des pointes
 eg. Chlorpromazine, Chloroquine, Amiodarone,
Clarithromycin, Disopyramide, Domperidone,
Antipsychotic, hypomagnesemia
 The U wave is a small deflection that, when
present, follows the T wave and has the same
orientation as the T wave. Its magnitude is
increased in hypokalemia.
 The RR interval is the time interval from the
beginning of one QRS complex to the
beginning of the next QRS complex and
represents the cardiac cycle length. If the RR
interval is measured in seconds, the heart rate
= 60/RR., Therefore, at a normal heart rate of
60 to 100/min, the RR interval is 0.6 to 1.0
seconds.
WOLFF-PARKINSON-WHITE SYNDROME
 Accessory conduction pathway from
atria to ventricle (bundle of Kent),
bypassing AV node.
 As a result, ventricles begin to
partially depolarize earlier, giving rise
to characteristic delta wave on ECG.
 May result in reentry current leading
to supraventricular tachycardia.
 Holosystolic, high-pitched "blowing murmur,"
 Mitral, loudest at apex and radiates toward axilla.
Enhanced by maneuvers that increase TPR (e.g.,
squatting, hand grip) or LA return (e.g., expiration).
MR is often due to ischemic heart disease, mitral
valve prolapse, or LV dilation.
 Tricuspid —Loudest at tricuspid area and
radiates to right sternal border. Enhanced by
maneuvers that increase RA return (e.g.,
inspiration). TR is due to RV dilation or
endocarditis, Rheumatic fever can cause both.
 Crescendo-decrescendo systolic ejection
murmur following ejection click (EC; due to
abrupt halting of valve leaflets). LV Pressure
>> aortic pressure during systole. Radiates to
carotids/apex.
 "Pulsus parvus eltardus"—pulses weak
compared to heart sounds. Can lead to
syncope. Often due to age-related calcific
aortic stenosis or bicuspid aortic valve
 Holosystolic,harsh-sounding murmur.
Loudest at tricuspid area.
 Late systolic crescendo murmur with
midsystolic click (MC; due to sudden tensing of
chordae tendineae).
 Most frequent valvular lesion. Loudest at S2.
Usually benign.
 Can predispose to infective endocarditis.

 Can be caused by myxomatous degeneration,

rheumatic fever, or chordae rupture.
 Enhanced by maneuvers that increases TPR
(e.g,. squatting, hand grip).
 Immediate high-pitched "blowing" diastolic
murmur.
 Wide pulse pressure when chronic; can
present with bounding pulses and head
bobbing.
 Often due to aortic root dilation, bicuspid
aortic valve, or rheumatic fever.
 Follows opening snap (OS; due to tensing
of chordae tendineae).
 Delayed rumbling late diastolic murmur.
LA >> LV pressure during diastole.
 Often occurs secondary to rheumatic
fever.
 Chronic MS can result in LA dilation.
 Enhanced by maneuvers that LA return
(e.g.. expiration).
 Continuous machine-like murmur. Loudest
at S2.
ATRIOVENTRICULAR (AV) BLOCKS

First-Degree AV Block

Rate: Depends on rate of underlying rhythm

Rhythm: Regular
PR Interval: Prolonged (0.20 sec)
QRS: Normal (0.06–0.10 sec)
Clinical Tip: Usually AV block is benign, but if associated
with an acute MI, it may lead to further AV defects.
2nd degree AV Block
THIRD- DEGREE AV BLOCK
 Conduction between atria and ventricles is absent
because of electrical block at or below the AV node.
 ―Complete heart block‖ is another name for this rhythm.
 Rhythm: Usually regular, but atria and ventricles act
independently
 P Waves: Normal (upright and uniform); may be
superimposed on QRS complexes or T waves
 PR Interval: Varies greatly
 QRS: Normal if ventricles are activated by junctional
escape focus; wide if escape focus is ventricular
ECG TRACINGS

 Atrialfibrillation: Chaotic and erratic

baseline (irregularly irregular) with no
discrete P waves in between irregularly
spaced QRS complexes.
ATRIAL FLUTTER
A rapid succession of identical, back-to-back
atrial depolarization waves. The identical
appearance accounts for the ―sawtooth‖
appearance of the flutter waves.
VENTRICULAR TACHYCARDIA (VT).
In VT, ectopic impulses originate in the ventricles at a
regular, rapid rate of 100 to 250/min. It is most frequently
caused by a re-entry mechanism; in a small minority of
cases it is caused by the firing of an ectopic focus.
VENTRICULAR FIBRILLATION

A completely erratic rhythm with no identifiable

waves. Fatal arrhythmia without immediate CPR
and defibrillation.
PREMATURE VENTRICULAR CONTRACTIONS (PVCS)

 Usually PVCs result from an irritable ventricular focus.

 PVCs may be uniform (same form) or multiform (different
forms). Rhythm: Irregular whenever a PVC occurs
 P Waves: None associated with the PVC
 PR Interval: None associated with the PVC
 QRS: Wide (0.10 sec), bizarre appearance
 Patients may sense the occurrence of PVCs as skipped
beats.
 in a bigeminy pattern (i.e., each sinus beat
is followed by a PVC).
 A premature ventricular contraction (PVC)
occurs when an ectopic ventricular
pacemaker inserts an ectopic beat before
the next sinus beat occurs.
 The ectopic impulse spreads through the
ventricles via an abnormal route but is
typically not conducted retrograde through
the AV node to the atria.
 PVCs occur both in normal and in disease
hearts.
 (1) In patients with normal hearts, PVCs are
not associated with decreased life
expectancy.
 (2) In patients with heart disease PVCs may
be a marker for a higher risk of other
ventricular arrhythmias and sudden death.
MEAN ARTERIAL PRESSURE
 MAP = 2⁄3 diastolic pressure + 1⁄3 systolic
pressure.
 Pulse pressure = systolic pressure –
diastolic pressure.
 Pulse pressure is proportion to stroke
volume.
 CARDIAC OUTPUT (CO)
 Cardiac output (CO) = (stroke volume) × (heart rate).
 Fick principle:

 During exercise, CO ↑ initially as a result of an ↑ in SV.

After prolonged exercise, CO ↑ as a result of an ↑ in HR.
 If HR is too high, diastolic filling is incomplete and CO ↓
(e.g., ventricular tachycardia).
CARDIAC OUTPUT VARIABLES
PRELOAD AND AFTERLOAD
STARLING CURVE:
 Force of contraction is proportional to initial length
of cardiac muscle fiber (preload).
EJECTION FRACTION
 Stroke volume (SV) represents the volume
of blood pumped by the ventricle per beat.
 RESISTANCE, PRESSURE AND FLOW

Pressure gradient drives flow from high

pressure to low.
CORONARY PERFUSION
 Resting coronary blood flow is usually well
preserved until there is severe narrowing
(stenosis) of the vessel.
 With exercise, a normal coronary artery is
able to dilate and increase coronary flow
four to five times its resting value.
 When there is a 50% reduction in the
diameter of the lumen, there is a reduction
in the ability for the vessel to dilate normally
and the flow reserve is reduced.
CARDIAC AND VASCULAR FUNCTION CURVES
HEART SOUNDS:
Sounds:
 S1—mitral and tricuspid valve closure. Loudest
at mitral area.
 S2—aortic and pulmonary valve closure.
Loudest at left sternal border.
 S3—in early diastole during rapid ventricular
filling phase. Associated with ↓ filling pressures
and more common in dilated ventricles (but
normal in children and pregnant women).
 S4 ("atrial kick") —in late diastole. High atrial
pressure. Associated with ventricular
hypertrophy. left atrium must push against stiff
LV wall.
PHASES: LEFT VENTRICLE

 1. Isovolumetric contraction — period between

mitral valve closure and aortic valve opening:
period of highest O2 consumption
 2. Systolic ejection —period between aortic
valve opening and closing,
 3. Isovolumetric relaxation —period between
aortic valve closing and mitral valve opening
 4. Rapid filling—period just after mitral valve
opening
 5. Reduced filling-period just before mitral valve
closure.
CARDIAC CYCLE:
JUGULAR VENOUS PULSE (JVP)

a wave—atrial contraction.

c wave—RV contraction (Tricuspid valve

bulging into atrium).

v wave- T atrial pressure due to filling against

closed tricuspid valve.

 S2 splitting: aortic valve closes before pulmonic;

inspiration increases this difference.
SPLITTING OF HEART SOUND
 Normal splitting—inspiration leads to drop in
intrathoracic pressure, which increases capacity
of pulmonary circulation. Pulmonic valve closes
later to accommodate more blood entering lungs;
aortic valve doses earlier because of decrease
return to left heart.
 Wide splitting—seen in conditions that delay
RV emptying (pulmonic stenosis, right bundle
branch block). Delay in RV emptying causes
delayed pulmonic sound (regardless of breath).
An exaggeration of normal splitting.
 Fixed splitting—seen in ASD. ASD leads to
left-to-right shunt and therefore increase flow
through pulmonic valve such that regardless of
breath, pulmonic closure is greatly delayed.
 Paradoxical splitting—seen in conditions
that delay LV emptying (aortic stenosis, left
bundle branch block). Normal order of valve
closure is reversed so that P2 sound occurs
before delayed A2 sound. Therefore on
inspiration, the later P2 and earlier A2 sounds
move closer to one another, "paradoxically"
eliminating the split.
POWER CAPSULE
Systolic ejection murmurs
 Aortic stenosis
 Pulmonic stenosis
 ASD
Pan systolic murmurs
 Mitral regurgitation
 Tricuspid regurgitation
 VSD
Diastolic murmurs
 Aortic regurgitation
 Pulmonic regurgitation
 Mitral stenosis
 Tricuspid stenosis
CARDIOVASCULAR RESPONSE TO
EXERCISE
A. Definitions
 1. Isotonic or dynamic exercise is predominantly
aerobic, is performed against a constant load
(isotonic), and involves rhythmic contractions of
flexor and extensor muscle groups (dynamic).
 2. Isometric or static exercise (i.e., weight lifting)
refers to activity that is predominantly fueled by
anaerobic breakdown of glucose to lactate, is
performed at a relatively constant muscle length
(isometric), and involves minimal or no movement
(static).
CARDIOVASCULAR RESPONSE TO ISOTONIC
EXERCISE

 1. Initial anticipatory sympathetic outflow

occurs even before exercise begins,
resulting in increased heart rate, increased
cardiac output, and decreased venous
compliance.
 2. Shortly after the beginning of exercise
muscle blood flow increases up to 15 times
its resting value as a result of vasodilatation
mediated by local factors such as hypoxia
and changes in K+, H+, and ATP
concentrations.
 3. Circulating catecholamines and direct
sympathetic stimulation of the heart increase
the heart rate and the inotropic state.
 a. Early in exercise, increased stroke volume is
the most important adjustment.
 b. Later (beyond 50o/o of maximal work
capacity), increased heart rate becomes more
important in maintaining the cardiac output.
 c. At maximum exercise in well-conditioned
individuals, cardiac output can be doubled by
increases in stroke volume and tripled by
increases in heart rate.
BARORECEPTORS AND CHEMORECEPTORS

Receptors:
 1. Aortic arch transmits via vagus nerve to medulla
(responds only to ↑ BP)
 2. Carotid sinus transmits via glossopharyngeal nerve
to medulla (responds to ↓ and ↑ in BP).
Baroreceptors:
 1. Hypotension—↓ arterial pressure
→↓stretch→↓afferent baroreceptor firing → ↑ efferent
sympathetic firing and ↓ efferent parasympathetic
stimulation → vasoconstriction, ↑ HR, ↑ contractility, ↑
BP. Important in the response to severe hemorrhage.
 2. Carotid massage—↑ pressure on carotid artery
→↑stretch→↑afferent baroreceptor firing →↓HR.
CHEMORECEPTORS:

 1. Peripheral—carotid and aortic bodies

respond to ↓ PO2 (< 60 mmHg), ↑ PCO2,
and ↓ pH of blood.
 2. Central—respond to changes in pH and
PCO2 of brain interstitial fluid, which in turn
are influenced by arterial CO2. Do not
directly respond to PO2. Responsible for
Cushing reaction— ↑ intracranial pressure
constricts arterioles → cerebral ischemia →
hypertension (sympathetic response) and
reflex bradycardia.
 Note: Cushing triad = hypertension,
bradycardia, respiratory depression.
CIRCULATION THROUGH ORGANS

 Liver: Largest share of systemic cardiac

output.
 Kidney: Highest blood flow per gram of
tissue.
 Heart: Large arteriovenous O2 difference. ↑
O2 demand is met by ↑ coronary blood flow,
not by ↑ extraction of O2.
NORMAL PRESSURES
Note: the pulmonary vasculature is unique in that
hypoxia causes vasoconstriction. In other organs,
hypoxia causes vasodilation.
CAPILLARY FLUID EXCHANGE
Starling forces determine fluid movement through
capillary membranes:
 1. Pc = capillary pressure––pushes fluid out of capillary
 2. Pi = interstitial fluid pressure––pushes fluid into capillary

 3.π c = plasma colloid osmotic pressure––pulls fluid into

capillary

 4.π i = interstitial fluid colloid osmotic pressure––pulls fluid

out of capillary.
 Thus, net filtration pressure,Pnet = [(Pc − Pi) − (πc − πi)].
 Kf = filtration constant (capillary permeability).
 Net fluid flow = (Pnet)(Kf).
EDEMA
 excess fluid outflow into interstitium commonly
caused by:
 1. ↑ capillary pressure (↑ Pc; heart failure)

 2. ↓ plasma proteins (↓ πc; nephrotic syndrome,

liver failure)
 3. ↑ capillary permeability (↑ Kf; toxins, infections,
burns)
 4. ↑ interstitial fluid colloid osmotic pressure (↑ πi;
lymphatic blockage)
CVS PATHOLOGY
CONGENITAL ABNORMALITY OF THE
HEART
Congenital heart disease
 Right-to-left shunts (early cyanosis)–– ―blue
babies‖
 1. Tetralogy of Fallot (most common cause of
early cyanosis)
 2. Transposition of great vessels

 3. Truncus arteriosus

 4. Tricuspid atresia

 5. Total anomalous pulmonary venous return

(TAPVR)
LEFT-TO-RIGHT SHUNTS (LATE CYANOSIS)–
―BLUE KIDS‖ –
 1. VSD (most common congenital cardiac anomaly)
 2. ASD (loud S1; wide, fixed split S2)

 3. PDA (close with indomethacin)

 Frequency––VSD > ASD > PDA.

 ↑ pulmonary resistance due to arteriolar thickening.
→ progressive pulmonary hypertension; right-to-left
shunt (Eisenmenger‘s).
EISENMENGER’S SYNDROME
 Uncorrected VSD, ASD, or PDA
leads to progressive pulmonary
hypertension. As pulmonary
resistance ↑, the shunt reverses
from L → R to R → L, which
causes late cyanosis (clubbing
and polycythemia).
 TETRALOGY OF FALLOT (PROVE).

 1. Pulmonary stenosis (most important determinant for

prognosis)
 2. RVH

 3. Overriding aorta (overrides the VSD)

 4. VSD
 Early cyanosis is caused by a
right-to-left shunt across the
VSD. On x-ray, boot-shaped
heart due to RVH. Patients suffer
―cyanotic spells.‖

 Tetralogyof Fallot is caused by

anterosuperior displacement of
the infundibular septum.
TRANSPOSITION OF GREAT
VESSELS

 Aorta leaves RV (anterior)

and pulmonary trunk
leaves LV
(posterior)→separation of
systemic and pulmonary
circulations.
 Not compatible with life
unless a shunt is present to
allow adequate mixing of
blood (e.g., VSD, PDA, or
patent foramen ovale).
 COARCTATION OF THE AORTA

 Infantile type––aortic stenosis

proximal to insertion of ductus
arteriosus (preductal).
 Adult type––stenosis is distal to
ductus arteriosus (postductal).
Associated with notching of the ribs
(due to collateral circulation),
hypertension in upper extremities,
weak pulses in lower extremities.
 Associated with Turner‘s
syndrome.
PATENT DUCTUS ARTERIOSUS

 Infetal period, shunt is right to

left (normal). In neonatal
period, lung resistance ↓ and
shunt becomes left to right with
subsequent RVH and failure
(abnormal). Associated with a
continuous, ―machine-like‖
murmur. Patency is maintained
by PGE synthesis and low O2
tension.
CONGENITAL CARDIAC DEFECT ASSOCIATIONS
HYPERTENSION
 Defined as BP ≥ 140/90.
 Risk factors: ↑ age, obesity, diabetes,
smoking, genetics, black > white > Asian.
 Features 90% of hypertension is 1°
(essential) and related to ↑ CO or ↑ TPR;
remaining 10% mostly 2° to renal disease.
Malignant hypertension is severe and rapidly
progressing.
 Predisposes to Atherosclerosis, stroke,
CHF, renal failure, retinopathy, and aortic
dissection.
HYPERLIPIDEMIA SIGNS

 Atheromas: Plaques in blood vessel walls.

 Xanthomas: Plaques or nodules composed
of lipid-laden histiocytes in the skin,
especially the eyelids.
 Tendinous xanthoma: Lipid deposit in
tendon, especially Achilles.
 Corneal arcus: Lipid deposit in cornea,
nonspecific (arcus senilis).
ARTERIOSCLEROSIS

 Monckeberg Calcification in the media of

the arteries, especially radial or ulnar.
Usually benign; ―pipestem‖ arteries.
 Arteriolosclerosis Hyaline thickening of
small arteries in essential hypertension.
Hyperplastic ―onion skinning‖ in malignant
hypertension.
 Atherosclerosis Fibrous plaques and
atheromas form in intima of arteries.
BLOOD VESSELS HISTOLOGY

 Three layers
1. Tunica intima – layer of flattened endothelial
cells
2. Tunica media – muscular layer
3. Tunica adventitia – supporting layer with nerve
fibres and vessels
Between intima and media – internal elastic
lamina
Between media and adventitia – external
elastic lamina
CONGENITAL ANOMALIES OF VESSELS

 Berry aneurysms
1. Focal weakenings in cerebral vessel walls,
resulting in an outpouching
2. Most common at branch points in the anterior
circle of Willis and at the bifurcation of middle
cerebral artery
3. Symptoms - rare before age 20, after that they
may burst and cause subarachnoid
hemorrhage (most frequent cause of SAH)
4. Ass. with polycystic kidney disease
CONGENITAL ANOMALIES…

Arterivenous fistulas
 Rare

 Abnormal communication between a vein and

an artery
 May result from trauma

 Diverts blood from arterial – venous

circulation
Increased venous return

Increase work load on right side of heart

Right heart failure

ARTERIOSCLEROSIS
 Diffuse thickening of arterioles and small
arteries, resulting in narrowing of the lumen and
ischemia of involved tissue
 Kidney is particularly vulnerable to
arteriosclerosis
 Monckeberg medial calcific sclerosis –
Medial calcification of medium sized arteries
(femoral, tibial, radial, ulnar). ―Pipestem
arteries‖. May be detected by X- Ray
Monckeberg medial calcific sclerosis
HYALINE ARTERIOSCLEROSIS

1. Associated with diabetes, hypertension,

and old age
2. Hyaline thickening of arterioles leading to
narrowing of the lumen
3. Eosinophilic material in the intima and
media
4. Degenerative process
5. Best recognized in arterioles of adipose
tissue
HYPERPLASTIC ARTERIOSCLEROSIS

1. Associated with malignant hypertension

2. There is necrotizing vasculitis, fibrinoid
necrosis
3. Onion skin hyperplasia
4. Concentric thickening of the intima,
deposition of basophilic ground
substance, smooth muscle proliferation,
and hypertrophy of the adventitia
ATHEROSCLEROSIS

 Definition – lipid deposition and intimal

thickening of large and medium sized
arteries, leading to fatty streaks and
atheromatous plaques
 Distribution of disease – aorta, coronary,
carotid, cerebral, iliac
 Causes narrowing of the vessel lumen,
weakening of the media, progression to
ulceration, calcification, thrombosis,
aneurysm
ATHEROSCLEROSIS
 Risk factors

Major Minor
Hyperlipidemia obesity
Hypertension Sedentary lifestyle
Smoking stress
Diabetes Male gender
age
Family history
Elevated homocysteine
ATHEROSCLEROSIS…
 Grossly
White or pale yellow plaques 0.5-1.5 cm in
diameter bulging into the lumen with soft "gruel-
like" center
 Microscopically, atherosclerosis presents( from
inside the lumen to the outer vessel wall) as:
a. A fibrous cap composed of smooth muscle
cells, collagen, connective tissue matrix, and
scattered leukocytes
b. A cellular zone composed of smooth muscle
cells, macrophages and lymphocytes
c. A central core composed of necrotic cells,
cholesterol clefts, lipid-filled foam cells, and
plasma proteins
ATHEROSCLEROSIS
 Complicated atheromatous plaques
1. Seen in advanced disease
2. Arise when calcification and thickening cause
ischemia of the intima
3. Fissure, ulceration, and rupture of atheromas into
the lumen may cause:
 a. Thrombus formation with occlusion of the
vessel leading to infarction of the tissues
 b. Cholesterol emboli
 c. Hemorrhage into the lesion
 d. Aneurysmal dilatation
ATHEROSCLEROSIS..
 Fatty streak
 Elevated, poorly demarcated, yellow intimal
lesions less than 2 mm wide and 1 cm long
 Present in children as young as 1 year
 Composed of lipid-containing cells
(macrophages and smooth muscle cells),
collagen, elastic fibers, proteoglycans, and
extracellular lipid
 Most common in thoracic aorta
ATHEROSCLEROSIS…
 Etiology of atheromatous plaques

1. Response to injury
 a. Endothelial injury - due to
hypertension, hyperlipidemia, tobacco etc
 b. Injury may lead to increased
permeability of plasma proteins, platelet
and inflammatory cell adherence, and
thrombus formation
 c. Chemical mediators may induce
migration and proliferation of smooth
muscle cells from the media into intima
 d. Production of abundant connective
tissue matrix (collagen, elastic fibers,
proteoglycans) by smooth muscle cells

2. The loss of growth control hypothesis

suggests that smooth muscle proliferation
in the media may be the initial event.
 ANEURYSMS
 Focal, abnormal, dilatations of arterial vessels as a
result of wall weakness
 May lead to rupture, compression of nearby
structures, thrombus formation or embolism

Atherosclerotic aneurysms
1. Occur sec. to atheroma formation
2. Usually in abdominal aorta below renal arteries
3. Ass. With HTN
4. Half of these over 6 cm rupture within 10 yrs
ANEURYSMS

Syphilitic aneurysms:
1. Involve ascending aorta
2. Causes obliterative endarteritis of vasa vasorum
so causes ischemia and smooth muscle atrophy
3. May cause aortic insufficiency
4. Grossly, ―tree bark appearance‖
 Microaneurysms – small aneurysms seen in HT
and DM
 Mycotic aneurysms – due to bacterial infection
 Berry aneurysm – circle of Willis
ANEURYSMS
 Aortic dissecting aneurysm
1. Blood from vessel lumen enters an intimal
tear and dissects through layers of media
2. Severe tearing pain radiating to back.
3. May compress and obstruct aortic
branches.
4. Degeneration and cystic medial necrosis
of media.
5. HT and Marfan syndrome – predisposing
factors
VASCULITIS

An inflammation of the vessels - may be

localized (due to trauma, infections,
toxins) or systemic
VASCULITIS

Large vessel Medium vessel Small vessel

Giant cell Polyarteritis Wegener

arteritis nodosa granulomatosis
Takayasu Kawasaki Churg Strauss
arteritis disease syndrome
Microscopic
polyangiitis
POLYARTERITIS NODOSA (PAN)
 Young adults
 M>F
 Affects all organs (kidney, heart, muscle) except
lung
 Small and medium size arteries affected
(bifurcations mostly)
Clinically
1. low grade fever, wt loss , malaise
2. Hematuria, renal failure, hypertension
3. Abdominal pain, diarrhea, GI bleed
4. Myalgia, arthralgia
PAN….
Pathology
1. Segmental necrotizing vasculitis
2. Three stages
Acute lesion – fibrinoid necrosis and
neutrophils
Healing lesions – fibroblast proliferation
Healed lesions – nodular fibrosis and loss of
internal elastic lamina
Thrombosis, infarction , aneurysm
PAN…
 LAB Findings
1. Hepatitis B antigen positive (30%cases)
2. Perinuclear antineutrophil cytoplasmic
autoantibodies (P-ANCA)
Autoantibody againts myeloperoxidase,
only found in the microscopic form
(microscopic polyangiitis)
 Diagnosis – arterial biopsy
 Treatment – steroids, cyclophosphamide
 Long term remission rate – 90%
OTHER ANCA-POSITIVE VASCULITIDES

 Microscopic polyangiitis: Like Wegener‘s but

lacks granulomas. p-ANCA.
 1° pauci-immune crescentic glomerulonephritis:
Vasculitis limited to kidney. Pauci-immune =
paucity of antibodies.
 Churg-Strauss syndrome: Granulomatous
vasculitis with eosinophilia. Involves lung, heart,
skin, kidneys, nerves. Often seen in atopic patients.
p-ANCA.
 All affect small vessels.
 STURGE-WEBER DISEASE
 Congenital vascular disorder
that affects capillary-sized
blood vessels. Manifests with
port-wine stain on face and
leptomeningeal angiomatosis
(intracerebral AVM).
 Affects small vessels.
 TEMPORAL ARTERITIS (GIANT CELL)
 Most common form
 Females>males
 Elderly population
 Ass. With HLA – DR4
 large and medium arteries of the head
 MC – cranial artery (temporal, facial, ophthalmic)
 Clinically –
1. Throbbing headache
2. Tender, firm temporal arteries
3. Visual disturbances
4. Facial pain
5. Polymyalgia rheumatica : flu like symptoms + joint
involvement
TEMPORAL ARTERITIS…
 LAB – elevated ESR
 Pathology
1. Segmental granulomatous vasculitis
2. Multinucleated giant cells
3. Fragmentation of internal elastic lamina
4. Intimal fibrosis with luminal narrowing
 Diagnosis – temporal arterial biopsy
 Treatment – steroids (dramatic response)
Headache + tenderness at the
temples + elevated ESR=temporal arteritis
 WEGENER GRANULOMATOSIS

 Wegener‘s Characterized by triad of focal necrotizing

vasculitis, granulomatosis necrotizing granulomas in
the lung and upper airway, and necrotizing
glomerulonephritis.
 Symptoms Perforation of nasal septum, chronic
sinusitis, otitis media, mastoiditis, cough, dyspnea,
hemoptysis, hematuria.
 Findings c-ANCA is a strong marker of disease;
chest x-ray may reveal large nodular densities;
hematuria and red cell casts.
 Treatment Cyclophosphamide and corticosteroids.

 Affects small vessels.

TAKAYASU ARTERITIS ( PULSELESS
DISEASE)
 Most common in Asia
 Young and middle aged women (15 – 35)
 Medium sized to large arteries
 Aortic arch and its branches
 Clinically - Ocular disturbances (visual
abnormalities, retinal hemorrhages),
neurologic abnormalities,
Weak pulses in the upper extremities
 Pathology – Granulomatous vasculitis with
massive intimal fibrosis. Fibrous thickening of
wall of aortic arch. Narrowing of orifices of
major arterial branches
KAWASAKI DISEASE
 Mucocutaneous lymph node syndrome
 Infants and young children (<4yrs)
 Japan, Hawaii
 Coronary artery mostly affected
 Clinical features – acute syndrome consisting of:
Fever, conjunctivitis, erythema Erosions of oral
mucosa changes in lips/oral mucosa (―strawberry
tongue‖), Generalized maculopapular skin rash,
Lymphadenopathy
 Pathology – segmental necrotising vasculitis,
weakened vascular wall so aneurysm formation
BUERGER DISEASE
 Thromboangiitis obliterans
 Young males (under 40yrs)
 Ass. with heavy cigarette smoking
 Common in Israel, India, Japan
 Recurrent acute and chronic inflammatory disease
 Small and medium sized arteries and veins
 Involves the extremities
 Pathology - presents with neutrophilic inflammatory
infiltrate, mural thrombosis with microabscess and
giant cells
 Clinical features - severe pain in the affected
extremity, ulcers, gangrene, and thrombophlebitis.
RAYNAUD’S DISEASE
↓ blood flow to the skin due to arteriolar
vasospasm in response to cold temperature
or emotional stress.
 Most often in the fingers and toes (see Color
Image 106). Called Raynaud‘s phenomenon
when 2° to a mixed connective tissue
disease, SLE, or CREST syndrome.
 Affects small vessels.
HYPERSENSITIVITY ANGIITIS
 Leucocytoclastic vasculitis
 Affects small vessels usually skin
 May also affect lung, kidney (causes
crescentric glomerulonephritis)
 Distinguished from PAN by involvement of
smaller vessels
 Pathology - neutrophilic inflammation with
or without fibrinoid necrosis
 Clinical features - often ass. with well
defined clinical syndromes which involve
hypersensitivity reaction to an exogenous
antigen
HENOCH-SCHONLEIN PURPURA
 Most common form of childhood
systemic vasculitis. Skin rash
(palpable purpura), arthralgia,
intestinal hemorrhage, abdominal
pain, and melena. Follows URIs.
Multiple lesions of the same age.
 Hypersensitivity angiitis
clinically presents with - Purpura,
petechiae, necrotic ulceration
mostly on skin of feet and ankles
 VENOUS DISEASES
 Thrombophlebitis - inflammation and thrombus formation
of veins
 90% occur in deep leg veins like iliac, femoral, popliteal
(DVT)
 Pathology – Virchow‘s triad includes endothelial injury,
alterations in blood flow, hypercoagulability of blood
 Clinical features
Can occur . secondary to:
Clotting disorders (deficiency of antithrombin III, protein
C, or protein S), heart disease( CHF, myocardial
infarction, valvular diseases), immobilization (bed rest),
neoplasia, advanced age, pregnancy, oral
contraceptives etc.
 Unilateral leg swelling, erythema, Homan‘s sign positive
VENOUS DISEASES
Varicose veins
 Dilated tortuous veins due to increased
intraluminal pressure
 Superficial veins of lower extremities
F > M
 Prolonged standing
 Edema, thrombosis, ulceration
 Rarely a source of emboli
 Esophageal varices – due to portal HT
 Anal region (hemorrhoids) – due to
constipation
VASCULAR NEOPLASMS
Benign tumors Hemangiomas
a. Capillary hemangiomas - form unencapsulated,
well-defined masses of capillaries with little
connective tissue, usually occurs in the skin and
mucous membranes
b. Cavernous hemangiomas - form sharply defined,
sponge-like tumors composed of, large, dilated,
cavernous vascular spaces,, usually occur on the
skin, mucous membranes, and viscera, rarely
clinically significant except for their cosmetic effects
c. von Hippel-Lindau disease – autosomal dominant,
gene 3p, syndrome of multiple cavernous
hemangiomas involving the cerebellum, brain stem,
liver, pancreas ,and eyes. Associated with renal cysts
and RCC
VASCULAR NEOPLASMS
Vascular ectasias (telangiectasias)
 Developmental abnormality
 Can mimic benign vascular neoplasms
a. Nevus flammeus- flat birthmark on the head or neck,
spontaneously regresses
b. Port wine stain- may grow proportionately with the
child and may be associated with Sturge-Weber
syndrome
c. Spider telangiectasias- radial array of tiny arterioles,
commonly occuring in pregnant women, patients with
hepatic cirrhosis. In men – due to elevated estrogen
levels or liver disease (alcoholism)
TELANGIECTASIA
 Arteriovenous malformation in small
vessels. Looks like dilated capillary.
 Hereditary hemorrhagic telangiectasia
(Osler- Weber-Rendu syndrome)––
autosomal-dominant inheritance. Presents
with nosebleeds and skin discolorations.
 Affects small vessels.
VASCULAR NEOPLASMS
 Malignant tumors
 Hemangiosarcomas - growths of atypical,
anaplastic endothelial cells, commonly
occur in skin, breast, liver, and soft tissues.
Sharply defined red nodules
 Microscopically - show varying degrees of
anaplasia and vessels of different sizes
 Hepatic angiosarcomas are tumors caused
by toxic exposures (vinyl chloride, arsenic)
VASCULAR NEOPLASMS

Kaposi Sarcoma
 Low grade malignant tumor of endothelial
cells
 Ass. With HHV -8, one third of AIDS patients
 Grossly – multiple red purple patches,
plaques, nodules
 Microscopically – proliferation of spindle
shaped endothelial cells, slit like vascular
spaces
 Classic European form – European or
Mediterranean men, plaques on lower
extremities
 Transplant ass. form – pts on
immunosupression for organ transplants,
inv. Skin and viscera
 AIDS ass. Form – homosexual males, AIDS
pts. Skin, GI tract, LN, lungs. Responsive to
interferon alpha, chemo.
 African form – African children, lymphatic
spread
EMBOLUS TYPES
 Fat, Air, Thrombus, Bacteria, Amniotic fluid,
Tumor.
 Fat emboli are associated with long bone
fractures and liposuction.
 Amniotic fluid emboli can lead to DIC, especially
postpartum.
 Pulmonary embolus––chest pain, tachypnea,
dyspnea.

 An embolus moves like a FAT BAT.

Approximately 95% of pulmonary emboli arise
from deep leg veins.
DEEP VENOUS THROMBOSIS
 Predisposed by Virchow‘s triad:

 1. Stasis

 2. Hypercoagulability

 3. Endothelial damage

 Can lead to pulmonary embolism.

BACTERIAL ENDOCARDITIS
LIBMAN-SACKS ENDOCARDITIS (LSE)
 Verrucous vegetations occur on both sides
of the valve (can be associated with mitral
regurgitation and, less commonly, mitral
stenosis). Seen in lupus.

 SLE causes LSE.

RHEUMATIC HEART DISEASE
CARDIAC TAMPONADE
 Compression of heart by fluid (e.g., blood,
effusions) in pericardium, leading to ↓ CO.
 Equilibration of diastolic pressures in all 4
chambers.
 Findings: hypotension, ↑ venous pressure (JVD),
distant heart sounds, ↑ HR, pulsus paradoxus; ECG
shows electrical alternans (beat-to-beat alternations
of QRS complex height).
 Pulsus paradoxus (Kussmaul’s pulse)—↓ in
amplitude of pulse during inspiration. Seen in
severe cardiac tamponade, asthma, obstructive
sleep apnea, pericarditis, and croup.
PERICARDITIS

 Serous: Caused by SLE, rheumatoid arthritis, viral

infection, uremia.
 Fibrinous: Uremia, MI (Dressler‘s syndrome),
rheumatic fever.
 Hemorrhagic: TB, malignancy (e.g., melanoma).

 Findings: pericardial pain, friction rub, pulsus

paradoxus, distant heart sounds. Findings include
ECG changes with diffuse ST-segment elevation.
 Can resolve without scarring or lead to chronic
adhesive or chronic constrictive pericarditis.
SYPHILITIC HEART DISEASE
 3° syphilis disrupts the vasa vasorum of the
aorta with consequent dilation of the aorta
and valve ring.
 May see calcification of the aortic root and
ascending aortic arch. Leads to ―tree bark‖
appearance of the aorta.
 Can result in aneurysm of the ascending
aorta or aortic arch and aortic valve
incompetence.
 CARDIAC TUMORS
 Myxomas are the most common 1° cardiac tumor in
adults (see Color Image 88).
 90% occur in the atria (mostly LA).
 Myxomas are usually described as a ―ball-valve‖
obstruction in the LA (associated with multiple
syncopal episodes).
 Rhabdomyomas are the most frequent 1° cardiac
tumor in children (associated with tuberous
sclerosis).
 Metastases most common heart tumor (melanoma,
lymphoma).
 Kussmaul‘s sign: ↑ in jugular venous pressure on
inspiration.
ISCHEMIC HEART DISEASE
 Possible manifestations:
 1. Angina (CAD narrowing > 75%):

 a. Stable––mostly 2° to atherosclerosis
(retrosternal chest pain with exertion)
 b. Prinzmetal‘s variant––occurs at rest 2° to
coronary artery spasm
 c. Unstable/crescendo––thrombosis but no
necrosis (worsening chest pain)
 2. Myocardial infarction––most often acute
thrombosis due to coronary artery
atherosclerosis; results in myocyte necrosis
 3. Sudden cardiac death––death from cardiac
causes within 1 hour of onset of symptoms,
most commonly due to a lethal arrhythmia
 4. Chronic ischemic heart disease––
progressive onset of CHF over many years due
to chronic ischemic myocardial damage
CONGESTIVE HEART FAILURE
 inability of the heart to deliver a sufficient cardiac
output to meet the metabolic demands of the
peripheral tissues, despite normal or elevated
cardiac filling pressures.
Pathophysiology:
 1. Increased afterload
 2. Increased preload
 3. Severe valvular disease
 4. Chronic tachy- or bradyarrhythmias
 5. Impaired myocardial function
FACTORS INVOLVED IN THE DEVELOPMENT OF
CHRONIC CHF

 a. Sympathetic nervous system. Plasma

norepinephrine concentration is commonly elevated
in patients with CHR while myocardial tissue levels
of catecholamines are depleted. Systemic
vasoconstriction and tachycardia are also common
findings.
 b. Renin-angiotensin-aldosterone system.
Plasma renin levels are elevated in some patients
with CHF.
 C. Antidiuretic hormone. Antidiuretic hormone
levels are frequently elevated in CHF.
 Hemodynamic and hormonal factors contribute to
sodium retention by the kidneys and development of
peripheral and pulmonary edema, which characterize
advanced forms of CHF.
Symptoms
 1. Dyspnea
 2. Orthopnea: Recumbency results in a rise in the
position of the diaphragm and a decrease in ventilatory
reserve. More importantly, it causes increased venous
return from the dependent portions of the body,
augmenting right ventricular output and further
increasing pulmonary capillary pressure
 3. Paroxysmal nocturnal dyspnea (PND):
 4. Weight gain
SIGNS
 Cardiomegaly(eccentric or volume overload
hypertrophy)
 Thchycardia

 Arterial pressure may be high, normal, or, if cardiac

failure is severe, low (shock).
 Pulsus alternans (variations in blood pressure
associated with alternating weak and strong left
ventricular contractions) may be present if left
ventricular dysfunction is very severe.
 Respiratory rate is commonly elevated.

 Temperature may be markedly below normal if the

cardiac output is very low.
Right heart failure most often results from left
heart failure. Isolated right heart failure is usually
due to cor pulmonale.
 pulmonary rales,
 Severe pulmonary edema may also be associated
with wheezing secondary to bronchial wall edema or
bronchospasm.
 Central venous pressure (CVP) is commonly elevated
in patients with CHF:
 A. Jugular venous distension.
 b. Positive Kussmaul sign: ]ugular venous pressure
increases with inspiration.
 Hepatojugular reflex. Jugular venous pressure
increases more than 2 cm after approximately 1
minute of heavy pressure exerted by the examiner's
hands over the patient‗s abdomen while the patient
breathes normally.
 Hepatomegaly. If right ventricular failure is present,
the liver may become congested and enlarged.
 Edema, anasarca.

 Pleural effusions.

 Ascites.

 Cyanosis.
CLASSIFICATION OF CHF
 1. Clinically, CHF is usually classified by the
severity of impairment of exercise performance
according to the New York Heart Association
Functional Classification:
 a. Class I: no limitations of activity; no symptoms
with ordinary physical activity
 b. Class II: slight limitation of physical activity;
symptoms with ordinary activity
 c. Class III: marked limitation of physical activiry;
symptoms with lighter-than-ordinary activity
 d. Class IV: symptoms present at rest
STRATEGIES FOR TREATING CHF

 Reduce afterload (vasodilators) (e.g.,

captopril, hydralazine, nifedipine,
nitroglycerine) to reduce left ventricular
afterload.
 Reduce preload (diuretics) (e.g.,
furosemide, thiazides) to reduce
intravascular volume and ventricular
preload.
 Increase contractility (+ inotropes) (e.g.,
digoxin, dobutamine) to improve ventricular
contractility
INFARCTS: RED VS. PALE
 Red (hemorrhagic) infarcts occur in loose
tissues with collaterals, such as liver, lungs,
intestine, or liver, or following reperfusion.
 Pale infarcts occur in solid tissues with
single blood supply, such as heart, kidney,
and spleen. REd = REperfusion.
EVOLUTION OF MI
 Coronary artery occlusion: LAD > RCA >
circumflex.
 Symptoms: diaphoresis, nausea, vomiting, severe
retrosternal pain, pain in left arm and/or jaw,
shortness of breath, fatigue, adrenergic symptoms
DIAGNOSIS OF MI

 In the first 6 hours, ECG is the gold standard.

 Cardiac troponin I rises after 4 hours and is elevated for
7–10 days; more specific than other protein markers.
 CK-MB is predominantly found in myocardium but can
also be released from skeletal muscle.
 AST is nonspecific and can be found in cardiac, liver,
and skeletal muscle cells.
 ECG changes can include ST elevation (transmural
infarct), ST depression (subendocardial infarct), and
pathological Q waves (transmural infarct).
 MI COMPLICATIONS

 1. Cardiac arrhythmia––important cause of

death before reaching hospital; common in first
few days
 2. LV failure and pulmonary edema

 3. Cardiogenic shock (large infarct––high risk of

mortality)
 4. Ventricular free wall rupture → cardiac
tamponade; papillary muscle → severe mitral
regurgitation; and interventricular septal rupture
→ VSD
 5. Aneurysm formation––↓ CO, risk of
arrhythmia, embolus from mural thrombus
 6. Fibrinous pericarditis––friction rub (3–5
days post-MI)
 7. Dressler‘s syndrome––autoimmune
phenomenon resulting in fibrinous
pericarditis (several weeks post-MI)
CARDIOMYOPATHIES- DILATED (CONGESTIVE)
CARDIOMYOPATHY

 Most common cardiomyopathy (90% of

cases). Systolic dysfunction ensues.
Etiologies include chronic Alcohol abuse,
Beriberi, Coxsackie B virus myocarditis,
chronic Cocaine use, Chagas‘ disease,
Doxorubicin toxicity, and peripartum
cardiomyopathy.
Heart dilates and looks like a balloon on chest
x-ray.
HYPERTROPHIC CARDIOMYOPATHY
 Hypertrophy often asymmetric and involving the
interventricular septum.
 Diastolic dysfunction ensues.

 Normal heart size.

 50% of cases are familial, autosomal dominant.

 Cause of sudden death in young athletes.

 Findings: loud S4, apical impulses, systolic

murmur.
 Treat with β-blocker or non-dihydropyridine
calcium channel blocker (e.g., verapamil).
RESTRICTIVE/OBLITERATIVE
CARDIOMYOPATHY

 Major causes include sarcoidosis,

amyloidosis, postradiation fibrosis,
endocardial fibroelastosis (thick fibroelastic
tissue in endocardium of young children),
Loffler‘s syndrome (endomyocardial fibrosis
with a prominent eosinophilic infiltrate), and
hemochromatosis (dilated cardiomyopathy
can also occur).
 Diastolic dysfunction ensues.
CARDIOLOGY-PHARMACOLOGY
By Dr. Suyash Sharma
ANTIHYPERTENSIVE
 decreasing vascular tone, intravascular volume, or
cardiac contractility.
A. CENTRAL-ACTING SYMPATHOLYTIC AGENTS
MOA Uses S/A
1. Clonidine ↓ mod-to-severe Causes sedation,
Cloni Sympathetic out essential( i.e., dry mouth and
dine flow centrally. It idiopathic) HTN. insomnia,
also acts narcotic nightmares, and
peripherally by withdrawal, depression.
stimulating (ethanol Orthostatic
presynaptic α2 withdrawal), for hypotension,
receptors thereby the diagnosis of Rebound
inhibiting Norepi. pheochromocyto hypertensive
release & ↓ ma, renal crisis can occur
vascular tone and hypertension. after abrupt
heart rate withdrawal.
B. AGENTS ACTING AT PERIPHERAL ADRENERGIC
RECEPTORS

Beta-adrenergic blockers:
 Cardio selective(β1)- atenolol, acebutolol,
esmolol, metoprolol, betaxolol
 Non cardioselective (e.g., propranolol,
nadolol, timolol, pindolol, labetalol,
etoprolol,)
 Pindolol and acebutolol have intrinsic
sympathomimetic activity (ISA) and -less
negative Inotropic and chronotropic effects.
preferred in patients with decreased cardiac
functioning or a tendency for bradycardia.
 Drugs with ISA do not increase serum
triglycerides or decrease H DL lipids.
 Labetalol blocks both β and α, receptors.
↓peripheral vascular resistance without a
concomitant reflex tachycardia. It also has
some intrinsic sympathomimetic activity at β
2 receptors, which may contribute to
vasodilatation.
 BETA BLOCKERS
MOA Uses S/A

Decreased •Essential hypertension See next

cardiac output •SVT, VT slide
Inhibition of •Angina,
renin secretion •Acute MI (↓risk of reinfarction and death),
•hypertrophic cardiomyopathies (to
decrease ventricular outflow obstruction),
•hyperthyroidism (propanolol),
• Anxiety states (e.g., stage fright),
•Migraine headache (prophylaxis),
• glaucoma (timolol and betaxolol to reduce
secretion of aqueous humor),
•hypertensive emergencies, and
•pheochromocytoma (labetalol).
SIDE EFFECTS OF BB
 Bronchospasm (C/I in Asthma)
 Masking of the sympathetic responses to
hypoglycemia (contraindicated in patients with
diabetes, mellitus),
 A negative inotropic effect (exacerbates or
precipitates congestive heart failure), an
increase or precipitation of heart block or
bradycardia, and aggravation of vasospasm.
 Hallucinations, nightmares, depression and
impotence (less with lipid-insoluble agents) can
also occur.
 Rebound hypertension, angina, or rarely
even MI, may occur after abrupt withdrawal.
 GI: include nausea, diarrhea, or
constipation.
 Drug interaction decreased metabolism of B
blockers with cimetidine and
chlorpromazine.
 Lipids: Increased triglyceride levels and
decreased HDL cholesterol levels are also
seen (except with drugs with intrinsic
sympathomimetic activity).
 Impotence
2. ALPHA-ADRENERGIC BLOCKERS
 a. Prazosin, terazosin, and doxazosin (α1 selective)
 Phentolamine, tolazoline, and phenoxybenzamine
(nonselective α -blockers)
 PRAZOSIN, TERAZOSIN, AND DOXAZOSIN (Α 1
SELECTIVE)

Block, α-mediated •mild-to moderate postural

vasoconstriction essential HTN hypotension and
increase •CHF (preload reflex tachycardia
afterload and and afterload (usually after the
preload do not reduction), first dose),
increase the heart •pheochromocyto dizziness
rate during long- ma (prazosin), (commonly seen
term therapy. •BPH with prazosin),
sedation, and
headache.
Priapism
B. PHENTOLAMINE, TOLAZOLINE, AND
PHENOXYBENZAMINE (NONSELECTIVE Α -
BLOCKERS)

 blockadeof peripheral vascular α-

adrenergic receptors (both α1 and α2)
phentolamine tolazoline phenoxybenzami
ne
Competitive Competitive Noncompetitive
antagonist antagonist binds to α
receptors
Use: Use: Hypertensiveirreversibly
diagnosis of emergencies due Use: Raynaud's
pheochromocytom to phenomenon
a pheochromocytom
a, peripheral
S/A vascular disease
sedation, miosis, Raynaud's Same
postural phenomenon
hypotension, and Same
reflex tachycardia
 When patients stand, baroreceptors in the
carotids and aorta typically sense decreased
blood flow as blood pools in the venous system
due to gravity.
 This leads to a sympathetic response which
stimulates α1-adrenergic receptors, causing a
reflexive vasoconstriction and increased
resistance in order to maintain blood pressure.
 If a patient is taking an α1-adrenergic blocking
agent, this reflexive vasoconstriction and
increased resistance is blocked, and patients
often experience orthostatic hypotension.
 ADRENERGIC NEURON BLOCKERS
Reserpine Guanethidine
blocking the uptake of inhibits the releaseo f stored
neurotransmitters into norepinephrine
their storage vesicles from stimulated peripheral
leading to depletion of sympathetic nerve endings
catecholamine and
serotonin. Use: severe hypertension
Decrease cardiac output
and peripheral vascular orthostatic hypotension,
resistance sexual dysfunction
USE: mild-to-moderate (delayed or retrograde
hypertension, though it is ejaculation), and fluid
rarely used. retention.
S/A: sedation, bradycardia,
vasodilatation congestion,
flushing, conjunctival
congestion),diarrhea, and
depression with high suicide
risk (contraindicated in
patients with a history of
depression
CARDIAC DRUGS: SITES OF ACTION
CARDIAC DRUGS: SITES OF ACTION
 Cardiac sarcomere is shown above with the cellular
components involved in excitation-contraction
coupling. Factors involved in excitation-contraction
coupling are numbered.
 (1) Na+/K+ ATPase;

 (2) Na+-Ca2+ exchanger;

 (3) voltage-gated calcium channel;

 (4) calcium pump in the wall of the sarcoplasmic

reticulum (SR);
 (5) calcium release channel in the SR; (6) site of
calcium interaction with troponin-tropomyosin
system.
 Β1 receptors are Gs, and activate prolein kinase A
which phosphorylates L-type Ca++channels andd
phospholamban, both of which increases
intracellular Ca during the contraction.
 Cardiac glycosides Digoxin––75%
bioavailability, 20–40% protein bound, t1/2 = 40
hours, urinary excretion.
 Mechanism Direct inhibition of Na+/K+ ATPase
leads to indirect inhibition of Na+/Ca2+ exchanger/
 antiport. ↑ [Ca2+]i→positive inotropy.

 Clinical use CHF (↑ contractility); atrial fibrillation (↓

conduction at AV node and depression of
 SA node).
 Toxicity: May cause ↑ PR, ↓ QT, scooping of ST
segment, T-wave inversion of ECG. Also ↑
parasympathetic activity: nausea, vomiting,
diarrhea, blurry yellow vision, Arrhythmia.
 Toxicities of digoxin are increased by renal
failure (↓ excretion), hypokalemia (potentiates
drug‘s effects), and quinidine (↓ digoxin clearance;
displaces digoxin from tissue-binding sites).
 Antidote Slowly normalize K+, lidocaine, cardiac
pacer, anti-dig Fab fragments, Mg2+.
 Class I A agents: Class I A agents decrease the rate
of cardiac conduction by slowing the rate of phase
0 depolarization, slowing conduction, and prolonging
repolarization. This is primarily due to the blockade of
activated Na* channels.
 Class I B agents: The class I B agents decrease the
action potential duration by shortening the phase 3
repolarization. They have little effect on
depolarization. Because they block inactivated
sodium channels, they are useful in disorders in which
the myocardium becomes hypoxic or depolarized
(e.g., post MI, digitalis toxicity).
 Class IC agents (flecainide, encainide, propafenone,
and moricizine). The class IC agents induce
considerable phase 0 depression by strongly
binding to Na+ channels. They slow impulse
conduction in all cardiac tissue, especially in the His-
 Class II agents (B-adrenergic blockers). The
antiarrhythmic efficacy of these agents stems from their
suppression of phase 4 depolarization and their
inhibition of AV node conduction. They also decrease
myocardial contractility. Beta-adrenergic blockers used
as antiarrythmics include propranolol, acebutolol,
esmolol, and sotalol.
 Class III agents are all capable of prolonging the action
potential duration and increasing the effective
refractory period (ERP), i.e., the period during which
an action potential will only be stimulated via a strong
impulse. They block K+ channels and prolong
repolarization. They have no effect on phase 0
depolarization or the resting membrane potential
 Class IV agents: The Ca2+-channel blockers
increase the conduction time through the AV node
by blocking the slow calcium channels. They are
used for treatment of supra-ventricular
tachycardia (they protect ventricles from fast atrial
rates).
ANTIARRHYTHMIC CLASS 1 NA CHANNEL
BLOCKER
OTHER ANTIARRHYTHMICS

 Adenosine ↑ K+ out of cells →

hyperpolarizing the cell. Drug of choice in
diagnosing/abolishing AV nodal arrhythmias.
Very short acting (~ 15 sec). Toxicity
includes flushing, hypotension, chest pain.
 K+: Depresses ectopic pacemakers in
hypokalemia (e.g., digoxin toxicity).
 Mg2+ : Effective in torsades de pointes and
digoxin toxicity.
 Calcium-channel blockers differ in their clinical
effects:
 Nifedipine, nicardipine and nimodipine primarily
decrease peripheral resistance →↓ blood
pressure.
 Verapamil and diltiazem primarily reduce AV node
conduction
 Electrical cardioversion should be avoided with
digitalis intoxication because VF can be induced as
a result of a reduced fibrillation threshold. The
tissue is depolarized due to the pump block..
RENIN-ANGIOTENSIN SYSTEM (RAS)
THROMBOLYTIC AGENT
 Thrombolytic agents include streptokinase,
urokinase, and tissue plasminogen activator
(t-PA). These agents act by promoting the
conversion of plasminogen to plasmin. Plasmin, in
turn, acts to cleave fibrin and to dissolve clots