CV Objs W 2014 Up 2017

FMED 402: Cardiovascular
Week ONE Hypertension

WEEK OBJECTIVES
1. Describe the structure and function of blood vessels

Vessels have 3 layers:
1. INTIMA: endothelium in direct contact with blood, some underlying connective tissue
2. MEDIA: mixture of smooth muscle and CT
3. ADVENTITIA: mostly loose CT.
ARTERIES
VEINS
thick wall relative to lumen size

tunica media most prominent
concentric smooth muscle
predominate in media
concentric elastic tissue laminae
produced by smooth muscle cells
Elastic (Conduit Arteries)
-elastic recoil: expands in systole,
recoils in diastole
Muscular (Distributing) Arteries
***bear names
-prominent tunica media: smooth
muscle with many concentric elastic
laminae
-adventitia has less elastic tissue than
media, but more collagen.
thin and distensible

often collapsed in histologic sections
collagen rather than elastin in media
relatively thick adventitia plus vasa
vasora
flap like valves- prevent backflow.
Large veins
-Capacitance vessels under low pressure
Arterioles
-mainly regulate blood pressure
-<1mm diameter
-media has 1-2 layers of smooth muscle
cells.
Venules
-thin porous walls, diapedesis in
inflammation
-thinner walls, irregular lumens,
discontinuous layer of smooth muscle cells
in media.
Muscular Veins
-thin media
-prominent adventitia: mostly collagen and
smooth muscle cells.
-lack elastic laminae.
-has vasa vasora.
-interior valves counter gravity
Capillaries: single layer of flattened endothelial cells and pericytes on basement

membrane. Small diameter: 7-10um, accommodates 1 RBC. Thin enough for gas exchange.
Tight: endothelium has tight junctions e.g. BBB
Fenestrated: allow rapid passage of water and small solutes. e.g. in endocrine/renal
tissues
Sinusoidal: large diameter, porous, discontinuous lining, no basement membrane
e.g. liver/spleen/bone marrow.
2. Express the determinants of blood flow as equations: (lecture)
a. Blood Flow (Q) = Arterial Pressure (P) / Peripheral Resistance (R)
b. Cardiac Output (CO) = Bood Pressure (BP) / Systemic Vascular Resistance
(SVR)
Peter Chen, Alia Dharamsi, Sebastian Ko, Justin Mui, Aalia Sachedina, Indeep Sehkon MD 2014. Updated for
MD 2017 by J^2N
2 factors of blood flow (Q) like current
Pressure (P) like voltage, and Resistance (R) like resistance

Q = P/R (derived from Pouiselles Law) like I = V/R
Cardiac output (CO), Blood Pressure (BP), and Resistance (SVR) are related by the following
equation:
CO = BP / SVR
o Note that BP = MAP = DP + 1/3(SP-DP)
MAP = mean arterial pressure
PP = pulse pressure = SP-DP
o Note that CO = (HR) x (SV)
SV = stroke volume
Normal values
CO ~ 5 L/min
SVR ~ 0.018 mmHg/ml/min
in order to determine the cause of abnormal BP, compare pts values with these
normal values see if CO or SVR contributes more
Pulmonary Artery (Swan Ganz) Catheter
Estimates CO via Thermodilution (then CO = BP / SVR to solve for unknowns)
o Indicator = cooled saline; injected; mixes w/ warm blood in RV; temp
change measured by thermister in distal port
o Also measures RVP, PAP, and Pulmonary Wedge Pressure (~LAP)
3. List the neural and humoral factors that regulate blood pressure (Courneya Text
Chpt. 9, Lecture Notes)
A. The sympathetic and parasympathetic autonomic nervous system
o
Arterial baroreceptor response:

Arterial baroreceptors are complex sensory nerve endings that are found at
the carotid sinus and the aortic arch.
They respond to stretching by increasing their firing rate and are sensitive to
pressures between 50 to 200 mmHg.
The carotid sinus baroreceptor is innervated by the glossopharyngeal nerve
(IX) while the aortic arch baroreceptor is innervated by the vagus nerve (X).
Increasing the blood pressure in either the aortic arch or carotid sinus causes
an increase in baroreceptor firing rate, triggering the following reflex
responses:
Increase in PNS (vagal) output to the heart decrease in HR and
contractility
ii.
Decrease in SNS activity to the heart decrease in HR and
contractility
iii.
Decrease in SNS activity to the peripheral vascular vessel relaxes
smooth muscles, thereby decreasing SVR
The opposite is true in the presence of decreased blood pressure
Prolonged exposure (>10 min) of baroreceptors to high pressures leads to a
resetting of the range over which the baroreceptors respond.
i.
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Arterial Baroreceptor Response Under Normal Blood Pressure
B. Arterial baroreceptor response (new for 2017s, pasted from objectives):

i. Arterial baroreceptors are complex sensory nerve endings that
are found at the carotid sinus and the aortic arch.

ii.
They respond to stretching by increasing their firing rate and
are sensitive to pressures between 50 to 200 mmHg.
iii.
The carotid sinus baroreceptor is innervated by the
glossopharyngeal nerve (IX) while the aortic arch baroreceptor
is innervated by the vagus nerve (X).
iv.
Increasing the blood pressure in either the aortic arch or
carotid sinus causes an increase in baroreceptor firing rate,
triggering the following reflex responses:
Increase in PNS (vagal) output to the heart decrease in HR and
contractility
Decrease in SNS activity to the heart decrease in HR and
contractility
Decrease in SNS activity to the peripheral vascular vessel relaxes
smooth muscles, thereby decreasing SVR
v.
The opposite is true in the presence of decreased blood
pressure
vi.
Prolonged exposure (>10 min) of baroreceptors to high
pressures leads to a resetting of the range over which the
baroreceptors respond.
C. The rennin-angiotensin-aldosterone system and arginine vasopressin (AVP or
ADH)
o
Arterial baroreceptor response:

The arterial baroreceptor response is also responsible for controlling RAAS
and AVP
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Decreasing the blood pressure in either the aortic arch or carotid sinus
causes a decrease in baroreceptor firing rate, triggering the following
responses.
i.
Increased renal SNS nerve activity rennin release activation of
RAAS
o Actions of RAAS system mediated by Angiotensin II
Increase in Na+ reabsorption at proximal tubule
Vasoconstriction of renal and systemic blood vessels
Triggers release of aldosterone
Aldosterone increases Na+ reabsorption at the distal
tubule and collecting duct in exchange for K +
Stimulates thirst and triggers further release of
vasopressin (Boron)
ii.
Increased release of vasopressin from posterior pituitary gland
increased reabsorption of water at the collecting duct and has
moderate vasoconstriction effect.
Overview of ReninAngiotensinAldosterone System
D. Local factors for Systemic Vascular Resistance: Endothelins, Nitric Oxide and
Adenosine
o
Endothelins (ETs)
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Nitric Oxide
Synthesized and release from endothelial cells
Produced from L-Arginine by Nitric Oxide Synthase
Acts as a vasodilator
Family of peptides that are synthesized and released from endothelial cells
ETs, acting at ETA receptors in vascular smooth muscle cells, are
vasoconstrictors
ETs, acting at ETB receptors on endothelial cell membranes, causes release of
nitric oxide
Endothelin in lung vasculature:
Hypoxia is a potent stimulated of ET release. This causes local
vasoconstriction and directs blood away from poorly oxygenated
areas.
Nitroglycerin breaks down to Nitric Oxide and is therefore a treatment for

angina
Acts as a venodilator decreases preload and therefore oxygen
demand
Acts as a vasodilator of coronary arteries increases O2 supply
NO activates cGMP-dependent protein kinase (PKG) to phosphorylate
myosin light chain kinase(MLCK) and prevent myosin/actin interaction
Adenosine (Not Testable According to CV Forum)

Synthesized and released in myocardial cells during states of hypoxia,
ischemia or strenuous work.
Produced from the breakdown of adenosine monophsophate (AMP)
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Acts as vasodilator
4. For hypertension explain the following:

a. classification of primary vs. secondary
Primary hypertension
Cause of hypertension is unknown
Genetics likely play a role
Obesity, diabetes mellitus, hyperlipidemia as a group are liked to hypertension
(metabolic syndrome)
Some of suggested that an enhanced response to catecholamines play a role in
hypertension or the primary cause of hypertension
All in all, hypertension is likely to be a mix of nature and nurture
Secondary hypertension
95% of patients seem to have primary hypertension (5-10% have secondary)
Secondary hypertension ought to be suspected in the following instances:
o When it occurs at the extremes of age with unexpected target organ damage
o When it occurs abruptly
o When response to therapy is atypical
o When renal failure is present
o When hypokalemia or hypercalcemia are present
The approach to diagnosis of secondary hypertension can be as simple as ABCDE
o A accuracy, sleep apnea, primary aldosteronism
o B - bruits, bad kidneys
o C catecholamines, coarctation of aorta, cushings syndrome
o D diets, prescription drugs (corticosteroids, NSAIDs, oral contraceptives or
high doses of estradiol, non-prescription drugs
o Erythropoietin, endocrine disorders
b. Etiologies
There are many different potential causes or risk factors for hypertension. Outlined here are
some standered ones:
Age age is considered to be one of the prime factors in high blood pressure because
the chances of developing hypertension increase with age.
o As you age, the blood vessels inside the body begin to constrict, hence
reducing the volume of blood flow. As a result increased amount of pressure is
exerted by the blood so it can pass through the narrowing blood vessels.
Race - it has been found that people with darker skin tone are more susceptible to the
development of high blood pressure as compared to individuals with lighter skin color.
o The hereditary factors cause the transmission of the condition from one
generation to the next generation.
Smoking - Even exposure to secondhand smoke is considered to be one of the major
factors resulting in elevation of blood pressure.
o The chemicals present in such products often get accumulated over the walls
of the blood vessels and arteries and lead to high blood pressure in individuals.
Other common causes
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Various other common factors considered to be possible causes of

hypertension, according to the Mayo Clinic, include reduction in levels of
vitamin D, low potassium levels, excessive consumption of alcohol, and stress,
among others.
c. Diagnosis
Diagnostic criteria for hypertension seem to continually change over the years
Hypertension can be made when systolic is above 160 or diastolic is above
100mmHg averaged across three separate visits at least a week apart
Up to 5 visits may be necessary when BP is 140-160/90-100mmHg range
Ambulatory BP is an alternative means to detect hypertension as opposed to
additional office visits (mean awake systolic BP greater than 135 or the diastolic
greater than 85)
The target values are lowered with patients with diabetes (before diagnosis of
hypertension) or chronic renal failure (>130/80mmHg)
Hypertension can be diagnosed if it is above 180/110mmHg on the 2 nd visit
d. Complications if untreated (target organ damage)

Complications of hypertension are but are not limited to:
i.
Verebrovascular disease (stroke)

Stroke is the 3rd most common cause of death in NA
It is caused by abrupt disruption of the blood supplying an area of the brain
Hypertension is the number one risk factor for stroke and for every 2-3 mmHg
reduction in systolic BP the incidence of stroke could be reduced by 10%
ii. Coronary artery disease

Coronary heart disease (CHD) is a narrowing of the small blood vessels that supply
blood and oxygen to the heart. CHD is also called coronary artery disease.
This could lead to other ailments like angina or heart attack
iii. Left ventricular hypertrophy
While ventricular hypertrophy occurs naturally as a reaction to aerobic
exercise and strength training, it is most frequently referred to as a pathological
reaction to cardiovascular disease, or high blood pressure.
While LVH itself is not a disease, it is usually a marker for disease involving the heart.
[2]
Disease processes that can cause LVH include any disease that increases
the afterload that the heart has to contract against, and some primary diseases of the
muscle of the heart.
iv. Abdominal aortic aneurysm
Abdominal aortic aneurysm (also known as AAA, pronounced "triple-a") is a
localized dilatation (ballooning) of the abdominal aorta exceeding the normal
diameter by more than 50 percent, and is the most common form of aortic aneurysm.
Approximately 90 percent of abdominal aortic aneurysms occur infrarenally (below
the kidneys), but they can also occur pararenally (at the level of the kidneys)
or suprarenally (above the kidneys).
v. Chronic renal failure
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Hypertension is the 2nd leading cause of end-stage renal disease

Autoregulation normally buffers the renal microvascular from high BP, but once
vascular injury develops this protective mechanism is compromised
Over time, the arterioles remodel by rearrangement of the smooth muscle later
around a constricted lumen and in some vascular beds there is loss of flow through a
region
The net effect is increased vascular resistance within the kidneys, parenchymal
scarring
Functionally, this results in disordered sodium and water excretion along with
potassium excretion
Albumin spills into the urine
e. both pharmacologic and non-pharmacologic treatment

Please look at Week objectives 6 and 7 for information regarding this.
f. impact of a chronic disease on quality of life
The impact of chronic disease can vary from people to other people
This is especially true with hypertension since it is usually asymptomatic
Having a chronic disease can result in some forms of depression, even if the it is
asymptomatic
o This is due to taking extra medication and being aware that the patient
themselves have a chronic disease state (causing potential stress).
Financial burdens may come into play (paying for medication etc.)
5. Outline the process of excitation/contraction coupling in terms of:

a. The relationship between electrical (action potential) and mechanical
(contraction) activities in myocardium
Cardiac Muscle Structure
Almost identical to skeletal muscle

Key differences:
o Smaller SR
o T-tubules are larger in diameter (200nm)
o Longitudinal elements of tubule system (function unclear)
o Excitation-contraction coupling occurs in both dyads and triads
o Very large mitochondria (40% of cell volume) since cardiac muscle is almost
exclusively dependant on oxygen metabolism
Calcium-Induced Calcium Release

1. Ca2+ enters the myoplasm of the cell through voltage-gated Ca2+ channels located
in the sarcolemma of t-tubules (occurs during the plateau phase of action
potential)*note: this increase in Ca2+ inside the cell is not enough to produce a
contraction forceful enough to maintain cardiac output
2. Ryanodine receptors located in the SR membrane directly opposite the voltage-gated
channels (not physically coupled!) open in response to the increase in intracellular
Ca2+ concentration.
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3. When the Ryanodine receptors open, they release a large amount of Ca2+ from the
SR into the myoplasm. *note: this produces enough force to maintain cardiac output.
4. 2 pumps are responsible for restoring the Ca2+ concentrations:
1) the Na/Ca exchanger pumps out the Ca2+ that entered the myoplasm via the
voltage-gated Ca2+ channels
2) the SR Ca ATPase pumps the Ca2+ that entered the myoplasm via the
Ryanodine Receptors back into the SR
b. The mechanism by which beta-agonists affect the rate (chronotropy) and force
(ionotropy)of myocardial contraction.
Stimulation of 1 adrenergic receptors produces:
increased heart rate (positive chronotropic effect)

increased force of contraction (positive ionotropic effect)
increased rate of relaxation (positive lusitropic effect)
In combination, these effects cause the heart to beat faster and more forcefully =
INCREASED CARDIAC OUTPUT.
All of the changes are produced by the action of protein kinase A on key regulatory proteins
that regulate the intracellular Ca2+ concentration.
c. The relationship between cellular energy generation and contractility.
Please refer to Energy utilization chart (last page of Dr.Moores lecture)
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Indications
Diuretics
Drug
-Thiaizides
(hydrochlorothiazide)
-Loop
(furosemide)
-K+ sparing
(spironolactone)
-Inhibit reabsorption of
Na+.
-Loop diuretics and
thiazides also act as
vasodilators (esp
important for thiazides)
hypertension
-Edema
cardioselectiv
e (1)- atenolol,
metoprolol
-noncardioselective
(1 &2)propannolol,
nadolol, timolol
-mixed & labetolo,
carvedilol
-partial
Dihydropyridine
s: Nifedipine,
amlodipine,
felodipine,
nicardipine
-block 1 receptors:
reduce HR and SV,
reduce renin secretion
-direct inhibitory effects
on SNS
-mixed a and b
antagonists additionally
cause vasodilation via a
blockage.
- HTN, chronic
heart failure,
arrhythmia,
angina, post
myocardial
infarction,
other non
cardio
indications
(migraine,
public
speaking
anxiety,
-HTN
-prevent/treat
coronary
spasm in
variant
angina
-prevent
cerebral
artery spasm
after brain
hemorrhage
blockers- DHPsCalcium channel
MOA
Beta blockers
6. Describe the pharmacology of the following drugs (Source: lecture notes, Goodman and Gilmans
pharmacology)
- L-type calcium channel

antagonists: block influx
of calcium through Ltype channels, inhibit
contraction of smooth
muscle vasodilation.
- DHPs have greater
selectivity for the
vasculature (the nonDHPs have greater
selectivity at the heart).
Contraind
ications
Hypovolem
ia
- severe
electrolyte
abnormaliti
es
Side effects
Miscellaneous
- electrolyte
disturbances (Na,
K)
- Dehydration,
subsequent renal
dysfunction
- non
selective
(b1 &b2)
for
asthmatics
-2nd degree
heart block
bradycardi
a
-acute
heart
failure.
-pregnancy
(teratogeni
c)
-conditions
in which
tachycardia
is harmful:
coronary
artery
disease,
aortic/mitra
-fatigue
-bradycardia/heart
block
-hypotension
-CNS effectsinsomnia,
nightmares,
depression
-Raynauds
phenomenon (cold
extremities e.g.
fingers)
-hypoglycemia
-vasodilation
related symptoms:
flushing, dizziness,
headache,
tachycardia.
- requires
functioning kidney
to exert effects.
- thiazides are
weaker than loop
diuretics, b/c it acts
downstream of
where
most of Na+
-beta blockers
useful for
myocardial ischemia
and infarcation
(reduce O2 demand)
-generally avoided
for elderly, younger
patients tend to
respond well
-DHPs induce a
baroreceptormediated reflex
tachycardia to
counter the lowered
BP from
vasodilation.
-DHPS metabolized
by CYP3A4.
-Grapefruit juice
inhibits metabolism
Peter Chen, Alia Dharamsi, Sebastian Ko, Justin Mui, Aalia Sachedina, Indeep Sehkon MD 2014. Updated for MD 2017 by J^2N
ACE inhibitor
Captopril,
ramipril,
enalapril,
fosinopril,
lisinopril,
monopril,
perindopril,
quinapril,
benazepril,
cliazpril.
-ACE converts ATIATII,

and breaks down
bradykinin.
-By inhibiting ACE, ACEi
decreases vasodilation
(ATII vasoconstricts,
bradykinin vasodilates),
and decreases Na+ and
H2O reabsorption (ATII
cause aldosterone
secretion)
-HTN, CHF,
post
myocardial
infarction
-Pregnancy
(teratogeni
c, cause
fetal
hypotensio
n)
-renal
dysfunction
Angiotensin receptor blockers
Losartan,
Candesartan,
Irbesartan,
Valsartan,
Eprosartan,
Telmisartan
-HTN, chronic
congestive
Heart failure
-For patients
who require
ACEi, but
cannot
tolerate
cough
-Pregnancy
(teratogen)
blockersAlpha 1
-e.g. Prazosin,
terazosin,
doxazosin
-Angiotensin 1 (AT1)
antagonist: blocks
actions of ATII
vasodilation, natriuresis
(less aldosterone)
-effect of ARB is
downstream of ACE.
Therefore, compared to
ACEi, has no effect on
bradykinin levels (less
vasodilation?).
-However, ACE is not the
only enzyme that
converts AT1ATII, so
ARBs
might have more
-inhibits
vasoconstriction
reduce arteriolar
resistance, increase
venous capacitance
lowers peripheral
Hypertension,
congestive
heart failure.
-dry cough (due to

increased
bradykinin)
-hyperkalemia
(reduced
aldosterone)
-hypotension
-renal dysfunction
(vasodilates
efferent arteriole,
decreases GFR.
More prominent in
volume depleted
-Well tolerated
-dizziness,
hypotension
-Hyperkalemia
when used with
K+ supplements,
or K+-sparing
diuretics
-Renal failure
(same reason as
for ACEI)
-angioedema,
much rarer than
with ACEI
-ACEi may be useful

in diabeticsprotects kidneys by
reducing
intraglomerular
pressure
(vasodilates efferent
arteriole), and
overall reduces
systemic BP.
-Postural
hypotension
-reduce plasma
triglycerides and
total LDL, increase
HDL.
-rarely used
-not recommended
as monotherapy:
used in conjunction
with diuretics, beta
blockers..etc.
- less cough than

ACEI, possibly due
to lack of increased
bradykinin.
Direct vasodilators
antagonistsAldosteroneInhibitorsDirect Renin
Aliskiren
Spironolactone,
Eplerenone
-Hydralazine
-Directly inhibits renin

eynzyme.
-Compared to ACEI and
ARBs: ACEI and ARBS
might cause a
compensatory effect
(produce more renin, use
AT2 or AT3 receptors
etc). Renin inhibitors
may
shut
down entire
-blocks
aldosterone
receptors in the
collecting duct.
-relaxes arteriolar
smooth muscle, does not
affect venous smooth
muscle. Exact MOA
unclear.
-HTN
-Heart failure
(investigating
)
-pregnancy
-Generally welltolerated
-Diarrhea
coadministere
d with
thiazide or
loop diuretic
to treat
edema and
hypertension.
-particularly
useful for
-Hypertension
-peptic
ulcers
-hyperkalemia (it
is a K+ sparing
diuretic)
-spironolactone
may cause
gynecomastia,
impotence,
decreased libido,
hirsutism, GI
symptoms.
-effects due to
pharmacologic
effects of drug:
headache,
nausea, flushing,
hypotension,
palpitations,
tachycardia,
angina pectoris
-Immunological
reactions (lupus
-Use with
extreme
caution in
elderly
patients,
patients
with
coronary
artery
disease
(possibility
-rarely used
- can be used in
patients with CHF
who cannot tolerate
ACEI or AT1 receptor
antagonists, and in
pregnant women
hypertensive
emergencies e.g.
preeclampsia.
Page 13 of 141
CV Week 1 Hypertension
Case Objectives
1. Delineate the diagnostic criteria for the diagnosis of hypertension
2. Understand the importance of global cardiovascular risk factor assessment in

patients with hypertension.
The risk of cardiovascular disease depends on blood pressure, coexistent risk facts
and whether there is hypertensive damage to target organs.
o Since hypertension can lead to cardiovascular disease, it is important to assess
other risk factors in order to tailor a treatment plan for your patient.
MD 2017 by J^2N
Page 14 of 141
Risk factors for cardiovascular disease include:

o Family History
o Age & Sex
o Cholesterol
o Smoking
o Diabetes Mellitus
o Body weight & Obesity
o Sedentary Lifestyle
o Alcohol & Drugs
o Diet (Na+ intake)
o Left ventricular hypertrophy
Models can be used to predict an individual's risk of cardiovascular disease to define

the expected benefits and harms of treatment. Each prediction model has different
variables incorporated.
o Risk prediction models:
Framingham (USA)
Cardiovascular disease life expectancy model (USA & CAN)
3. Explain the role of the screening cardiovascular examination and laboratory

investigations in a patient with hypertension (both in determining etiology and
screening for target organ damage)
The cardiovascular is crucial to a patients well being
It is important to take into consideration the potential sequalae of hypertension as
well as risk factors
o Mainly, the role of the examination is to assess:
Whether the patient has End organ damage (eyes, kidneys, brain and
heart)
The extent of damage done to the body by the ailment
Whether the patient has extraneous risk factors that may increase the
likely hood of hypertensive sequalae (myocardial infarction, stroke, TIA
etc.)
If the patient has a need for additional medical treatment in the way of
their complications
It is not so much the disease of hypertension that we are worried about, but instead
we are more concerned about the consequences of it, and the long term ill effects
that chronic high blood pressure may have on the body.
Laboratory results may also play an important role in how we view hypertension
General tests that may be ordered include:
Urinalysis - ordered to help assess kidney function

Hematocrit may be ordered as part of the Complete Blood Count (CBC) to evaluate
the ratio of fluid to solids in the blood
BUN (Blood Urea Nitrogen) and/or Creatinine to detect and monitor kidney
dysfunction or to monitor the effect of medications on the kidneys
Potassium may be ordered as part of the Electrolyte panel, which also includes
sodium, chloride, and carbon dioxide (CO2); used to evaluate and monitor the balance
of the bodys electrolytes; some high blood pressure medications can upset the balance
by causing excessive sodium and potassium loss
Fasting Glucose ordered to determine if blood glucose levels are within healthy
ranges
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Page 15 of 141
Calcium may be ordered to determine how much total calcium or ionized calcium is
circulating in the blood; increased activity of the parathyroid glands, which produces an
increase in serum calcium, is associated with hypertension
TSH (Thyroid Stimulating Hormone) and T4 may be ordered to detect and monitor
thyroid dysfunction
Lipid Profile may be ordered to evaluate levels of total cholesterol, HDL cholesterol,
LDL cholesterol and triglycerides
The Basic Metabolic Panel (BMP) includes several of the tests listed above, so it may be
ordered instead of the individual tests. Specific tests that may be ordered based on the
patients medical history, physical findings, and routine laboratory test results to help
detect, diagnose, and monitor conditions causing secondary hypertension include:
Aldosterone and Renin to help detect the overproduction of aldosterone by the

adrenal glands (which may be due to a tumor)
Cortisol to detect an overproduction of cortisol that may be due to Cushings

syndrome
Catecholamines and Metanephrines to measure epinephrine, norepinephrine, and

theirmetabolites primarily to help detect the presence of a pheochromocytoma that can
cause episodes of severe hypertension
As part of the diagnostic process and to help evaluate the status of vital organs, the doctor
may order or perform one or more of the following:
ECG (Electrocardiography) to evaluate the heart rate and rhythm and look for
evidence of heart damage
Eye Exam to look at the retina for changes in the blood vessels (retinopathy)
Physical Exam to help evaluate the kidneys, to look for abdominal tenderness, to
listen for bruits (the sound of blood flowing through a narrowed artery), to examine the
thyroid gland in the throat for any enlargement or signs of dysfunction, and to detect
any other clinical signs as they present
Imaging scans, such as X-ray or ultrasound of the kidneys or X-ray of the chest
4. Outline a diagnostic approach for differentiating primary from secondary

causes of hypertension.
Primary
Secondary
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Page 16 of 141
Most common type of Htn

Idiopathic Htn (Usually)
Genetics likely to play role
Littles Disease mutation noted
where there is renal sodium retention
and therefore increased water
retention.
Obesity, DM, hyperlipidemia linked to
Htn (Metabolic syndrome)
Alchoholism
Evidence to suggest catecholamine
response Increased SNS
(epinephrine) leading to increased
exaggerated vasoconstriction in some
Pt
Increased SNS also increase BP via HR,
SV, SVR, and RAAS
Patients younger than 40 tend to have
high CO and normal SVR over time,
get vascular hypertrophy and
increased SVR as well as LV
hypertrophy systolic function may
get impaired, CO falls back.
(Progression to normal CO and high
SVR)
Rare
Occurs secondary to a primary,
identifiable cause (many
different ones possible)
Suspected when Htn occurs at
extremes of age with
unexpected organ damage,
abrupt occurance, response to
therapy atypical, renal failure
present, hypokalemic or
hypercalemic.
AAABBCCCDDDEE approach to
hypertension
Aortic coarctation,
hyperparathyroidism
Hyperaldosteronism
Sleep Apnea
Renal Failure
Pheochromocytoma
Cushings Syndrome
Drugs
ABCDE
3xA: Accuracy (are you screwing up?), apnea (sleep), aldosteronism

2xB: Bruits (renal stenosis increased RAAS), bad kidneys (chronic renal failure
fluid retention)
3xC: Catecholamines (pheochromocytoma), coarctation of aorta, Cushings (elevated
cortisol, leading to increased Na retention)
3xD: Diet with increased sodium, Drugs (prescription; Corticosteroids, NSAIDs, oral
contraceptives), Drugs (Non-prescription; Nicotine, ephedra, meth/cocaine)
o Contraceptives in case probably dismissed this as a possibility of secondary
Htn too quickly. Probably better to stop contraception first and see if there is an
effect.
o Case of doc moving too quickly.
2xE: E-po, Endocrine disorders
5. Discuss the management of hypertension

Source: Lillys, http://www.bcguidelines.ca/gpac/guideline_hypertension.html#part2
Lifestyle modification
a. Weight reduction
a. Maintain BMI 18.5-24.9 kg/m2, waist circumference <40 for men,
<35 for women.
b. BP reduction follows weight loss in large portion of hypertensive patients who
are >10% above ideal weights
c. 10kg weight loss associated with 5-20mmHg fall in systolic BP.
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b. Exercise:
a. 30-60minutes of moderate intensity dynamic activity 4-7 days a week
(e.g. walk 3km in 30 minutes once per day, or walking 1.5km in 15
minutes 2x per day, jogging, cycling, swimming)
b. Regular aerobic exercise show to contribute to BP reduction, over and above
any resulting weight loss
c. Mechanism: lower resting HR, lower levels of circulating catecholamines,
suggests fall in sympathetic tone.
c. Diet:
a. Besides caloric restriction that contributes to weight loss, eating more fruits,
vegetables, and low-fat dairy products, fibre, whole grains, protein
sources that are reduced in saturated fats and cholesterol has been
shown to lower BP (DASH diet- dietary approaches to stop hypertension)
d. Smoking:
a. Complete cessation of smoking, exposure to 2nd hand smoke is
recommended.
b. Smoking transiently increases BP (nicotine on autonomic ganglia), as well as
risk of development of sustained hypertension.
c. Also has atherogenic effect.
e. Sodium
a. Recommend <1500mg per day for adults <50yo.
i. 1300mg for 51-70yo.
ii. 1200mg for >70yo.
b. In essential hypertensive patients: ~50% found to have BP that vary with Na+
intake.
f. Alcohol
a. <2 drinks per day, <14 drinks per week for men, (<9drinks/wk for women)
g. Potassium, calcium, magnesium intake
a. Supplementation of K+, Mg, Ca is not recommended for the prevention or
treatment of hypertension.
h. Relaxation therapy
a. Stress often causes BP to rise.
Medical (Antihypertensive pharmacology)
Source: http://www.bcguidelines.ca/gpac/guideline_hypertension.html#part2
See Week objective #6 for MOA of each class of drug.
Treatment of Uncomplicated hypertension

o For first line treatment, use monotherapy with low-dose thiazide diuretic.
o If BP still not adequately controlled, use combination therapy by adding one or
more of the following agents:
Angiotensin converting enzyme inhibitor (ACEI)
Angiotensin II receptor blocker (ARB) if ACEI intolerant
Long-acting dihydropyridine calcium channel blocker (DHP-CCB)
Treatment for HTN complicated by co-morbid conditions
o Special considerations need to be made for co-morbid conditions e.g. coronary
heart disease, myocardial infarction, heart failure, chronic kidney disease,
diabetes mellitusetc.
Specific contraindications to antihypertensive medications
o Contraindications
Asthma: Non-cardioselective beta blockers (e.g. propanolol)
2o or 30 heart block: beta blockers; non-DHP CCB
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Relative contraindications
COPD: beta blockers
Gout: thiazide diuretics
Heart failure: Non-DHP CCB; alpha blockers
Renal insufficiency: Potassium sparing agents
Depressing: beta blockers; central alpha agonists; reserpine.
Invasive (Surgical excision of tumors and endovascular procedures) (Lillies)

Endovascular procedures
o Renovascular hypertension:
Percutaneous catheter interventions or surgical reconstruction of the
stenosed vessel.
o Coarctation of the Aorta
Excision of the narrowed aortic segment
Transcatheter interventions (balloon dilatation with or without stent
placement)- usually for older children, adults and patients with recurrent
coarctation after previous repair.
Resections of tumors
o Pheochromocytoma- surgical resection of tumor (usually in adrenal medulla)
o Primary aldosteronism: surgical removal of the adrenal adenoma.

Week TWO Development of the Heart & Consequences of Maldevelopment
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WEEK OBJECTIVES
1. Describe cardiac anatomy:

a. Chambers, valves, pericardium, great vessels (Source: Grays Anatomy, Lillys)
*heart and roots of great vessels = enclosed by pericardial sac (fibrous pericardium +
serous parietal pericardium); visceral pericardium (epicardium) adheres to heart exterior
Chambers and Valves
R. atrium
o Contributories = SVC, IVC, coronary sinus (feeds along coronary sulcus, enters left
to IVC)
o Crista terminalis = internal division (smooth muscular ridge)
Front of SVC opening front of IVC
o Sinus of venae cavae = smooth wall, posterior to crista terminalis (derived from
R. horn of sinus venosus)
o Atrium proper = rough musculi pectinati, anterior to crista terminalis (derived
from primitive atrium)
o Fossa ovalis depression on interatrial septum w/ prominent limbus fossa
ovalis border/margin
R. ventricle
o Cone shaped RV Outflow Tract (infundibulum/conus arteriosus)
pulmonary trunk
Inner wall = smooth muscle (derived from bulbus cordis)
o Inflow portion trabeculae carnae
o Moderator band (septomarginal trabecula) = large trabeculae carnae
crossing ventricular cavity
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Carries R. bundle branch of conduction system anterior ventricular

muscle
3 papillary muscles
attach to tricuspid valve leaflets via chordae tendinae
leaflets attached to fibrous ring supporting valve
Pulmonary valve = apex of RVOT (3 semilunar cusps attached to fibrous
ring)
o
L. atrium
o
o
o
o
o
Contributories = 4 pulmonary veins into posterior half

Inflow portion = smooth walls (derived from proximal pulmonary veins)
Anterior half musculi pectinati (derived from primitive atrium)
**NO CRISTA TERMINALIS
valve of foramen ovale on interatrial septum
L. ventricle
o Thickest myocardial layer (wall thickness ~ 3x that of R. ventricle)
o LVOT = aortic vestibule smooth walls (derived from bulbus cordis)
o Trabeculae carnae fine and delicate compared to that of R. ventricle
o 2 large papillary muscles (larger than those in R. ventricle)
o chordae tendinae = thicker, less numerous than those in R. ventricle)
o Mitral valve (2 cusps) secured to fibrous ring
o Aortic valve = 3 semilunar cusps secured by fibrous ring
R and L aortic sinuses R and L coronary arteries
Pericardium
2 layered sac enclosing heart

o inner serosal/visceral pericardium/epicardium adheres to wall
exterior
o visceral pericardium reflects back on itself @ level of great vessels
parietal pericardium/outer serosal layer
o tough outer fibrous layer
o Pericardial cavity is filled with fluid to reduce friction
Functions
o Fix heart w/in mediastinum limits motion
o Prevent extreme dilatation during periods increased intracardiac volume
o
Barrier limit spread of infection from adjacent lungs
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Great Vessels
Vena cavae
o SVC, IVC
Pulmonary Artery
o Pulmonary trunk, R. pulmonary artery, L. pulmonary artery
Pulmonary veins
o R. superior, R. inferior, L. superior, L. inferior
Aorta
o Brachiocephalic artery, L. common carotid artery, L. subclavian artery
b. Orientation within mediastinum (where are the chambers) (lab)
Base of Heart (posterior face)
o L.A.; small portion of R. A.; proximal parts of SVC, IVC, pulmonary veins
o Fixed posteriorly to pericardial wall; esophagus is immediately posterior
Apex
o Inferolateral portion of L.V. (5th intercostal space, mid-clavicular line)
Anterior Surface
o Mostly R.V.; some R.A. on right; some L.A. on left
Diaphragmatic Surface (inferior surface)
o L.V.; small portion of R.V. (separated by interventricular groove)
o Separated from base of heart by coronary sinus
o Extends from base apex
L. Pulmonary Surface
o Faces L. lung ; L.V.; portion of L.A.
R. Pulmonary Surface
o Faces R. lung; R.A.
c. Embryological development (lecture)
Formation of the CV system begins in the 3rd week of gestation (from mesodermal
cells)
o Fusion of heart primordia to form a single endocardial tube by day 22
primitive heart beats by around day 22 or 23 (notes say 4 th week), blood circulates by
4th week
tube develops 4 distinct regions: sinus venosus, atrium, ventricle, truncus
arteriosus
4 structures that will separate the 4 chambers
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o
o
o
o
1)
2)
3)
4)
tube
o
o
o
o
Endocardial Cushions
Interventricular Septum
Aorticopulmonary (Spiral) Septum
Interatrial Septum
does not remain straight folds up (before above structures formed)

atrium and sinus venosus superior and posterior
ventricles inferior to atria and great vessels
great vessels superiorly and somewhat anteriorly
brings different regions so that the interventricular septum, interatrial
septum and spiral septum meet at endocardial cushions
Refer to Website for Fetal Heart Folding: http://pie.med.utoronto.ca
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Interventricular Septum formed from 2 parts:

o 1) muscular interventricular septum (most)
o 2) membranous interventricular septum small region @ top of IV
septum formed from cells that migrate from inferior edge of spiral septum,
endocardial cushions, and muscular IV septum
Spiral Septum spirals down truncus arteriosus divides it in - two vessels
are twisted around each other
o lower edge of spiral septum fuses w/ endocardial cushions and IV septum
Interatrial Septum formed from 2 septa septum primum and septum
secundum
o lungs not fn in fetus oxy blood flows from placenta to RA through opening
to left side
o 3 openings:
1st Foramen (Ostium) Primum
obliterated when inferior edge of septum primum fuses w/
endocardial cushions
2nd Foramen Secundum
before septum primum closes, superior part breaks down
leaving foramen (ostium) secondum
3rd Foramen Ovale
septum secundum (stiff) grows from superior part of atrium on
the RHS of the septum primum grows toward endocardial
cushion but does not reach covers foramen secundum
septum primum is flexible; when RAP>LAP (before birth)
blood flows from RA LA
once lungs fn, LAP>RAP pushes septum primum against
septum secundum and seals off foramen ovale becomes
depression (fossa ovalis) in RA in adults
Sinus Venosus
o RIGHT side incorporated into smooth-walled portion of RA (sinus
venarum)
o LEFT side coronary sinus
Pulmonary Veins
o 4 vessels gradually form from one single vessel that incorporates into LA
(smooth-walled portion of LA)
o embryonic atrium forms rough walled atrial appendage of LA
Ductus Arteriosus
o shunt passes blood from pulmonary A aorta (bypass lungs)
closes shortly after birth leaves ligamentum arteriosum
2. Describe fetal circulation: (self directed, lecture)

a. blood flow pattern before birth:
i. Ductus venosus, Foramen ovale, Ductus arteriosus
The maternal placenta supplies the fetus with freshly oxygenated blood.
Approximately half of the blood returning form the placenta via the umbilical vein
is shunted through the ductus venosus directly to the inferior vena cava.
o The ductus venosus, allows oxygenated blood from the placenta to
bypass the liver.
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Blood returing to the fetal heart through the inferior vena cava passes a
unidirectional flap in the interatrial sepptum cell the foramen ovale
o The foramen ovale allows blood to travel directly form the right attrium
to the left atrium, thus bypassign the non-functional, fluid filled lungs
The blood in the left atrium passes into the left ventrical via the mitral valve and
is pumped out through the aortic valve and into the aorta to supply the fetal
systemic circulation.
Some deoxygenated blood does not go through the foramen ovale; instead, it
returns from the head and neck via the superior vena cava, passes into the right
ventrical through the tricuspid valve where it is then pumped through the
pulmonary valve and into the pulmonary arteries.
o Note: It is important that some blood enters the Right ventricle in order
to ensure proper development and prevent hypotrophy.
Since pulmonary vascular resistance in very high (fetal pulmonary arterioles are
mostly closed and there is no air in the lungs), blood in the main pulmonary artery
is divered through the ductus arteriousus.
o The ductus arteriosus allows blood to travel from the main pulmonary
artery to the aorta, thus bypassing the non-functional, fluid-filled lungs.
ii. Pressure differences of right vs left cardiac chambers
In the fetal heart, the pressure in the right atrium is higher than the left atrium
o Pressure differential is the result of normal venous return to the right
atrium from the body combining with the flow from the umbilical vein,
which greatly exceeds the pressure generated by the small volume of
blood coming back to the left atrium from the non-functional fetal lungs.
b. Oxygenation:
i. Pattern of oxygenation through the circulation
Blood returning from the placental via the umbilical vein is oxygenated blood.
Oxygenated blood entering the right atrium from the inferior vena cava (blood
from placenta) mixes with deoxygenated blood entering from the superior vena
cava (blood from head and neck) to form mixed blood.
Mixed blood that reaches the left ventricle is pumped into the fetal systemic
circulation to supply the needs of the fetus.
ii. Properties of fetal hemoglobin vs. adult hemoglobin

Fetal Hemoglobin (HbF 22)
Produced after the first 10 to 12 weeks of development where hemoglobin
production switches from the embryonic hemoglobin to fetal hemoglobin.
Fetal hemoglobin has a higher affinity for O 2 than adult hemoglobin.
o Allows fetus better access to O2 from maternal blood at the placenta
Predominate form of hemoglobin in utero.
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Fetal hemoglobin level fall to 1-2% by age 1, but can persist is there is a
congenital blood disorder.
Adult Hemoglobin (HbA 22 and HbA2 22)

There are many types of adult hemoglobin with HbA being the predominate one
(~95%)
The transition from fetal hemoglobin to adult hemoglobin occurs 6 months after
birth and is complete by 1 year.
There are a number of other hemoglobin forms that are found in disease states
o Hemoglobin H (4), Hemoglobin Barts (4), Hemoglobin S (2S2) etc.
c. Describe changes in pulmonary vascular resistance after birth
The fall in pulmonary vascular resistance (due to the opening of pulmonary

arterioles) lowers the right atrial pressure
Increased venous return from the lungs to the left atrium raises the left atrial
pressure
o The combination of these events reverses the inter-atrial pressure
gradient seen in the fetus and closes the foramen ovale
d. Describe transition to adult circulation
The baby takes its first breath, the lungs fill with air, alveolar hypoxia is relieved
and the pulmonary arterioles open and fill with blood, thus dropping the
pulmonary resistance
o There is an increase in negative pressure with the first breaths thereby
helping to draw more blood flow to the lungs.
The umbilical arteries constrict and the umbilical cord is severed. The source of
oxygenated blood now switches from the placenta to the babys lungs.
Closure of the three fetal shunts:
o Ductus venosus Blood flow from the umbilical cord is terminated at
birth.
o Foramen ovale refer to Part c above
o Ductus areteriosus refer to Part e below
e. Describe regulation of the ductus arteriosus

i. Prostaglandins and Oxygen
At birth, a combination of a higher concentration of oxygen in the blood and the

withdrawal of placental vasodilating prostaglandins results in constriction of the
ductus arteriosis, thereby closing the communication between the main
pulmonary artery and the aorta
Fetal Circulation
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3. Describe the cardiac cycle in the adult: (lecture)

a. flows and pressures in great vessels and cardiac chambers.
b. valve function
c. Wiggers diagram
**Note, all of (a), (b), and (c) will be explained by the Wiggers digram**
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Legend:
AP Aortic pressure (has the highest pressure for the majority of the cardiac cycle)
LAP Left atrial pressure
LVP Left ventricular pressure
LVV left ventricular volume
1.During ventricular diastole (right before contraction of the ventricle)
Ventricular filling is occurring (with the mitral valve continuously open)
o During this whole stage, LAP > LVP, fascilitating filling of left ventricle (but
keep in mind that ventricular filling is largely passive)
The left atrium also contracts, increasing the LVV slightly
Aortic valve closed during this time
2. Ventricle contracts (isovolumetric contraction)
Left ventricle contracts (increasing the LVP)
o LVP rises above the LAP (this closes the mitral valve producing the S1
sound)
Left ventricle continues to contract
o The volume of blood in the left ventricle is unchanging at this point (which
makes this contraction isovolumetric)
Isovolumetric continuous contraction of the left ventricle causes an
enormous and rapid increase in pressure in the left ventricle (rapid
increasing LVP)
The LVP finally surpasses the AP, allowing the Aortic valve to open
(marking the end of isovolumetric contraction)
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This also causes a small pressure increase in the left atrium (small increase in
the LAP), since the large increase in LVP causes the mitral valve (which is
closes) to bulge into the left atrium slightly (and therefore increasing the LAP
slightly)
3. Ejection phase
The LVP > AP at this point (as the ventricle is still contracting during the first part of
this phase)
o This results in ejection of blood out of the left ventricle, so LVV drops sharply
As the ventricle starts to relax, the LVP and the AP start to drop (the LVP drops faster)
o Once the LVP drops below the AP, the aortic valve closes [S2 heart sound]
(**note there is a slight delay of the aortic valve closing from the time LVP
drops below AP. This is due to the great momentum of blood exiting the left
atrium and into the aorta, keeping the aortic valve open for slightly longer
This will again produce an isovolumetric situation (see next stage)
During this stage, the mitral valve remains closed, but the LAP increases to a small
degree on a steady incline (there is left atrial filling from the pulmonary veins)
4. Ventricle relaxes (Isometric relaxation)
Both aortic valve and mitral valve are closed
o The ventricle dilates and continues to relax
The LVP drops sharply
During this time though, the LVV is staying constant (just like how
it was in stage 2
The LVP finally drops below the LAP, causing opening of the mitral valve,
marking the end of isovolumetric relaxation
5. Diastole and ventricular filling
Once the mitral valve opens (when LAP > LVP), passive ventricular filling occurs
o The AP drops
o The LVV rises steadily
This continues until the left atrium contracts, which causes the LAP, LVP and LVV to
increase slightly
6.The cycle continues for another round
**Note. This is only a description of the left heart. The right heart is exactly the
same except:
- Pressures are much smaller
- Tricuspid valve instead of mitral valve
- Pulmonary valve instead of aortic valve
- Right atrium and ventricle instead of left atrium and ventricle
- Pulmonary trunk instead of aorta
4. Heart Sounds (genesis and significance)

S
closure of the atrioventricular (mitral and tricuspid) valves
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1
S
2
S
3
high frequency
pulmonic closure (P2): best heard in the 2-3 intercostal space L
sternal border
aortic closure (A2): best heard in the 2-3 intercostal space R sternal
border
expiration: heard as one sound
inspiration: heard as 2 sounds: physiological splitting
tensing of chordae tendinae during rapid filling and
expansion of the ventricle
S
4
occurs in early systole

normally heard as one sound
high frequency
caused by vibrations of the valves and the walls of the heart that
occur as a result of their elastic properties when the flow through the
valves is suddenly stopped
best heard at the apex
closure of the semi-lunar (pulmonic and aortic) valves
normal finding in children and young adults implies the presence of

a supple ventricle capable of normal rapid expansion in early diastole
often a sign of disease in older adults, ex. volume overload,
increased transvalvular flow during advanced mitral or tricuspid
regurgitation
ventricular gallop
atria vigorously contracting against a stiffened ventricle
occurs late in ventricular diastole (coinciding with atrial
systole/contraction)
can indicate a disease in ventricular complicance resulting from
ventricular hypertrophy or myocardial ischemia
atrial gallop
* Gallop Murmur/ Gallop Rhythm = S1 and S2 plus S3 and/or S4
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Splitting of S2:
Listen to S2 splitting using the diaphram, over the pulmonic area. A2 is very load and
drowns out S2 if you listen for splitting in the aortic area.
Normal Physiologic Splitting:
Expansion of the chest during inspiration
causes negative intrathoracic pressure, which
transiently increases the capacity of the
pulmonary vessels, causing:
-
temporarily delay in diastolic back pressure of

the pulmonary artery responsible for closure
of the pulmonic valve = DELAYED P2 (more
blood going to lungs)
decreased venous return to the heart
reduced filling of LV reduced stroke volume
during the next systolic contraction less
time needed for LV to empty = EARLIER A2
widened splitting:
Increase in the time interval between A2 and
P2, such that they are audibly separately even
during expiration and become more widely
separated in inspiration
Expiration
Inspiration
S2 on expiration appears as one
sound
Expiration
Inspiration
usually result of delayed closure of the

pulmonic valve, which occurs in right bundle
branch block (RBBB) and pulmonic stenosis
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fixed splitting:
Abnormally widened interval between A2 and
P2 that persists unchanged through the
respiratory cycle.
-
Most common cause: ASD chronic volume

overload of R side circulation results in high
capacitance, low resistance pulmonary
vascular system delays back pressure
responsible for closure of pulmonic valve P2
occurs later than normal.
Pattern of splitting does not change between
expiration and inspiration because:
Inspiration does not substantially increase
further the already elevated pulmonary
vascular capacitance
Increased filling of RA is balanced by decrease
in L to R transatrial shunt, eliminating
respiratory variations in RV filing
paradoxical/reverse splitting:
Audible separation of A2 and P2 during
expiration that disappears on inspiration
(opposite of normal).
Reflects abnormal delay in the closure of the
aortic valve such that it follows P2.
Since P2 is delayed during inspiration and A2
is earlier (like in the normal situation) the two
sounds become superimposed
Most common cause : left bundle branch block
(LBBB)
Also occurs when ventricular ejection is
greatly prolonged (such as during aortic
stenosis)
Expiration
Inspiration
Expiration
Inspiration
Heart Murmurs
Murmur = sound generated by turbulent flow.
Mechanisms:
1. normal flow across a partial

obstruction
2. increased flow through normal
structures
3. ejection into a dilated chamber

4. regurgitant flow across an
incompetent valve
5. abnormal shunting
6.
7. Description:
1. Timing: systolic, diastolic, or continuous
8.
2. Intensity: grading system:

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9. Systolic Murmurs:
10.
1/6 barely audible
11.
2/6 faint but immediately audible
12.
3/6 easily heard
13.
4/6 easily heard, palpable thrill
14.
5/6 very loud, heard with stethoscope lightly placed on chest
15.
6/6 audible without stethoscope directly on chest wall
17.
Diastolic Murmurs:
18.
1/4 barely audible
19.
2/4 faint but immediately audible
20.
3/4 easily heard
21.
4/4 very loud
16.
22.
3. Pitch: frequency
23. High = large pressure gradient between chambers
24. Low = less pressure gradient between chambers
25.
4. Shape: how the murmur changes in intensity from onset to completion

26. Crescendo-decrescendo (ejection):
27. Decrescendo:
28. Uniform:
29.
5. Location: region of maximum intensity

30. Auscultory areas:
31.
Aortic Area: 2-3 intercostal space R of sternum
32.
Pulmonic Area: 2-3 intercostal space L of sternum
33. Tricuspid Area: lower-left sternal border
34. Mitral Area: cardiac apex
35.
6. Radiation: patterns of transmission, which relate to the direction of turbulent flow

36.
7. Response to manoeuvres: simple manoeuvres that alter the hearts loading

conditions can affect the intensity of murmurs and help distinguish between similar
murmurs
37.
Ex. standing upright, Valsalva (forceful expiration vs. a closed airway),
clenching fists
5. Congenital cardiac abnormalities Describe: (lecture)
38.
Incidence and Etiology (Tintinallis; Standring: Grays Anatomy)

Incidence: Congenital heart defects occur in approximately 8/1000 births.
Etiology: In general, only a small proportion of the anomalies are directly attributable
to genetic or environmental factors; the majority are the result of multifactorial
events (genetics + environmental- Viruses (rubella), drugs (retinoic acid), alcohol,
maternal disease (diabetes, lupus))
o 10% associated with genetic syndromes e.g. trisomy 21, Turner syndrome,
Noonan syndrome, or heart defects that accompany other organ malformations
in conditions such as VACTERL association (Verterbral anomalies, Anal atresia,
Cardiac anomalies, Tracheoesophageal fistulas, Esophageal atresia, Renal and
Limb anomalies, and single umbilical artery).
o 90% are from isolated embryologic malformation or as yet undefined genetic
lesions.
39.
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40. Embryogenesis
Isomerism (Lecture notes; Libby: Braunwalds Heart Disease)
41.
o Isomerism describes the situation in
which both atrial appendages have
either left or right anatomical
features (bilateral right or bilateral
left atrial appendages)
o Occurs when rotation of the
abdominal and thoracic contents go
wrong rotation of cardiac skeleton
goes wrong as well.
42.
o Right Isomerism: 2 morphologic
right atria.
Results in a pattern of visceral
abnormalities sometimes described as asplenia syndrome- Liver is
midline, both lungs are trilobed, both bronchi are symmetrical and short,
spleen is hypoplastic or absent (more prone to bacterial infections with
capsule e.g. Streptococcus pneumoniae and H. influenzae).
Heart abnormality:
IVC may connect to either right atrium, SVC are often lateralized
and separate.
the pulmonary veins are draining anomalously to one or other
right atrium, but frequently this is indirect and/or obstructed.
Often have AV septal defectpresents with cyanosis.
43.
o Left Isomerism: 2 left sided atria.
Two left lungs and bronchi, tend to have polysplenia, frequently have
malrotation of the gut.
Heart abnormality usually less severe than right isomerism. Tend to
develop atrial arrhythmias (normal SA node is a RA structure, therefore
often absent in left isomerism).
Intrahepatic IVC absent in 90%, hepatic veins drain directly into atria.
44.
How flow through the heart affects chamber development (Lillys)

o In general, when there is increased pressure and volume on a heart chamber,
the heart wall thickens (no source?)
o Before birth, there is more pressure and volume on the RV, thus the RV wall is
thicker than the LV
o After birth, the LV receives higher volume and pressure, therefore the wall
thickness increases, becoming thicker than the RV.
45.
46.
47.General features of Hx, physical exam and investigations (Lecture notes)
Hx:
o Pregnancy Hx, family Hx of CHD/sudden death
o Feeding/Growth, Activity, Color, Breathing, Wake/sleep, faints/spells,
palpitations, exercise tolerance, Chest pain.
Physical exam
o Vital signs. BP in 4 limbs
o Work of breathing
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Vascular congestion/liver (enlarged?)/lungs (sounds)/soft tissues (signs of

edema)
o Cardiac activity/rhythm
o Murmurs timing and quality
o Look for signs of cyanosis/clubbing
Investigations
o Basic lab testing: CBC (look for anemia)/Renal/Electrolytes/Liver function
o ECG
o Echocardiography
o Radiography: CT/MRI/PET/nuclear
o Cardiac catheterization-hemodynamics angiocardiography
48.
49.Classification and pathophysiology (give examples) (Kliegman: Nelson
Textbook of Pediatrics, Lillys, Lecture N.)
50.
L to R shunts (acyanotic)
o The pathophysiological denominator in this group is communication between
the systemic and pulmonary sides of the circulations, which results in shunting
of fully oxygenated blood back into the lungs
o Symptoms of heart failure: tachypnea, chest retractions, nasal flaring,
wheezing. HR and SV increased (increase in SNS). Increased catecholamines +
increased work of breathing cause increased total body O2
consumptionsweating, irritability, failure to thrive.
o Examples: ASD, VSD, AV canal, PDA
51.
Obstructive lesions
o Obstruction can occur at the valve, below the valve, or above it.
o ***In Lillys these also are classified under acyanotic lesions. In Kliegmans,
these are further classified as acyanotic lesions that cause an increased
PRESSURE LOAD, whereas the LR shunts are classified as acyanotic lesions
that cause an increased VOLUME LOAD.
o Symptoms:
Pulmonic stenosis: signs of right sided heart failure (hepatomegaly,
peripheral edema)
Aortic stenosis: signs of left sided heart failure (pulmonary edema, poor
perfusion), as well as right sided failure (hepatomegaly, peripheral
edema)
Coarctation of aorta: upper body hypertension and diminished pulses in
lower extremities
o Examples: valvular pulmonic stenosis, valvular aortic stenosis, coarctation of
the aorta, triscuspid/mitral stenosis
52.
R to L shunts (cyanotic)
o Results from defects that allow poorly oxygenated blood from the right side of
the heart to be shunted to the left side, bypassing the lungs. Involves both an
obstruction to pulmonary blood flow and a pathway by which systemic venous
blood can shunt from RL and enter systemic circulation (e.g. patent foramen
ovale, ASD, VSD)
o Examples: Tetralogy of Fallot, Eisenmenger Syndrome
53.
54.
Mixing lesions
o
MD 2017 by J^2N
Page 35 of 141
o
o
o
Caused by abnormal ventricular-arterial connections, or total mixing of

systemic venous and pulmonary venous blood within the heart.
Examples: D-transposition of the great arteries, cardiac defects with a common
atrium or ventricle
***Classfied as cyanotic in Lillys. In Kleigmans, RL shunts are classified as
cyanotic lesions with decreased pulmonary blood flow, whereas mixing
lesions are classified as cyanotic lesions with increased pulmonary blood flow)
MD 2017 by J^2N
55.
6. For each of the following lesions listed below, describe: (Source: Lillys)
56.
57.
63.
A
64.
Anatomy
58.
F
lows/
volum
es,pr
essur
es, O2
59.
Pathoph
ysiologySig
ns and
Symptoms
60.
Dia
gnostic
features
61.
N
atural
Histor
y if
not
repair
ed
62.
Prin
ciples of
Treatment
65.-LR
shunt
68.-oxy blood
shunted
LARA
75.-CXR
=enlarged
RA, RV, PA
80.-could
remain
asymp.
69.-volume
overload in RA,
RVRA
enlargement
atrial
tachyarrythmia
s
76.-ECG = RV
hypertrop
hy w/ RA
enlargeme
nt;
partial/co
mplete R.
bundle
branch
block
79.occasi
onal
PVD
ES
hypox
emia
+
cyano
sis
66.volum
e
overlo
ad in
RA +
RV
67.increa
sed O2
sat. in
R side
and
pulmo
nary
circula
tion
70.-dyspnea on
exertion,
fatigue,
recurrent lower
resp. tract
infections
71.-R sided vol
overload
widened fixed
splitting of S2
(P2 is late)
77.-Doppler
Echo (high
sensitivity
) shows
RA, RV
enlargeme
nt,
transatrial
shunt
72.-increased flow
across tricuspid
valvemiddias
tolic murmur
78.-cardiac
cath
shows O2
sat in RA
81.-invasive
surgery
direct
suture
closure/peri
cardial
synthetic
patch
82.percutaneo
us repair w/
closure
device via
IV cath
73.-dilatated RV
contractionpa
lpable systolic
impulse (RV
heave)
> SVC
74.
83.*PVD = pulmonary vascular disease; ES = Eisenmenger Syndrome; CHF = congestive heart failure (tachypnea, poor
feeding, failure to thrive, frequent lower respiratory tract infections)
84.
85.
86.
Anatomy
87.
F
lows/
volum
es,pr
essur
es, O2
88.
Pathoph
ysiologySig
ns and
Symptoms
89.
Dia
gnostic
features
90.
N
atural
Histor
y if
not
repair
ed
91.
Prin
ciples of
Treatment
92.
V
93.
94.-LR
shunt
97.-oxy blood
shunted LVRV
95.volum
e
overlo
ad in
RV,
PA, LA,
LV
98.-large
VSDsCHF
96.increa
sed O2
sat. in
RV
and PA
100.
dilatated RV
contractionpa
lpable systolic
impulse (RV
heave)
99.-turbulent flow
thru
VSDholosysto
lic murmur @ L
sternal border
101.
-if ES,
decreased
holosystolic
murmur,
palpable RV
heave, loud P2,
cyanosis
102.
turbulent
flowdamage
to
endocardium
bacterial
endocarditis
103.
104.
CXR
=cardiom
egaly,
prominent
PA
105.
ECG = LV
hypertrop
hy w/ LA
enlargeme
nt; RV
hypertrop
hy if PVD
106.
Doppler
Echo
determine
location,
direction,
magnitud
e of VSD;
estimate
RV
systolic
pressure
108.
occasi
onal
PVD (if
severe
VSD)
ES
hypox
emia
+
cyano
sis
109.
-VSD
may
spontaneou
sly close by
2yo
110.
invasive
surgical
closure
indicated
for pts w/
CHF/PVD
111.
pharmocolo
gical
antibiotic
prophylaxis
for
endocarditi
s
107.
cardiac
cath
shows O2
sat in RV
> RA
112.
*PVD = pulmonary vascular disease; ES = Eisenmenger Syndrome; CHF = congestive heart failure (tachypnea, poor
113.
114. 115.
121. 122.
P
Anatomy
116.
F
lows/
volum
es,pr
essur
es, O2
117.
Pathoph
ysiologySig
ns and
Symptoms
118.
Dia
gnostic
features
119.
N
atural
Histor
y if
not
repair
ed
120.
Prin
ciples of
Treatment
123.
LR
shunt
126.
-oxy
blood shunted
from aortaPA
124.
volum
e
overlo
ad in
LA, LV
127.
-LA
dilatationsatri
al fib
135.
CXR =LA,
LV, PA
enlargeme
nt
139.
occasi
onal
PVD
ES
hypox
emia
+
cyano
sis in
LOWE
R
EXTRE
MITY
ONLY
140.
-PDA
may
spontaneou
sly close in
1st mnths
125.
increa
sed O2
sat. in
PA
128.
moderate
PDAsfatigue,
dyspnea,
palpitations
129.
-large
PDAsCHF
130.
turbulent flow
thru
PDAcontinuo
us machine-like
murmur @ L
subclavicular
region
131.
-if PVD,
decreased
pressure
gradientshort
ened murmur
132.
-if
136.
ECG = LA,
LV
enlargeme
nt; RV
hypertrop
hy if PVD
137.
Doppler
Echo
visualize
+demonst
rate flow
thru PDA;
estimate
R side
systolic
pressure
138.
cardiac
cath
(unnecess
ary)
shows O2
141.
pharmocolo
gical
indomethac
in (PG
synthesis
inhib) to
close PDA
142.
invasive
surgery for
definitive
closure via
division/liga
tion
143.
-IV
catheter
occluding
coil/other
vasc
occlusion
device
144.
ESlower
extremity
cyanosis+clubb
ing, upper
extremities not
affected b/c
does not affect
proximal aorta
sat in PA
> RV
133.
turbulent
flowdamage
to
endotheliume
ndarteritis
134.
145.
146.
147.
148.
149. 150.
Anatomy
151.
F
lows/
volum
es,pr
152.
Pathoph
ysiologySig
ns and
153.
Dia
gnostic
features
154.
N
atural
Histor
y if
155.
Prin
ciples of
Treatment
essur
es, O2
156. 157.
T
158.
RL
shunt
159.
volum
e
overlo
ad in
LV
160.
decrea
sed O2
sat. in
LV +
aorta
Symptoms
161.
-deoxy
blood shunted
from
RVLVdyspn
ea on exertion,
irritability,
cyanosis,
clubbing,
hyperventilatio
n (syncope,
convulsions in
extreme cases)
162.
-severe
pulm valve
stenosispalpa
ble RV heave,
single S2 (no
P2)
163.
turbulent flow
thru stenotic
RVOTsystolic
ejection
murmur
164.
not
repair
ed
165.
CXR =
bootshaped
heart
(enlarged
RV,
undersize
d PA)
166.
ECG = RV
hypertrop
hy, R axis
deviation
167.
Doppler
Echo
visualize
RVOT
anatomy,
misaligne
d VSD, RV
hypertrop
hy
168.
cardiac
cath
(same
findings
as Echo);
show O2
sat in
LV<LA
169.
LV
overlo
ad
170.
chroni
c
cyano
sis
171.
palliative
surgical
LR shunt
b/t aorta
and PA,
until
definitive
surgical
repair
172.
invasive
surgery to
close VSD;
enlarge
RVOT w/
pericardial
patch
173.
pharmocolo
gical
antibiotic
prophylaxis
for
endocarditi
s
174.
175.
176.
177. 178.
Anatomy
179.
F
lows/
volum
es,pr
essur
es, O2
180.
Pathoph
ysiologySig
ns and
Symptoms
181.
Dia
gnostic
features
182.
N
atural
Histor
y if
not
repair
ed
183.
Prin
ciples of
Treatment
184. 185.
T
186.
2
paralle
l
circuit
s
deoxy
blood
cyclin
g thru
periph
ery;
oxy
blood
cyclin
g thru
pulm
circuit
187.
188.
-deoxy
blood shunted
from R
heartperipher
yR heart
extreme
hypoxia,
cyanosis
189.
-rapidly
progressing
cyanosis as
PDA
closesblue
babies
190.
-RV faces
systemic
pressurespal
pable RV
heave
191.
-not
many
prominent
murmurs
193.
CXR =
normal;
slightly
narrower
base
196.
lethal,
medic
al
emerg
ency
194.
ECG = RV
hypertrop
hy
197.
pharmacolo
gical
prostagland
in
infusion
open PDA
198.
Rashkind
percutaneo
us
procedure
= create
interatrial
communica
tion via
balloon
catheter
195.
Doppler
Echo
visualize
abnormal
disconcor
dant
ventriculo
arterial
connectio
ns
199.
Jatene
surgical
procedure
arterial
switch
(must also
relocate
coronary
arteries to
transected
aorta)
192.
200.
201.
202. 203.
Anatomy
204.
F
lows/
volum
205.
Pathoph
ysiologySig
ns and
206.
Dia
gnostic
207.
N
atural
Histor
208.
Prin
ciples of
es,pr
essur
es, O2
209. 210.
A
211.
norma
l flow
directi
on
212.
upper
extre
mity
hypert
ension
213.
poor
lower
extre
mity
perfusi
on
214.
Symptoms
215.
-LV
hypertrophyp
rogressive CHF
symptoms
216.
compensatory
dilatation of
collateral
intercostal
arteries
bypass coarct
and provide
blood to desc
aortamay
erode rib
undersurface
217.
-if
preductal
coarct +
PDAdifferenti
al
cyanosisuppe
r body well
perfused w/ O2;
lower body
supplied by
RL flow of
deoxy blood
thru PDA
218.
decreased
pressure post-
features
221.
CXR =
inferior
notching
of
posterior
ribs
(dilated
intercostal
collateral
arteries);
indented
aorta
222.
ECG = LV
hypertrop
hy
223.
Doppler
Echo
confirms
diagnosis;
assesses
pressure
gradient
across
coarct
224.
MRI
demonstr
ates
length
y if
not
repair
ed
Treatment
226.
chroni
c
lower
body
cyano
sis
231.
pharmacolo
gical
prostagland
in infusion
in severely
obstructed
neonates
open PDA
227.
decrea
sed
perfus
ion to
lower
limbs
228.
secon
dary
hypert
ension
in
upper
body
229.
pressu
re
differe
ntial
b/t
upper
and
lower
body
232.
invasive
surgery
end to end
reanastamo
sis and
direct
repair of
coarct w/
synthetic
patch
233.
transcathet
er balloon
and stent
for
recurrent
coarct
234.
pharmocolo
gical
antibiotic
prophylaxis
coarct weak
and delayed
femoral pulses
219.
increased
pressure precoarctelevate
d BP in upper
body
and
severity
225.
cardiac
cath
unnecessa
ry
230.
exerci
seinduce
d
fatigu
e
(claudi
cation
)
for
endocarditi
s
235.
220.
turbulence thru
coarctmidsys
tolic murmur
236.
237.
7. Pharmacology Understand and describe the following drugs: (selfdirected)

238.
a. Furosemide
Furosemide is a sulfonamide-derived loop diuretic used in the
management of edema associated with congestive heart failure,
cirrhosis, and renal disease, including the nephrotic syndrome.
239.
Mechanism of action:
o Furosemide is a loop diuretic that inhibits sodium and chloride
re-absorption by competing with chloride for the Na+/K+/2Clsymporter in the ascending limb of the loop of Henle (results in
a decrease in intracellular Na, K and Cl)
It also inhibits the absorption of sodium and chloride in
the proximal and distal tubules
o In addition, furosemide increases the excretion of calcium,
magnesium, bicarbonate, ammonium, and phosphate.
240.
241.
242.
CV Week 2 Development of the Heart and
Consequences of Maldevelopment
243. Case Objectives
1. (refer to Week Objective #1)
244.
Describe cardiac anatomy:
245.
246.
247.
248.
249.
250.
251.
252.
253.
254.
255.
256.
257.
258.
259.
260.
Right Atrium
3 openings:
o SVC
o IVC
o Cardiac Sinus
Fossa ovalus (former foramen ovale) can be seen on the atrial septum
Contains the right auricle (is rough walled musculi pectinati)
The rest of the atrium contains the musculi pectinati (rough wall)
The opening of the tricuspid valve can be seen inferiorly
261.
262.
Right Ventricle
Opens at tricuspid valve and pulmonary valve
Thicker wall than right atrium, but thinner than left ventricle
Its walls connect to the papillary muscles (which connect to the tricuspid
valve)
Moderator band can also be seen near the inferior surface
263.
264.
Left Atrium
Usually four openings from the pulmonary veins (can be more)
Contains the left auricle (smaller flap than the right auricle)
Contains a rough wall throughout except where the pulmonary veins enter
Mitral valve can be seen in inferior surface
Fossa ovalus can be seen on atrial septum (although more difficult to see
compared to the right atrium
265.
266.
Right Ventricle
Very thick wall
Lined with papillary muscles
Opens to the aortic valve
267.
268.
Tricuspid valve
Separates right atrium and ventricle
Has 3 leaflets
Connected to chordae tendinae (which then connect to papillary muscles in
the left ventricle)
269.
270.
Mitral valve
Separates left atrium and ventricle
Has 2 leaflets
Connected to chordae tendinae (which then connect to papillary muscles in
the left ventricle)
271.
272.
Pulmonary valve
Separates right ventricle and pulmonary trunk
Has 3 semilunar shaped leaflets
o Not anchored by chordae tendinae (These are anchored by the
Anulus)
273.
274.
Aortic valve
Separates left ventricle and aorta
Has 3 semilunar shaped leaflets
o Not anchored by chordae tendinae (These are anchored by the
Anulus)
Behind the cusps there are ostia (which lead to coronary arteries)
275.
276.
277.
278.
279.
280.
281.
Pericardium
The heart and roots of the great vessels are enclosed by a fibroserous sac
called the pericardium
Two layers
o Inner serosal layer
Visceral pericardium adheres to the external wall of the heart
This layer reflects back on itself to form the inner side of the
outer pericardium (parietal pericardium)
o Outer fibrous layer
Two components
Parietal pericardium (inner surface)
Fibrous pericardium (outer surface
Note: In between both layers is the pericardial fluid, maintaining a
environment with minimal resistance
282.
283.
284.
285.
Aorta
Thick walled artery carrying blood from left ventricle systemically
Major branches include
o Left coronary artery
o Right coronary artery
o Brachiocephalic artery
o Left carotid artery
o Left subclavian artery
286.
Is split up into
o Ascending aorta
o Arch of aorta
Starts and ends at sterna angle or vertebrae 4/5
o Descending aorta
287.
288.
Pulmonary Trunk
o Carries blood from right ventricle to lungs
o Bifurcates into right and left pulmonary arteries
o Not as thick as the aorta
o Usually bifurcates at sternal angle, posteriorly to ascending aorta
289.
2. Refer to Week Objective
290.
3. Sounds. Describe genesis of, and significance of: (Source: Lillys). Also
see Week objective #4
S1: Caused by closure of mitral and tricuspid valves in early systole
o Significance: Accentuated or Diminished S1 is associated with various
heart abnormalities
Accentuated S1
Shortened PR interval
Mild mitral stenosis
High cardiac output states of tachycardia
Diminished S1:
Lengthened PR interval
Mitral regurgitation
Severe mitral stenosis
Stiff left ventricle.
291.
S2: Caused by closure of aortic and pulmonic valves
o Significance: abnormal pattern of splitting of S2 suggests heart
abnormalities
292.
293.
Gallop rhythm (S3)
294.
o S3 is caused by the tensing of the chordate tendinae during rapid
filling and expansion of the ventricle. It occurs after the opening of
the AV valves, during ventricular filling.
o In middle aged/older adults, sindicates volume overload due to CHF,
or Advanced mitral/tricuspid regurgitation that causes increased
transvalvular flow.
o The ventricular gallop is referring to a pathologic S3.
295.
296.
297.
298.
299.
300.
301.
302.
303.
304.
305.
306.
307.
Murmurs
o For general causes and descriptions of murmurs, see week objective
#4
Systolic murmurs
308.
309.
310.
311.
312.
313.
314.
315.
316.
317.
318.
319.
320.
321.
322.
323.
324.
325.
326.
327.
328.
Diastolic murmurs
329.
330.
Continuous murmurs
331.
332.
333.
4. Refer to Week Objective

334.
5. Refer to Week Objective #6
335.
336.
337.
338. FMED 402: Cardiovascular

339.
Week THREE Cardiac Electrical Function &

Dysfunction
340.
341. WEEK OBJECTIVES
1. Describe nodal, purkinje and ventricular/atrial action potentials

342.
343.
ION CHANNELS
344.
345.
346.
347.
348.
349.
(a function of
time)
Open
Inactivate
d
Closed
(a function of
membrane
potential)
350.
351.
Action Potentials:
352.
Working
myocardium
353.
Sequence of Events
Fast, voltage-gated Na+ channels open.

The membrane permeability to Na+
becomes much greater than the
membrane permeability to K+. Na+ ions
enter the muscle cell.
The membrane potential rises swiftly
towards ENa due to inward Na+ current
(INa), but ENa is never reached because
3. K+ channels carrying the transient
outward current (Ito) begin to open at
the end of Phase 0, as the Na+ channels
inactivate
369.1.
Ph
a
s
e
2.
0
370.
NB. Decrease conduction
speed by prolonging Phase 0
371.
Phase 0 gives rise to the
QRS complex in an ECG
354.
Primary
Currents:
355.
Phase 0: INa
356.
Phase 1: Ito
357. Phase 2: ICa or

Isi
373.1.
Ph 2.
a
s
e
Na+ channels are inactivated

K+ channels carrying the transient
outward current (Ito) are all open by
now, allowing K+ to leave the cell.
These are special K+ channels that open
and inactivate quickly.
MD 2017 by J^2N
52
358. Phase 3: IK
359.
Phase 4: IK1 or IKir
360.
361.
362.
363.
Primary
Currents:
364.
Phase 0: INa
365.
Phase 1: Ito
366. Phase 2: ICa or

Isi
367. Phase 3: IK
368.
Phase 4: IK1 or IKi
1 3. Ito partially repolarizes the membrane

(by about 10mV)
4. During this phase, the slower Ca2+
channels begin to open as well.
However since they are slow to open,
their effect is not seen until phase 2
375.
Ph 1.
a
s 2.
e
377.
early plateau:
Ca2+ channels continue to open,
allowing Ca2+ to enter the cell.
K+ channels that produce Ito are still
open, allowing K+ to leave the cell.
378.
late plateau
2 1. Ca2+ channels are all open by now and
the membrane permeability to Ca2+ is
(
high. Ca2+ rushes into the cell,
p
producing the slow inwards current Isi or
l
ICa. This opens the RyR2 receptors (see
a
CV week 2) causing the muscle cell to
t
contract.
e
2. By this time, the K+ channels that
a
produce Ito have become inactive
u
3. The membrane potential rises towards
ECa due to inward Ca2+ current, but ECa is
p
never reached because
h
4. The delayed rectifier K+ channels begin
a
to open, producing IK, which opposes ICa
s
e
)
376.
380.1.
Ph 2.
a
s 3.
e
3
ICa channels inactivate

The membrane potential rapidly returns
to baseline as IK becomes fully active
The inward rectifier opens during the
latter part of phase 3. It conducts an
outward current, IKir or IK1 and completes
repolarization. These are special K+
channels that open as the membrane
potential gets more negative, and are
the reason that the RMP of myocardial
cells is so close to EK. This low RMP
ensures that more of the Na+ channels
are closed, hence more are available to
open in Phase 0, allowing for a faster
MD 2017 by J^2N
53
depolarization.
4. Late in phase 3, all of the inactivated
channels begin to close: INa, Ito and ICa
channels
382.1.
Ph
a 2.
s
e
The IKir channels are fully open and

clamp the RMP close to EK.
The remaining inactivated channels
close
4
383.
384.
385.
cha
n
n
e
l
386.
(
most)
open
durin
g
387.
(
most)
inactiv
ate
during
391.
INa
392.
e
arly
Phase
0
397.
Ito
398.
l
ate
Phase
0/
early
Phase
1
404.
l
ate
Phase
1/
Phase
2
393.
la
te
Phase
0/ early
Phase 1
399.
la
te
Phase 2
403.
ICa
o
r
I
s
388.
(most)
clos
e
dur
ing.
.
394.
late
Pha
se 3
389.
m
ost
activi
ty in
390.
directi
on
of
ion
flow
395.
P
hase 0
396.
Na+ in
400.
late
Pha
se 3
401.
P
hase 1
402.
K+ out
405.
ea
rly
Phase 3
406.
late
Pha
se 3
407.
P
hase 2
408.
411.
412.
413.
P
hase 3
414.
K+ out
417.
418.
419.
420.
Ca2+
in
409.
IK
415.
410.
l
ate
Phase
2
416.
l
MD 2017 by J^2N
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K
1
o
r
I
ate
Phase
3
hase 4
K+ out
K
ir
421.
***Purkinje Cells:
422.
The AP of the Purkinje cells is the same as for working myocardium, except
that Purkinje cells also express the funny current (I f), so phase 4 has a slower, upward
sloping depolarization.
423.
424.
Pacemaker cells:
SA node, AV node,
bundle of His
426.
Sequence of Events
425.
note: Pacemaker cells
have no active Na+
channels and no RMP,
hence they are in a
constant state of partial
depolarization
427.
434. 1. Ca2+ channels open, producing the
Pha
slow inwards current Isi or ICa. Since ICa
428.
s
is slower than INa, the rate of rise of
e
the AP is slower
0 2. The membrane permeability to Ca2+ is
high, and the membrane potential
rises towards ECa due to inward Ca2+
current, but ECa is never reached
because
3. The delayed rectifier K+ channels
begin to open, producing IK, which
opposes ICa
4. As the IK channels open, the ICa
channels begin to inactivate
436. 1. Ca2+ channels inactivate
Pha 2. IK repolarizes the membrane
429.
Primary
s 3. The funny current, If , activates. The
Currents:
e
funny currents in an inward positive
430. Phase 0: Isi or ICa
3
current that carries both K+ and Na+
(but Na+ more readily) and opposes
431. Phase 3: IK
the repolarization. Like IKir, it becomes
more active as the membrane
432. Phase 4: If
potential gets more negative.
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433.
438.
Pha
s
e
4
439.
diastolic depolarization
1. The delayed rectifier current (IK) is

open during this phase, but closes
with time
2. As the delayed rectifier channels
close, If depolarizes the membrane
until threshold potential is reached
at which point the Ca2+ channels
open.
440.
NB. Shorten phase 4 to
increase heart rate.
441.
442.
443.
444.
cha
n
n
e
l
445.
(
most)
open
durin
g
446.
(
most)
inactiv
ate
during
447.
(most)
clos
e
dur
ing.
.
453.
448.
m
ost
activi
ty in
449.
directi
on
of
ion
flow
450.
ICa
o
r
I
451.
e
arly
Phase
0
452.
ea
rly
Phase 3
454.
P
hase 0
455.
457.
l
ate
Phase
0
463.
l
ate
Phase
3
458.
Ph
ase 4
459.
Phase
4
460.
P
hase 3
461.
K+ out
464.
465.
466.
P
hase 4
467.
Na+
and
K+
IN
Ca2+
in
s
i
456.
IK
462.
I
f
468.
469. Refractory period
470. Absolute Refractory Period: Cannot initiate another AP because Na+ are in their
inactive configuration
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471.
472.
Relative Refractory Period: As the
membrane potential becomes more negative, more
Na+ channels have switched from inactive to closed
more available to open AP happens faster
473.
474.
475.
476.
477. Conduction velocity
478. Controlled by 3 factors:
1. Size of cells:
479.
smaller cells = greater resistance to flow of current = slower conduction
velocity
2. Number of Gap Junctions between cells
480.
more gap junctions = easier for current to flow between cells = faster
conduction velocity
3. Rate of Rise of AP
481.
Faster rate of rise of AP = faster speed of conduction of AP
482.
483.
488. size
493. # of gap
junctions
498. rate of
rise of AP
503.
Con
duction
Velocity
484.
P
urkin
je
Cells
489. larg
est
494. mos
t
499. fast
est
504. 4m/
s
485.
B
undl
e of
His
490.
486.
v
entricl
e
/atria
491.
495.
496.
500.
501.
505. 2m/
s
506. 0.5m/
s
487.
S
A and
AV
nodes
492. small
est
497. least
502. slowe
st
507. 0.05
m/s
508.
509. Normal route of excitation:
510. SA nodeatrial muscle cellsAV nodeBundle of HisPurkinje cellsventricular
muscle cells
511.
512.
513.
514.
515.
516.
517.
518.
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519.
520.
521.
522.
523.
524.
525.
526.
527.
528.
529. 2. Describe the anatomy of the cardiac electrical system with particular
reference to:
530.
SA node, atria, AV node, bundle of His, LBB, RBB, Purkinje fibers
531.
The cardiac electrical system is a system of fast, conducting specialized cardiac

muscle cells: the pathway that the action potential takes in order to spread to atrial
and cardiac muscle cells.
The normal route of excitation is: SA nodeatrial cellsAV nodeBundle of
HISPurkinje cellsventricle cells.
The conduction velocity is Purkinje > Bundle of HIS > ventricles and atria > SA and
AV nodes.
o Conduction velocity is controlled by
size of cells (smaller cells=greater resistance=slower)
# of gap junctions
Rate of rise of action potential (phase 0)
The intrinsic firing rates are:
o SA node: 60-100 bpm
o AV and bundle of HIS: 50-60 bpm
o Purkinje system: 30-40.
*The cardiac skeleton is a band of fibrous tissue at the base o the atria that prevents
electrical conduction from the atria to the ventricles (the only pathway through is the
Bundle of His).
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532.
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533.
3. Explain the following
a. Lead placement and derivation, including einthovens triangle
Bipolar Limb Leads (Einthovens triangle)
I, II, III (note: all measuring in FRONTAL plane)
535.
534.
Unipolar Limb Leads
aVR, aVL, aVF (note: all measuring in FRONTAL plane)
aVR = augmented V lead R
536.
Precordial/Chest Leads
6 chest leads (note: all measuring in HORIZONTAL plane)
going anterior posterior
V1-6 = +ve ends of precordial leads (no -ve end, just 0 reference)
b. How the AP gives rise to the ECG
537.
If no electrical activity OR if membrane surface is homogenously charged isoelectric flat line

o Eg. pause @ AV node (II)
If wave of depol moves TOWARDS +ve end of lead UPWARD deflection
o Eg. R wave (II)
If wave of depol moves AWAY from +ve end of lead DOWNWARD deflection
o Eg. Q and S waves (II)
If wave of repol moves TOWARDS +ve end of lead DOWNWARD deflection
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538.
If wave of repol moves AWAY from +ve end of lead UPWARD deflection
o Eg. T wave (II)
c. Normal waves (P, QRS, T) and intervals (PR, QRS, QT)
P wave (Atrial Depol)

o Usually UPWARDS in I, II,
and III
o Flat segment b/t P and Q =
all current slowed in AV
node
QRS (Ventricular Depol)
o Same depol path = diff
wave form in diff leads
o Q = 1st downward
deflection after P
o R = 1st upward deflection
after P
o S = 1st downward deflection after R
T wave
o Last cells to depolarize (epicardium/visceral pericardium) = first to
repolarize
539.
repolarization wave = opp direction as depolarization wave
540.
D. Develop an organized approach to interpreting ECG rhythm strips (refer
to intro to ECG rhythm analysis)
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541.
542.
1. Rate (normal rate = 60-100 bpm)
o 300 / (# of big squares b/t each QRS complex) = ___ bpm
o little square = 0.04 s , big square = 5 (0.04 s) = 0.2 s
2. Rhythm (regular, irregular w/ pattern, or irregular w/out pattern)
o note: to determine presence of pattern in irregular rhythms, take separate
paper and draw ticks for each QRS, and each P wave shift paper
forward along ECG strip to see if any ticks match up w/ subsequent QRS
or P wave
o for sinus rhythm
upright P wave
every P wave followed by QRS
every QRS preceded by P
PR interval = 0.12 s 0.2 s
3. P waves (4 questions)
o Present?
o Same shape and size?
same P wave types 1 atrial pacemaker
different P wave types >1 atrial pacemaker
o How many P waves per QRS? (normally 1)
o What is the relationship b/t P and QRS?
4. PR interval
o note: PR interval = beginning of P wave beginning of ANYTHING that
represents QRS
o normal = 0.12 s 0.2 s (3-5 small squares)
o Short or long?
o Constant or changing?
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545.
o If no P waves, no PR interval
5. QRS complex
o normal = 0.12 s (3 small squares)
o wide or narrow?
Wide think about LBB, RBB, ventricular pacemaker, AV node
pace
Narrow indicates pacemaker and conduction along His-Purkinje
highway, likely SA node pace
** delta wave = gradual incline in QR segment WPW
** ST segment = end of S beginning of T
543.
544.
4. Be able to diagnose the following rhythms if given an ECG tracing
546.
Normal Sinus Rhythm
Rate (60-100), Rhythm, P wave (up-going, all the same 1 per QRS) PR interval (3 5
squares = 120 to 200 ms) and QRS complex (narrow, 3 squares = 120 ms) are all
normal.
o Recall, each small box on an ECG = 40 ms
o Determine rate by divining 300 with the number of big square between each
QRS complex
SA node is the pacemaker
Normal electrical conduction through the heart
o SA node AV node Bundle of His Left and right bundle branches
Purkinje fibers
547.
548.
Sinus Bradycardia
Rate < 60
Normal electrical conduction through heart aside from SA node firing at slower rate
Commonly found in healthy adults, especially athletes
549.
550.
551.
Sinus Tachycardia
Rate > 100
Normal electrical conduction through heart aside from SA node firing at faster rate
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Maximum sinus rate is about 180 200, therefore, anything above that rate
means that the SA node is not involved (except in babies).
Commonly found during activity of exercise, fear and pain.
Other causes: volume depletion, increases metabolic demand, impaired cardiac filling
and decreased afterload
o
552.
553.
554.
First Degree Heart Block
Long PR interval (slow conduction in the AV node)
Each P wave is associated with a QRS complex
Can co-exist with other abnormalities such as sinus bradycardia
Can be caused by ischemia or fibrosis of the AV node
555.
556.
557.
558.
559.
560.
Second Degree Heart Block Type 1 (Wenchebach or Morbitz Type I)
Regularly irregular rhythm (i.e. pattern present)
o Regularly missing QRS complexes
More P waves than QRS complexes
PR interval increases with each heart beat until it is so long that the signal doesnt
reach the ventricles and the depolarization is blocked at the AV node
561.
562.
563.
Second Degree Heart Block Type 2 (Morbitz Type II)
Irregularly irregular rhythm (i.e. no pattern present)
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o Randomly missing QRS complexes

More P waves than QRS complexes
PR interval is constant
More likely to develop into a Type III block
564.
565.
566.
567.
Third Degree Heart Block Complete Heart Block (AV Disassociation)
Atrial rate faster than the ventricular rate
P waves are not associated with QRS complexes
o They are not conducted to the ventricles (100 % unrelated to the QRSs)
o They may become buried
o More P waves than QRS complexes
PR intervals are random
Usually QRS complexes are wide. Rarely, it can be narrow if a low junction pacemaker
is present to give rise to ventricular beats via the conduction system.
SA node and an ectopic site in the ventricle are the pacemakers of the atria and
ventricles respectively
568.
569.
Atrial Flutter
Atrial rate usually at 300
Ventricular rate 150, 100, or 75 depending on block
Rhythm is usually regularly irregular, but can be irregularly irregular if AV block is
variable
Atrial rate exceeds the rate at which the AV node can conduct; therefore, there is a
physiological block at the AV node due to the inherent refractory period.
Characteristic saw-tooth P waves
Common block patters are 2:1 (AV node blocks every 2nd atrial impulse) or 3:1 (AV
node blocks every 3rd atrial impulse)
o Other patters such as 4:1 or 5:1 also exist
Ectopic atrial site is the pacemaker (rate is too fast for SA node).
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570.
571.
572.
Atrial Fibrillation
Rhythm is irregularly, irregular
No P waves, but background noise present
High amount of uncoordinated electrical activity in atria which results in quivering
o AV node conducts this activity when it can and as fast as it can
Multiple ectopic atrial sites are acting as the pacemaker
Increases danger of blood clots formation during atrial fibrillation. Can lead to
embolism.
573.
574.
575.
Supraventricular Tachycardia
Any narrow tachycardia where QRS complexes are narrow and P waves are not
obvious.
Tachycardic rhythm that originates from a location above the bundle of his
Applies to many rhythms
576.
o
o
o
o
Sinus Tachycardia
Atrial Tachycardia
Atrial Flutter
Atrial Fibrillation
o
o
Multifocal Atrial Tachycardia

(MAT)
o
- 3 or more P wave
morphologies
Junctional Tachycardia
Reentry Tachycardia
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o
o
Sinus Nodal Reentrant Tachycardia

Same as AVNRT, but localized in or near the SA node
AV Nodal Reentrant Tachycardia (AVNRT) Refer to Week
Objective 5 for diagram
Most common cause of SVTs
Reentry pathway localized to the AV node
Requires two pathways:
o Alpha Normal conducting and normal refractory
o Beta Slow conducting and fast refractory
Triggered by a premature atrial impulse
o
o
AV Reentrant Tachycardia (AVRT)
Second most common cause of SVTs
Occurs in the presence of accessory pathways, or bypass
tracts
o Errant strands of myocardium that bridge the
mitral or tricuspid valves
Result of 2 or more conducting pathways: the AV node
and 1 or more accessory pathways that also connects to
the atria with the ventricles and can conduct impulses in
the anterograde manner, a retrograde manner, or both
o Conduction in the anterograde manner results in
pre-excitation of the ventricles resulting in the
production of a delta wave (as seen in WPW)
Reentry circuits are most commonly established by
impulses traveling in an anterograde manner via the AV
Node and in a retrograde manner via the accessory
pathway from the ventricle to the atria Orthodromic
AVRT
Antidromic AVRT occurs when a premature impulse
travels in the opposite direction: anterograde through
the accessory pathway and retrograde through the AV
Node
o
o
o
o
o
o
o
o Ventricular Tachycardia
Rate is elevated between 100 - 250
P waves are absent
Wide QRS complex
Sustained ventricular ectopic pacemaker
Bottom line: Wide QRS and Fast Rate
Can easily cause cardiac arrest; therefore, call a code blue immediately
o
o
o Ventricular Fibrillation
Uncoordinated activity only
High amount of uncoordinated electrical activity in ventricles which results in
quivering
Multiple ectopic ventricular sites are acting as the pacemaker
No ventricular contractions
o No cardiac output, pulse, or blood pressure
One example of cardiac arrest
Call a code blue and use a defibrillator
o
o
o
o
o
o
o
o
o
o
o Asystole
Absence of any systolic function
No electrical activity in the heart flat line
Usually indicates that the patient has been un a pulseless rhythm for a period
of time and sustained hypoxic damage of the heart and brain where recovery
in no longer possible
Progression of electrical failing of the heart:
o Brady or Narrow Complex Tach. V. Tach. V. Fib. Agonal
Asystole
Call a code blue for legal reasons; call the morgue for practical reasons
o
o
o
o
o
5. Explain the causes and underlying mechanisms of

tachycardias and bradycardias
a. automaticity (brady and tachy)
Automaticity (essentially the pacemaker) can be altered either
to cause bradycardia or tachycardia:
o Bradycardia
The body can induce sinus node decrease and bradycardia by
Increasing parasympathetic drive

Decreasing phase 4 slope (vagus nerve and
cholinergic stimulation of the SA node reduce the
probability that the pacemaker channels are open)
o Increasing the threshold value (the probability of
calcium channels in phase 0 being open is
reduced)
o Resting membrane potential (for lack of a better
term) is more negative (increasing the probability
that the potassium channels are open at rest)
o If the rate of the SA node pacemaker cells is slowed enough, an
escape rhythm can persist, meaning that other conducting tissues
(such as the AV node or the his-perkinge system) can take over the
pacemaker role, except
o
at a much slower rate (depending on
what the pacemaker tissue is)
o Tachycardia
o
The body can induce sinus node increase and
tachycardia by
o Decreasing the parasympathetic drive
o Increasing the phase 4 slope (B1 adrenergic
stimulation on the SA node increases the
probability of the pacemaker channels to be open)
o Making the threshold value more negative
(increasing the probability that voltage sensitive
channels are capable of opening in phase 0)
o Making the RMP more positive (for lack of a better
term)
o Ectopic beat formation along the conduction
pathway faster than that produced by the SA node may also cause
tachycardias. This usually happens with over-stimulation of the
sympathetic nervous system, hypoxia, ischemia, electrolyte
disturbances, drug toxicities (digitalis)
o Abnormal automaticity may also occur where injury to membranes
o
become leaky allowing atrial or
ventricular cells to become partially
o
depolarized causing ectopic beats
and tachyarrhythmias (most commonly
o
seen in V-tach)
o
o b. re-entry circuits (tachy)
Re-entry circuits happen when electrical signals are cycled around in a
continuous circuit over and over again, therefore, depolarizing muscle tissue
at very fast rates
These cause tachycardias and other arrhythmias in the heart
o
o
o
o
In order to produce a re-entry circuit, one needs a number of pathological
requirements to be met.
o 2 parallel conducting pathways through muscle that are separated by
a non-conducting area
o One pathways which has slower conduction than the other. This zone
has a slow conduction and fast recovery from refractoriness
o An ectopic premature beat
Normally, impulses are sent down the 2 pathways, spread to further tissues,
and are extinguished when they run into each other below (Case A)
After a premature beat however, the electrical impulse is unable to travel
down the alpha pathway (since it is still in refractory period
o Since the beta pathway has fast recovery, this is able to conduct the
impulse
By the time the impulse travels around to the junction after the alpha
pathway, the alpha pathway has fully recovered from the refractory period
and is able to depolarize in a retrograde fashion.
This retrograde wave then is able to travel back down the beta wave (fast
recovery) and also back up to the atria, causing a re-entry tachyarrhythmia
o
o
o
o
o
o
o
o
o
o
o
o
o
o c. after-depolarizations (tachy)
After-depolarizations are considered to be a form of tachy arrhythmia.
There are 2 ways in which this can be initiated:

o Early after-depolarizations
This can occur during the plataue phase of the action potential
(phase 2) or the repolarization phase (phase 3)
Most sodium channels are in the inactivated state at this point
Some unknown pathological change may cause some sodium
channels to be abnormally activated, causing a self
propagating action potential
This is usually what happens in torsades de pointes
o
Late
o
o
after-depolarizations
This happens after repolarization is complete
This usually happens in states where there is high intracellular
calcium concentrations, or when there is excessive
catecholamine stimulation
It is thought that the high calcium concentration in the cell
activates the sodium-calcium exchanger, causing more sodium
to enter the cell, causing depolarization
o
o
d. conduction block (brady usually)
o
o
A conduction block occurs when an impulse reaches an area in the heart
that is electrically un-excitable
This may be transient, permanent or unidirectional
Conditions such as ischemia, fibrosis, inflammation or certain drugs may
cause this
If the block happens secondary to refractoriness of cells, it is considered a
functional block
If it is due to damage it is considered a fixed block
Blocks in conduction may happen anywhere along the AV, his-perkinge
system
Depending where the block is, and how strong the block is, escape rhythms
may be produced in the conducting tissue, although at a much slower
pacemaker rate. This is most frequently seen the third degree heart block
Please see week objective 4 on more information on 1 st, 2nd and 3rd degree
heart block
o
6. Describe the pharmacologic and nonpharmacologic treatment of
tachycardias (anti- arrhythmics and radio frequency ablation).
o
7. Describe the treatment of tachycardias and bradycardias (conservative,
pharmacologic and invasive) (lecture/self directed)
Bradycardia- depends on presence of symptoms and risk of

syncope/death
i. Conservative: stop medications that may be contributing to
bradycardia and terat any reversible conditions (hypothyroidism,
ischemia)
ii. Invasive: pacemaker
2. Sinus node bradycardia
i. Symptomatic: pacemaker
ii. Asymptomatic: no treatment
3. AV node bradycardia
i. First degree AV block: no treatment
ii. Second degree AV block:
o Type 1: no treatment
o Type 2: pacemaker
iii. Third degree AV block: pacemaker
o
o Tachycardia
Conservative: treatment of medical conditions contributing to
tachycardia (sepsis, hyperthyroidism), avoiding tachycardiogenic
medications,
ii. Pharmacologic: anti-arrhythmic medication
iii. Invasive: cardioverter/defibrillator implantation, catheter ablation
i.
o Pharmacological Interventions (see LI #8 for pharmacology)

Sodium channel blockers
a. Procainamide, disopyramide
b. Lidocaine, mexiletine
c. Propafenone, flecainide
II. Beta-blockers- acebutolol, metoprolol
III. Potassium channel blockers- amiodarone, sotatol, dronedarone, ibutilide,
dofetilide
IV. Non-dyhydropiridine calcium channel blockersverapamil, diltiazem
o Other. Digoxin, adenosine
I.
o Catheter ablation
FR energy delivered to mycaridal tissue, disrupts arrhytmia substrate
o
Cardioverter/defibrillator implantation
Cardioversion sync shock with QRS complex. Good for SVTs or organized
Ventricular Tachycardia.
o
Vagal Maneuvers: AV node is well innervated by PNS fibers and

is responsive to vagal maneuvers
Valsalva, carotid sinus massage, diving reflex

Terminate junctional (AV nodal) reentry tachycardias by increasing cardiac
PS tone via vagal nerve
1.
2.
3.
4.
5.
o Valsalva Maneuver
Increase in intrathoracic pressure causes an increase in aortic pressure.
A transient baroreceptor response to decrease blood pressure results.
Pressure in aorta falls because intrathoracic pressure compresses veins
resulting decrease in venous return. Cardiac output is decreased and
therefore no stimulation of baroreceptors.
Decrease in baroreceptor stimulation results in vasoconstriction and an
increase in periph. resistance
Release of pressure at the end of the maneuver restores cardiac output,
but increased peripheral resistance remains
Baroreceptors detect an increase in blood pressure, and response by
decreasing cardiac output (decrease in heart rate)
o
o
o
o
o
o
o
o
8. Describe the hemodynamic consequences of

tachycardias and bradycardias (including preload, CO,
BP and coronary flow)
Hemodynamics = the study of flows, volumes and pressures
of blood within the body (heart and circulatory system)
Cardiac Output (CO) =
the amount of blood pumped by the
heart each minute (units: L/min).
Stroke Volume (SV) =
volume of blood pumped per beat
CO = SV per
x HR
Heart Rate (HR) = number of contractions
minute
Frank-Starling Law:
the heart will pump what it receives
o
o
o
o
Preload =
the volume (load) filling the ventricle prior to
contraction; equivalent to end-diastolic volume. When preload is
increased, according to the Frank-Starling Law, there will be a
compensatory increase in SV to accommodate it.
Afterload = wall stress experienced by the ventricle as it contracts to

produce a pressure necessary to open the aortic valve and eject blood
into the systemic circulation
P = pressure generated by ventricle
r = radius of ventricle
Wall stress =
h = thickness of
ventricle
Chronic exposure to high afterload triggers a compensatory

response whereby the ventricular wall thickens to reduce wall
tension. Over time, this hypertrophy can disrupt the normal
intracellular handling of calcium, and the ventricle may become
a less efficient pump, leading to heart failure.
Bradycardia decreases CO and thereby decreases arterial pressure. The

reduced pressure can lead to syncope and other symptoms related to
hypotension.
o
Tachycardia
Tachycardia reduces SV and CO. The SV is reduced because of decreased

ventricular filling time and decreased preload at high rates of contraction. If
the tachyarrhythmia is associated with abnormal ventricular conduction, the
synchrony and therefore the effectiveness of ventricular contraction will be
impaired leading to reduced CO.
Tachycardia also increases myocardial oxygen demand. This can cause
angina, particularly in patients with underlying coronary artery disease.
Chronic states of tachycardia can lead to systolic heart failure.
o
Bradycardia
o 8. Describe the pharmacology of:

o Class I, II, III, and IV anti-arrhythmics
*The principle of antiarrhythmic therapy is to abolish the mechanisms by
which tachyarrhythmias occur
o Increased automaticity of pacemaker or nonpacemaker cells
Treat by: 1) reducing slope of phase 4 depolarization 2) prolong
refractory period
o Re-entrant pathways
Treat by: 1) lengthen refractory period 2) additionally impair
impulse propagation within the already slowed retrograde limb
(fully abolish conduction within it)
o Triggered activity
Suppress early/delayed after-depolarizations.
MOA of antiarrthymics
o
o
o
o
o Digoxin
o Positive inotropy effect, prlong refractory period of AV node.
Mechanical effect: increases contractility of the heart
o MOA: inhibition of sarcolemmal Na K ATPase pump increases
intracellular [Na+] reduces Ca2+ extrusion from cell by the Na-Ca
exchanger more Ca is pumped into SR more Ca is released in
next AP greater force of contraction .
Electric effect: slows conduction velocity and prolong refractory period of the
AV node
o Electrical effects include directly affecting the cardiac tissue, as well
as enhancing vagal tone and reducing sympathetic activity.
o Digoxin has lots of toxic electrical effects when it reaches the toxic
range e.g. ectopic/re-entrant rhythms, high degree AV block,
complete heart block.
Clinical uses:
o Heart failure: increases contractility, augments cardiac output.
o Antiarrhythmic agent for
atrial fibrillation, atrial fluttler- reduces # of impulses through
AV node, therefore slows ventricular rate.
PSVT: enhances vagal tone slows impulse conduction, prolong
refractive period I interrupt re-entrant circuits that pass
through AV node.
o Atropine
Anticholinergic- competitively bind to muscurinic receptors, suppresses
vagal stimulationincreases HR and enhanced AV nodal conduction.
Clinical use: for symptomatic bradyarrhythmias that require treatment. Only
increases HR acutely- has a transient effect. Pacemakers are needed for a
more sustained action.
o
o
o
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o CV Week 3 Cardiac Electrical Function and

Dysfunction
o Case Objectives
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1. Cardiac Anatomy See week objective

2. Explain the following: Normal waves (P, QRS, T) and
intervals (PR, QRS, QT) Refer to Week Objective #3c
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b. Normal physiological events associated with the ECG

waves and intervals
d. Diagnostic criteria for, and be able to diagnose the

following rhythms if given an ECG tracing
Refer to Week Objective #4
3. Explain the causes and underlying mechanisms of
tachycardias Please see Week objective 5
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4. Differentiate between supraventricular and ventricular
tachycardias
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Ventricular Tachycardia
Wide QRS
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Supraventricular Tachycardia
Narrow QRS (normal)
BUT some SVTs can result in wide QRS complexes: SVT with aberrancy
To differentiate SVT with aberrancy from VT:
o VT: if patients with history of MI, CHF, LV dysfunction
o SVT: If vagal manoevers affect the rhythm
o SVT: If ECG during SVT is morphologically similar to ECG during
normal sinus rhythm
o VT: no relationship between P waves and QRS (dissociation), QRS
complexes in V1-V6 chest leads are similar in appearance
(concordance of precordial QRS complexes)
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Summary table:
SVT with Abberency
QRS morphology same as when in

normal sinus rhythm
Rhythm responds to vagal
manoevers
VT
No relationship between P wave

and QRS complexes
Concordance of QRS complexes in
chest leads (V1-V6)
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5. Describe the treatment of tachycardias (conservative,
pharmacologic and invasive)
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Refer to Week objective #6.
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6. Describe the hemodynamic consequences of tachycardia
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Refer to Week objective #7.
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7. Describe the pharmacology of: (refer to Week Objective 8)
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a. Adenosine
o IV adenosine causes transient heart block in the AV node, decreasing
HR
o Commonly administered to patients with AV nodal reentry arrhythmia
Binds the A1 receptor inhibition of adenylyl cyclase
reduction in cAMP hyperpolarization by increase efflux of K+
o Also causes endothelial dependant relaxation of smooth muscles
surrounding arteries.
Relaxation of smooth muscles causes dilation of arteries.
o Side Effects:
Facial flushing, a temporary rash on the chest,
lightheadedness, diaphoresis or nausea. All are due to its
vasodilating effects
Classically associated with a sense of impending doom
Chest pain (angina pectoris-like)
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o Note: Some anti-arrhythmic drugs (Class Ic Na+ and Class III
K+) can be pro-arrhythmic (rare).
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E.g. Class Ic Na+: Flecainide, Propafenone
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Class III K+: Amiodarone, Sotalol
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o FMED 402:
Cardiovascular
o Week FOUR Atherosclerosis and
Ischemia
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WEEK OBJECTIVES:
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1. Describe:
a. The cellular and metabolic mechanisms of atherogenesis and

the roles of T cells, monocytes, macrophages, platelets, smooth
muscle cells
Atherogenesis: refers to the formation of atheromatous (focal

thickenings) lesions in the arterial intima
Response to injury hypothesis

o Repetitive endothelial injury Increased permeability, leukocyte adhesion and
thrombosis Accumulation of LDL and oxidized products in vessel wall
Migration of monocytes into Transformation of monocytes into macrophages
and then foam cells Platelet adhesion Activated platelets, macrophages,
vascular wall cells release factors to recruit smooth muscle cells (SMC) SMC
proliferation and extracellular matrix production Lipid accumulation both
extracellularly and within cells (macrophages and SMCs).
Characteristics
o Leading cause of mortality in western world
o Starts in early childhood and progresses asymptomatically through adult life
o Later in life atherosclerosis is clinically expressed as coronary disease, stroke,
transient ischemic attack, peripheral artery disease
Multifaceted, progressive, inflammatory disease that affects large and medium sized
arteries (aorta, carotid, coronary, femoral arteries)
Characterized by accumulation of lipids and fibrous elements
Affects coronary, cerebral and peripheral circulations
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Atherosclerosis:
Both atherogenesis and atherosclerosis have common characteristics:
Associated with multiple risk factors

Inflammatory processes play a fundamental role in disease development
o both innate and adaptive immune responses have a role
Atherosclerosis represents a specific form of chronic inflammatory process
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atherosclerotic lesions possess all the necessary features of chronic

inflammation
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Structurally ECs line cavities/lumens and act as a dynamic (selectively permeable)

barrier between the flowing blood and surrounding tissues
Functionally ECs allow bidirectional exchange via diffusion, transcytosis, specific
transport. They also release NO (vasodilator), ET (vasoconstrictor) etc
NO: vasodilator with both protective and atherogenic influences
o Endothelial NO synthase eNOS: enzyme present in endothelial cells, helps
to generate NO with atheroprotective characteristics
enhances vascular relaxation, inhibition of platelet aggregation,
inhibition of endothelial dependent monocyte adhesion
o Inducible NO synthase iNOS: enzyme present in macrophages, produces NO
with antimicrobial functions based on potent oxidative properties
NO binds with H2O2 or O2 radicals to produce highly reactive
peroxynitrite radicals
It is now well accepted that normal endothelial cells play an important role in vascular
homeostasis and can limit the development or progression of atherosclerosis
Consequences of endothelial cell dysfunction
o Dysfunction is a systemic process that occurs early in atherosclerosis and
contributes to pathogenesis of atherosclerosis
Allows for interaction between elements of the blood and arterial wall
components
Upregulates synthesis of proteins that induce recruitment of platelets,
monocytes, and lymphocytes
Results in excessive inflammatory and fibroproliferative responses
o Inflammatory processes play a central role in the genesis of atheroma and its
thrombotic complications
Factors leading to EC dysfunction include
o Hypercholesteremia, hypertension, diabetes, obesity, smoking, physical injury
to ECs, transplant rejection
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c. Describe the risk factors for atherogenesis
Non-modifiable
Age: death rates from ischemic heart disease rise with each decade, even into
advanced age
Gender: premenopausal women are relatively protected against atherosclerosis,
postmenopausal incidence of atherosclerotic related disease increases and eventually
exceeds that of men
Race: atherosclerosis is much less prevalent in CA, SA, Africa and Asia.
Family history: familial clustering of risk factors like hypertension, atherosclerosis, IHD
(ischemic heart disease), diabetes and familial hypercholesteremia
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b. Describe the role of endothelial cells (ECs) in the prevention

of atherosclerosis
Modifiable
Behavioural: diet/exercise/alcohol/smoking
Physiological: obesity, hypertension, hyperlipidemia, hyperhomocysteinemia,
diabetes
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Traditional: hypercholesteremia
Non-traditional: lipoprotein A, hyperhomocystinemia, herpes, Chlamydia, oxidative
stress, depression (associated with platelet aggregation)
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d. Mechanism by which cholesterol, hypertension, smoking

promote atherogenesis
1. Hypercholesterolemia:
o Impairs endothelial cell function by increasing local production of reactive

oxygen species. O2 free radicals accelerate the decay of NO, which dampens its
vasodilator activity and thereby increases local shear stress. When present in excess, LDL
can accumulate in the subendothelial space more readily.
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2. Hypertension:
o Major risk factor for atherosclerosis. Hemodynamic disturbances (high BP)

cause endothelial cell dysfunction and are a major risk factor for atherogenesis.
Hypertension increases the risk of IHD and if left untreated 50% of hypertensive patients
will die of IHD, CHF, and 30% will die from stroke. LVH represents a marker of long
standing functional hypertension
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3. Smoking:
o Toxins from cigarette smoke also cause endothelial cell dysfunction. Cigarette
smoking is a well-established risk factor in men. Prolonged smoking increases the risk of
death from IHD by 200%.
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2. Describe and/or explain:
a. The principal non-modifiable and modifiable risk factors for

atherosclerosis and particularly coronary atherosclerosis
b. The strength of evidence for each of the risk factors and the
level of risk conferred
Source: lecture notes, Dr. Francis, evidence from INTERHEART study
Non-modifiable risk factors
o Age
Over time, blood vessels are exposed to factors that damage the endothelium
Initiate a repair and inflammatory process that initiates the formation of
atherosclerotic plaques
Damaging factors:
o Food molecules: trans fats, sat fats, high dietary cholesterol
o Elevated levels of harmful lipoproteins (LDL or remnant lipoproteins)
o Harmful chemicals in cigarette smoke
o Elevated blood glucose
o Elevated BP
o Cytokine molecules released into bloodstream from sites of inflammation
o Gender
Men generally have earlier onset of coronary heart disease than do women
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thought to be largely due to protective effects of estrogen on blood vessel wall and
endothelium
protective effect lost during menopause (estrogen production by the ovaries stops)
protective effect lost in pre-menopausal women if diabetic (but still effective in
smokers and those with genetic dyslipidemia)
factors attributing to earlier vascular disease in men:
o lack of estrogen
o lower HDL-C
o increased abdominal (visceral) fat
o higher rates of smoking
o Family History / Genetic predisposition
positive family Hx of premature vascular disease as defined by onset of vascular
disease symptoms or events in first degree relatives before age 60
factors affecting risk of early familial vascular disease:
o elevated LDL cholesterol or low HDL cholesterol levels
o presence of hypertension/diabetes
o elevated lipoprotein (a) [ Lp(a)]
o additional risk factors yet to be identified
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Modifiable risk factors
Known modifiable risk factors account for 90% of the population

attributable risk in men and 94% in women of MI. We already know most
of the major predictors of atherosclerosis and how to prevent it!
o Diet
trans and sat fats and high cholesterol contribute directly to endothelial damage and
plaque development
calorie excess contributes to weight gain, abdominal obesity, hypertension, diabetes
(all are independent risk factors for atherosclerosis)
higher levels of fruit and vegetable intake are independently associated with reduced
risk of coronary events
o Exercise
sedentary lifestyle is a predictor of increased vascular events
Benefits of exercise (even in the absence of weight loss): reduced blood pressure,
reduced LDL-C and triglycerides, reduced progression of impaired glucose tolerance
to type 1 diabetes mellitus, increased HDL-C, and improved heart function
o Dyslipidemia
Definition: elevated LDL cholesterol and reduced HDL cholesterol
LDL
Elevated LDL levels (and its main protein component apolipoprotein B) can
accumulate in the artery wall and taken up as either aggregated LDL or oxidized LDL
by macrophages or smooth muscle cells in the artery, leading to foam cell formation
and atherosclerotic lesions
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In the presence of other risk factors that damage blood vessel endothelium, even
lower levels of LDL can cause harm (therefore in the presence of known CV disease or
several major CV risk factors, the recommended level of LDL is set lower)
Triglyceride levels do not correlate as strongly with CV disease as LDL, but increased
triglyceride levels on LDL make LDL more likely to be digested into smaller and
denser particles, making it more harmful (therefore high triglycerides can be
atherogenic if LDL or apoB levels are also high)
HDL
HDL (and its main protein component apolipoprotein A-I) are protective against CV
disease: level of HDL in blood inversely correlated to risk for CV
Protective actions:
o reverse cholesterol transport: ability to remove access cholesterol delivered to
arterial cells by LDL
o ability to induce relaxation of artery wall
ratio of apoB/apoA-a = strongest modifiable predictor of risk for MI
currently no effective therapeutic way of raising HDL levels
Cholesterol Profile
need to decide if the high cholesterol is due to environmental factors (diet, exercise)
or genetic (inherited) factors
generally, total cholesterol > 4.5mmol/L, triglycerides >3mmol/L, HDL<0.7 mmol/L
are likely due to genetic factors (cant usually be corrected with lifestyle alone)
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o Smoking
contains chemicals that dissolve in blood upon inhalation and damage the lining of
arteries
chemicals + damage to endothelium = constriction of blood vessels and reduction of
blood flow to tissues (including the heart)
harm is immediately reduced when smoking stopped
long term risk to blood vessels mostly gone 2 yrs after quitting
o Psychosocial Stress
major predictor for risk of MI
stress = blood cortisol and adrenaline levels + endothelial damage +
atherogenesis (relationship not well understood under investigation)
o Hypertension
chronic high BP = endothelial damage + thickening of arterial walls impairs
relaxation of artery additional stress on heart to pump against higher resistance
elevated systolic and diastolic BP increase CV risk
reducing BP through diet, exercise, weight loss, restriction of salt intake, and
medications is shown to reduce risk of MI and stroke
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Diabetes
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diabetics have a 2-4x higher risk of MI

thought to be due mostly to abnormalities in lipid levels seen in diabetics (small
dense LDL, triglycerides, HDL)
not yet proven that normalizing blood sugar reduces this risk, may worsen CV
outcomes if blood sugar lowered too much
most effect at reducing CV: LDL-C levels, maintaining lower blood sugar levels
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Abdominal Obesity
visceral fat releases more inflammatory factors than increased subcutaneous fat
outside the abdomen
inflammatory factors damage to blood vessel endothelium = risk of
atherosclerosis
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c. the concepts of risk assessment and multiple risk factors
1) Initial interaction and history of ischemic vascular disease

Age/apparent age, demeanour, marital status, occupation
Past history of known vascular disease (previous MI, stroke, TIA, peripheral
vascular disease, angina, previous coronary bypass or angioplasty, presence of
atherosclerosis) places individual into secondary prevention category
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2) Dyslipidemia
Cholesterol profile (and previous cholesterol profiles, and steps taken: lifestyle
modifications, medications, non-prescription Tx, side effects)
If triglycerides high, previous pancreatitis?
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3) Smoking
Current or past smoker? Include number of pack-years if past smoker
Thinking or willing to think about quitting? Past attempts to quit?
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4) Elevated blood glucose or known diabetes
When first detected/diagnosed?
Gestational diabetes in women
Recent blood sugar or haemoglobin A1c if available
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5) Hypertension
Hx of hypertension? When detected/diagnosed? On medications?
If on meds, is BP controlled?
If monitor BP at home, what are typical recent at-home readings?
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6) Weight History
Has weight changed in last few years
BMI and waist circumference measurements
Plan to improve diet and exercise
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7) Alcohol Intake
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Intake per week or per month

Recommend reduced alcohol intake if excess weight or triglycerides present
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8) Psychosocial stress
Ask if experiencing stress, anxiety or depression (scale of 1-10) and reason
Sleep patterns (identify possible sleep apnea)
Attempts to reduce stress?
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9) Other past history
General health
inflammatory diseases (rheumatoid arthritis, lupus), thyroid disease, kidney
disease have impact on risk for CV disease and lipid disorders
other major illnesses (including physically limiting illnesses)
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Medications
Rx, supplements or vitamins, ASA
Diuretics, -blockers, glucocorticoids, retinoids, estrogen can adversely affect lipid
levels
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Dietary Assessment
General enquiry (level of fat, junk food, meat, fish, fruit and vegetables, simple
carbs fruid juices and soda pop)
Skipped meals, restaurant eating, frequency of travel and shift work
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CV related family Hx
Evidence of vascular disease/event in male first degree relatives before age 55 or
female first degree relatives before age 65 (now simplified to before age 60 for
both)
Ask about risk factors for all first degree relatives with known CV
Familial diabetes?
Other (not first degree) family members with CV disease
Familial high cholesterol?
Record age of death of grandparents
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13)
CV risk Physical Examination
BMI (kg/m2) and waist circumference (narrowest pt between costal margin and
iliac crest)
Abdominal obesity: major predictor of insulin resistance
o Caucasians: >102cm in men, >88cm in women
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14)
o Asians/South Asians: >90cm in men, >80cm in women

BP measurements (sitting and if elevated, supine)
Pulses, heart sounds
Physical signs of inherited dyslipidemia:
o Corneal arcus: white ring overlying outer edge of iris in the eye
o Xanthelasma: flat or raised yellow patches on the eyelids or just below the
eyes
o Planar xanthomas of the palms: orange-brown palm creases
o Tendon xanthomas: thickening/nodules in Achilles tendons/extensor tendons
of hands/ patellar tendons)
o Eruptive xanthomas: single or bunches of reddish-yellow bumps over the
back, buttocks, hands, elbows, feet
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Framingham Risk Score and other risk assessment tools
People at higher risk for CV disease:
o Known to have had a CV event, ischemic heart disease or peripheral
vascular disease
o Diabetics
o Chronic kidney disease (GFR <30 ml/min/m2)
For those in primary prevention category, use the Framingham Risk Score (FRS) to
calculate the 10yr risk of non-fatal MI or coronary death (most effective at
estimating risk for Caucasian males)
Factors considered when calculating the FRS:
o Age
o Total cholesterol
o Smoking
o HDL
o Systolic BP
The FRS is doubled in the presence of premature vascular disease in a first degree
relative and adjusted upwards based on the presence of other risk factors such as
elevated Lp(a) or hs-CRP
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d. The concepts of primary and secondary prevention of

coronary atherosclerosis
Primary Prevention
process of inhibiting the development of disease (symptoms and events) before it

happens
includes diet, stress-reduction, and medications
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Secondary Prevention
preventing complication of established disease

post MI or CVA treatment
prevention of vascular events after the presence of disease is detected
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e. The principles of preventive therapies directed at elevated

cholesterol, smoking, hypertension, lack of exercise and mental
stress.
1) Healthy diet
May involve consultation with dietician
General concepts: fruit and vegetable intake, fiber intake, meat and simple
carbohydrate intake, more chicken and fish, smaller portions, no skipped meals,
food spread throughout day
2) Exercise
Recommendations should be feasible, start with simple to achieve goals
3) Dyslipidemia
Restriction of dietary fat and simple carbohydrates
Regular exercise
Medications (especially in cases of genetic dyslipidemia)
4) Smoking cessation
Aids available: nicotine replacement (gum, patch, inhaler), varenicline, bupropion
5) Hypertension
Home BP cuffs
Reduction of weight, regular exercise, dietary salt reduction
medications
6) Stress management
Psychotherapy, exercise, meditation, efforts to improve personal relationships
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3. Describe how these factors influence myocardial supply and

demand:
o
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o
o Heart rate and diastolic time
HR: The higher the heart rate, the higher the O 2 demand.
Diastolic time: Coronary flow occurs mostly in diastole, therefore, the longer the
diastole time, the greater the supply.
o This is one of the reasons beta blockers are used to treat ischemia- it slows the
HR, therefore augmenting the time spent in diastole
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o Systolic and diastolic arterial pressures
See Coronary perfusion gradient below. Arterial pressures affect the aortic root
pressure, therefore affecting the coronary perfusion gradient equation. E.g. If you
have a low diastolic pressure, you will have a low diastolic aortic root pressure, and
therefore less flow through the coronary arteries.
The Mean BP also affects the intraventricular pressure. This is a factor in Laplaces
law (wall stress=rp/2h). Therefore, the greater the BP, the higher the intraventricular
pressure, and the higher the O2 demand.
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o Coronary resistance and coronary perfusion gradient
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Coronary resistance: As coronary resistance rises, coronary blood flow decreases.
o External compression: when the myocardium contracts, it squeezes the
coronary blood vessels, therefore limiting flow.
o Intrinsic Control:
Metabolic factors (usually as a consequence of ischemia)- local
metabolites accumulate e.g. adenosine, lactate, acetate, H+, CO 2, cause
vasodilation.
Endothelial factors: normally a vasodilatory state predomninates.
Responding to different stresses, endothelial cells can release
vasodilators (NO, prostacyclin, EDHF), or vasoconstrictors (endothelin 1)
Neural factors: sympathetic receptors predominate- a1 vasoconstriction
and b2 vasodilatation.
Myogenic- autoregulation of smooth muscle: constricts in increased
blood flow (eue to stretch and opening of Trp channels, allowing Ca2+ to
enter cells)
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Coronary perfusion gradient
o Coronary perfusion gradient= Aortic root pressure- LV pressure
o During systole, the aortic root pressure and LV pressure are equal , therefore
the coronary perfusion gradient is 0, and there is usually no coronary flow
o During diastole, the aortic root pressure is much higher than the
intraventricular cavity pressure, so myocardial supply occurs mostly in diastole.
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o LV end diastolic pressure (preload)
Preload affects the radius of the LV at the onset of systole. Therefore, the greater the
preload, the greater the radius, the greater the wall stress (afterload), and the greater
demand for oxygen of the myocardium
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Wall stress=rxp/(2h)
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o LV Wall thickness
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According to the equation Wall stress=rxp/(2h), wall thickness (h) is inversely related
to wall stress (force is spread over a greater muscle mass). Therefore, a
hypertrophied heart has lower wall stress and O2 demand per gram of tissue.
o However, the thicker the wall, the more grams of tissue you have. So it is a fine
balance between decreasing demand per gram of tissue and how many grams
you have.
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o LV wall stress and law of Laplace
Law of Laplace: Wall stress=rxp/(2h).
The greater the wall stress, the greater the O2 demand per gram of myocardium.
o Therefore according to the equation, 3 things can increase demand.
increased radius,
increased intraventricular pressure (affected by resistance of aortic
valve, peripheral vascular resistance, compliance of aorta and major
vessels)
decreased wall thickness
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o Exercise
During exercise, heart rate and contractility both increase the O 2 demand of the
heart.
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o 4. Describe the histology of the heart and cardiac valves (histo
lecture/laboratory)
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o Heart wall layers ~ Blood vessel layers
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Intima = endocardium
Media = myocardium
Adventitia = epicardium (has mesothelial layer)
Endocardium (intima of heart)

1. Endothelium = simple squamous epithelium
2. SUBendothelial CT
o loose CT
o collagen and elastic fibers (elasticity)
o embedded fibroblasts (responsible for fibrosis)
o some SMC
o note: varies in thickness eg. thicker in atria b/c atrial more compliant than
ventricles need more CT/elasticity
o note: contains cardiac conduction system (modified myocardial cells) eg.
Purkinje fibers in ventricle
o Epicardium/Visceral Pericardium (adventitia of heart)

Inner layer of pericardial sac
Loose fatty CT
Nutrients, Protective cushion and conduit for coronary vasculature and nerves
(autonomic and sensory)
Note: simple squamous mesothelium secretes lubricant serious fluid to
decrease friction in pericardial cavity
o Myocardium
Contractile myocardial cells
o Usually central nuclei
o Striated w/ myofibrils
o High capillary:fiber ratio
o Numerous mitochondria
o Long lived cells (not much regenerative capacity) accumulate lipofuscin in
tertiary lysosomes (perinuclear)
o Branched (skeletal muscle is linear)
o
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Fibers arranged into fascicles

Fibrous CT b/t fascicles
o Conduit for vessels and nerves
Rich capillary network around fascicles
Intercalated Disc (unique to myocardium!)
o Withstand stress forces
o End-to-end Mechanical and electrical linkage b/t myocardial cells
o 1. Fascia adherens (transverse)
anchor actin from myofibrils to sarcolemma
o 2. Desmosomes (transverse)
link intermediate filaments
focal mechanical adhesion b/t fibers
o 3. Gap junctions (axial)
contain connexons, electrical coupling b/t fibers
membranes of 2 myofibrils contacted
eg. increased in Purkinje fibers for cardiac conduction
synchronized contractility
Denser A band (overlap of actin and myosin); Lighter I band (actin anchoring site)
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Endocrine Function
Atrial myocardial cells produce and secrete ANP
o Atrial specific granules exocytosed into endothelium of adjacent capillares
(in response to myocardial stretch)
o ANP = CV homeostasis, BP regulation, fluid electroylate balance
Impluse Generating and Conduction System (SA node, AV node, LBB, RBB, Purkinje)
Modified myocardial cells
NO EPICARDIUM PRESENT
Septum = surrounded by endocardium; thick myocardial core
Purkinje fibers
o large diameter fibers (specialized for conduction, NOT impulse
generating)
o in SUBendocardium (along w/ CT, elastin, collagen, SMC)
o some in deep myocardium
o lots of glycogen, mito, gap junctions
note: appear washed out b/c glycogen removed
Cardiac Valves
Folds of endocardium ; central core of dense fibrous CT
Attach to annuli fibrosi of cardiac fibrous skeleton
Note: Cardiac fibrous skeleton = all throughout heart!
o site for attachment of muscle cells and around valves
Attached @ free edge via chordae tendinae to papillary muscles
Dense fibrous CT core rich in elastic and collagen fibers
Scattered fibroblasts
Note: Avascular! Lacks blood vessels and lymphatics
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o
o
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o 5. Describe the coronary anatomy
The largest components of the coronary vessels lie within the loose CT of the
epicardium.
The coronary arteries bring oxygenated blood to the heart, while the coronary veins
take away deoxygenated blood.
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o
o
a. Left coronary: Left main, Left anterior descending (LAD),
Circumflex, diagonals.
The left main coronary artery originate from the left coronary sinus (aka left sinus of
Valsalva), an opening in the root of the aorta
o Travels between the left atrium and the pulmonary trunk to reach the AV
groove and divides into the LAD and circumflex
o
Left anterior descending (LAD) coronary artery

Travels within the anterior interventricular groove towards the apex
Gives off diagonal branches
Supplies the anterior surface of the left ventricle
Gives off septal branches
Supplies the anterior two thirds of the interventricular septum and
the apical portion of the anterior papillary muscle
o
Circumflex coronary artery

Travels within the left atrioventricular groove and passes around the left
border of the heart to reach the posterior surface.
Gives off obtuse marginal branches
Supplies the lateral and posterior wall of the left ventricle
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o
o
o b. Right coronary: Right main, Posterior descending
The right main coronary artery originate from the right coronary sinus (aka right
sinus of Valsalva), an opening in the root of the aorta
o
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Travels in the right Atrioventricular groove, passing posterior to between the

right atrium and right ventricle
o Gives off marginal branches
Supplies the right ventricle, including the SA and AV nodes
o Gives rise to the right posterior descending artery
Comprised of the distal part of the right main coronary artery
Travels from the inferoposterior aspect of the heart to the apex
Supplies the inferior and posterior walls of both ventricles and the
posterior one third of the interventricular septum
o
o c. Conductance and resistance vessels
Conductance vessels
o Epicardial and myocardial penetrating vessels
o Larger in diameter, less flow resistance
o Compressed by the contracting cardiac muscle during systole
o
Resistance vessels
o Arterioles and capillaries
o Smaller in diameter
o Surrounded by vascular smooth muscle and can change their diameter in
response to stimuli
Eg. Endothelial nitric oxide (NO), Adenosine
o Precapillary sphincters can vary flow through the coronary capillaries
o
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o d. Coronary sinus.
Coronary veins accompany the coronary arteries and converge into the coronary
sinus
o Located along the posterior surface of the heart in the atrioventricular grove
o Empties deoxygenated blood into the right atrium
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6. The pathophysiology of myocardial ischemia and infarction

a. Define and describe the pathophysiology of myocardial
ischemia, angina (stable and unstable and atypical) and
myocardial infarction
o
o Myocardial ischemia:
A state where oxygen supply is insufficient to the myocardium to meet its needs
because of inadequate perfusion
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Can be broken down into demand ischemia (usually due to exercise) or supply
ischemia (usually secondary to some sort of blockage like a rupture of a vulnerable
plaque)
For the heart, increased oxygen demand needs to be met by increasing coronary flow
because
o Myocardium depends almost completely on aerobic metabolism
o Oxygen extraction by the myocardium cannot be increased any further than it
already is
o The myocardium cannot incur a significant oxygen debt
o
o Angina stable:
Stable angina is usually due to atherosclerotic stenosis (narrowing) of the coronary
artery walls of the myocardium
o This reduces coronary reserve
o The amount of narrowing depends on
Geometry of the stenosis
Degree of residual capacity for dilation
Presence of platelet aggregation and thrombus
One of the common features of stable angina is chest pain on exertion
Usually the artery must be greater than 75% occluded in order to cause these
symptoms
Adenosine is released locally in response to ischemia
o This dilates the blood vessel but also stimulates nerve fibers that ultimately
lead to the classic finding of chest pain
Stable angina is usually relieved by rest
o
o Angina unstable:
This is quite similar to stable angina except for the fact that this usually occurs at rest
or minimal exertion
The artery of concern may be greater than 90% occluded
Unstable angina generally means the loss of predictability of anginal attacks due to
worsening of the stenosis
o
o Angina atypical:
Patients with atypical angina do not typically have the classic symptoms of chest
pain, but instead have the other symptoms such as weakness, faintness, sweating
and nausea
This is more commonly seen in patients with diabetes
The pathophysiology of atypical angina is the same as angina though
o
o Myocardial infarction:
This basically refers to death and permanent damage to the myocardial tissue
secondary to ischemia
Myocyte death can begin after 15-20 minutes of severe ischemia
After damage (happening in the first 12 hours), an inflammatory stage begins where
PMNs begin to influx. These may stick around for up to 5 days
o Myocyte nuclei disappear
o Phagocytosis of myocytes begin with macrophages
Granulation tissue then begins to form for up to 3 weeks
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o Reperfusion may occur

o Collagen formation begins at this point
Scar tissue formation
o At this stage there is a decrease in inflammatory cells with increasing collagen
deposition
o Begins to look white in appearance
o
o
o b. Discuss the concepts of atherosclerotic coronary artery
stenosis, the vulnerable plaque, plaque rupture and coronary
thrombosis
o
Atherosclerotic coronary artery stenosis usually is a strong predictor for myocardial
ischemia or infarction
Usually it is not the actual stenosis that ends up causing possible infarction and tissue
death
Enough build up of lipid and platelets along with fiber in the intima of the
myocardium, may cause partial blockage, but also potential for embolism formation
A vulnerable plaque is characterized by a thin fibrous cap with a large soft lipid
cholesterol pool underneath it.
o These characteristics together with the usual hemodynamic pulsating
expansion during systole and elastic recoil contraction during diastole
contribute to a high mechanical stress zone on the fibrous cap making it prone
to rupture
Plaque rupture is caused when this vulnerable plaque is able to dislodge itself from
the wall of the artery and embolize through the blood
This is the usual cause for the sudden onset myocardial infarctions
o Vulnerable plaques are able to rupture, travel through the blood and occlude a
smaller diameter artery further downstream, causing ischemia and infarction
The simple definition of a coronary thrombus is the formation of a blood clot inside
one of the coronary blood vessels that will obstruct the flow of blood through the
circulatory system
o A travelling clot is called an embolus
o
o c. Discuss myocardial infarction from the perspectives of the
progression of infarction from subendocardial to epicardial, the
determinants of infarct size, the gross and microscopic changes
seen in the various stages of myocardial infarction and the
consequences and complications of myocardial infarction at the
pathological and clinical levels
o
o
Progression of infarction from subendocardial to epicardial (subendocardial
more vulnerable to ischemia and infarction
o Greater degree of systolic fiber shortening in the subendocardium (high oxygen
demand. Normally there is more flow to the subendocardium than there is to
the subepicardium
o There is a greater dependence on diastolic coronary flow (almost no flow in
systole due to occlusion of vessels because of contracting muscle around
them)
o There is poor collateral vessel development
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Flow to the endocardium may be reduced by

Coronary atherosclerosis
Left ventricular hypertrophy
Heart failure with increased LVEDP
o Infarction spreads from subendocardium to subepicardium
o
o
Determinants of infarct size
o Severity and duration of ischemia
o Size of area at risk
Region supplied by a specific coronary segment
o Collateral coronary circulation
The less collateral vessels, the larger the infarct
o Pre-ischemic state of myocardium eg. Hypertrophy, ischemic conditioning
o Reperfusion of ischemic vascular bed
Spontaneous lyses of coronary thrombi
Effects of therapy
Fibrinolytic therapy
Angioplasty
Coronary bypass grafting
o Myocardial oxygen demand
Heart rate
Blood pressure and LVEDV (wall tension)
Contractility
Therapies
o Myocardial oxygen supply
Diastolic perfusion pressure and time (HR and rhythm)
Anemia
Hypoxia
Therapies
o
o
Gross and microscopic changes that are seen at the different stages of
myocardial infarction
o Stage of ischemic injury (12 hours)
Micro
EM changes in myocytes and their membranes within the first 1520 min
Wavy fibers intracellular edema
Coagulation necrosis hypereosinophilic myocytes
Contraction band necrosis compaction of Z-lines of sarcomeres
Macro
If no reperfusion of infracted area then pallor due to extrusion of
erythrocytes from capillary bead
If reperfused then hemorrhagic from blood vessel bursting
o Stage of inflammation (12hrs 5 days)
Micro
Influx of PMNs
o If no reperfusion, then they collect at the borders of the
infarct
o If reperfusion, then they are distributed diffusely
o
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Macrophages are seen after about 5 days

Myocyte nuclei start to disappear and myocytes become
attenuated and separated
o Phagocytosis of myocytes occur
Macro
Yellow centre with hyperemic border (not reperfused)
Prominent hemorrhage (reperfused)
Stage of granulation tissue formation (1-3 weeks)
Micro
Residual macrophages, revascularization, fibroblasts and early
collagen formation
Macro
Infarct turning from yellow to gray
Stage of scar formation (2-8 weeks)
Micro
Decrease in inflammatory cells with increasing collagen deposition
and prominent capillary vessels
Macro
Infarct changing from gray to white as collagenization becomes
complete
o
Complications of infarction
Death
Half of all patients will have this outcome
Usually due to ventricular arrhythmia (VT or VF)
Necrosis may have not even happened become death could have
occurred well before the tissue became necrotic
Arrhythmias
Arises from ischemic but non-infarcted tissue at the MI border zone
Major determinant of post discharge mortality
Ventricular dysfunction
Happens when greater than 25% is dysfunctional
May lead to dyspnea or pulmonary edema
Late outcomes may be heart failure, myocardial stunning, myocardial
hibernation
Cardiogenic shock
When infarction of over 40% of myocardium occurs
Low CO and BP, which exacerbate the ischemia
Recurrent infarction
Usually happens 2-10 days after original event
Infarct expansion
Expansion of infarct without additional necrosis
Causative factors include infarct size, afterload, infarct artery patency
Myocardial rupture
Can occur in 2 time frames
Most in the first few days after an MI
Some occur in 2nd week after an MI
Most often occurs at the border of the infarct
High mortality
o
o
o
o
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LV free wall location

Hemopericardium/tamponade
IVS
CHF
Papillary muscles
Right ventricular infarction
Usually associated with transmural inferior LV MI
Pericarditis
Almost always requires a transmural infarct in order to manifest
Mural thrombus
May embolize and cause other complications like stroke
Results from stagnant blood in one area of the heart (usually from an
over inflamed wall or aneurysm
Ventricular aneurysm
Usually from transmural infarcts and greater than 2 coronary artery
disease
May cause arrhythmias
Usually composed of scar tissue
o
o
o
o
o
o
o
7. Describe the d/dx of chest pain and findings in history, physical and
appropriate investigations for stable angina, unstable angina, NSTEMI, STEMI
o Stabl
e
angin
a
o Unsta
ble
angin
a
o (parti
al
occlu
sion,
no
necro
sis)
o NSTE
MI
Transient subendothelial ischemia

Occurs with exertion/stress
Pain can radiate to jaw, left arm, left shoulder
Transient change in ECG: ST depression
Resolves with rest or Nitro
Subendocardial ischemia
Occurs without cause (at rest), gets worse, lasts 1520 minutes
Transient change in ECG: ST depression, T wave
inversion/depression
Does not respond to nitro
Subendocardial tissue ischemia + necrosis

ST depression, T wave inversion/depression
Test for troponin I or T or CK MB in blood
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o (parti
al
occlu
sion,
necro
sis)
o STEMI
o (full
occlu
sion,
tissue
necro
sis,
ST
eleva
tion)
Transmural tissue necrosis

ST elevation
o
o
o
Commn Causes of Acute Chest Pain

o
CLINI
CAL
DESC
RIPTI
ON
Retros
ternal
chest
pressu
re,
burnin
g, or
heavin
ess;
radiati
ng
occasi
onally
to
neck,
jaw,
epigas
trium,
should
ers,
left
o
S
o
A
KEY
DISTINGUIS
HING
FEATURES
Precipitated
by exercise,
cold weather,
or emotional
stress;
duration 210 min
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o
o
S
CLINI
CAL
DESC
RIPTI
ON
KEY
DISTINGUIS
HING
FEATURES
Typically
<20 min;
lower
tolerance for
exertion;
crescendo
pattern
Sudden onset,
usually lasting
30 min;
often
associated
with
shortness of
breath,
weakness,
nausea,
vomiting
Pericardial
friction rub
Marked
severity of
unrelenting
pain; usually
occurs in
setting of
hypertension
or underlying
arm
o
o
R
Same
as
angina
, but
may
be
more
severe
Sharp,
pleurit
ic pain
aggra
vated
by
chang
es in
positio
n;
highly
variab
le
durati
on
o
A
o
P
o
A
Same
as
angina
, but
may
be
more
severe
Excruc
iating,
rippin
g pain
of
sudde
n
onset
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o
o
S
CLINI
CAL
DESC
RIPTI
ON
in
anteri
or of
chest,
often
radiati
ng to
back
o
o
P
o
P
o
o
P
Sudde
n
onset
of
dyspn
ea
and
pain,
usuall
y
pleurit
ic with
pulmo
nary
infarct
ion
Subst
ernal
chest
pressu
re,
exacer
bated
by
exerti
on
Pleurit
ic
pain,
usuall
y
brief,
over
involv
ed
area
KEY
DISTINGUIS
HING
FEATURES
connective
tissue
disorder such
as Marfan
syndrome
Dyspnea,
tachypnea,
tachycardia,
signs of right
heart failure
Pain
associated
with dyspnea
and signs of
pulmonary
hypertension
Pain pleuritic
and lateral to
midline,
associated
with dyspnea
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CLINI
CAL
DESC
RIPTI
ON
Burnin
g
disco
mfort
in
midlin
e
o
S
o
T
o
S
Sudde
n
onset
of
unilat
eral
pleurit
ic
pain,
with
dyspn
ea
KEY
DISTINGUIS
HING
FEATURES
Midline
location,
associated
with coughing
Abrupt onset
of dyspnea
and pain
Aggravated
by large meal
and
postprandial
recumbency;
relieved by
antacid
Relieved by
antacid or
food
o
o
o
E
o
P
Burnin
g
subste
rnal
and
epigas
tric
disco
mfort,
10-60
min in
durati
on
Prolon
ged
epigas
tric or
subste
rnal
burnin
g
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CLINI
CAL
DESC
RIPTI
ON
Prolon
ged
epigas
tric or
right
upper
quadr
ant
pain
o
S
o
G
o
P
Prolon
ged,
intens
e
epigas
tric
and
subste
rnal
pain
KEY
DISTINGUIS
HING
FEATURES
Unprovoked
or following
meal
Risk factors
including
alcohol,
hypertriglycer
idemia,
medications
May be
reproduced
by pressure
over affected
joint;
occasionally,
swelling and
inflammation
over
costochondral
joint
May be
reproduced
with
movement of
neck
Reproduced
by palpation
or movement
Sudde
n
onset
of
intens
e
fleetin
g pain
Sudde
n
onset
of
fleetin
g pain
Const
ant
pain
o
C
o
C
o
T
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o
o
S
CLINI
CAL
DESC
RIPTI
ON
KEY
DISTINGUIS
HING
FEATURES
of chest wall
or arms
o
o
H
o
P
Prolon
ged
burnin
g pain
in
derma
tomal
distrib
ution
Chest
tightn
ess or
aching
, often
accom
panie
d by
dyspn
ea
and
lasting
30
minut
es or
more,
unrela
ted to
exerti
on or
move
ment
Vesicular
rash,
dermatomal
distribution
Patient may
have other
evidence of
emotional
disorder
o
o
o
o
o
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o
o
o
o
8. Describe conservative, pharmacological and invasive

(percutaneous transluminal angioplasty, coronary stenting,
revascularization surgery) therapies for:
a. Stable angina
b. Acute coronary syndromes (unstable angina, NSTEMI, STEMI)
o
I
oExercise
SSmoking
cessation
Diet
Stress
reduction
o Pharm
acolo
gical
Tx
o Invasive
Tx
o Acute
angina
episod
e:
Sublingual nitro
o
o Preven
tion of
recurre
nt
episod
es:
organic nitrates
-blockers
Ca2+ channel blockers
o
o Preven
tion of
MI:
o ***Revas
cularizati
on:
PCI (PTCA)
Coronary stents
Drug-eluting stents
Coronary artery bypass
graft (CABG)
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o
I
o
U
Aspirin
(antithrombotic)
Lipid-regulating
therapy
ACE inhibitors
o Pharm
acolo
gical
Tx
o Same
as for
stable
angina
, but
admini
stered
more
aggres
sively
o
N
o Additio
nal
antithr
omboti
cs:
heparin
o As
o Invasive
Tx
o Same as
for stable
angina,
but use
invasions
earlier in
patients
with
high-risk
features
(ST
deviation
,
elevated
Trop-I,
multiple
CV risk
factors)
o Primary
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above
but
admini
stered
immed
iately
o For
STEMIs
only:
PCI:
immediat
e
angioplas
ty and
usually
stenting
fibrinolytics
***Indications for Revascularization:
(1) Patients symptoms of angina do not respond adequately to anti-anginal drugs

(2) Unacceptable side effects of medications occur
(3) Patient is found to have high risk CAD for which revascularization is known to improve
survival
o
-
Percutaneous coronary interventions (PCIs): Percutaneous

transluminal coronary angioplasty (PTCA):
Performed under fluoscopy

balloon-tipped catheter inserted through peripheral artery (usually femoral, brachial
or radial) and manoeuvred into the stenotic segment of a coronary vessel
balloon is then inflated under high pressure to dilate the stenosis, after which it is
deflated and the catheter removed from the body
requires an accessible lesion in the coronary artery, with small amount of patent
lumen
Approximately 1/3 of patients develop recurrent symptoms within 6 months due to
restenosis of the dilated artery
o
Coronary Stents
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Slender, cagelike stainless-steel support devices that in their collapsed configuration

can be threaded into the region of stenosis by a catheter
placed at the time of PCI
once in place, opened by expanding a balloon in its interior, after which the balloon is
removed
stents are thrombogenic, so a combination of oral antiplatelets must be given after
stent implantation
compared to PTCA, results in larger luminal diameter, decreased restenosis rates, and
reduced need for repeat angioplasties
Risk of restenosis due to neointimal proliferation (migration of smooth muscle cells &
production of ECM)
o
Drug-eluting Stents
incorporates antiproliferative medication released from stent over 2-4 weeks

effective at preventing neointimal proliferation and restenosis
o
note: percutaneous revascularization techniques work better than

medications for angina, but do not reduce the risk of MI or death in
stable CAD
Coronary Artery Bypass Graft (CABG)
grafting portions of a patients native blood vessels (saphenous veins, internal

mammary arteries) to bypass obstructed coronary arteries
requires a bypassable lesion
o - >50% stenosis in left main coronary artery or two to three vessel
disease with diabetes

o - Preferable to angioplasty when there is significant disease of more
than 2 vessels
o
9. Describe the Pharmacology:
o Nitrates (nitroglycerin, isosorbide dinitrate, isosorbide mononitrate)

MOA:
o Stimulates release of NO.
o venodilatation- reduces venous return to the heart, therefore decreases
workload of the heart.
o Also has a vasodilatory effect on the coronary vesselsincrease perfusion.
Effect: decreases cardiac workload, decreases O 2 demand.
Indications: symptomatic treatment for acute ischemic episodes. May be also
taken for short term prophylaxis.
o No evidence for improved survival or prevent infarctions.
Contraindications: preload dependent patients- aortic stenosis, RV dysfunction,
Viagra users.
SE: headache, lightheadedness, palpitations.
o
o Beta Blockers
MOA: beta receptor antagonists, blocks the inotropic and chronotropic effect.
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Effect: reduces myocardial oxygen demand by slowing HR and contractility. By

slowing HR, it also increases coronary blood flow by increasing time spent in diastole.
Indications: CAD
Contraindications: obstructive airway disease, LV dysfunction, marked
bradycardia/heart block, insulin treated diabetic patients
SE: fatigue, sexual dysfunction.
o
o Calcium channel blockers (nondihydropyridine calcium channel blockersverapamil and diltiazem)
MOA: antagonize voltage-gated L-type calcium channels.
Effect: Reduce inotropy and slow heart rate. Minor vasodilatory effect.
Indications: reserved for those in whom ischemia persists despite beta blocker and
nitrate therapies, or for those with contraindications for beta blockers
Contraindications: LV systolic dysfunction.
o
o Lipid Lowering agents (Statins, Niacin, Fibric acid derivatives,
Cholesterol intestinal absorption inhibitors, bile acid binding agents.
MOA of statins: HMG-CoA reductase inhibitors. Inhibit rate limiting enzyme
responsible for cholesterol biosynthesis. Resulting reduction in intracellular
cholesterol increases LDL-receptor expressionincreases clearance of LDL in
bloodstream.
o MOA of other agents:
Bile acid binding resins: increase secretion of bile acids
Nicotinic acid: lower VLDL secretion and LDL formation, increase HDL
formation
Fibrates: lower VLDL secretion, increase triglyceride removal.
Effect:
o lower LDL. Also lowers VLDL, and raise HDL.
Also has other potential benefits: increase NO, fibrinolytic activity. Inhibit
smooth muscle proliferation, monocyte recruitment, matrix degrading
enzymes. May also inhibit inflammation.
No effect on ischemic symptoms, used over long period of time, may slow
progression of plaques.
o
o ASA
MOA: irreversible cyclooxygenase inhibitioninhibit platelet synthesis of
thromboxane A2 (a potent mediator of platelet activation)
Effect: anti-thrombotic actions through inhibition of platelet aggregation. Also has
anti-inflammatory properties.
Indications: CAD
Contraindications: gastric bleeding, allergies.
Should be continued indefinitely in all patients with CAD.
o
o Heparin (unfractionated heparin UFH, low molecular weight heparins
LMWHs)
MOA:
o binds to and increase potency of antithrombin III (inactivates clot-forming
thrombin)
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inhibits coagulation factor Xa slow thrombin formation and further clot

development.
Effect: anticoagulant
Indications:
o standard therapy for UA and NSTEMI- produce cardiovascular outcomes, and
reduce likelihood of progression from UA to MI.
o Adjunctive antithrombotic therapy after fibrinolysis or PCI in STEMI.
o
o Fibrinolytics (alteplase tPA, reteplase rPA, tenecteplase TNK-tPA)
MOA: stimulate the natural fibrinolytic system: transform inactive precursor
plasminogen into active protease plasminlyses fibrin clots.
Effect: accelerate lysis of the occlusive intracoronary thrombus.
Indications: fibrinolytic therapy in STEMI. ONLY for STEMI!
Contraindications: underlying bleeding disorder, active peptic ulcer disease, recent
stroke, recovering from recent surgery, pregnancy, intracranial tumor/AVM, suspected
aortic dissection or pericarditis.
o
o
o
o CV Week 4 - Atherosclerosis and Ischemia
o
o
Case Objectives
o
o
1. Describe: Risk factors (modifiable and non-modifiable) for
atherosclerosis
o
Refer to Week Objective
o 2. Define and Describe:

o a. Determinants of myocardial O2 demand and supply
Refer of Week Objective
o b. Myocardial ischemia and infarction

o c. Angina (Stable vs. unstable)

o
o
o
o
3. Describe findings in history, physical, and appropriate

investigations for myocardial ischemia and myocardial infarction
o
o
o 4. Describe treatment for stable angina and MI
5. Pharmacology
o
o
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o
o
o
o
o
o
o
o

Week FIVE Cardiac Structure and Consequences of
Dysfunction
o
WEEK OBJECTIVES
o
o 1.Describe the Frank-Starling curve
o a. normal heart vs failing heart

o
The frank starling curve
represents the relationship
between the amount of blood
present at the end of diastole in
the left ventricle, and the stroke
volume of the subsequent systole
The relationship states that an
increase in volume will elicit an
increase in stroke volume,
ejecting the extra blood out of the
heart (but only to a certain point
until the heart becomes
overloaded with blood)
o If the heart is overloaded,
the cross linking of actin
and myosin become to stretched that they are no longer in contact and cannot
contract
Point a represents a normal individual at rest with normal contractility of the heart
o As there is an increase in volume, there is an appropriate increase in stroke
volume
Point b represents an individual with cardiac failure occurring at rest
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His system has compensated in order to deal with a failing heart by increasing
the end-diastolic volume in order to illicit a larger stroke volume (since patients
with cardiac failure has diminished contractility and therefore decreased
amounts of stroke volume
Point c represents an individual who has cardiac failure but is volume overloaded
(so they have a larger end-diastolic volume in a sense)
o At this point in the curve (which is more flat than the normal individual), the
actin and myosin cross links are maximally stretched, and any further
stretching may cause a decrease in stoke volume
o Since at this point any increase in volume would not cause an increase in
stroke volume, the patient accumulates fluid and causes backup, leading to
symptoms like pulmonary congestion
o
o 2. Heart Valves
o
o a) Describe normal function of valves

preserve one-way flow of blood thorugh heart
AV valves open during diastole
SL valves open during systole
o b) define stenosis and regurgitation insufficiency

Stenosis: valve orifice is narrowed
o resistance to flow when valve is open
o need excess pressure in proximal chamber to maintain flow through valve
(gradient)
o if stenosis is gradual then less likely to have decrease in SV at rest
Regurgitation/insufficiency/incompetence (valve leaks)
o abnormal functional anatomy of closed orifice
o leak or backflow when valve is closed
o AV valves leak in systole, SL valves leak in diastole
o EDV of ventricle increases, increased SV
Total SV = Forward SV + Regurgitant volume
if regurgitation develops gradually the increase in total SV usually is
sufficient to allow forward SV to be maintained near normal at rest,
although exercise reserve is decreased
o
o
o
o
o
c) describe the effects of stenosis and regurgitation of the semilunar and

AV valves on preload, afterload, wall
stress and remodelling. Differentiate between chronic, gradual
progression of regurgitation and acute onset of regurgitation
Stenosis:
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in stenosis the pressure in the upstream

chamber needs to be increased in order to
maintain flow through the stenotic valve
increased pressure increases wall stress
(LaPlace) and therefore increases afterload
to counteract the increase pressure the
ventricle undergoes concentric hypertrophy
(widens thickness of the ventricular wall)
the increased muscle mass requires more O2
total
as ventricles hypertrophy the compliance
falls, raising EDP and therefore atrial and
proximal pressures rise
since there are no valves proximal to the
atrium the increased pressure is transmitted
to the proximal circulation
the atrium hypertrophies as well
as stenosis gets worse over time there is
increased limitation of CP with exercise and
eventually at rest
L stenosis-->increased pulmonary capillaries
and pulmonary edema
R stenosis-->increased systemic venous
pressure and peripheral edema
o
o
o Regurgitation:
regurgitant valves leak some blood from the ventricle back into the atrium (or great
vessel) during systole, which then comes back into the ventricle during diastole
increase in ventricular preload
total stroke volume increases but Total SV=normal SV + regurgitant volume so the
forward SV is close to normal
ventricle is able to increase the ejection of blood via Starling effect
o if the regurgitation happens gradually, ventricle has time to increase
compliance and therefore the LVEDV increase may not result in a significant
rise in LVEDP
o If regurgitation occurs acutely and is severe, the increase in LVEDV may result
in a marked increase of LVEDP resulting in increases of LA and pulmonary
capillary pressure which may result in marked dyspnea on exertion or even at
rest with pulmonary edema, and low CO
afterload increase due to increase EDV (LaPlace) and ventricle undergoes eccentric
hypertrophy to reduce wall stress
increase cardiac muscle mass leads to increased O2 consumption
if regurgitation becomes more severe over time there is a limitation to CO with
exercise and even at rest
as EDV increases, and ventricle hypertrophies, the EDP rises and pressure rises in
chambers proximal to the first affected chamber
o
d) describe key features of the history and physical exam in Aortic/mitral

stenosis, Aortic/mitral regurgitation
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o
o
Aortic Stenosis
Etiology- Degenerative, Bicuspid AV, Rheumatic
o Clinical course
Usually asymptomatic for many years
Characterized by systolic ejection murmur
o maximal at R2ics at sternal edge, radiating to the carotids
o must be differentiated from an innocent murmur
o increases in intensity and duration as the severity of the stenosis increases
o as CO falls (late stage) might diminish
carotid pulse contours gradually become delayed and diminished
early echo shows abnormal AV morphology and increased peak ejection velocity
ECG will eventually show LVH
chest X ray will show enlarged aorta and possibly AV calcification
o LV no enlarged until late in the course when it becomes visible on CXR (shows
congestive heart failure)
Symptoms occur late and carry a bad prognosis
o Angina
o Syncope
o
e) understand the principles of management of valvular stenosis and

valvular regurgitation (conservative, pharmacological, invasive *but no
details) 2017: treatment: (conservative, pharmacological and
invasive)
CHF
o Management
Diagnose using physical, ECG, CXR and echo (often asymptomatic at this stage)
Symptoms carry a bad prognosis
Surgical valve replacement or percutaneous valve replacement can improve
prognosis
o
o
o
Aortic regurgitation
Etiology
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Rheumatic, congenital, traumatic, endocarditis, aortic root

o
o Clinical Course
Usually asymptomatic for many years
First abnormality noted is often diastolic decrescendo murmer
Diastolic murmers are always pathological and require investigation
There is often an aortic systolic murmur (larger SV)
As LV hypertrophies apex beat may be displaced
Widened pulse pressure, water hammer pulse, nailbed capillary pulsations
Echo can show abnormal AV morphology (early sign) and regurgitant jet from Aorta to
LV
o Echo LV internal dimension is increased
this is used as an important determinant of clinical course
ECG eventually shows LVH
CXR will show enlarged Ao, LV enlargement and eventually signs of CHF
Exertional dyspnea occurs
Angina and syncope are less common than with AS
Prognosis with symptoms is poor
o
o Management
Sometimes beta blockers provide symptom improvement
Moderate to high levels of exercise are safe
Manage systemic hypertension aggressively
o If normal BP may benefit form use of ACEi
Monitor LV function
Valve replacement
o Onset of symptoms with exertional dyspnea or low CO require surgical valve
replacement or repair
Acute onset or sudden progression of AR is generally a surgical emergency
o
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o
o
o Mitral Stenosis
o
o Etiology- Rheumatic, rarely congenital, LA tumor or thrombus
o
o Clinical course
More common in women than men
Apical murmur with snap
o First pre systolic then accompanied by early diastolic rumble and eventually
heard through diastole
o Difficult to detect by untrained ears but is characteristic and occurs early in
disease course
Echo shows abnormal MV morphology and reduced area, high velocity transmitral
velocity, elevated PA pressure and RV dysfunction
ECG shows LA hypertrophy, RA hypertrophy (eventually)
CXR shows LA enlargement, MV calcification, pulmonary venous redistribution, RV
enlargement, pulmonary congestion
First symptom is usually exertional dyspnea
o May be brought on by pregnancy when a marked increase in CO results in a
marked rise of LA pressure
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Rales, JVD and edema may develop

Evidence of low CO may become prominent
Development of AF or other atrial tachyarrhythmias can precipitate a marked
increase in LA pressure and fall in CO
o Atrial thrombus might form, particularly with AF and may cause stroke or
peripheral embolus
o
o Management
Mitral stenosis tend to progress more rapidly than AS
o Intervention may be necessary earlier to relieve dyspnea before RVF and
pulmonary congestion
Surgical repair or replacement is necessary and sometimes needed as initial
intervention
Medical management is important but only as adjunct to definitive valve repair or
replacement
o Anticoagulation is required for AF or previous stroke or peripheral embolus
o
o
o
Etiology- myxomatous degernation, prolapse, LV dysfunction and

enlargement, rheumatic, disrupted chordae tendinae/papillary muscle
apparatus, annular calcification, endocarditis, hypertrophic
cardiomyopathy
Clinical course-
MR gradually develops= usually asymptomatic

Pansystolic murmur maximal at apex and radiating to axilla
ECHO shows abnormal MV morphology, increased LA dimension, increased L internal
dimension and MV regurgitant jet
ECG shows LA hypertrophy and LVH (volume overload)
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CXR shows LA and LV enlargment and may even show RV enlargement and
pulmonary vascular redistribution/congestion at later points
Most prominent symptom is dyspnea, first on exertion and eventually at rest
o Fatigue from low CO may become prominent
Arrhythmias and pregnancy are likely to bring on symptoms, but their impact on
symptoms tends to be less dramatic than in the case with MS
o
Management
Eventually need repair or replacement

o Those with parked symptoms may not do as well post op as those who are
referred for surgery at a point where LV dysfunction is documented but
symptoms are not yet present
Medical management of tachyarrhythmias and CHF are important but should only be
adjuncts to definitive valve repair or replacement
o
o
o
o
o
o
o
o
o
o
3. Calculate ejection fraction (using an equation).

Ejection Fraction: The fraction of end-diastolic volume ejected from the
ventricle during each systolic contraction (normal range: 50-75%)
o
EF = SV/end-diastolic
volume
o
o
o
o 4. Describe the pressure-volume loops for the cardiac cycle.
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o
o Point a: mitral valve opens.
Atrial pressure exceeds ventricular pressure
o a-b: diastolic filling
As the ventricular volume increases during diastole, it is associated with a small rise
in pressure. The amount of pressure that rises per volume is associated with the
compliance of the myocardium.
o Point b: mitral valve closes
Due to contraction of ventricles, the pressure of the ventricles exceed that of the
atrium, and the MV closes
o b-c: isovolumetric contraction
Both the MV and the AV are closed, so the volume stays constant while the pressure
shoots up as the ventricle contracts.
o c: AV opens
Ventricular pressure > aortic diastolic pressure, AV is forced open.
o c-d: systolic ejection
The volume decreases as blood is ejected, but pressure continues to rise until
ventricular relaxation occurs. The pressure along this curve represents the afterload
(the pressure that the ventricle ejects against)
o d: AV closes
Aortic pressure exceeds ventricular pressure.
o d-a: isovolumetric relaxation
Both valves are closed as the ventricles relaxes, causing the volume to stay constant
while pressure drops.
o ** b is the pressure and volume at the end of diastole
o **d is the pressure and volume at the end of systole.
o
o
o
o
o
o
o
o
o
o Changes to Pressure-Volume Curve with different preloads
o
As the preload increases (e.g. from 1 to 2), the increased EDV increases, which
augments the SV via the Frank Starling mechanism.
Similarly, if the preload decreases (e.g. due to a stiff ventricle, which decreases
compliance), the SV decreases.
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Note that the End systolic volume (ESV) does not change with a change in preload.
o
o
o Changes to Pressure-Volume Curve with different afterloads
o
With an increase in afterload, more
ventricular work is expended in overcoming
the
resistance to ejection and less fiber
shortening takes place. In other words, more
time/energy is spent in isovolumetric
contraction before the valve can open,
therefore less time is allotted for systolic
ejection.
The result is a lower SV and an increased
ESV.
***The ESPVR line depicts the relationship
between the afterload and ESV- it is
approximately linear.
o
o
o
Changes to Pressure-Volume Curve with different contractility

o
The slope of the ESPVR line is a function of
cardiac
contractility
o When contractility is increased, the
slope
increases.
Therefore, when contractility increases, you
get an
increase in SV and therefore a decrease in ESV
o
o
o
o
o
5. Describe the compensatory

responses to low cardiac output
o
o CO = HR X SV (SV typically a larger determinant)
1. Raise HR (reflex tachycardia)
2. Neurohormonal avtivation via RAAS and SNS
o Raise SVR to shunt blood to vital organs (SNS peripheral vasoconstriction)
o note: may eventually be detrimental since this would result in increased
afterload, which would decrease SV and initiate a vicious cycle
**SV determined by preload, contractility, afterload, and valve function

o
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3. Ventricular Remodeling
o Increase wall thickness h to reduce wall stress in response to high pressure
and afterload
CONCENTRIC hypertrophy ie. relative wall thickness increases
wall tension decreases SV (thus CO) increases
note: increased muscle mass requires more O2, so this is a fine
balance
o
Increase chamber size (dilatation) to reduce wall stress in response to

increased volume and too much preload
ECCENTRIC hypertrophy
note: increased muscle mass requires more O2, so this is a fine
balance
6. Explain how to evaluate and treat a patient with low blood

pressure
You must determine the underlying cause of hypotension
o There are 4 different types causes of acute hypotension (shock) each with its
own set of overt characteristics:
o
Hypovolemic Shock
Cardiogenic Shock
Distributive Shock
Obstructive Shock
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Signs and Symptoms used to differentiate between the 4 types of shock

o High vs Low Systemic vascular resistance (SVR)
o High vs Low Cardiac output (CO)
Use BP = CO x SVR equation
o Presence or absence of fever
o Previous cardiac history myocardial infarction, valvular defect
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Types of
Shock
Cause
Treat
ment
Due to
inadequate
circulating
volume
IV fluids
(preloa
d)
Blood
transfus
ion
Hemorrhagic
Non-hemorrhagic
o Burns
o Vomiting
o Dehydration
SVR increased
CO decreased
Due to
inadequate
coronary
profusion
Acute MI
Acute valvular dysfunction
Myocardial contusion (disruption of heart rhythm)
SVR increased
CO decreased
Due to
excessive
blood
vessel
dilation
Septic Shock
Anaphylaxis (Histamines)
Neurogenic Shock
o Trauma of spinal cord
leading to loss of SNS
function
IV fluids
(preloa
d)
Inotrop
e
(contra
ctility):
doubutamine or
dopamine
Stop
bleedin
g
SVR decreased
CO - inc,
dec, or same
doubutamine or
dopamine
Control
arrhyth
mia and
reverse
ischemi
a
IV fluids
(preloa
d)
Inotrop
e
(contra
ctility):
Vasoco
nstricto
r
(afterlo
ad):
norepinephrine
Due to
physical
obstruction
of the
great
vessels or
heart
SVR increased
CO -
doubutamine or
Treat
underlyi
ng
cause
IV fluids
(preloa
d)
Inotrop
e
(contra
ctility):
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Cardiac tamponade
Tension pneumothorax
Pulmonary embolism
Air embolism
decreased
dopamine
Remove
obstruc
tion
7. Understand the following concepts as they relate to cardiac

remodeling:
a. wall stress and the law of laplace
In the heart, once there is a

pressure increase (due to things
like hypertension or aortic
stenosis) or if there is a volume
overload (in something like mitral
regurgitation), P or r will rise
respectively.
o This will increase wall
stress which will cause an
increase in myocardial
oxygen demand
The heart will then
adaptively increase
its thickness
(hypertrophying)
causing a decrease
in wall tension and
leading to a decrease in myocardial oxygen demand
b. cardiac hypertrophy
As mentioned before, cardiac hypertrophy is a normal adaptive response elicited by
the heart from a prolonged increase in pressure or volume
o 15% of the general population
o 50% of the population with moderate hypertension
o 90% of people with cardiovascular disease
Although this is an adaptive response, there are a number of negative outcomes
involved long term
o Increased dysfunction after ischemia (explained later)
o Increased infarct size after an MI
o Sudden death
o Heart failure
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c. define and describe 2 patterns of pathological cardiac

hypertrophy
There are 2 main forms of hypertrophy depending on what the original
predisposing factor was
Concentric
Eccentric
Type
Relat
ive
wall
thick
ness
Resul
ts
from
Incre
Conce
ntric
More
Pressur
e
overlo
ad
Yes
Eccen
tric
Less
Volum
e
overlo
ad
Yes
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ased
LV
mass
Incre
ased
contr
actili
ty
Incre
ased
LV
EDV
Chan
ge in
lengt
h of
myoc
yte
Chan
ge in
Xsecti
onal
area
of
myoc
yte
Yes
No
Yes
(only
when
dilated
)
Increas
e by
5%
Yes
(only
when
dilated
)
Increas
e by
30%
Increas
e by
150%
Increas
e by
50%
d. Describe the adaptive response to prolonged workload
In response to an increased workload, the heart undergoes:

o Quantitative changes
Structural changes described above
o Qualitative changes
Decreasing the amount of work done by SR Ca2+ ATPase
More Ca 2+ stays outside of SR
Increasing contractile proteins
Increasing glycolysis and decreasing fatty acid oxidation
Increasing cardiac NE/EPI receptors
Increasing ANP/BNP expression
If ischemia is followed by the prolonged workload, it is important to note that the
amount of cardiac work preformed by the heart drops off significantly compared to a
non-hypertrophied heart
e. Compare and contrast pathological and physiologic cardiac

hypertrophy
Pathological and physiological cardiac hypertrophy are very different from one
another
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Type
Pathol
ogical
Adap
tive
Long
term
bene
fit
Inter
stitia
l
fibro
sis
Fetal
Gene
Expr
essio
n
Cardi
ac
funct
ion
Yes
Physi
ologic
al
Yes
No
Yes
Yes
No
Increas
e
Stays
the
same
Decrea
ses
over
time
Asso
ciatio
n
with
heart
failur
e
Reve
rsible
Yes
Increas
es or
stays
the
same
no
No (Yes
if you
treat
HTN)
Yes
Also important is the hearts response to ischemia after a prolonged work load
o Recall that in a hypertrophied heart due to heart failure, work cardiac work
would drop significantly after an ischemic event
o In a physiological hypertrophied heart, the cardiac work response is the
opposite
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8. Heart failure. Describe the following:
a) Causes and Pathophysiology of Heart Failure Inability of the

heart to pump blood at sufficient rate (low CO) to meet metabolic
demands of the body, or to do so at abnormally high filling pressures, or
both.
Preload May be low (stiffness, pericardial constriction, MV stenosis, itnracardiac

mass), resulting in low CO Heart failure
Afterload High afterload reduced SV (Htn, AV Stenosis)
Contractility Reduced Low CO
Neurohormonal
MOA: Vasoconstriction and salt/water retention
Neural: SNS
Low CO Decreased pressure barorecptors in carotid sinus/aortic arch alter firing

Decreased PNS and Increased SNS
o Increased HR via beta-1 receptors
o Increased ventricular contractility
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o
o
Arterial/venous vasoconstriction via alpha receptors (NB, this increases VR too)

Increase renin release via stimulation of JG beta-1 receptors
Hormonal
RAA Axis: Decreased renal artery perfusion pressure due to reduced CO, decreased
salt delivery to macula densa, and stimulation of JG beta-1 receptors by SNS
Increased renin secretion from granular cells in JG apparatus Renin converts
angiotensinogen to angiotensin I Angiotensin I (via ACE) Angiotensin II
o Vasoconstriction
o Increased intravascular volume by stimulating thirst via hypothalamus,
increased aldosterone from adrenal cortex (increased sodium/water resorption
at distal convoluted tubule)
o Increased ADH secretion from posterior pituitary more water resorption by
increased water retention in the distal nephron, and systemic vasoconstriction.
Endothelins Released from endothelial tissue and acts by vasoconstriction
Natriuretic peptides
o Released in response to increased intracardiac pressure by atrial cells
(Mechanoreceptors triggered by stretch, release ANP). Ventricular cells release
BNP by the same means.
o Stimulate sodium and water excretion (decreased preload)
o Vasodilation decreased SVR and increased forward CO (less afterload)
o Inhibition of renin secretion
o Antagonizes effects of angiotensin II (see above)
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b) Important findings in History, physical, investigations
Symptoms
Left Sided
o Dyspnea on exertion (a very prominent sign of left ventricle failure). Why?
There are two possible explanations: pulmonary venous congestion &
decreased forward blood flow. Here is a summary:
If pulmonary venous pressure exceeds 20 mmHg, there is transudation
of fluid into pulmonary interstitium & congestion of lung parenchyma.
Because of decreased lung compliance, the patient must generate a
greater negative intrathoracic pressure to move the same volume of air.
Also, excess fluid in interstitium compresses the walls of bronchioles &
alveoli, thereby increasing the resistance to airflow and requiring greater
effort of respiration.
In addition, increased interstitial lung volumes stimulate juxtacapillary
receptors (J receptors) that mediate rapid shallow breathing
o But, some patients even have dyspnea despite absence of lung congestion.
This may be due to reduced blood flow to the overworked respiratory muscles
and accumulation of lactic acid.
o Dulled mental status: because reduced forward flow results in decreased
cerebral perfusion
o Decreased urine output: because of reduced renal perfusion. But, this usually
turns into nocturia at night because blood flow is redistributed to the kidney,
promoting renal perfusion and diuresis.
o Orthopnea: this is the sensation of labored breathing while laying flat, and is
relieved by sitting upright. It results from redistribution of intravascular blood
from abdomen and lower extremities toward the lungs.
o Paroxysmal nocturnal dyspnea: this is severe breathlessness that awakens the
patient from sleep 2 to 3 hours after going to bed. Results from gradual
reabsorption into the circulation of lower extremity interstitial edema after
lying down, with subsequent expansion of intravascular volume and increased
venous return to the heart and lungs.
o Hemoptysis (coughing up blood): results from rupture of engorged bronchial
veins
o Fatigue: due to insufficient forward blood flow to organs/muscles
Right Sided
o Right upper quadrant discomfort: two reasons: 1) liver become engorged and
its capsule is stretched 2) anorexia and nausea may result from edema within
GI tract.
o Peripheral edema: this usually involves the ankles and feet and results from
increased hydrostatic venous pressure. Some patients notice weight gains due
to this edema.
Physical Signs
Cachexia (frail, wasted appearance)

Diaphoresis: happens in decompensated left-sided heart failure and is due to
increased sympathetic nervous activity
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Cool extremities: due to peripheral vasoconstriction

Tachypnea
Sinus tachycardia: due to increased sympathetic nervous activity
Pulsus alternans: alternating strong and weak contractions detected in the peripheral
pulse. It is a sign of advanced ventricular dysfunction.
Pulmonary rales: created by popping open of small airways that had been closed off
by edema fluid prior to inspiration
Coarse rhonchi and wheezing: due to compression of conduction airways by
pulmonary congestion
Loud P2: due to the loud component of P2 because the pulmonic valve is forcefully
closed due to increase in pulmonary vascular pressures
S3: due to abnormal filling of the dilated chamber
S4: may be heard. Results from forceful atrial contraction into a stiffened ventricle
and is common in states of decreased left ventricular compliance (diastolic
dysfunction)
Mitral regurgitation murmur: sometimes auscultated in left-sided heart failure if the
valve annulus is stretched and the papillary muscles are spread widely apart from on
another because of left ventricular dilatation, thus preventing full closure of the mitral
leaflets in systole
Parasternal right ventricular heave: represents right ventricular enlargement so
sign of right side failure
Tricuspid regurgitation murmur: due to right ventricular enlargement
Distention of jugular veins: due to elevated systemic venous pressure caused by right
heart failure
Hepatomegaly: due to elevated systemic venous pressure caused by right heart
failure
Edema: accumulates mostly in ankles and feet. Results from increased systemic
venous pressure
Laboratory Tests
Normally, mean left atrial pressure is 10 mmHg. When it exceeds 20 mmHg, X-rays
will show indistinctness of the vessels and presence of Kerley B lines. If it exceeds
25-30 mmHg, alveolar pulmonary edema may develop.
Chest radiograph may show cardiomegaly, defined as a cardiothoracic ratio of greater
than 0.5.
A high right atrial pressure also causes enlargement of the azygous vein, a finding
visualized by chest radiography.
Pleural effusions may be present in either right or left-sided heart failure, but most
common when bilateral failure is present.
Ventricular function can be assessed by a number of noninvasive tests, including
echocardiography, and radionuclide ventriculography
In some cases, cardiac catheterization is necessary to determine the cause of heart
failure, including valvular ischemic etiologies.
Elevated BNP LV dysfunction and prognostic marker
Elevated neurohormonal and cytokine stimulation prognostic marker (IE, elevated
SNS hormones is adverse marker)
c) Right sided vs Left sided Failure
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d) systolic vs diastolic failure
Right
o Causes: L failure, pulmonic valve stenosis, R ventricular infarct, parenchymal
pulmonary disease, pulmonary vascular disease
o Effects: Ankle edema, liver enlargement, ascites, elevated JVP
Left
o Causes: Loss of contractility (secondary to MI, MR, AoR, pathological
hypertrophy), excessive afterload, or impaired diastole
Systolic dysfunction (LoC/Afterload) Volume builds up in ventricle
Pressure becomes elevated Back pressure, pulmonary congestion.
Also, low cardiac output.
Diastolic dysfunction impaired relaxation (secondary to LVH, ischemia,
cardiomyopathies) filling occurs at higher pressures back pressure
Diastolic dysfunction impaired filling due to obstruction no filling
low SV Failure
e) Acute vs. Chronic Failure
Acute
Reduced CO
Decreased tissue perfusion
Increased pulmonary
congestion/peripheral
congestion
Orthopnea/PND
Cough
Increasing abdominal girth
(ascites)
Peripheral edema
Fatigue associated with
systolic or diastolic
dysfunction, valve
dysfunction, cardiac rhythm
abnormalities
Distressed
Elevated JVP, audible S3,
crackles in both fields,
tachypnea and tachycardia
MANAGEMENT DIFFERENT
FROM CHRONIC
Chronic
Dyspnea
Orthopnea/PND
Fatigue
Weakness
Exercise Intolerance
Dependent edema
Cough
Weight gain
Abdominal distension
Normal HR/RR
Not distressed
Nocturia
Cool extremities
Uncommonly:
Cognitive impairment
Altered mental state from
normal
Nausea
Abdominal discomfort
Oliguria
Anorexia
Cyanosis
f) Compensated vs. Decompensated
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Compensated = damaged pump and doing well (compensation mechanisms restore

heart function):
o Adequate forward perfusion
o absence of backward congestion
o minimal symptoms or physical signs of heart failure
Decompensated = damaged pump (compensation mechanisms no longer working)

o inadequate forward perfusion or
o presence of backward congestion
o significant symptoms or physical signs of heart failure
(See previous objective for compensations to low CO and long term

effects)
g) Complications (Left)
Pulmonary edema (Dyspnea, orthopnea, PND)

Renal perfusion drop (Increased RAAS contributing to pulmonary edema. If perfusion
drops enough renal failure)
Brain Hypoxic encephalopathy with irritability, loss of attention span, restlessness
stupor/coma
Reduced CO Ischemia/infarcts
g) Complications (Right)
Hepatomegaly congestion.
o Also, especially with L failure, centrilobular necrosis and fibrosis
Elevated pressure in portal vein and tributaries portal hypertension varices
Congestive splenomegaly
Chronic bowel edema (ascites)
Kidney congestion greater fluid retention, peripheral edema, azotemia (impaired
nitrogen excretion)
Brain as above
Pleural/Pericardial pleura effusions and pericardial effusions
Sub-Q tissues: Peripheral edema
h) Treatment
Acute
Monitor
o Vital signs
o Close observation of fluid balance
o CVP/Arterial line for Pt who may require pressors/inotropes
Investigations
o Bloodwork: CBC, electrolytes, BUN, Cr, Glucose, Troponin
o CXR
o ECG
Therapy
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o
o
o
Oxygen until hypoxemia corrected first by FiO2, then CPAP/BiPAP, then

intubate
If below meds dont work intraaortic balloon pump
Medications
Lasix (Loop diuretic)*
Natriuretic Peptides
Nitroglycerin*
Inotropes
Pressors
* indicates contraindicated if hypotensive. NB that the goal of treatment
is to reduce preload, pulmonary edema, wall stress, increase CO, and
maintain BP
Chronic
Investigations Bloodwork, ECG, CXR, Echo

Management
o Exercise training
o Salt/fluid restriction
o Weight management
o Medications
ACEi (Reduce preload and afterload)
Beta-blockers (Reduce cardiac workload)
ARB (Reduce preload and afterload)
Digoxin (Inotrope, negative chronotrope, anti-arrhythmic)
Nitrates (Reduce preload and some afterload)
Spironolactone (Aldosterone blocker) (Reduce preload)
o Procedures
Cardiac Resynchronization Therapy
ICD
Revascularization if indicated
Cardiac transplant
9. Descibe the following features of cardiac rehabilitation:
a. exercise in the healthy vs. the diseased heart

Lower VO2 max in diseased heart due to lower SV
Effects of exercise training
1) Reduces HR and systolic BP (SPB) response to a given submaximal workload
delays angina
2) Increase peak coronary flow improves endothelial function
3) Improvement in CV and respiratory function
maximal O2 uptake (central and peripheral adaptations)
Lower minute ventilation (alveolar + dead space ventilation)
Lower myocardial O2 cost
Lower HR for a given VO2 (but does not affect maximum HR) and BP
Increased capillary density in skeletal muscle
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Increased lactate threshold

Increased ischemic threshold
4) Reduction of CAD risk factors
Reduce resting systolic and diastolic BP
Increase HDL, decrease triglycerides
Reduce body fat, waist circumference
Reduce insulin need, improved glucose tolerance
5) Changes in systemic circulation during exercise
systolic BP (due to sympathetic arterial vasoconstriction: alpha 1
constriction to blood vessels of the viscera and periphery)
systemic vascular resistance (due to skeletal muscle vasolidation)
resulting in diastolic BP (larger vascular sink)
Risks of exercise
1) Reduces rate pressure product= HR x SBP
2) Acutely increases the risk of a medical event
Vigorous exercise (6 METS)
SNS/catecholamines
vagal stimulation
ischemia
max VO2
Outpatient Cardiac rehab:
1 major CV complication/50,000 to 120,000 patient hours; 2
fatalities/1.5million patient hours
Very Rare!
3) lactate threshold
the point where lactate production > metabolism via the Krebs cylcle (occurs
in >40% of max VO2 in normal individuals)
4) VO2 max
The maximum about of O2 taken in, transported and used while performing at
peak intensity
Fick Equation: VO2= (HRmax SVmax) (CaO2max CvO2max)
CaO2 = arterial oxygen content
CvO2 = venous oxygen content
5) Metabolic equivalents
Definition: MET or the standard metabolic equivalent is a unit used to
estimate the amount of oxygen used by the body during physical activity.
1 MET = the energy (oxygen) used by the body at rest (set by convention to
3.5 ml O2kg-1min-1)
Activity that burns 3 to 6 METs is considered moderate-intensity physical
activity.
Activity that burns > 6 METs is considered vigorous-intensity physical
activity.
10. Describe the pharmacology of:
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Inotropes and pressors: dopamine, dobutamine, epi and norepi
Used to treat for Acute CHF
MOA:
o beta adrenergic agonists increase availability of intracellular Ca2+ increase
force of ventricular contraction (shift frank-starling curve upwards) increase
SV and CO at any end diastolic volume.
o Alpha adrenergic agonists increase vasoconstriction in periphery
Norepinephrine more effect on alpha 1
Epinephrine more effect on Beta 1 and 2
Effects:
o Increases inotropy, chronotropy, and vasoconstriction of periphery.
Indications: more useful for patients with systolic ventricular dysfunction (as
opposed to pure diastolic failure)
o Administered IV, for temporary hemodynamic support for acutely ill,
hospitalized patients.
Morphine (for its role in CHF) Marx: Rosen's Emergency Medicine

MOA:
o Cause release of vasoactive histamine peripheral vasodilation
o Central sympatholytic effect
o Reduces systemic catecholamines decrease HR, BP, contractility
Effect:
o decreased central venous return decreased preload
Improves pulmonary congestion
o Decreases myocardial oxygen demand.
o Reduces agitation, sense of SOB.
Indications: Acute heart failure with pulmonary congestion
Diuretics
MOA: promote elimination of sodium and water through the kidney
Effect: reduce intravascular volume decrease venous return decrease preload
decrease diastolic pressure.
o Goal is to reduce end diastolic pressure without affecting SV.
Is possible if patient is on the flat portion of the Frank-Starling curve.
Indications: In the case of HF, indicated when there is evidence of pulmonary
congestion (rales), or peripheral interstitial fluid accumulation (edema)
Adverse effects (specific for HF patients):
o overly virgorous dieresis causing decrease in CO
o electrolyte disturbances (e.g. hypokalemia) arrhythmias
o in patients with LV diastolic dysfunction, be extra careful to avoid overdiuresis
(patients require elevated siastolic filling pressure to adequately function)
Examples
o Loop diuretics: furosemide (Lasix), torsemide, bumetanide.
o Thiazide diuretics: hydrochlorothiazide, metolazone.
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Nitrates (nitroglycerine)
Used to treat for Acute CHF and Chronic CHF
MOA: vasodilator, primarily venous vasodilator increase venous
capacitancedecrease venous return to heart reduce LV preloadLV diastolic
pressure fallpulmonary hydrostatic pressure fall
Effect : pulmonary congestion improves
Adverse effects: see diuretics.
ACE inhibitors
Used to treat for Chronic CHF
MOA: Inhibits renin-angiotensin-aldosterone system
o inhibit formation of AII (vasoconstrictor)vasodilation of both venous and
arteriolar circuits
o Inhibit aldosterone levels facilitate sodium elimination lower intravascular
volume
o Increase bradykinin levels vasodilation
Effects:
o reduce pulmonary congestion
o limit maladaptive ventricular remodelling in patients
o shown to reduce HF symptoms, improve stamina, reduce need for
hospitalization, extend survival in patients with chronic HF.
Contraindications: pregnancy, renal dysfunction
Adverse effect: dry cough, hyperkalemia, hypotension, renal dysfunction,
angioedema.
Examples: Captopril, ramipril, enalapril, fosinopriletc
ARBs
MOA: inhibit AII effects directly by blocking AII receptors.
Effect:
o more complete inhibition of RAAS system then ACE inhibitors, since AII is not
just formed by ACE.
o However, since ARBs do not inhibit ACE, ACE will continue to break down
bradykinin, and therefore ARBs do not have the potentially beneficial rise in
serum bradykinin (and therefore vasodilation)
Indications:
o Used as 2nd line therapy for HF patients after ACEi (e.g. cannot tolerate cough)
Does not show superiority in improving patient survival over ACEi.
Contraindications: pregnancy
Examples: Losartan, Candesartan, Irbesartanetc.
Beta blockers
MOA: beta receptor antagonists. How it causes the effects below remain unclear.
Effect: paradoxically, it improves CO, reduce hemodynamic deterioration, and
improved survival.
Examples: propanolol, atenolol, metoprolol
Contraindications: asthmatics, ACUTE HF.
MD 2017 by J^2N
138
Side effects: fatigue, bradycardia/Heart block, hypotension, CNS effects, Raynauds

phenomenon (cold extremities), Hypoglycemia.
Digoxin (2017 dont have this here but elsewhere)

MOA: Inotrope and increased PS activity
Effect:
o Inotropic action through Na/K/ATPase block.
Less Na exiting the cell, higher intracellular NA, lower Na
electrochemical gradient for Na-Ca exchanger, lower Ca exiting the cell,
higher Ca concentration in cell
Increased contractility, SV, CO
In heart failure sympathetic tone is increased to increase CO. Digoxin
increases contractility, SV, CO thereby reducig the need for sympathetic
compensation
Reduces sympathetic tone in heart failure
o Increased PS activity via vagus nerve
Decrease HR, vasodilation
Indications:
o CHF (third line in adults, first line in children)
Digoxin increases contractility
o Atrial fibrillation
Decreases AV node conduction and slows ventricular rate
Contraindications:
o Quinadine, verapamil, atorvastatin, lasix increase risk of toxicity with digoxin
Side effects:
o GI, CNS (confusion, dizziness, agitation), CV (arrhythmias and heart block),
Visual (orange tinted vision, visual disturbances)
Management of Heart Failure (again, not on 2017 objectives but

Im sure its good/elsewhere)
Acute: diuretic, morphoine, NTG, inotropes
NOT beta blockers, or ACE inhibitors

Chronic: ACE inhibitor, B blocker, Diuretic, Digoxin
Classification of Heart failure
ACC/AHA Stage
NYHA Functional Class
A. At risk for heart

failure but without
structural heart disease
None
MD 2017 by J^2N
139
or symptoms
B. Structural heart
disease but without
heart failure
I. Asymptomatic HF: no
symptoms
C. Structural heart
disease with prior or
current heart failure
symptoms
II. Mild HF: symptomatic

with moderate exertion
III. Moderate HF:
symptomatic with
minimal exertion
D. Refractory heart
failure requiring
specialized interventions
Severe HF: symptomatic

at rest
MD 2017 by J^2N
140
CV Week 5 - Cardiac Structure and Consequences of

Dysfunction
Week Objectives
Case Objectives
1. Heart Valves
Refer to Week Objective 2
2. Heart Failure
3. Pharmacology
MD 2017 by J^2N
141

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FMED 402: Cardiovascular

Week ONE Hypertension

1. Describe the structure and function of blood vessels

thick wall relative to lumen size

thin and distensible

Capillaries: single layer of flattened endothelial cells and pericytes on basement

2 factors of blood flow (Q) like current

Pressure (P) like voltage, and Resistance (R) like resistance

Arterial baroreceptor response:

Arterial Baroreceptor Response Under Normal Blood Pressure

B. Arterial baroreceptor response (new for 2017s, pasted from objectives):

are found at the carotid sinus and the aortic arch.

Arterial baroreceptor response:

Overview of ReninAngiotensinAldosterone System

Nitroglycerin breaks down to Nitric Oxide and is therefore a treatment for

Adenosine (Not Testable According to CV Forum)

4. For hypertension explain the following:

Various other common factors considered to be possible causes of

d. Complications if untreated (target organ damage)

Verebrovascular disease (stroke)

ii. Coronary artery disease

Hypertension is the 2nd leading cause of end-stage renal disease

e. both pharmacologic and non-pharmacologic treatment

5. Outline the process of excitation/contraction coupling in terms of:

Almost identical to skeletal muscle

Calcium-Induced Calcium Release

increased heart rate (positive chronotropic effect)

blockers- DHPsCalcium channel

- L-type calcium channel

-ACE converts ATIATII,

Angiotensin receptor blockers

-dry cough (due to

-ACEi may be useful

- less cough than

-Directly inhibits renin

2. Understand the importance of global cardiovascular risk factor assessment in

Risk factors for cardiovascular disease include:

Models can be used to predict an individual's risk of cardiovascular disease to define

3. Explain the role of the screening cardiovascular examination and laboratory

Urinalysis - ordered to help assess kidney function

Aldosterone and Renin to help detect the overproduction of aldosterone by the

Cortisol to detect an overproduction of cortisol that may be due to Cushings

Catecholamines and Metanephrines to measure epinephrine, norepinephrine, and

4. Outline a diagnostic approach for differentiating primary from secondary

Most common type of Htn

3xA: Accuracy (are you screwing up?), apnea (sleep), aldosteronism

5. Discuss the management of hypertension

Treatment of Uncomplicated hypertension

Invasive (Surgical excision of tumors and endovascular procedures) (Lillies)

FMED 402: Cardiovascular

1. Describe cardiac anatomy:

Carries R. bundle branch of conduction system anterior ventricular

Contributories = 4 pulmonary veins into posterior half

R and L aortic sinuses R and L coronary arteries

2 layered sac enclosing heart

Barrier limit spread of infection from adjacent lungs

does not remain straight folds up (before above structures formed)

Interventricular Septum formed from 2 parts:

2. Describe fetal circulation: (self directed, lecture)

ii. Pressure differences of right vs left cardiac chambers

ii. Properties of fetal hemoglobin vs. adult hemoglobin

Adult Hemoglobin (HbA 22 and HbA2 22)

The fall in pulmonary vascular resistance (due to the opening of pulmonary