INTERNAL MEDICINE TRANS NO.

1 2nd SEMESTER

o The tunica media of the arteries are

ILO ILO DOCTORS’ CO LL EGE O F MEDICIN E
Molo, Iloilo City
made-up of several layers of smooth-
S.Y. 2018-2019 muscle cells, while the veins just contain a
few layers of them
BATCH 2021 o The adventitia of the larger arteries have
DISCIMUS SAPIENCIA UT VIRTUS
their own vasculatures, the vasa vasorum,
which nourish the outer aspects of the
tunica media
INTERNAL MEDICINE
o The adventitia of the some veins are
BLOCK 1 thicker than the intima
LECTURER: DR. ESTEPAR Arteries
MAIN TOPIC: INTRODUCTION TO CARDIOLOGY - The tone of the muscular arterioles regulates
blood pressure and flow through various arterial
BASIC BIOLOGY OF THE CARDIOVASCULAR SYSTEM beds
- These smaller arteries have relatively thicker
THE BLOOD VESSEL media relative to their adventitia
- Blood vessels participate in homeostasis on a - Medium-size arteries contain a prominent tunica
moment-to-moment basis and contribute to the media
pathophysiology of diseases on virtually every - Atherosclerosis commonly affects this type of
organ system muscular artery
- An understanding of the fundamentals of vascular - The larger elastic arteries have a much more
biology furnishes a foundation for understanding structural tunica media consisting of concentric
normal function of all organ systems and many bands of smooth-muscle cells interspersed with
diseases strata of elastin-rich extracellular matrix
sandwiched between layers of smooth-muscle
VASCULAR ULTRASTRUCTURES cells
- Capillaries Origin of Vascular Cells
- Veins - The intima often contains occasional resident
- Arteries smooth-muscle (SM) cells beneath the monolayer
Capillaries
- Smallest blood vessels
- Consist of a monolayer of endothelial cells in
close juxtaposition of occasional smooth-
muscle-like cells known as Pericytes
- Pericytes do not invest in the entire microvessel
to form a continuous sheath
Veins and Arteries
- Tunica Intima
o Monolayer of endothelial cells
o Continuous with those of the capillary
trees
- Tunica Media
o Middle layer
o Layers of smooth-muscle cells
- Tunica Adventitia
o Consists of looser extracellular matrix
o Occasional fibrolasts, mast cells and
nerve terminals

- Differences

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of vascular endothelial cells
- The embryonic origin of SM cells in various type of
artery differs:
o Upper body derive from neural crest
o Lower body from mesodermal structures
(somites)
- Bone marrow may also give rise to both vascular
endothelial cells and SM cells
Vascular Cell Biology
- Endothelium
o Is made up of Endothelial cells (EC)
 Are the cells of vascular intima
o Forms the interface between tissues and
blood compartment
o Regulates the entry of molecules and cells
into the tissue in a selective manner
o Has the ability to serve as a permselective
barrier
o Participates in the local regulation of the
blood flow and diameter size of the blood
vessel
o Produces endogenous substances
 Vasodilators – physiologic
conditions
 Prostacyclin
 Endothelium-derived
hyperpolarizing factor
 Nitric oxide (NO)
 Endothelin
 Potent vasoconstrictor
 Occurs when there is
Endothelial Dysfunction
o Oxidative Stress
 Occur when there is excessive
production of reactive oxygen
species, such as superoxide anion,
by endothelial and SM cells under
pathologic conditions such as
excessive exposure to angiotensin
II
 May lead also to inactivation of
NO
o Endothelial monolayer contributes
critically to inflammatory processes
involved in normal host defenses and
pathologic states
o Expresses leukocytes adhesion molecules
during infection and inflammatory process
o Regulate thrombosis and hemostasis
INTERNAL MEDICINE TRANS NO. 1 2nd SEMESTER
 Both NO and prostacyclin limit
and antagonize platelet activation
and aggregation
o Endothelial cell surface contains heparan
sulfate glycosaminoglycans that furnish an
endogenous antithrombin coating to the
vasculature
o It also participate actively in fibrinolysis
and its regulation
o They express receptors for plasminogen
activators and produce tissue-type
plasminogen activator
o Through local generation of plasmin, the
normal endothelial monolayer can
promote the lysis of nascent thrombi
Endothelial Functions in Health and Disease
- Homeostatic Phenotype
o Vasodilation
o Antithrombotic, profibrinolytic
o Anti-inflammatory
o Anti-oxidant
- Dysfunctional Phenotype
o Impaired dilatation, vasoconstriction
o Prothrombotic, antifibrinolytic
o Pro-inflammatory
o Proproliferative
Prooxidant
Clinical Assessment of Endothelial Function
- Non-invasively
o Forearm circulation is assessed by
performing occlusion of the brachial
artery flow with BP cuff, after which the
cuff is deflated
o Assess the change in brachial artery
diameter and blood flow using ultrasound
(Doppler)
- Invasively
o Use of agonists that stimulate release of
endothelial NO
 Acetylcholine
 Methacholine
o Measurement of change in coronary
diameter after intracoronary infusion
- Normal
o The increase in vessel diameter size of at
least 10%
o Increase in blood flow
o Reactive hyperemia
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- Abnormal Results
o Endothelial dysfunction
o Smaller increase in diameter (less than
10%)
o In extreme cases  paradoxical
vasoconstriction
Vascular Smooth-Muscle Cell
- The vascular SM cell is the major cell type of the
media layer of the blood vessels
- SM cell contraction and relaxation
o Controls the BP
o Regional blood flow
o LV afterload
- Venous SM cells
o Venous capacitance
o Influence the venous return of both
ventricles
- Proliferation and migration of arterial SM cells
contribute to development of arterial stenosis
o Atherosclerosis
 Hypertension
 Cerebral vascular disease –
ischemic stroke
 Coronary artery disease – Stable
angina and ACS
 Angioplasty and stent deployment
 Post-PCI restenosis
 Pulmonary hypertension
 Congenital Heart Disease with L-R
shunt anomaly
Vascular Smooth-Muscle Cell Function
- The principal function of the vascular SM cells is to
maintain vessel tone
- Vascular SM cells contract when stimulated by a
rise in intracellular calcium concentration after
calcium influx through the plasma membrane
- Voltage-dependent L-type calcium channels open
during membrane depolarization
o Regulated by:
 Na+ , K+ -ATPase pump
 Ca – sensitive K+ ion channel
- Vascular SM cell contraction is principally
controlled by the phosphorylation of myosin light
chain
- The steady state is maintained by the balance
between the actions of myosin light chain kinase
and myosin light chain phosphatase
INTERNAL MEDICINE TRANS NO. 1 2nd SEMESTER
- Myosin light chain kinase is activated by calcium
through the formation of calcium-calmodulin
complex
- SM contraction is sustained due to increased
myosin ATPase activity brought about by myosin
light chain phosphorylation
- Myosin light chain dephosphorylation, in contrary
would reduce SM cells contractile force
- Both cAMP and cGMP relax vascular SM cells
Control of Vascular SM Cell Tone
- Is governed by the autonomic nervous system and
by the endothelium
- In response to:
o Baroreceptors and chemoreceptors within
the aortic arch and carotid bodies
o Thermoreceptors in the skin
- 3 classes of autonomic nervous system
o Sympathetic
 Epinephrine
 Norepinephrine
o Parasympathetic
 Acetylcholine
o Nonadrenergic/noncholinergic
 Nitrergic – NO
 Peptidergic – substance P,
vasoactive intestinal peptide,
calcitonin gene-related peptide,
and ATP
Vascular Regeneration
- Growing new blood vessels can occur in response
to chronic hypoxia/tissue ischemia
- Angiogenesis – with the presence of vascular
endothelial growth factor, a signaling cascade is
activated that stimulates endothelial proliferation
and tube formation
- Development of coronary collateral vascular
networks in ischemic myocardium
Cardiac Ultrastructure
- About ¾ of the ventricle is composed of individual
striated muscle cells (myocytes)
- 60-140 um in length and 17-25 um in diameter
- Each cell contains multiple, rodlike crossbanded
strands (myofibrils) that run the length of the cell
and are, in turn, composed of serially repeating
structures, the sarcomeres
- Numerous mitochondria
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The Contractile Process
- The sliding filament model for muscle contraction
rests on the fundamental observation that both
the thick and thin filaments are constant in overall
length during both contraction and relaxation
- During activation, the actin filaments are
propelled further into the A band
- In the process, the A band remains constant in
length, whereas the I band shortens and the Z line
move toward one another
 Stroke Volume (SV) = end diastolic volume – end
systolic volume
 Cardiac Output (CO) = SV x Heart rate
 Blood pressure (BP) = CO x PVR (peripheral vascular
resistance)
CONTROL OF CARDIAC PERFORMANCE AND OUTPUT
3 Determinants of Ventricular Stroke Volume
1. Length of the muscle at the onset of contraction
(preload)
2. Tension that the muscle is called upon to develop
during contraction (afterload)
3. Contractility of the muscle (extent and velocity of
shortening at any given preload and afterload)
The Role of Muscle Length (Preload)
- Preload determines the length of the sarcomere at
the onset of the contraction
- The relation between the initial length of the
muscle fibers and the developed force has prime
importance for the function of the heart muscle
- Relationship forms the basis of the Starling’s Law
of the heart, which states that, within limits, the
force of ventricular contraction depends on the
end-diastolic length of the cardiac muscle; in the
intact heart the latter relates closely to the
ventricular end-diastolic volume
Cardiac Performance
- Ventricular end-diastolic or filling pressure is
sometimes used as a surrogate for the end-
diastolic volume
- As the heart fails (its contractility declines), it
delivers a progressively smaller stroke volume
from a normal or even elevated end-diastolic
volume
- The relationship between the ventricular end-
diastolic pressure and the stroke work of the
INTERNAL MEDICINE TRANS NO. 1 2nd SEMESTER
ventricle provides a useful definition of the level
of contractility of the heart
- An increase in contractility is accompanied by a
shift of the ventricular function curve upward and
to the left, while a shift downward and to the right
characterizes depression of contractility
Ventricular Afterload
- The load that opposes the shortening of the
muscles
- May be defined as the tension developed in the
ventricular wall during ejection
- The extent/velocity of shortening of the
ventricular muscle fibers at any level of preload
and of myocardial contractility is inversely related
to the afterload
- Determinants:
o Aortic pressure
o Ventricular volume
o Ventricular wall thickness
- Law of Laplace
o Indicates that the tension of the
myocardial fiber is a function of the
product of intracavitary ventricular
pressure and the ventricular radius
divided by the wall thickness
- Determinants of the aortic pressure
o Peripheral vascular resistance
o Physical characteristics of the arterial tree
 The degree of stiffness
Exercise
- Interactions among 3 determinants of stroke
volume
o Increase in preload
 Hyperventilation, pumping action
of exercising muscle and
vasoconstriction  increase in
venous return and ventricular
filling
o Decrease in afterload
 Arterial vasodilation in exercising
muscles
o Increase in contraction
 Inc. in circulating catecholamines
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 INTERNAL MEDICINE TRANS NO. 1 2nd SEMESTER

Interactions in the intact circulation of Preload,

ILO ILO DOCTORS’ CO LL EGE O F MEDICIN E
Contractility, and Afterload in Producing SV Molo, Iloilo City
S.Y. 2018-2019

BATCH 2021
DISCIMUS SAPIENCIA UT VIRTUS

INTERNAL MEDICINE
BLOCK 1
LECTURER: DR. ESTEPAR

MAIN TOPIC: APPROACH TO PATIENT WITH CVS

PROBLEMS

Cardiac Symptoms
- Result mostly from
o Myocardial ischemia
 Chest discomfort
o Disturbance of the contraction and/or
relaxation of myocardium
 Fatigue, peripheral edema,
ASSESSMENT OF CARDIAC FUNCTION dyspnea
- Ejection Function (F) o Obstruction to blood flow and valvular
o More sensitive index of cardiac function stenosis  heart failure
o Ration of SV to end-diastolic volume o Abnormal cardiac rhythm or rate
o Normal value = 67 + 8%  Palpitations, dyspnea,
hypotension, syncope
o Systolic function
- Elevated ventricular end-diastolic volume Cardinal Manifestations of Cardiac Diseases
o Normal value = 75 + 20ml/m2 - Can also be manifestations of other organ systems
- Elevated ventricular end-systolic volume - Dyspnea
o Normal value = 25+2ml/m2 o Pulmonary dse, marked obesity and
- Non-Invasive Techniques of measuring Myocardial anxiety
- Chest discomfort
Function o Result from variety of non-cardiac and
o Echocardiography cardiac causes other than myocardial
o Radionulide scintigraphy (nuclear ischemia
medicine) - Edema
o Cardiac MRI o Primary renal and hepatic disease
- End-systolic Left Ventricular Pressure-volume - Syncope
o Neurologic disorder
relationship
o Useful index of ventricular performance Characteristic Findings of Cardiac Patients
o Results are not dependent on the degree - Dyspnea/Chest Discomfort
of preload and afterload o Appears on exertion
o Disappears at rest
Diastolic Function - Heat murmurs
- Elevated arterial pressure
- Assessment of ventricular filling
o Abnormal EXG, CXR, and other imaging
- Increase in ventricular stiffness - Risk factors for CAD
o Ventricular hypertrophy o Cholesterol, DM II, smoking, Hx of stroke,
o Amyloid infiltration of the ventricle biomarkers (C-reactive CHON)
- Continuously measuring the velocity of blood flow Diagnosis
across the mitral valve using Doppler ultrasound - New York Heart Association
1. The underlying etiology
- Is the disease congenital, hypertensive, ischemic,

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or inflammatory in origin?
2. The anatomic abnormalities.
- Which chambers are involved? Are they
hypertrophied, dilated, or both?
- Which valves are affected?
- Are they regurgitant and/or stenotic? Is there
pericardial involvement?
- Has there been a myocardial infarction?
3. The physiologic disturbances.
- Is an arrhythmia present?
- Is there evidence of congestive heart failure or of
myocardial ischemia?
4. Functional disability
- How strenuous is the physical activity required to
elicit symptoms?
Family History
- Presence of cardiovascular disease in the family
o History of stoke, MI
- Presence of CV risk factors in the family
o Essential HPN, DM II,
hypercholesterolemia
- Mendellian transmission of single-gene
- Familial clustering of CV disease
PITFALLS IN CARDIOVASCULAR MEDICINE
1. Failure by the noncardiologist to recognize
important cardiac manifestations of
systemic illnesses, e.g., the presence of
mitral stenosis, patent foramen ovale,
and/or transient atrial arrhythmia in a
patient with stroke or the presence of
pulmonary hypertension and cor
pulmonale in a patient with scleroderma or
Raynaud’s syndrome. A cardiovascular
examination should be carried out to
identify and estimate the severity of
cardiovascular involvement that
accompanies many noncardiac disorders.
2. Failure by the cardiologist to recognize underlying
systemic disorders in patients with heart disease.
INTERNAL MEDICINE TRANS NO. 1 2nd SEMESTER
For example, hyperthyroidism should be tested for
in an elderly patient with atrial fibrillation and
unexplained heart failure. Similarly, Lyme disease
should be considered in a patient with unexplained
fluctuating atrioventricular block. A cardiovascular
abnormality may provide the clue critical to the
recognition of some systemic disorders. For
instance, an unexplained pericardial effusion may
provide an early clue to the diagnosis of
tuberculosis or neoplasm.
3. Overreliance on and overutilization of laboratory
tests, particularly invasive techniques for the
examination of the cardiovascular system. Cardiac
catheterization and coronary arteriography provide
precise diagnostic information that is critical to
clinical evaluation, which may be crucial in
developing a therapeutic plan in patients with
known or suspected CAD. Although a great deal of
attention has been directed to these examinations,
it is important to recognize that they serve to
supplement, not supplant, a careful examination
carried out by clinical and noninvasive techniques.
A coronary arteriogram should not be carried out in
lieu of a careful history in patients with chest pain
suspected of having ischemic heart disease.
Although coronary arteriography may establish
whether the coronary arteries are obstructed, and if
so the severity of the obstruction, the results of the
procedure by themselves often do not provide a
definite answer to the question of whether a
patient’s complaint of chest discomfort is
attributable to coronary arteriosclerosis and
whether or not revascularization is indicated
Disease Prevention and Management
- Prevention begins with risk assessment, followed
by attention to lifestyle, such as achieving optimal
weight and discontinuing smoking, and aggressive
treatment of all abnormal risk factors, such as
hypertension, hyperlipidemia, and diabetes mellitus
- After a complete diagnosis has been established in
patients with known heart disease, a number of
management options are usually available.
- Several examples may be used to demonstrate
some of the principles of cardiovascular
therapeutics:
o In the absence of evidence of heart
disease, a clear, definitive statement to
that effect should be made and the patient
should not be asked to return at intervals
for repeated examinations. If there is no
evidence for disease, such continued
attention may lead to the patient
developing inappropriate anxiety and
fixation on the heart.
o If there is no evidence of cardiovascular
disease but the patient has one or more
risk factors for the development of
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 INTERNAL MEDICINE TRANS NO. 1 2nd SEMESTER

ischemic heart disease a plan for their

reduction should be developed and the
patient should be retested at intervals to
assess compliance and that these risk
factors are in fact being reduced.
o Asymptomatic or mildly symptomatic
patients with valvular heart disease that is
anatomically severe should be evaluated
periodically, every 6 to 12 months, by
clinical and noninvasive examinations.
Early signs of deterioration of ventricular
function may signify the need for surgical
treatment before the development of
disabling symptoms, irreversible
myocardial damage, and excessive risk of
surgical treatment.
o In patients with CAD (Chap. 237),
available practice guidelines should be
considered in the decision on the form of
treatment (medical, percutaneous coronary
intervention, or surgical revascularization).
Mechanical revascularization, i.e., the
latter two modalities, may be employed too
frequently in the United States and
perhaps too infrequently in Eastern Europe
and developing nations. The mere
presence of angina pectoris and/or the
demonstration of critical coronary arterial
narrowing at angiography should not
reflexly evoke a decision to treat the
patient by revascularization. Instead, these
procedures should be limited to patients
with CAD whose angina has not
responded adequately to medical
treatment or in whom revascularization has
been shown to improve the natural history
(e.g., acute coronary syndrome, or
multivessel CAD with left ventricular
dysfunction).

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