The Cardiovascular System

AQSA YASIN
PATHOLOGIST&MICROBIOLOGIST
USA LECTURER
 INTRODUCTION
• Cardiovascular disease (CVD) is the leading
cause of death in the U.S.
• Nearly half of all Americans will die from CVD
• CVD is the leading cause of death for both
men and women
• 45% of all heart attacks occur in people under
the age of 65
• Most of CVD risk is lifestyle-related
 The Cardiovascular System

• Pulmonary circulation –
The part of the circulatory system governed by
the right side of the heart; the circulation of blood
between the heart and the lungs.

• Systemic circulation –
The part of the circulatory system governed by
the left side of the heart; the circulation of fluid
between the heart and the rest of the body.
⚫Major risk factors that CAN be changed –
These include:
⚫tobacco use
⚫high blood pressure
⚫cholesterol
⚫physical inactivity
⚫obesity, and diabetes
⚫Major risk factors that CAN’T be changed
– These include:

⚫heredity
⚫aging
⚫being male
⚫and ethnicity.
• Ischemic heart disease (IHD) is a broad term including
several closely related syndromes caused by myocardial
ischemia—an imbalance between cardiac blood supply
(perfusion) and myocardial oxygen and nutritional
requirements.

• Since cardiac myocytes generate energy almost

exclusively through mitochondrial oxidative
phosphorylation
• cardiac function is strictly dependent upon the
continuous flow of oxygenated blood through the
coronary arteries.
• In more than 90% of cases, IHD is a
consequence of reduced coronary blood flow
secondary to obstructive atherosclerotic
vascular disease.

• Thus, unless otherwise specified, IHD usually

is equal with coronary artery disease (CAD).
• The manifestations of IHD are a direct consequence
of the insufficient blood supply to the heart.
• The clinical presentation may include one or more
of the following cardiac syndromes:
•Angina pectoris (literally, “chest pain”). Ischemia
induces pain but is insufficient to cause myocyte
death.
• Angina can be stable (occurring at certain levels of
exertion), can be caused by vessel spasm or can be
unstable (occurring with progressively less exertion
or even at rest).
• Myocardial infarction (MI). This occurs when
the severity or duration of ischemia is
sufficient to cause cardio myocyt death.

• Sudden cardiac death (SCD). This can occur as

a consequence of tissue damage from MI.
 Myocardial Infarction
• Myocardial infarction (MI), also commonly referred to
as “heart attack,” is necrosis of the heart muscle
resulting from ischemia.
• The major underlying cause of IHD is atherosclerosis;
while MIs can occur at virtually any age, the frequency
rises progressively with aging and with increasing risk
factors for atherosclerosis.
• However, menopause—with declining estrogen
production—is associated with exacerbation of coronary
artery disease, and IHD is the most common cause of
death in older adult women.
 Pathogenesis
• The vast majority of MIs are caused by acute
thrombosis within coronary arteries.
• In 10% of MIs, however, transmural infarction
occurs in the setting of small vessels disease
like vasculitis.
• sub endocardial infraction
• Occasionally, limited to the inner third of the
myocardium, in this thrombi or emboli are
absent.
• In this setting, a prolonged period of increased
demand (e.g., due to tachycardia or
hypertension) can lead to ischemic necrosis of
endomyocardium, the portion of the heart
that is most distal to the epicardial vessels.
 Coronary Artery Occlusion
In a typical MI, the following sequence of events
takes place:
• An atheromatous plaque is eroded or suddenly
disrupted by endothelial injury, intraplaque
hemorrhage, or mechanical forces, exposing
subendothelial collagen and necrotic plaque
contents to the blood.
• Platelets adhere, aggregate, and are activated,
releasing thromboxane A2, adenosine diphosphate
(ADP), and serotonin—causing further platelet
aggregation.
 Coronary Artery Occlusion
• Activation of coagulation by exposure of
tissue factor and other mechanisms adds to
the growing thrombus.
• Within minutes, the thrombus can evolve to
completely occlude the coronary artery.
 Myocardial Response to Ischemia
• Loss of blood supply has profound functional,
biochemical, and morphologic consequences
for the myocardium.
• Within seconds of vascular obstruction,
aerobic metabolism ceases, leading to a drop
in adenosine triphosphate (ATP) and
accumulation of potentially noxious
metabolites (e.g., lactic acid) in the cardiac
myocytes.
• The functional consequence is a rapid loss of
contractility, occurring within a minute or so
of the onset of ischemia.
• Ultrastructural changes (including myofibrillar
relaxation, glycogen depletion, cellular and
mitochondrial swelling) are also seen.
• These early changes are reversible. Only
prolonged ischemia lasting at least 20 to 40
minutes causes irreversible damage and
coagulative necrosis of myocytes
Patterns of Infarction
• The location, size, and morphologic features of an
acute myocardial infarct depend on multiple
factors:
• Size and distribution of the involved vessel
• Rate of development and duration of the occlusion
• Metabolic demands of the myocardium (affected,
for example, by blood pressure and heart rate)
• Extent of collateral supply
Pattern of myocardial infarction
Based on the size of the involved vessel and the
degree of collateral circulation, myocardial
infarcts may take one of the following
patterns:
• Transmural infarctions
• involve the full thickness of the ventricle and
are caused by epicardial vessel occlusion
through a combination of chronic
atherosclerosis and acute thrombosis;
• such transmural MIs typically yield ST segment
elevations on the electrocardiogram (ECG) and
can have negative Q waves with loss of R wave
amplitude.
• These infarcts are also called ST-segment
elevated MIs (STEMIs).
• Subendocardial infarctions are MIs limited to
the inner third of the myocardium;
• these infarcts typically do not exhibit ST
segment elevations or Q waves on the ECG
tracing (so-called “non–ST-segment elevated
MIs” or “NSTEMIs”),
• although they can have ST-segment
depressions or T wave abnormalities.
• Microscopic infarcts occur in the setting of
small-vessel occlusions.

• These can occur in the setting of vasculitis,

mural thrombi, or vessel spasm due to
elevated catecholamines, as may occur in
extreme emotional stress, or as a
consequence of cocaine use.
Infarct Modification by Reperfusion
• Indeed, late restoration of blood flow into
ischemic tissues can incite greater local
damage than might otherwise have occurred
— so-called “reperfusion injury”
• The factors that contribute to reperfusion injury
include the following:
• Mitochondrial dysfunction. Ischemia alters the
mitochondrial membrane permeability, which allows
proteins to move into the mitochondria. This leads to
swelling and rupture of the outer membrane, releasing
mitochondrial contents that promote apoptosis.
• Myocyte hypercontracture. During periods of ischemia,
the intracellular levels of calcium are increased as a
result of impaired calcium cycling. After reperfusion,
the contraction of myofibrils is uncontrolled, causing
cytoskeletal damage and cell death.
• Free radicals, including superoxide anion
(•O2− ), hydrogen peroxide (H2O2),
hypochlorous acid (HOCl), nitric oxide and
hydroxyl radicals (•OH).
• These are produced within minutes of
reperfusion and cause damage to the
myocytes by altering membrane proteins and
phospholipids.
• Platelet and complement activation also
contribute to microvascular injury.
 Clinical Features
• The classic MI is indicated by severe, crushing
substernal chest pain (or pressure) that can
radiate to the neck, jaw, epigastrium, or left
arm.
• In contrast to angina pectoris, the associated
pain typically lasts several minutes to hours,
and is not relieved by nitroglycerin or rest.
• MIs present with the atypical signs and symptoms,
and may even be entirely asymptomatic.
• Such “silent” infarcts are particularly common in
patients with underlying diabetes mellitus (in which
autonomic neuropathy may prevent perception of
pain) and in older adults.
• Pulse generally is rapid and weak, and patients are
often diaphoretic (sweating) and nauseous
(particularly with posterior wall MIs).
• Dyspnea is common.
• Electrocardiographic abnormalities are important
for the diagnosis of MI; these include Q waves, ST
segment changes, and T wave inversions.

• The laboratory evaluation of MI is based on

measuring blood levels of macromolecules that leak
out of injured myocardial cells through damaged cell
membranes.
• These molecules include myoglobin, cardiac
troponins T and I (TnT, TnI), creatine kinase (CK;
myocardial isoform, CK-MB), and lactate
dehydrogenase
 Consequences and Complications of
Myocardial Infarction
• Contractile dysfunction. In general, MIs affect left
ventricular pump function in proportion to the
volume of damage.
• Severe “pump failure” (cardiogenic shock) occurs in
roughly 10% of patients with transmural MIs and
typically is associated with infarcts that damage 40%
or more of the left ventricle.
• Arrhythmias. MIs lead to myocardial irritability and
conduction disturbances that can cause sudden
death.
• MI-associated arrhythmias include heart block of
variable degree (including asystole), bradycardia,
ventricular premature contractions or ventricular
tachycardia, and ventricular fibrillation.

• The risk for serious arrhythmias is greatest in the first

hour and declines thereafter.
• Chamber dilation. Because of the weakening of
necrotic muscle, there may be uneven stretching,
thinning, and dilation of the infarcted region

• Mural thrombus. With any infarct, the combination

of decreased myocardial contractility (causing stasis),
chamber dilation, and endocardial damage can foster
mural thrombosis, eventually leading to left-sided
thromboembolism.

• Progressive heart failure