Cardiovascular Diseases
I. Vascular Endothelium and their Response to Injury
A. Review of endothelial cells activation in response to environmental stimuli.
Endothelial cells are activated by;
- Bacterial products and viruses
- Inflammatory cell mediators and complement
- Hemodynamic stress and lipid products
- Advanced end glycosylated products
Endothelial cells respond by;
- Elaborating adhesion molecules, chemokines and growth factors.
- MHC molecules, pro- and anticoagulant moieties
- Vasoconstriction and vasodilation as a result of exposure to mediators
B. Intimal Thickening in Response to Injury
Vascular injury stimulates smooth muscle cell growth. Damage of the vascular wall,
including endothelium comprises;
- Smooth muscle cell migration from media to intima
- Multiplication of intimal cells
- Synthesis and deposition of extracellular matrix
II. Vascular Diseases
Vascular wall injury may be caused by;
- Weakening
- Narrowing
- Damage to endothelium
A. Atherosclerosis
- characterized by intimal lesions called fibrofatty plaques or atheromas.
- primarily affects elastic arteries, large and medium sized arteries.
1. Etiology
- Age; slow progressive disease at childhood, develops slowly over decades
- Sex; frequency of myocardial infarction (MI) is the same in both sexes by age 60-70
- Hyperlipidemia; low-density lipoproteins (LDL) is the major component associated with
increased risk.
- Hypertension; is a major risk factor at all ages but after 45, hypertension is a stronger risk
factor than hypercholesterolemia.
- Cigarette Smoking; well-established risk factor in men, accounts for recent increases in
incidence and severity of atherosclerosis in women.
- Diabetes Mellitus; the incidence of MI is twice as high in diabetics.
- Elevated Plasma Homocysteine; patient’s with high levels of homocysteine have premature
vascular disease.
2. Pathogenesis - Atherosclerosis is a chronic inflammatory response of the arterial wall
initiated by some form of injury to the endothelium.
Factors which Damage Endothelium
- Lipids
- Toxins
- Hemodynamics
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Events leading to Atheromatous Plaque Formation
1) Chronic endothelial injury with resultant increased permeability and increased leukocyte adhesion.
2) Insudation of LDL into vessel wall with modification of these lipids by oxidation.
3) Adhesion and migration of monocytes to intimal wall and their transformation into macrophages
and monocyte.
4) Adhesion of platelets to areas of denudation.
5) Release of factors from activated platelets, macrophages causing migration of smooth muscle from
the media into the intima
6) Proliferation of smooth muscle cells in the intima and accumulation of collagen and proteoglycans
7) Enhanced accumulation of lipids within cells and extracellularly (atheroma).
Components of an Atheromatous Plaque (found in the intima)
o Fibrous Cap
Smooth muscle, foam cells, lymphocytes, collagen, etc
o Necrotic Center
Cell debri, cholesterol clefts, etc
3. Hypertension
1. Causes of Essential Hypertension
- Environmental Factors; salt intake, stress, estrogens
- Genetic; defects in genes which determine; blood levels of pressor substances (ex.,
angiotensin II), reactivity of vascular smooth muscle to pressor substances, and smooth
muscle cell growth.
Important Points
- Hypertension accelerates atherogenesis
- Hypertension is associated with 2 forms of small vessel disease- Arteriolosclerosis
a) Hyaline arteriolosclerosis
- encountered in the elderly
- common in diabetes
- hyaline thickening/narrowing of lumen
- lumen obliteration (pathology)
b) Hyperplastic arteriolosclerosis
- acute or severe increases in blood pressure
- malignant hypertension
- onion skinning (pathology)
- narrowed lumen (pathology)
4. Diabetes Mellitus
- Advanced glycosylated end product formation occurs on lipids (LDL’s) in large vessels. This
retards LDL’s efflux from the vessel wall and enhances the deposition of cholesterol in the
intima accelerating atherogenesis.
5. Elevated Plasma Homocysteine
- Patients with this condition have premature vascular disease
- Homocysteine generates reactive oxygen species that may cause endothelial dysfunction.
Natural Hx of Atherosclerosis
o Myocardial Infarction
o Cerebral Infarction
o Gangrene of extremeties
o Abdominal aneurysms
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III. Aneurysms
- a localized abnormal dilation of a blood vessel that occurs most commonly in the aorta or the
heart.
Two Types
- True Aneurysm; blood remains in the confines of the circulatory system.
- Pseudoaneurysm; an extravascular hematoma that communicates with the intravascular
space.
Important Points
- Two most important causes include atherosclerosis and medial cystic degeneration.
- Infection that weakens major arteries are called mycotic aneurysms.
- Saccular aneurysms are spherical, can be filled with a thrombus
- Fusiform aneurysms are gradual, progressive and involve the entire circumference of the
vessel.
- Berry aneurysms is a thin walled outpouching at arterial branch points along the circle of
Willis.
A. Abdominal Aortic Aneurysm
1. most frequent location; abdominal aorta, below renal arteries above aorta bifurcation
2. most common cause; atherosclerosis, others include connective tissue disorders
3. Clinical Course
- Rupture into peritoneal cavity
- Occlusion of a branch by pressure or thrombus
- Embolism
- Compression of adjacent structure
B. Syphilitic Aneurysm
1. These aneurysms develop in the tertiary stage of syphilis
2. Involves small arteries but most devastating when it affects the vasa vasorum of the aorta.
3. Obliterative endarteritis, which affects small arteries, is an inflammatory condition
that narrows the lumens of the vasa causing ischemic injury of the aortic media.
4. Medial destruction results in loss of elastic support for the aorta and it becomes
dilated, producing a syphilitic aneurysm.
- Clinical Features
- Rupture of aneurysm
- Encroachment on mediastinal structure with resultant;
- Difficulty breathing
- Difficulty swallowing
- Cardiac disease
C. Dissecting Aneurysms
- a catastrophic illness characterized by dissection of blood in between and along the laminar
planes of the media, with a blood filled channel within the aortic wall.
- Epidemiology
- men 40 to 60 years old with long standing hypertension
- younger patients with a connective tissue disorder
- Etiology
- superficial transverse intimal tear in aorta, the cause of which is unknown
- once tear has occurred hypertension enhances hematoma progression within vessel
wall
Types
- Type A; deadly, involves all or portions of ascending and/or descending aorta
- Type B; begin distal to the subclavian artery.
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(Dissecting Aneurysms con’t)
Clinical Course
- Confused with myocardial infarction
- Present with sudden onset excruciating pain
- Rupture (into pleural, peritoneum, pericardium) death in seconds
D. Diseases of the Heart
1. Ischemic heart disease (IHD)
2. Myocardial infarction (MI)
- Ischemic heart disease
- a consequence of atherosclerosis of the coronary arteries and develops when blood flow
is inadequate to provide for oxygen demands of the heart
Angina Pectoris
- A symptom complex of IHD characteristics by paroxysmal and usually recurrent
attacks of substernal chest discomfort caused by transient cardiac ischemia that falls
short of inducing cellular necrosis.
- Stable Angina (SA)
- Caused by a reduction in coronary perfusion to a critical level by chronic stenosing
coronary atherosclerosis. The heart is rendered vulnerable to further ischemia and chest
pain develops whenever there is increased demand. SA is relieved by rest.
- Unstable Angina (UA)
- Induced by a disruption of an atherosclerotic plaque with superimposed thrombosis
and/or embolization/vasospasm (or both). The pattern of pain that occurs with
progressively increasing frequency is caused with progressively less effort. (referred to
as preinfarction angina).
- Prinzmetal Angina
- Episodic angina that occurs at rest and has been documented to be due to coronary artery
spasm.
Myocardial Infarction (MI)
Important Point
The subendocardial zone is normally the least perfused region of the
myocardium and therefore the most vulnerable to any reduction in blood
flow.
- Types
- Transmural; ischemic necrosis involves the full thickness of the ventricle wall in the
distribution of the coronary artery. (Completely obstructive)
- Subendocardial; an infarct that constitutes an area of ischemic necrosis limited to the
inner ⅓ or at most ½ of the ventricular wall.
- Pathogenesis
- Coronary Artery Occlusion
- Initial event is a sudden change in the morphology of an atheromatous plaque
- Subendothelial collagen is exposed, platelets undergo activation, adhesion,
aggregation and release of mediators that could cause spasm.
- Extrinsic coagulation cascade is activated
- Thrombus evolves and obstructs the entire lumen (transmural infarct)
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- Evolution of Morphological Changes in MI
½ -4hr ; waviness of fibers
4-12hr ; coagulation necrosis, edema, hemorrhage
12-24hr ; neutrophilic infiltrate
1-3days ; loss of nuclei, coagulative necrosis, neutrophil infiltrate
3-7days ; dead myofibrils, phagocytosis by macrophages
7-10days ; fibrovascular, granulation tissue
10-14days ; collagen deposition
2-8wks ; collagen deposition with decreasing cellularity
>2mo ; collagenous scar
Consequences and Complications of (MI)
- Contractile dysfunction
- Arrhythmias
- Myocardial rupture
- Pericarditis
- Mural thrombus formation
- Papillary muscle dysfunction
B. Jones, MD 2004
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