Download I.Cardiovascular pathology

ARTERIOSCLEROSIS
&
ATHEROSCLEROSIS
Overview
- Healthy arteries are flexible, strong and elastic. Their inside lining is
smooth so that blood can flow unrestricted. But, over time, too much
pressure in arteries can make the walls thick and stiff, sometimes restricting
blood flow to the organs and tissues. This process is called
arteriosclerosis or "hardening of the arteries.„
- Atherosclerosis is the most common form of arteriosclerosis. Although the
two terms are often used interchangeably, atherosclerosis refers to
hardening of the arteries caused by accumulation of fatty deposits (plaques)
and other substances.
- Atherosclerosis and arteriosclerosis can affect arteries anywhere in the
body. When arteries leading to limbs are affected, patient may develop
circulation problems in the arms and legs called peripheral arterial disease.
When arteries to the heart are affected, patient may have chest pain
(angina), a heart attack or coronary artery disease. When arteries in the
neck are affected, patient could have a stroke or a transient ischemic attack
(TIA). Atherosclerosis can also lead to a bulge in the wall of artery
(aneurysm).
- Some people with arteriosclerosis or atherosclerosis have no symptoms
until one or more arteries are so hardened that they cause a medical
emergency.
1
In atherosclerosis,
arteries are clogged
by an accumulation
of plaques — which are
made up of cholesterol
particles (lipoproteins), fat,
calcium, cellular waste
and other substances.
This is a normal coronary artery. The lumen is large, without any
narrowing by atheromatous plaque. The muscular arterial wall is of
normal proportion.
2
Signs & symptoms
Signs and symptoms usually develop gradually.
At first, symptoms may occur only after vigorous exertion,
when changed arteries can't supply muscles with enough
oxygen and nutrients. But, as the narrowing worsens, it takes
less and less exertion to surpass the ability of the artery to
supply adequate blood.
Arteriosclerosis and atherosclerosis most often affects
arteries in the heart, brain, kidneys, abdominal aorta and
legs.
This microscopic cross section of the aorta shows a large overlying
atheroma on the left. Cholesterol clefts are numerous in this atheroma.
The surface on the far left shows ulceration and hemorrhage. Despite this
ulceration, atheromatous emboli are rare (or at least, complications of
them are rare).
3
This high magnification of the atheroma shows numerous foam cells and
an occasional cholesterol cleft. A few dark blue inflammatory cells are
scattered within the atheroma.
This is a high magnification of the aortic atheroma with foam cells and
cholesterol clefts.
4
These three aortas demonstrate mild, moderate, and severe atherosclerosis from bottom to top. At the bottom, the mild atherosclerosis shows
only scattered lipid plaques. The aorta in the middle shows many more
larger plaques. The severe atherosclerosis in the aorta at the top shows
extensive ulceration in the plaques.
Here is an example of an
atherosclerotic aneurysm of the
aorta in which a large "bulge"
appears just above the aortic
bifurcation. Such aneurysms are
prone to rupture when they
reach about 6 to 7 cm in size.
They may be felt on physical
examination as a pulsatile mass
in the abdomen. Most such
aneurysms are conveniently
located below the renal arteries
so that surgical resection can be
performed with placement of a
dacron graft.
5
Microscopically, the tear (arrow) in this aorta extends through the media,
but blood also dissects along the media (asterisk).
An aortic dissection may lead to hemopericardium when blood
dissects through the media proximally. Such a massive amount of
hemorrhage can lead to cardiac tamponade.
6
Signs & symptoms
The specific signs and symptoms depend on which artery or arteries are
obstructed:
Heart. Obstruction of the arteries to the heart (coronary arteries) may
cause symptoms of heart attack, such as chest pain.
Neck. Obstruction of the carotid arteries in your neck may cause
symptoms of stroke, such as sudden numbness, weakness or dizziness.
Arms and legs. Obstruction of the arteries to the arms and legs may
cause symptoms of peripheral arterial disease, such as leg pain when
exercising (intermittent claudication).
Hardening of the arteries can also cause erectile dysfunction in men.
There are usually no signs or symptoms until one or more of the arteries is
so narrowed or clogged that patient develop severely reduced blood flow
(ischemia) or a blood clot, which can completely obstruct blood flow.
Some people have no symptoms until a blood clot blocks a narrowed
artery, causing a heart attack or stroke, or until an aneurysm ruptures,
causing serious internal bleeding.
This is the external appearance of a normal heart
The epicardial surface is smooth and glistening.
The amount of epicardial fat is usual. The left anterior descending coronary artery extends down
from the aortic root to the apex.
The anterior surface of the heart demonstrates
an opened left anterior descending coronary
artery.Within the lumen of the coronary can be
seen a dark red recent coronary thrombosis.
The dull red color to the myocardium as seen
below the glistening epicardium to the lower
right of the thrombus is consistent with
underlying myocardial infarction.
7
This is the normal appearance of myocardial fibers in longitudinal
section. Note the central nuclei and the syncytial arrangement of the
fibers, some of which have pale pink intercalated disks.
The earliest change histologically seen with acute myocardial infarction in
the first day is contraction band necrosis. The myocardial fibers are
beginning to lose cross striations and the nuclei are not clearly visible in
most of the cells seen here. Note the many irregular darker pink wavy
contraction bands extending across the fibers.
8
This high power microscopic view of the myocardium demonstrates an
infarction of about 1 to 2 days in duration. The myocardial fibers have
dark red contraction bands extending across them. The myocardial cell
nuclei have almost all disappeared. There is beginning acute
inflammation. Clinically, such an acute myocardial infarction is marked by
changes in the electrocardiogram and by a rise in the MB fraction of
creatine kinase.
In this microscopic view of a recent myocardial infarction, there is
extensive hemorrhage along with myocardial fiber necrosis with
contraction bands and loss of nuclei.
9
This myocardial infarction is about 3 to 4 days old. There is an extensive
acute inflammatory cell infiltrate and the myocardial fibers are so necrotic
that the outlines of them are only barely visible.
This is an intermediate myocardial infarction of 1 to 2 weeks in age. Note
that there are remaining normal myocardial fibers at the top. Below these
fibers are many macrophages along with numerous capillaries and little
collagenization.
10
There is pale white collagen within the interstitium between myocardial
fibers. This represents an area of remote infarction.
The aortic valve shows three thin and delicate cusps. The coronary artery
orifices can be seen just above.The endocardium is smooth, beneath
which can be seen a red-brown myocardium. The aorta above the valve
displays a smooth intima with no atherosclerosis.
11
This is coronary atherosclerosis with the complication of hemorrhage
into atheromatous plaque, seen here in the center of the photograph.
Such hemorrhage acutely may narrow the arterial lumen.
Cross sections of the anterior descending coronary artery demonstrate
marked atherosclerosis with narrowing. This is most pronounced at the
left in the more proximal portion of this artery. In general, the worst
atherosclerosis is proximal, where arterial blood flow is more turbulent.
More focal lesions mean that angioplasty or bypass can be more useful
procedures.
12
The coronary artery shown here has narrowing of the lumen due to build
up of atherosclerotic plaque. Severe narrowing can lead to angina,
ischemia, and infarction.
This section of coronary artery demonstrates remote thrombosis with
recanalization to leave only two small, narrow channels.
13
There is a severe degree of narrowing in this coronary artery. It is
"complex" in that there is a large area of calcification on the lower right,
which appears bluish on this H&E stain. Complex atheroma have
calcification, thrombosis, or hemorrhage. Such calcification would make
coronary angioplasty difficult.
There is a pink to red recent thrombosis in this narrowed coronary artery.
The open, needle-like spaces in the atheromatous plaque are cholesterol
clefts.
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Causes
In arteriosclerosis, the walls of the arteries become hard and thick,
sometimes interfering with blood circulation. The condition results from
the natural aging process or from atherosclerosis.
Atherosclerosis is a slow, complex disease that typically starts early
in life and progresses. The exact cause is unknown, but it may begin
with damage or injury to the innermost layer of the artery (the
endothelium).
CAUSES OF DAMAGE TO THE ENDOTHELIUM INCLUDE:
- Elevated levels of cholesterol
- High blood pressure
- A virus
- An allergic reaction
- An irritant, such as nicotine or drugs or too much homocysteine –
an amino acid present in the blood
- Certain diseases, such as diabetes
Causes: High blood cholesterol
Cholesterol is an important
component of cell membranes
and is vital to the structure and
function of all of the body's cells.
Cholesterol also is a building
block in the formation of certain
types of hormones (steroid
hormones).
There are no symptoms of high blood cholesterol. The only way to find
out if patient have high blood cholesterol is by having a blood test.
15
Causes: High blood cholesterol
Total cholesterol level: Normal value: < 200 mg/dL
- LDL (Low-density lipoprotein cholesterol) Carry cholesterol in the
plasma. LDL has been associated with heart disease and is sometimes
referred to as "bad cholesterol". Normal values < 130 mg/dL; Borderline:
130-159 mg/dL; High risk > 160 mg/dL
- HDL (High-density lipoprotein cholesterol) Also known as the "good
cholesterol". Higher levels of HDL have been shown to decrease the risk of
heart disease. Normal values: Male aprox. 44 mg/dL / Female approx.
55 mg/dL
- VLDL (Very-low-density lipoprotein) This type of lipoprotein is made up
of mostly triglycerides and small amounts of protein and cholesterol.
- Triglycerides Lipids that come both from animal and vegetable food
sources. Excess triglycerides are stored in the body as adipose (fat) tissue
and are used for energy. Fatty meals and alcohol can raise the triglyceride
level in the blood. Some HIV medications can dramatically elevate levels,
requiring lipid lowering medication to bring levels down. Normal values:
90-150 mg/dL. Elevated values: can result from diet, certain medications,
and conditions such as pancreatitis, nephrotic syndrome, and diabetes.
A coronary artery has been opened longitudinally. The coronary extends
from left to right across the middle of the picture and is surrounded by
epicardial fat. Increased epicardial fat correlates with increasing total body
fat. There is a lot of fat here, suggesting one risk factor for atherosclerosis.
This coronary shows only mild atherosclerosis, with only an occasional
yellow-tan lipid plaque and no narrowing.
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Causes: Risk factors for Hipercholesterolemia
Inactivity.
Lack of exercise may lower level of HDL cholesterol.
Obesity.
Overweight increases triglycerides, lowers HDL cholesterol and increases
VLDL cholesterol.
Diet.
Cholesterol naturally occurs in foods derived from animals, such as meat,
eggs and cheese. Eating a high-fat, high-cholesterol diet contributes to an
increased blood cholesterol level. Saturated and trans fats raise blood
cholesterol levels. Polyunsaturated fats lower blood cholesterol, but also
seem susceptible to oxidation. Over time, oxidation speeds buildup of
plaques inside your arteries. Monounsaturated fats may help lower
blood cholesterol and are resistant to oxidation.
Causes: Risk factors for Hipercholesterolemia
These factors increase the likelihood that high total cholesterol levels will
lead to atherosclerosis:
Smoking. Cigarette smoking damages the walls of blood vessels,
making them likely to accumulate fatty deposits. Smoking may also lower
the level of HDL cholesterol.
High blood pressure. By damaging the walls of arteries, high blood
pressure can accelerate the accumulation of fatty deposits on the walls of
the arteries.
Type 2 diabetes. This type of diabetes results in a buildup of sugar
levels in the blood. Chronic high blood sugar may lead to narrowing of
arteries. Controlling cholesterol and triglyceride levels may greatly reduce
the risk of complications from cardiovascular disease.
Family history of atherosclerosis. If a close family member
(parent or sibling) has developed atherosclerosis before age 55, high
cholesterol levels place the patient at a greater than average risk
of developing atherosclerosis.
17
Causes: Hypercholesterolemia - Prevention
EATING A HEALTHY DIET
Control total fat. Limit all types of fat — saturated, polyunsaturated, trans fatty
acids (trans fats) and monounsaturated — to no more than 30 percent of your total
daily calories. Limit dietary cholesterol. Daily limit for dietary cholesterol is 300
milligrams, or less than 200 milligrams if the patient have heart disease.
Eat foods with soluble fiber. As part of a low-fat diet, soluble fiber can help lower
total blood cholesterol level. Foods high in soluble fiber include oat bran, oatmeal,
beans, peas, rice bran, barley, citrus fruits, strawberries and apple pulp.
Eat more fish. Some fish — particularly fatty types prevalent in cold water, such as
salmon, mackerel and herring — contain high amounts of a unique type of
polyunsaturated fat called omega-3 fatty acids. Omega-3s may lower the level of
triglycerides.
Consider soya products. Soya compounds called isoflavones act like human
hormones that regulate cholesterol levels. Eating soya proteins can reduce the
levels of total cholesterol, LDL cholesterol and triglycerides. Eating soya may also
raise the level of HDL cholesterol, which may protect patient against heart disease.
Drink alcohol in moderation, if at all. Moderate consumption of alcohol may raise
level of HDL cholesterol. The best advice is to drink in moderation, if the patient
drink at all. Limit alcohol to one drink daily (for woman) or to no more than two drinks
daily (for man).
Reduce sugar intake. This is a way of lowering triglyceride levels. Ideally,
triglyceride levels should be lower than 150 mg/dL.
Causes: Hypercholesterolemia - Prevention
Exercising
Being overweight promotes a high total cholesterol level. Losing weight
improves cholesterol levels. Choose an aerobic activity. Get involved in
activities such as brisk walking, jogging, bicycling or cross-country skiing.
Build up the time and frequency of exercising. Gradually work up to
exercising for 30 minutes to 45 minutes at least three times a week. If the
patient is overweight or have been inactive for many years, it takes several
months to work up gradually to this level. The higher the level of physical
activity, the greater the rate of weight loss.
Not smoking
Cigarette smoking damages the walls of blood vessels, making them prone
to accumulating fatty deposits. After stop smoking, HDL cholesterol may
return to its former level.
18
Causes: High blood pressure
Blood pressure is determined by the amount of blood the
heart pumps and the amount of resistance to blood flow in
the arteries.
- A resting blood pressure reading below 120/80 millimeters of
mercury (mm Hg) is normal.
- If resting blood pressure is consistently 140/90 mm Hg or
higher, the patient has high blood pressure.
- A reading in between these levels (121-139/81-89 mmHg)
places in the prehypertensive category.
- A reading of 115/75 mm Hg is the level above which the risk
of cardiovascular complications starts to increase.
- Uncontrolled high blood pressure can increase risk of stroke,
heart attack, heart failure and kidney failure. Fortunately, high
blood pressure can be detected with a simple test.
Causes: high blood pressure
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higher.
19
Causes: High blood pressure – signs & symptoms
Most people with high blood pressure have no signs or symptoms, but
people often think that headaches, dizziness or nosebleeds are common
warning signs and symptoms of high blood pressure. It's true that a few
people with early-stage high blood pressure have a dull ache in the back of
their heads when they wake in the morning. Or perhaps they have a few
more nosebleeds than normal.
Headaches, dizziness or nosebleeds typically don't occur until high blood
pressure has reached a more advanced stage — one that's possibly lifethreatening. Even so, most people with the highest blood pressure
readings don't experience any of these symptoms.
Other signs and symptoms sometimes associated with high blood
pressure generally are caused by other conditions that can lead to high
blood pressure. Such signs and symptoms include:
excessive perspiration, muscle cramps, weakness, frequent urination,
rapid or irregular heartbeat (palpitations)
Causes: High blood pressure – causes
In 90-95 % of high blood pressure cases, there's no
identifiable cause. This type of high blood pressure is called
essential (idiopathic) hypertension or primary hypertension.
It differs from secondary hypertension, in which the increased
pressure results from another underlying condition, such as:
kidney disease, adrenal disease, thyroid disease, abnormal
blood vessels, preeclampsia (a significant increase in blood
pressure during the last three months of pregnancy), or sleep
apnea.
The cause of secondary hypertension also can be medications,
including birth control pills, cold remedies, decongestants, over-the-counter
pain relievers and some prescription drugs, or illegal drugs, such as cocaine
and amphetamines. This type of hypertension may have a more rapid onset
and cause higher blood pressure than does primary hypertension, which tends
to develop gradually over many years.
20
Causes: High blood pressure – risk factors
There are four major risk factors of high blood pressure that
can't be controlled. They are:
Age. The risk of high blood pressure increases when patient
get older.
Race. High blood pressure occurs far more frequently in
blacks than in any other racial group (data from the United
States). High blood pressure in blacks generally develops at
an earlier age than it does in whites. Plus, it's more likely to
lead to serious complications such as stroke or heart attack.
Sex. In young adulthood and early middle age, high blood
pressure is more common in men than in women, but the
opposite is true for men and women age 60 and older.
Family history. High blood pressure tends to run in families.
Causes: High blood pressure – risk factors
The risk factors that can be controlled or managed include:
- Obesity.
- Inactivity.
- Tobacco use.
- Sodium sensitivity and salt intake (People who are sodium sensitive
retain sodium more easily, leading to fluid retention and increased blood
pressure).
- Low potassium intake. (Potassium helps balance the amount of sodium in
the cells. If potassium level is low, accumulation of sodium may occur).
- Excessive alcohol. (Exactly how or why alcohol increases blood pressure
isn't understood. But over time, heavy drinking can damage your heart
muscle).
- Stress. (High levels of stress can lead to a temporary but dramatic increase
in blood pressure. Stress also can promote high blood pressure if patient then
try to relax by eating more, using more nicotine or drinking more alcohol).
Patients may also be at increased risk of high blood pressure if they
have certain chronic conditions. Examples include high blood
cholesterol, diabetes and sleep apnea.
21
Causes: High blood pressure – risk factors
High blood pressure in children:
more often than in adults, indicates that something else
is wrong, and the increase in blood pressure is a sign of
an underlying condition. In general, high blood
pressure in children is uncommon. However, as an
increasing number of children become less physically
active and more obese, a greater percentage of them are
developing high blood pressure.
Causes: High blood pressure – complications
- Damage to the arteries: arteriosclerosis/atherosclerosis, aneurysms.
- Thickening of the heart's main pumping chamber (left ventricular
hypertrophy): can eventually lead to heart failure.
- A blocked or ruptured blood vessel in the brain. This can lead to stroke.
High blood pressure is a risk factor for both types of stroke — ischemic stroke
and hemorrhagic stroke.
- Weakened and narrowed blood vessels in the kidneys. This can prevent
these organs from functioning normally.
- Thickened, narrowed or torn blood vessels in the eyes. This can result in
vision loss.
- METABOLIC SYNDROME. This syndrome is a cluster of disorders of the
body's metabolism — including high blood pressure, high insulin levels,
excess body weight and abnormal cholesterol levels. High blood pressure
predisposes to having other components of the syndrome. The more
components are present, the greater risk of developing diabetes, heart
disease or stroke.
Having high blood pressure may also lessen bility to think, remember
and learn related to ageing. Uncontrolled high blood pressure has even
been linked to cognitive decline and dementia.
22
Causes – diabetes mellitus
Diabetes mainly occurs in two forms:
Type 1 diabetes.
This type develops
when pancreas makes
little or no insulin. It
affects between 5 %
and 10 % of people
with the disease.
Causes – diabetes mellitus
Type 2 diabetes. This type is far more common than type 1,
affecting between 90 % and 95 % of people with diabetes over age
20. It occurs when the body is resistant to the effects of insulin or the
pancreas produces some, but relatively not enough, insulin to
maintain a normal glucose level.
23
Causes – diabetes mellitus
Other types of diabetes:
Maturity-onset diabetes of youth (MODY). This is a rare, inherited form of
type 2 diabetes that usually affects teenagers.
Gestational diabetes. This type of diabetes sometimes develops during
pregnancy — generally in the second or third trimester. It affects between 2
% and 5 % of pregnant women and occurs when hormones produced by
the placenta interfere with the effects of insulin. Gestational diabetes
usually disappears immediately after the baby is born, but about half the
women who experience gestational diabetes develop type 2 diabetes later
in life. In rare cases, type 1 diabetes also can develop during pregnancy,
leading to high blood sugar levels after delivery that require insulin therapy.
About 1 % to 2 % of all diagnosed cases of diabetes result from illnesses or
medications that interfere with the action of insulin. These include inflammation or surgical removal of the pancreas, adrenal gland disorders, malnutrition, infection, and the use of corticosteroid drugs, such as prednisone.
This distal portion of coronary artery shows significant narrowing. Such
distal involvement is typical of severe coronary atherosclerosis, such as
can appear with diabetes mellitus or familial hypercholesterolemia. This
would make a coronary bypass operation difficult.
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ARTERIOSCLEROSIS / ATHEROSCLEROSIS
Risk factors
- Hardening of the arteries occurs over time, so the risk
increases with ageing.
- The condition is most common in middle-aged and older
adults.
THE RISK OF DEVELOPING THIS DISEASE ALSO INCREASES with:
- High blood pressure
- High cholesterol
- High levels of homocysteine in your blood
- Diabetes
- Chronic kidney disease
- Obesity
- Smoking
- Trouble managing stress
- A family history of early heart disease
ARTERIOSCLEROSIS / ATHEROSCLEROSIS
Complications
-Whatever the cause, once the inner wall of an artery is damaged,
blood cells called platelets often clump at the injury site to try to
repair the artery. Eventually, fatty deposits (plaques) made of
cholesterol and other cellular waste products also accumulate and
harden, narrowing the space in arteries.
- Organs and tissues that are served by these narrowed
vessels don't get an adequate supply of blood. The body may
respond to the shortage of blood by increasing blood pressure to
maintain adequate blood flow. The increase in blood pressure
leads to further blood vessel damage and inflammation around the
plaques. Eventually pieces of the fatty deposits may rupture and
enter the bloodstream. This can cause a blood clot to form at the
site and damage many organs, such as in a heart attack. A blood
clot can also travel to other parts of the body and partially or
totally block the flow of blood to important organs.
25
This is the left ventricular wall which has been sectioned lengthwise to
reveal a large recent myocardial infarction. The center of the infarct
contains necrotic muscle that appears yellow-tan. Surrounding this is a
zone of red hyperemia. Remaining viable myocardium is reddish- brown.
This cross section through the heart demonstrates the left ventricle on
the left. Extending from the anterior portion and into the septum is a large
recent myocardial infarction. The center is tan with surrounding
hyperemia. The infarction is "transmural" in that it extends through the
full thickness of the wall.
26
One complication of a transmural
myocardial infarction is rupture of
the myocardium.
This is most likely to occur in the
first week between 3 to 5 days
following the initial event, when the
myocardium is the softest.
The white arrow marks the point of
rupture in this anterior-inferior
myocardial infarction of the left
ventricular free wall and septum.
Note the dark red blood clot forming
the hemopericardium.
The hemopericardium can lead to
tamponade.
LEFT: This is the tricuspid
valve. The leaflets and thin and
delicate. Just like the mitral
valve, the leaflets have thin
chordae tendineae that attach
the leaflet margins to the
papillary
muscles
of
the
ventricular wall below.
RIGHT: In cross section, the
point of rupture of the
myocardium is shown with the
arrow. In this case, there was a
previous myocardial infarction
3 weeks before, and another
myocardial infarction occurred,
rupturing through the already
thin ventricular wall 3 days
later.
27
This is infective endocarditis. The aortic valve demonstrates a large,
irregular, reddish tan vegetation. Virulent organisms, such as
Staphylococcus aureus, produce an "acute" bacterial endocarditis, while
some organisms such as Streptococcus viridans produce a "subacute"
bacterial endocarditis.
The more virulent bacteria causing the acute bacterial form of
infective endocarditis can lead to serious destruction, as shown
here in the aortic valve. Irregular reddish tan vegetations overlie
valve cusps that are being destroyed. Portions of the vegetation can
break off and become septic emboli.
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