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Coronary artery disease

Coronary artery disease (CAD) occurs when the arteries that

supply blood to the heart muscle (the coronary arteries) becomehardened and narrowed.

The arteries harden and narrow due to buildup of a materialcalled plaqueon their inner walls. The buildup of plaque is

known as atherosclerosis.

As the plaque increases in size, the insides of the coronaryarteries get narrower and less blood flows through them.

Eventually, blood flow to the heart muscle is reduced, and,because blood carries much-needed oxygen, the heart muscle is

not able to receive the amount of oxygen it needs.

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Developmental process of atherosclerosis

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Reduced or cutoff blood flow and oxygen supply to the

heart muscle can result in:

Angina is chest pain or discomfort that occursAnginawhen the heart does not get enough blood.

A heart attack happens when a blood clot.Heart attack

develops at the site of plaque in a coronary artery andsuddenly cuts off most or all blood supply to that partof the heart muscle. Cells in the heart muscle begin to

die if they do not receive enough oxygen-rich blood.This can cause permanent damage to the heart muscle.

http://www.nhlbi.nih.gov/health/dci/Diseases/Angina/Angina_WhatIs.htmlhttp://www.nhlbi.nih.gov/health/dci/Diseases/HeartAttack/HeartAttack_WhatIs.htmlhttp://www.nhlbi.nih.gov/health/dci/Diseases/HeartAttack/HeartAttack_WhatIs.htmlhttp://www.nhlbi.nih.gov/health/dci/Diseases/Angina/Angina_WhatIs.html

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Angina

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When severely affected by atherosclerosis, the flow of blood through theaorta can be hindered and oxygen deficiency (ischemia) or gangrene can

develop.

Atherosclerosis is also the primary underlying cause of heart attacks, strokes,arrhythmias and aortic aneurysms, which are blood-filled dilations of thevessel wall. The rupture of an aneurysm can be deadly due to the

hemorrhaging it causes.

Atherosclerosis is generally thought to result from the gradual build-up ofcholesterol, fibrin, fatty materials, calcium, and other substances inside the

arteries, where they form plaques.

Many scientists believe that these plaques develop at sites of arterial injuriesrelated to high blood pressure, smoking, diabetes, and other knownatherosclerosis risk factors.

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Coronary artery disease (CAD) is caused by arteriosclerosis (the thickeningand hardening and loss of elasticity of the inside walls of arteries).

Arteriosclerosis can be catagorized into three patterns based onpathophysiology and clinical and pathological consequences.

1. Atherosclerosis: The most important and frequent pattern characterized byintimal lesions called atheromas, or atheromatous or fibrofatty plaques.

2. Monckeberg medial calcific sclerosis : Characterized by palpable calcificdeposits in muscular arteries but do not encroach on the vessel lumen. Seen

in persons above age 50.

3. Arteriosclerosis: affects small arteries and arterioles. Two anatomicvariants: a) hyaline and b)hyperplastic, both associated with thickening of

vessel walls with luminal narrowing that may cause downstream ischemicinjury. Often associated with hypertension and diabetes mellitus.

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.This is a normal coronary artery with

no atherosclerosis and a widely

patent lumen that can carry as much

blood as the myocardium requires.

The degree of atherosclerosis is much

greater in this coronary artery, and

the lumen is narrowed by half. A small

area of calcification is seen in the

plaque at the right

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Monckeberg's medial calcific sclerosis, the most insignificant form

of arteriosclerosis (both atherosclerosis and arteriolosclerosis are definitely significant).

Note the purplish blue calcifications in the media; note that the lumen is unaffected by

this process. Thus, there are usually no real clinical consequences.

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This is hyperplastic arteriolosclerosis, which most often

appears in the kidney in patients with malignant hypertension.

The arteriolar wall is markedly thickened

and the lumen is narrowed

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Atherosclerosis

Atherosclerosis is characterized by intimal lesionscalled atheromas, or atheromatous or fribrofattyplaques, which protrude into and obstruct vascular

lumens and weaken the underlying media.

They may lead to serious complications.

Atherosclerotic lesions are classified into six types :

isolated foam cells(fatty dots), fatty streaks,intermediate lesions, atheromas, fibroatheromas and

complicated lesions

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American Heart Association classification of human athrosclerotic lesions

from the fatty dot (type I) to the complicatedtype VI lesion.

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Fatty streaks earliest lesion of atherosclerosis, composed oflipid-filled foam cells.Begin as multiple yellow, flat spots less

than 1 mm in diameter that coalesce into elongated streaks 1cmlong or longer.

They contain T lymphocytes and extracellular lipid in smalleramounts than in plaques.

Fatty streaks appear in aortas of some children below age 1 yearand all children older than 10 years.

Coronary fatty streaks begin to form in adolescence and inanatomic sites prone to develop plaques.

Fatty streaks often occur in areas of the vasculature that are notsusceptible to developing atheromas later in life.

Although fatty streaks may be precursors of plaques, not all fattystreaks are destined to become fibrous plaques or more

advanced lesions.

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Atherosclerotic plaques develop primarily in elastic arteries (e.g.,

aorta, carotid and iliac arteries) and large and medium-sizedmuscular arteries (e.g., coronary and popliteal arteries).

Symptomatic atherosclerotic disease most often involves thearteries supplying the heart, brain, kidneys and lower

extremities.

Consequences : Myocardial infarction (heart attack), Cerebralinfarction (stroke), aortic aneurysms and peripheral vasculardisease (gangrene of the legs). Also acutely or chronically

diminished arterial perfusion, such as mesenteric occlusion,sudden cardiac death, chronic ischemic heart disease andischemic encephalopathy.

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Atheroma or atheromatous plaqueconsists of a raised focal lesion initiatingwithin the intima, having a soft, yellow grumus core of lipid (cholesterol and

cholesterol esters), covered by a firm, white fibrous cap.

Also called fibrous, fibrofatty, lipid or fibrolipid plaques, atheromatous

plaques appear white to whitish yellow and impinge on the lumen of theartery. Size : 0.3 to 1.5cm in diameter but sometimes coalesce to form larger

masses.

Atherosclerotic lesions usually involve only a partial circumference of thearterial wall (eccentriclesions)and are patchy and variable along the vessel

length.

Distribution of atherosclerotic plaques : in humans, the abdominal aorta isusually much more involved than the thoracic aorta and lesions tend to be

much more prominent around the origins (ostia) of major branches.

In descending order (after the lower abdominal aorta),the most heavilyinvolved vessels are the coronary arteries, the popliteal arteries, the internal

carotid arteries and the vessels of circle of Willis.

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In small arteries, atheromas can occlude lumens,compromise blood flow to distal organs and cause

ischemic injury

Plaques can undergo disruption and precipitatethrombi that further obstruct blood flow.

In large arteries, plaques encroach on the subjacentmedia and weaken the affected vessel wall, causing

aneurysms that may rupture.

Extensive atheromas can be friable and shed emboli

into the distal circulation.

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Here is occlusive coronary atherosclerosis. The coronary at the left is narrow

by 60 to 70%. The coronary at the right is even worse with evidence for previo

thrombosis with organization of the thrombus and recanalization such that the

are three small lumens remaining, one of which contains additional recent thromb

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Atherosclerotic plaques have three principal components :

1) cells, including SMCs, macrophages and other leukocytes

2) ECM, including collagen, elastic fibers and proteoglycans and

3) intracellular and extracellular lipid.

These components occur in varying proportions and

configurations in different lesions.

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Schematic diagram of the mechanism of intimal thickening, emphasizing

smooth muscle cell migration to and proliferation and extracellular matrix

Elaboration in the intima.

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The superficial fibrous cap is composed of SMCs and relativelydense ECM.

Beneath and side to the cap (shoulder) is a cellular area

consisting of macrophages, SMCs and T lymphocytes.

Deep to the fibrous cap is a necrotic core, containing adisorganized mass of lipid (cholesterol and cholesterol esters),cholesterol clefts, debris from dead cells, foam cells, fibrin,

variably organized thrombus, and other plasma proteins.

Foam cells are large, lipid-laden cells that derive from bloodmonocytes (tissue macrophages), SMCs also can imbibe lipid to

become foam cells.

Though typical atheromas contain abundant lipid, many so-called fibrous plaques are composed mostly of SMCS and fibrous

tissue.

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Plaques generally continue to change and progressivelyenlarge through cell death and degeneration, synthesis

and degradation (remodelling) of ECM, and

organization of thrombus.

Atheromas often undergo calcification.

Patients with advanced coronary calcification appear to

be at increased risk for coronary events.

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.AMild atherosclerosis composed of fibrous plaques, one of which

is denoted by the arrow

B. Severe disease with diffuse and complicated lesions.

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Advanced lesions of atherosclerosis :

Focal rupture, ulceration or erosion of the luminal surface ofatheromatous plaques , resulting in exposure of highlythrombogenic substances that induce thrombus formation ordischarge of debris into the bloodstream, producingmicroemboli composed of lesion contents (cholesterol emboli or

atheroemboli).

Superimposed thrombosis, the most feared complication,usually occurs on disrupted lesions (those with rupture,ulceration, erosion or hemorrhage) and may partially or

completely occlude the lumen. Thrombi may heal and becomeincorporated into and thereby enlarge the intimal plaque.

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A coronary thrombosis is seen microscopically

occluding the remaining small lumen of this

coronary artery. Such an acute coronary thrombosisis often the antecedent to acute myocardial infarction.

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Coronary artery with atherosclerotic plaques. There is recent hemorrhage

into the plaque. This is one of the complications of atherosclerosis. Such

hemorrhage could acutely narrow the lumen and produce an acute coronary

syndrome with ischemia and/or infarction of the myocardium.