Cardiovascular pathology

Question 1

What kind of tissue is this and what are some key characteristics of this tissue type?

Answer 1

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.

Question 2

What is this a cross-section of?

Answer 2

This is a normal coronary artery. The lumen is large, without any narrowing by atheromatous plaque. The muscular arterial wall is of normal proportion.

Question 3

Which valve is this?

Answer 3

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.

Question 4

What valve is this?

Answer 4

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.

Question 5

What is in this image?

Answer 5

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.

Question 6

What is shown here?

Answer 6

The coronary artery shown here has narrowing of the lumen due to build up of atherosclerotic plaque.

Question 7

What is occurring in this coronary artery?

Answer 7

This section of coronary artery demonstrates remote thrombosis with recanalization to leave only two small, narrow channels.

Question 8

What is occurring in this coronary artery?

Answer 8

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.

Question 9

What is shown here?

Answer 9

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.

Question 10

What is the arrow pointing at?

Answer 10

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.

Question 11

This is a magnified atheroma. What are some histological characteristics seen here?

Answer 11

This high magnification of the atheroma shows numerous foam cells and an occasional cholesterol cleft. A few dark blue inflammatory cells (lymphocytes) are scattered within the atheroma.

Question 12

What is the white arrow pointing at?

Answer 12

A fatty streak in the aorta.

Question 13

What disease is seen in these aortas? Rank them from least to most severe.

Answer 13

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.

Question 14

What is seen here?

Answer 14

This high magnification microscopic view of an aortic atheroma shows prominent foam cells as well as cholesterol clefts.

Question 15

This cross section shows…

Answer 15

…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).

Question 16

What pathological process led to this gross appearance?

Answer 16

This is severe atherosclerosis of the aorta in which the atheromatous plaques have undergone ulceration along with formation of overlying mural thrombus.

Question 17

What is seen in the vessel on the far right?

Answer 17

This is the left coronary artery from the aortic root on the left. Extending across the middle of the picture to the right is the anterior descending branch. This coronary shows severe atherosclerosis with extensive calcification. At the far right, there is an area of significantnarrowing.

Question 18

Answer 18

At high magnification, the dark red thrombus is apparent in the lumen of the coronary. The yellow tan plaques of atheroma narrow this coronary significantly, and the thrombus occludes it completely.

Question 19

Answer 19

A thrombosis of a coronary artery is shown here in cross section. This acute thrombosis diminishes blood flow and leads to ischemia and/or infarction with damage to the myocardial fibers. This can be evidenced clinically by the onset of chest pain–angina.

Question 20

Answer 20

Coronary atherosclerosis is shown here complicated by hemorrhage into the atheromatous plaque. Such hemorrhage acutely may narrow the arterial lumen.

Question 21

Answer 21

Cross sections of this 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.

Question 22

Answer 22

Within the lumen of the LAD 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.

Question 23

This is the left ventricular wall which has been sectioned lengthwise to reveal…….?

Answer 23

This is 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.

Question 24

Location? How old?

Answer 24

Anteroseptal, ~1 week. The center is tan with surrounding hyperemia.

Question 25

Describe the earliest histological changes associated with MI.

Answer 25

The earliest change histologically seen with acute myocardial infarction in the first day is **coagulation/gragmented/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.**

Question 26

Answer 26

These images are of an MI that is 1-2 days old. The necrotic 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 the second image, there is hemorrhage as well.

Question 27

How old is this MI? What are the associated histological changes?

Answer 27

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.

Question 28

How old is this MI? What are the associated histological changes?

Answer 28

This is an intermediate myocardial infarction of 1 to 2 weeks in age. Note that there are remaining normal myocardial fibers at the top. The neutrophils died off, and macrophages replaced them as main inflammatory cells. There are also numerous capillaries (responsible for the dark red border formed around the infarct after ~1 week).

Question 29

How old is this MI? What are the associated histological and clinical changes?

Answer 29

At 3 to 4 weeks of age the intermediate myocardial infarction shown involving a papillary muscle at low power have decreasing cellularity along with more prominence of collagen. Note that there are remaining normal red myocardial fibers. Cardiac biomarkers are not positive at this stage and myocardial rupture is unlikely. The degree of cardiac failure depends upon the extent of myocardial loss

Question 30

Answer 30

The heart is opened to reveal the left ventricular free wall on the right and the septum in the center. There has been a remote myocardial infarction that extensively involved the anterior left ventricular free wall and septum. The white appearance of the endocardial surface indicates the extensive scarring.

Question 31

How old is this MI? What are the associated histological changes?

Answer 31

The myocardium shown demonstrates pale fibrosis with collagenization following healing of a myocardial infarction. There is minimal cellularity; a few remaining viable red myocardial fibers are present. This stage is reached about 2 months following the initial ischemic event. This collagenous scar is nonfunctional for contraction and will diminish the ejection fraction. Such a scar will not rupture.

Question 32

When is rupture most likely to occur after an MI?

Answer 32

In cross section, the point of rupture of the myocardium is shown with the arrow. 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.

Question 33

Answer 33

There has been a previous extensive transmural myocardial infarction involving the free wall of the left ventricle. Note that the thickness of the myocardial wall is normal superiorly, but inferiorly is only a thin fibrous wall. The infarction was so extensive that, after healing, the ventricular wall was replaced by a thin band of collagen, forming an aneurysm. Such an aneurysm represents non-contractile tissue that reduces stroke volume and strains the remaining myocardium. The stasis of blood in the aneurysm predisposes to mural thrombosis.

Question 34

What is shown, and what does this predispose the patient to?

Answer 34

A cross section through the heart reveals a ventricular aneurysm with a very thin wall at the arrow. Note how the aneurysm bulges out. The stasis in this aneurysm allows mural thrombus, which is present here, to form within the aneurysm.

Question 35

Answer 35

There is a tear (arrow) located 7 cm above the aortic valve and proximal to the great vessels in this aorta with marked atherosclerosis. This is an aortic dissection.

Question 36

Answer 36

Microscopically, the tear (arrow) in this aorta extends through the media, but blood also dissects along the media (asterisk).

Question 37

What complication of aortic dissection is pictured?

Answer 37

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.

Question 38

Answer 38

Here, the aortic dissection went into the muscular wall. In any case, an aortic dissection is an extreme emergency and can lead to death in a matter of minutes. The blood can dissect up or down the aorta. Blood dissecting up around the great vessels can close off the carotids. Blood can dissect down to the coronaries and shut them off.

Question 39

Answer 39

The right carotid artery is compressed by blood dissecting upward from a tear with aortic dissection. Blood may also dissect to coronary arteries. Thus patients with aortic dissection may have symptoms of severe chest pain (for distal dissection) or may present with findings that suggest a stroke (with carotid dissection) or myocardial ischemia (with coronary dissection).

Question 40

What is pictured in this cross section? What are some complications?

Answer 40

This microscopic cross section of the aorta demonstrates a red blood clot that is compressing the aortic lumen. This occurred as a result of aortic dissection in which there was a tear in the intima followed by dissection of blood at high pressure out through the muscular wall to the adventitia. This blood dissecting out can lead to hemopericardium, cardiac tamponade, and hemothorax.

Question 41

What is a condition that can predispose a patient to this?

Answer 41

This aortic dissection occurred just above the aortic root in a patient with Marfan's syndrome.

Question 42

This patient has Marfan syndrome. What pathological changes are seen?

Answer 42

Mitral valve prolapse. The leaftlets of the mitral valve are redundant, and the one on the far left is ballooned upward. The chordae tendineae that hold the leaflets become long and thin.

Question 43

Answer 43

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 group produce a "subacute" bacterial endocarditis.

Question 44

Answer 44

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.

Question 45

Answer 45

In this case, the infective endocarditis shows how the infection tends to spread from the valve surface onto adjacent endocardium. Shown here, vegetations extend onto the endocardial surfaces, and the infection is also extending into to underlying myocardium.

Question 46

Answer 46

Microscopically, the valve in infective endocarditis demonstrates friable vegetations of fibrin and platelets (pink) mixed with inflammatory cells and bacterial colonies (blue). The friability explains how portions of the vegetation can break off and embolize.

Question 47

Answer 47

Here is a valve with infective endocarditis. The blue bacterial colonies on the lower left are extending into the pink connective tissue of the valve. Valves are relatively avascular, so high dose antibiotic therapy is needed to eradicate the infection.

Question 48

Answer 48

Here, infective endocarditis involving the mitral valve has spread into the interventricular septum all the way to the tricuspid valve, producing a fistula (the hole in the center).

Question 49

Answer 49

Seen here involving the finger at the right are small splinter hemorrhages in a patient with infective endocarditis. These hemorrhages are subungual, linear, dark red streaks. Similar hemorrhages can also appear with trauma.

Question 50

What is this pathology, and who is predisposed to this disease?

Answer 50

The small pink vegetation on the rightmost cusp margin represents the typical finding with non-bacterial thrombotic endocarditis (or so-called "marantic endocarditis"). This is non-infective. It tends to occur in persons with a hypercoagulable state (**Trousseau's syndrome**, a paraneoplastic syndrome associated with malignancies) and in **very ill** persons.

Question 51

Answer 51

Here is another marantic vegetation (non-bacterial thrombotic endocarditis) on the leftmost cusp. These vegetations are rarely over 0.5 cm in size. However, they are friable and very prone to embolize.

Question 52

Answer 52

The valve is seen on the left, and a bland vegetation is seen on the right. It appears pink because it is composed of fibrin and platelets. It displays about as much morphologic variation as a brown paper bag. Such bland vegetations are typical of the non-infective forms of endocarditis.

Question 53

Answer 53

This patient has systemic lupus erythematosus. Here are flat, pale tan, spreading vegetations over the mitral valve surface and even on the chordae tendineae. These vegetations that can be on any valve or even on endocardial surfaces are consistent with Libman-Sacks endocarditis. These vegetations appear in about 4% of SLE patients and rarely cause problems because they are not large and rarely embolize. Note also the thickened, shortened, and fused chordae tendineae that represent remote rheumatic heart disease.

Question 54

Answer 54

The small verrucous vegetations seen along the closure line of this mitral valve are associated with acute rheumatic fever. These warty vegetations average only a few millimeters and form along the line of valve closure over areas of endocardial inflammation. Such verrucae are too small to cause serious cardiac problems.

Question 55

What disease caused this? What valves are most affected by this disease?

Answer 55

Mitral valve as seen from above in the left atrium. The mitral valve demonstrates the typical "fish mouth" shape with chronic rheumatic scarring. Mitral valve is most often affected with rheumatic heart disease, followed by mitral and aortic together, then aortic alone, then mitral, aortic, and tricuspid together.

Question 56

Answer 56

A window of adherent pericardium has been opened to reveal the surface of the heart. There are thin strands of fibrinous exudate that extend from the epicardial surface to the pericarial sac. This is typical for a fibrinous pericarditis.

Question 57

Answer 57

This is an example of a fibrinous pericarditis. The surface appears roughened from the normal glistening appearance by the strands of pink-tan fibrin.

Question 58

What is this pathology, and what is a diagnostic physical finding?

Answer 58

The epicardial surface of the heart shows a shaggy fibrinous exudate. This is an example of fibrinous pericarditis. This appearance has often been called a "bread and butter" pericarditis, but you would have to drop your buttered bread on the carpet to really get this effect. The fibrin often results in the the finding on physical examination of a "friction rub" as the strands of fibrin on epicardium and pericardium rub against each other.

Question 59

Answer 59

Fibrinous pericarditis. Microscopically, the pericardial surface here shows strands of pink fibrin extending outward. There is underlying inflammation. Eventually, the fibrin can be organized and cleared, though sometimes adhesions may remain.

Question 60

Answer 60

The pericarditis here not only has fibrin, but also hemorrhage. Thus, this is called a "hemorrhagic pericarditis". It is really just fibrinous pericarditis with hemorrhage. Without inflammation, blood in the pericardial sac would be called "hemopericardium".

Question 61

What is this, and what are some causes?

Answer 61

The surface of the heart with hemorrhagic pericarditis demonstrates a roughened and red appearance. Hemorrhagic pericarditis is most likely to occur with metastatic tumor and with tuberculosis (TB). TB can also lead to a granulomatous pericarditis that may calcify and produce a "constrictive" pericarditis.

Question 62

Answer 62

This is a purulent pericarditis. Note the yellowish exudate that has pooled in the lower pericardial sac that has been opened here. A bacterial organism is usually implicated in this process, and the infection typically spreads from the lungs.

Question 63

Answer 63

Microscopically, acute rheumatic carditis is marked by a peculiar form of granulomatous inflammation with so-called "Aschoff nodules" seen best in myocardium. These are centered in interstitium around vessels as shown here. The myocarditis may be severe enough to cause congestive heart failure.

Question 64

Answer 64

Here is an Aschoff nodule at high magnification. The most characteristic component is the Aschoff giant cell. Several appear here as large cells with two or more nuclei that have prominent nucleoli. Scattered inflammatory cells accompany them and can be mononuclears or occasionally neutrophils.

Question 65

Answer 65

Another peculiar cell seen with acute rheumatic carditis is the Anitschkow myocyte. This is a long, thin cell with an elongated nucleus.

Question 66

Answer 66

In time, chronic rheumatic valvulitis may develop by organization of the acute endocardial inflammation along with fibrosis, as shown here affecting the mitral valve. Note the shortened and thickened chordae tendineae.

Question 67

What drugs can be used to lyse clots in coronary vessels?

Answer 67

tissue plasminogen activator (t-PA) or streptokinase

Question 68

Causes of arterial thrombosis?

Answer 68

* atherosclerosis * endothelial injury * vasculitis * trauma

Question 69

What is the temporal sequence of pathologic changes following an acute MI?

Answer 69

* 20-40 mins: irreversible myocardial damage * 1-3 hrs: wavy fibers * 4-12 hrs: necrosis * next 24 hrs: progressive loss of myocardial zone

Question 70

What are the 3 types of post-MI rupture and what do they result in?

Answer 70

1. free wall rupture -\> hemopericardium/tamponade 2. IV septum rupture -\> L to R shunt 3. papillary muscle rupture -\> acute mitral insufficiency

Question 71

Major complications of acute MI?

Answer 71

* arrhythmias * sudden death * cardiogenic shock * aneurysm * mural thrombus

Question 72

What is the difference between type A and type B aortic dissection?

Answer 72

* Type A: proximal lesion, more common, more dangerous * Type B: doesn't involve ascending aorta, less common, better prognosis

Question 73

How much myocardium must a patient lose before signs and symptoms of cardiogenic shock manifest?

Answer 73

\>40% of LV

Question 74

What pathological changes are seen in athlete's heart?

Answer 74

Haphazardly arranged hypertrophied **septal** myocytes

Question 75

What are some complications of infective endocarditis?

Answer 75

* valve insufficiency * **ring abscess** * suppurative pericarditis * hemopericardium (rare) * **glomerulonephritis** (with hematuria, albuminuria, or renal failure) * arrhythmia * systemic embolization * atrial dilation if valve is insufficient

Question 76

What lab test is diagnostic of Libman Sacks endocarditis when combined with clinical indications?

Answer 76

ANA

Question 77

Answer 77

This section of myocardium shows amorphous deposits of pale pink material between myocardial fibers. This is characteristic for amyloid. Amyloidosis is a cause for an "infiltrative" or "restrictive" form of cardiomyopathy. It is a nightmare for anesthesiologists when intractable **arrhythmias occur during surgery** on such patients.

Question 78

What causes amyloidosis?

Answer 78

Protein misfolding, causing extracellular fibrils to aggregate and disrupt normal function.

Question 79

Answer 79

Cardiac amyloidosis. The atrophic myocardial fibers are separated by structureless, pink-staining amyloid.

Question 80

How do you diagnose amyloidosis?

Answer 80

Congo red staining

Question 81

What are some complications of amyloidosis?

Answer 81

* heart failure * restrictive cardiomyopathy * arrhythmias

Question 82

What does a healed (3+ months) MI look like histologically?

Answer 82

* no dead leukocytes remain * what was once myocardium is now scar tissue * no inflammation remains * fibrosis

Question 83

Name a risk factor for dilated cardiomyopathy.

Answer 83

History of alcoholism.

Question 84

What is the "classic" clinical presentation of SLE?

Answer 84

The triad of fever, joint pain, and rash in a woman of childbearing age

Question 85

What is a lab test that can be done to test for fibrous pericarditis, and why?

Answer 85

Urea nitrogen, because uremia is the most common systemic disorder associated with pericarditis

Question 86

What are the components of a thrombus?

Answer 86

Fibrin, platelets, and red cells.

Question 87

What causes arterial thrombosis? What causes venous thrombosis?

Answer 87

Arterial thrombosis is caused by endothelial damage (atherosclerosis, vasculitis, etc). Venous thrombosis is caused by blood stasis. Both are affected by hypercoagulable states (antithrombin or protein C deficiency)

Question 88

At what time after infarction are patients at the greatest risk for rupture of an acute MI?

Answer 88

4-7 days.

Question 89

What happens in an aortic dissection?

Answer 89

Intimal tear (often in proximal aorta) -\> blood enters aortic media and splits it apart -\> possible rupture into pericardium -\> hemopericardium & death

Question 90

What inherited disorder commonly causes aortic dissection? What is the molecular basis of this disorder?

Answer 90

Marfan syndrome. Autosomal dominant disorder resulting from a mutation in fibrillin (a glycoprotein secreted by fibroblasts, which allows elastic fiber deposition in the ECM).

Question 91

What is the difference between type A and type B aortic dissection?

Answer 91

Type A: proximal, common, dangerous. Type B: do not involve ascending aorta, better prognosis.

Question 92

What is the most common site for bacterial endocarditis in IV drug users?

Answer 92

Tricuspid valve.

Question 93

Name 3 general factors that predispose to endocarditis.

Answer 93

1. Abnormal flow (hemodynamically abnormal valves, congenital shunts, etc) 2. bacteremia (instrumentation, IV drugs, surgery) 3. abnormal immune response (neutropenia, immunodeficiency, immunosuppression)

Question 94

What are the most common causative organisms of infective endocarditis?

Answer 94

Mostly gram positive bacteria. In previously abnormal hearts, most often streptococci (S viridans). Staphylococci are also common.

Question 95

How can infective endocarditis lead to shock?

Answer 95

1. septicemia 2. bacterial release of endotoxins trigger TNF release 3. TNF promotes release of inflammatory mediators (IL-1, IL-6, IL-8, NO) 4. in high quantities, these mediators develop shock through systemic vasodilation, impaired contractility, and widespread endothelial injury

Question 96

What is non-bacterial thrombotic endocarditis? Compare it with infective endocarditis.

Answer 96

In some chronically ill patients (ie cancer), there is hypercoagulatbility of the blood, forming vegetations on normal valves. Valves are not distorted or destroyed, but there is still risk of systemic embolism. Infective endocarditis occurs on previously damaged valves (ie RHD) or on normal valves if the organisms are very virulent. In IE, valvular damage is either present before infection or caused by IE itself.

Question 97

What is the clinical presentation of nonbacterial thrombotic endocarditis?

Answer 97

* chronic illness * malignancies * trauma to valves

Question 98

What are the pathologic manifestations of acute RF?

Answer 98

1. Endocardium: vegetations (often on mitral valve) 2. Myocardium: myocarditis with widely disseminated Aschoff bodies (inflammatory lesions) 3. Epicardium: fibrinous/serofibrinous pericarditis, sometimes resulting in constrictive pericarditis

Question 99

What is the etiology of RHD?

Answer 99

Type II hypersensitivity reaction induced by GABHS. After initial GABHS infection, antibodies to streptococcal M proteins develop. These antibodies then cross-react with cardiac glycoprotein antigens.

Question 100

Describe an Aschoff body.

Answer 100

* a form of granuloma, with central necrosis in early stages of ARF * contains activated macrophages (Anitschkow cells), some of which converge into multinucleated Aschoff giant cells * also contains lymphocytes and plasma cells * over time, fibrosis of affected regions leads to chronic rheumatic heart disease, in which Aschoff bodies are no longer seen.

Question 101

Is the cardiac dysfunction in patients with ARF caused by valve dysfunction or myocardial damage?

Answer 101

Myocardial damage. Valvular damage becomes an issue years later, with valvular scarring and deformity. This most commonly affects mitral and aortic valves, with mitral stenosis being the most characteristic finding. Stenosis can lead to atrial fibrillation, thromboembolism, and if severe, heart failure.