Cv 14: Valvular Disease Pathology

Front 1

What is the function of normal cardiac valves?

Back 1

Maintain unidirectional flow

Front 2

What lines normal valves?

Back 2

Endothelium

Front 3

What kind of valves separate the ventricles and outflow tracts?

Back 3

Semilunar Valves: Aortic and Pulmonic

Front 4

What kind of valves separate the atrium and ventricles?

Back 4

AV Valves: Mitral and Tricuspid

Front 5

What do the AV valves attach to?

Back 5

Free margins attach to ventricular walls via chordae tendinae and papillary muscles

Front 6

What are the types of valvular heart disease?

Back 6

- Stenosis: failure to open completely
- Insufficiency: failure to close properly, may lead to functional regurgitation

Front 7

In general, what kind of processes cause stenosis?

Back 7

Chronic process affecting a valve cusp; causes a failure of valve opening

Front 8

In general, what kind of processes cause insufficiency?

Back 8

- Valvular incompetence d/t disruption of supporting structures (eg, aortic root dilation or LV dilation)
- Intrinsic disease of valve cusps
- Causes failure to close completely

Front 9

What are some valvular problems that can cause stenosis or insufficiency to the aortic valve?

Back 9

- Congenital: bicuspid aortic valve (most common)
- Calcification: in old age ("senile"), causes stenosis
- Dilation of Aorta: related to HTN and aging, causes insufficiency

Front 10

What are some valvular problems that can cause stenosis or insufficiency to the mitral valve?

Back 10

- Rheumatic Heart Disease: causes stenosis
- Myxomatous degeneration: causes insufficiency

Front 11

Which is more common: stenoses or insufficiencies?

Back 11

Stenoses >> Insufficiencies

Front 12

How can calcification affect cardiac valves? What valves are affected by calcification?

Back 12

Dystrophic calcification:
- Damage of wear and tear complicated by deposits of calcium phosphate
- Eg, calcific aortic stenosis, mitral annular calcification

Front 13

What are the risk factors for Calcific Valvular Disease?

Back 13

- Hyperlipidemia
- Hypertension
- Inflammation

Front 14

How does Calcific Valvular Disease compare to Atherosclerosis?

Back 14

They are distinct diseases, but they share some risk factors:
- Hyperlipidemia
- Hypertension
- Inflammation

Front 15

What is the most common of all valvular abnormalities?

Back 15

Calcific Aortic Stenosis (AS)

Front 16

When and to whom does Calcific Aortic Stenosis (AS) most commonly occur?

Back 16

* In 40s-50s: bicuspid, unicuspid aortic valves (1-2% of population, associated w/ Notch mutation)
- Also in 70s-80s: normal valves (age-related)

Front 17

What mutation is associated with developing Calcific Aortic Stenosis (AS)? At what point in life?

Back 17

Notch mutation; 40s-50s

Front 18

What are the clinical effects of having Calcific Aortic Stenosis (AS)?

Back 18

- Increased pressure in LV → Hypertrophy
- Angina, ischemia, and CHF
- Syncope

Front 19

What is the life expectation for Calcific Aortic Stenosis (AS)?

Back 19

If they have CHF, 50% will die within two years

Front 20

Morphologically, what happens in Calcific Aortic Stenosis (AS)?

Back 20

- Heaped up calcified masses in cusps, primarily at BASES
- Free cuspal edges NOT involved
- No fusion of commissures

Front 21

How do you treat Calcific Aortic Stenosis (AS)?

Back 21

Valve Replacement

Front 22

How does the type of aortic valve affect the likelihood of getting Calcific Aortic Stenosis (AS)?

Back 22

- Possible w/ tricuspid aortic valve (normal)
- Much more likely with a bicuspid aortic valve (congenital defect)

Front 23

What is it called when there is calcification of the mitral valve?

Back 23

Mitral Annular Calcification

Front 24

Morphologically, what happens in Mitral Annular Calcification?

Back 24

Degenerative calcific deposits on fibrous ring, at BASE of valve

Front 25

When and to whom does Mitral Annular Calcification most commonly occur?

Back 25

- Women >60 years old
- Increased in patients w/ myxomatous valves or elevated LV pressure

Front 26

Functionally, how does Mitral Annular Calcification affect a patient?

Back 26

- Usually does not affect valve function
- Calcifications are sites for thrombi / infection

Front 27

What is it called when the leaflets of the mitral valve become enlarged, hooded, redundant, or floppy (myxoid)?

Back 27

Myxomatous Degeneration of Mitral Valve (Prolapse)

Front 28

What does myxoid mean as it refers to Myxomatous Degeneration of Mitral Valve (Prolapse)?

Back 28

Deposition of mucoid material in valve
(blue = collagen in trichrome stain, indicates lots of ground substance)

Front 29

When and to whom does Myxomatous Degeneration of Mitral Valve (Prolapse) most commonly occur?

Back 29

- Very common (3% of adults)
- Usually affects young women

Front 30

Morphologically, what happens in Myxomatous Degeneration of Mitral Valve (Prolapse)?

Back 30

- One or both leaflets are enlarged, hooded, redundant, or floppy (myxoid)
- Prolapses or balloons back into LA during systole

Front 31

Functionally and clinically, how does Myxomatous Degeneration of Mitral Valve (Prolapse) affect a patient?

Back 31

- Usually no serious complications
- Hear mid-systolic click

- May cause regurgitation: late systolic or holosystolic murmur

Front 32

What is the cause of Myxomatous Degeneration of Mitral Valve (Prolapse)?

Back 32

- Unknown
- Could be a developmental anomaly of CT
- Feature of Marfan syndrome (fibrillin gene mutation) and other hereditary disorders

Front 33

What are some possible complications of Myxomatous Degeneration of Mitral Valve (Prolapse)?

Back 33

All uncommon:
- Infectious endocarditis
- Mitral insufficiency
- Thrombi on atrial surfaces leading to stroke or other systemic infarcts d/t emobli
- Arrhythmias → sudden death (most often in advanced mitral insufficiency)

Front 34

What can cause thrombi to form in the LA?

Back 34

Prolapse of leaflets of mitral valve causes them to rub on walls of atrium, which is irritating and can lead to thrombus formation

Front 35

How does Rheumatic Fever affect the heart valves?

Back 35

May cause Mitral Stenosis

Front 36

What is and causes Rheumatic Fever?

Back 36

- Acute, immunologically mediated, multi-system, inflammatory disease w/ major cardiac manifestations
- Hypersensitivity reaction induced by Group A Streptococcal (pyogenes) pharyngitis
- Antibodies against M protein cross react w/ glycoprotein antigens in heart, joints, and other tissues

Front 37

What morphological features are seen in Rheumatic Fever?

Back 37

- Widely distributed inflammatory lesions
- Pancarditis
- Aschoff Body (classic lesion)

Front 38

What are the features of Pancarditis seen in Rheumatic Fever?

Back 38

- Pericarditis
- Myocarditis w/ Aschoff bodies**
- Endocardium and L-sided valves w/ Fibrinoid Necrosis and verrucae
- Subendocardial (MacCallum) plaques: irregular fibrous thickening of endocardium

Front 39

What is the classic lesion of Rheumatic Fever?

Back 39

Aschoff Body:
- Foci of swollen eosinophilic collagen
- Surrounded by T cells, plasma cells, and macrophages
- Macrophages are plump - aka Anitschkow cells or caterpillar cells

Front 40

What is the special name for macrophages in Aschoff Bodies? When are these seen?

Back 40

- Anitschkow cells (aka caterpillar cells)
- Seen in Rheumatic Fever

Front 41

What happens to the endocardium in Rheumatic Fever?

Back 41

Fibrinoid necrosis and verrucae along lines of closure of valve cusps

Front 42

What are the complications due to inflammation and fibrosis in Rheumatic Fever?

Back 42

- Thickened valve leaflets
- Fusion of commissures (fishmouth or buttonhole deformities)
- Fusion / thickening of chordae tendinae
* Leads to Mitral Stenosis *

Front 43

What are the complications due to Mitral Stenosis in Rheumatic Fever?

Back 43

- LA dilation (sometimes thrombus formation)
- Reduced CO (mechanical obstruction prevents filling of LV)
- Pulmonary congestion, eventually RV hypertrophy, and R-sided heart failure

Front 44

Which valves are affected by Rheumatic Fever and at what incidence?

Back 44

- Mitral valve alone: 65-70%
- Mitral and aortic valves: 25%
- Tricuspid valve less often
- Pulmonary valve rare

Front 45

Is there a genetic component to Rheumatic Fever?

Back 45

Genetic susceptibility varies by individual; not all w/ Group A Strep infections develop rheumatic fever (estimate is 3%)

Front 46

How do you diagnose Rheumatic Fever?

Back 46

JONES Criteria:

- Preceding Group A Strep infection + 2 major manifestations OR 1 major and 2 minor

Major:
- Migratory polyarthritis (large joints)
- Carditis (pericardial friction rub, weak heart sounds, tachycardia, arrhythmia)
- Subcutaneous nodules (rare, extensor surfaces of joints)
- Erythema marginatum of skin (rare)
- Sydenham corea (involuntary, purposeless, rapid movements)

Minor (non-specific):
- Fever
- Arthralgia (joint pain)
- Elevated acute-phase reactants

Front 47

What organism is responsible for causing Rheumatic Fever?

Back 47

Group A (β-hemolytic) Streptococcus

Front 48

Who is most likely to get Rheumatic Fever?

Back 48

Children between 5 - 15 years (because they are more likely to have a Strep infxn)

Front 49

How do you diagnose acute Rheumatic Fever?

Back 49

- ASO (Anti-Streptolysin O) titers
- Antibodies to DNase B

- ASO and DNase B are proteins produced by Group A Strep

Front 50

How long after a Group A Strep infection, does Acute Rheumatic Fever occur? Chronic Rheumatic Fever?

Back 50

- Acute RF: 1-4 weeks after infection
- Chronic RF: years or decades after initial episode

Front 51

What is the prognosis for Acute Rheumatic Fever?

Back 51

- Good for primary attack
- Increased vulnerability to reactivation at a later date

Front 52

What is the sign of Chronic Rheumatic Fever? What is the treatment?

Back 52

- Valvular disease (valvulitis)
- Requires surgical repair of valves to improve outlook

Front 53

What are the two types of Infective Endocarditis?

Back 53

- Acute
- Subacute

Front 54

What kind of organism causes Acute Infective Endocarditis? How severe are the lesions? Treatment?

Back 54

- Highly virulent organism
- Usually occurs on normal valve w/ 50% mortality
- Causes necrotizing ulcerative invasive infection
- Requires surgery

Front 55

What kind of organism causes Sub-acute Infective Endocarditis? How severe are the lesions? Treatment?

Back 55

- Low virulence organism (Strep viridans)
- Usually occurs on deformed valve (already screwed up so don't need much virulence)
- Less destructive lesions
- Responds to antibiotics

Front 56

In whom is Infective Endocarditis more common?

Back 56

Patients w/ CV abnormalities:
- RHD (Rhematic Fever Disease)
- Myxomatous Mitral Valve
- Calcific Valvular Stenosis
- Artificial Valves

Host Factors:
- Neutropenia
- Immunodeficiency
- Malignancy
- Diabetes
- Alcoholics
- IV drug users

Front 57

What are some specific causes of Infective Endocarditis?

Back 57

- Strep viridans (50-60% of cases w/ infected, deformed valve)
- Staph aureus (10-20% of cases overall; most common in IVDA)
- Commensal organisms of mouth
- Staph epidermidis in prosthetic valves

Front 58

Which kind of valve problem is characterized by:
- Friable, large bulky destructive vegetations
- Fibrin, inflammatory cells and bacteria
- Eroded myocardium → ring abscesses

Which valves?

Back 58

Acute and Subacute Endocarditis
- Mitral and aortic valves most common
- Tricuspid valve in IV drug users

Front 59

What are the morphological characteristics that distinguish acute from subacute endocarditis?

Back 59

- Less valvular destruction
- Fibrosis and granulation tissue reaction at base of vegetation

Front 60

What valve is affected / damaged in infective endocarditis when patients are IV drug users? Why?

Back 60

Tricuspid valve - this is the first valve that the drug comes across when the drugs are injected in the venous system

Front 61

What are the histological features of Infective Endocarditis?

Back 61

- Clusters of bacteria (dark blue)
- Abundant acute inflammation (neutrophils / pus)

Front 62

How do you diagnose Bacterial Endocarditis?

Back 62

Duke Criteria:
- 2 major criteria OR
- 1 major and 3 minor criteria OR
- 5 minor criteria

Front 63

What are the major criteria for Bacterial Endocarditis / Duke Criteria?

Back 63

- Positive blood cultures
- Echo findings (valve-related mass / abscess)
- New valvular regurgitation (new murmur on auscultation)

(Need two major criteria, one major and three minor criteria, or five minor criteria)

Front 64

What are the minor criteria for Bacterial Endocarditis / Duke Criteria?

Back 64

- Predisposing heart lesion or IVDA
- Fever
- Uncommon findings from septic emboli (petechiae, splinter hemorrhages, Janeway lesions (palms, soles hemorrhagic lesions), Osler nodes (digits), Roth spots (retina))

(Need two major criteria, one major and three minor criteria, or five minor criteria)

Front 65

What are the possible complications of Bacterial Endocarditis?

Back 65

- Valvular insufficiency or stenosis (possible heart failure)
- Myocardial abscesses and possible perforation
- Vegetations could break-off → embolism (eg brain, kidneys, spleen, etc)
- Glomerulonephritis (immune complexes)

Front 66

How do you treat Bacterial Endocarditis?

Back 66

- IV antibiotics
- Valve replacement if necessary
- Prophylactic antibiotics after valve damage

Front 67

What are the types of Non-Infective Vegetations?

Back 67

- Non-bacterial thrombotic endocarditis
- Libman-Sacks endocarditis

Front 68

What is the mechanism of non-bacterial thrombotic endocarditis?

Back 68

- Depositions of small masses of fibrin, platelets, and other blood products on leaflets
- Often in debilitated patients (eg, cancer, sepsis)
- May result in emboli and infarcts

Front 69

What is the etiology of non-bacterial thrombotic endocarditis?

Back 69

- Hyper-coaguable states
- Associated w/ mucin-producing adenocarcinomas (DVTs and Trousseau syndrome)
- Endocardial trauma - Swan-Ganz catheter

Front 70

What are the morphological characteristics of non-bacterial thrombotic endocarditis?

Back 70

- Sterile
- Non-destructive
- Non-inflammatory
- Small (1-5 mm)
- Along lines of closure

Front 71

What is the etiology of Libman-Sacks Endocarditis?

Back 71

- Systemic Lupus Erythematosus (mitral and tricuspid valves involved; anti-phospholipid antibodies present)
- Primary Anti-Phospholipid Syndrome

Front 72

What are the morphological characteristics of Libman-Sacks Endocarditis?

Back 72

- Either or both sides of leaflets
- May also be on endocardium
- 1-4 mm verrucae w/ fibrinous material
- May have intense inflammation

Front 73

What is this an example of?

Back 73

Rheumatic Heart Disease

Front 74

What is this an example of?

Back 74

Infected Endocarditis

Front 75

What is this an example of?

Back 75

Non-Bacterial Thrombotic endocarditis

Front 76

What is this an example of?

Back 76

Libman-Sacks Endocarditis

Front 77

What are the features of Carcinoid Syndrome?

Back 77

- Produces many mediators (serotonin, kallikrein, bradykinin, histamine, prostaglandins, tachykinins)
- Symptoms: flushing, cramps, nausea, vomiting, diarrhea

Front 78

What mediators are released by Carcinoid Tumors?

Back 78

- Serotonin
- Kalliekrein
- Bradykinin
- Histamine
- Prostaglandins
- Tachykinin

Front 79

What are the symptoms of Carcinoid Syndrome?

Back 79

- 50% have plaque-like fibrosis, R-heart endocardium and valves
- Flushing
- Cramps
- Nausea
- Vomiting
- Diarrhea

Front 80

Why are there no symptoms at first w/ Carcinoid Syndrome?

Back 80

Serotonin and bradykinin (two of the chemical mediators) are inactivated by MAO in pulmonary vasculature AND also inactivated by passage through functioning liver

Front 81

On which side of the heart are the plaque-like fibroses more commonly found in Carcinoid Syndrome? Why?

Back 81

- 50% of patients w/ Carcinoid Syndrome have plaque-like fibrosis of R-heart endocardium and valves
- Usually occurs on R side because o finactivation of mediators by MAO in lung

Front 82

What is the cause of Carcinoid Syndrome?

Back 82

- Unknown
- Related to endothelial injury caused by vasoactive agents

Front 83

In what kind of patients does Carcinoid Syndrome occur in?

Back 83

- Patients w/ GI carcinoids that spread to liver (hepatic mets)
- Patients w/ carcinoids outside of portal system of venous drainage

Front 84

Why do patients w/ GI carcinoids w/ hepatic mets more likely to have carcinoid syndrome / heart disease?

Back 84

- Normally, bioactive proteins are inactivated by liver
- With mets to liver, secretion occurs directly into hepatic vein and reaches R-side of heart

Front 85

Why do patients w/ carcinoids outside of portal system of venous drainage get carcinoid syndrome / heart disease? Examples?

Back 85

- Direct secretion of mediators into systemic circulation
- Eg, carcinoids arising in ovary, testes

- Very high blood levels may prevent complete inactivation by lung MAO
- Eg, primary lung carcinoid

Front 86

What are the characteristics of the endocardial plaque-like thickenings seen in carcinoid heart disease?

Back 86

- Smooth muscle cells and collagen embedded in mucopolysaccharide matrix
- Tricuspid (insufficiency) and pulmonic (stenosis) valves equally affected

Front 87

Which valves are affected by Carcinoid Syndrome?

Back 87

- Tricuspid and pulmonic valves equally
- Usually tricuspid insufficiency or pulmonic stenosis

Front 88

What are the potential complications of an artificial, MECHANICAL heart valve?

Back 88

- Thromboembolic complications
- Infective endocarditis

Front 89

What are the potential complications of an artificial, BIOPROSTHESIS heart valve?

Back 89

- Structural deterioration
- 50% need a replacement within 15 years