Pathology Of Valvular Diseases

Question 1

Cardiac valve Stenosis etiology

Answer 1

Failure of a valve to open completely obstructing the forward flow
- almost always caused by calcifications or valvular scarring over mechanical damage

Question 2

Cardiac valvular disease insufficiency etiology

Answer 2

Results from failure of a valve to close completely causing regurgitation of blood through the valve
- caused by intrinsic diseases (infections) or by disruption of the supporting structures (ventricular/aortic root dilation)

Question 3

What are the two characteristics that determine the quality and timing of a murmur?

Answer 3

1) the nature
- regurgitation or stenosis

2) the severity
- chronic vs acute

Question 4

What is the most common congenital valvular lesion

Answer 4

Bicuspid aortic valve lesions

• found in 1-2% of all live births
• aortic valve has 2 valves instead of 3

most common mutation pathway is through the Notch signaling pathway

Question 5

Bicuspid aortic valves

Answer 5

Two valves that are unequal size
- the larger cuspid exhibits a midline raphe

They are usually asymptomatic during birth, but overtime they progress to stenosis due to increased attractedness to degenerative calcification

Question 6

What is the most common acquired valvular disease?

Answer 6

Aortic/mitral valve stenosis

(66%) of all recorded valve diseases

Question 7

Possible Changes in physiology during degenerative valve disease

Answer 7

1) Calcifications

2) Alterations in extracellular matrix
- disminished collagen And elastin
- increased amount of proteoglycans
- increased fibrosis

3) increased MMPs or MMP inhibitors (depending on the disease)
* note: these are inevitable aspects of gaining, however certain diseases/pathologies can speed this up*

Question 8

What is the approximate rate of valve open and closing per year in the average human?

Answer 8

40 million beats/year

Question 9

What is the most common cause of aortic stenosis?

Answer 9

Calcific aortic degeneration
- usually asymptomatic and is discovered accidentally usually through xrays

• the chances of getting calcific aortic degeneration is directly proportional to age, with being 70-80 yrs of age being the mark for it being almost a certainty you get it*
• Note: if the patient has bicuspid aortic valves, the age range is dropped to 40-50 yrs*

Question 10

Calcific aortic stenosis morphology

Answer 10

Generally marked by heaped up calcified masses on the outflow sides of the cusps

commissural fusion is NOT typical here

Question 11

Severe Calcific aortic stenosis clinical features

Answer 11

Valve orifices can be compromised up to 70-80% (1.5cm or less)
- in these cases, the left ventricle will induce concentric LVH

The concentric LVH is proved to ischemia (marked by angina)
- these symptoms, included w/ syncope and CHF are poor prognosis and often lead to death

Question 12

Myxomatosis (prolapse) mitral valve (MVP)

Answer 12

One or both mitral leaflets are “floppy” and prolapse during systole

• also called “primary mitral valve prolapse”
• Far more common in women than men (7x)

The basis for primary myxomatosis mitral valve is idiopathic, but is expected to be associated with the following:

• Marfan syndrome
• CT disorders
• Scoliosis or high-arched palate
• defective ECM

The mitral valves ballon and dilate, which can cause cordae tendonae to rupture

Question 13

Morphology of myxomatosis (prolapse) mitral valve

Answer 13

1) Thinning of the mitral valve fibrosa layer

2) Expansion of the middle spongiosa layer
- which causes increased myxomatous material build up on the valves

Question 14

Clinical features of myxomatous (prolapse) mitral valve

Answer 14

Mostly asymptomatic

In severe cases, can cause chest palpitations, dyspena or angina

• can also lead to CHF if the valves/chordae rupture
• can also lead to ventricular arrhythmias

Displays a midsystolic click with a regurgitation murmur right after

Question 15

What two cardiac issues are the most associated with primary myxomatosis mitral valve?

Answer 15

Infective endocarditis

SCD

Both of these have increased likelihood of occurring compared to normal (patients are more prone)

Question 16

Rheumatic fever

Answer 16

Acute immunologically mediated multi-system inflammatory disease
- usually occurs after a group A streptococcal infection (often also associated w/ pharyngitis)

Manifests often as rheumatic heart disease due to the autoimmunity having an affinity to cardiac tissues/ valves
- the most important clinical features are valvular scarring/inflammation (looks like fibrotic stenosis)

Question 17

Specific pathogenesis of rheumatic valvular disease

Answer 17

Acute:

• hypersensitivity reaction caused by the antibodies directed against group-A streptococcus molecules
• specifically, antibodies targeting M proteins in the streptococcal species often mistake valve proteins as the same thing
• binding of the antibodies causes macrophage and compliment activation

Chronic:

• overtime, scarring forms along the inflammation areas
• Aschoff bodies are replaced by fibrous scars
• retracted and thickened valve cusps w/ commissural fusion of both the valves and chordae tendineae (look like button holes)
• shows diffuse fibrosis on microscopic exams

Question 18

Aschoff bodies

Answer 18

Pathogenic diagnostic criteria for acute Rheumatic valvular disease

These are collections of lymphocytes, plasma cells and special large macrophages called “antischkow” cells, surrounded by a layer of fibrinoid necrosis

• these can be found anywhere in the heart
• turn into fibrous scars in chronic forms of rheumatic valvular disease

Question 19

Pancarditis

Answer 19

Pericardium that exhibits fibrinous exudate and verrucae (small vegetations) along the valves that is asymptomatic generally
- this is seen in some rheumatic fever cases

Question 20

Most important functional consequence of rheumatic valvular disease

Answer 20

Valvular stenosis and regurgitation

• stenosis is more likely though
• mitral valve alone is seen in 70% of cases
• combined mitral and aortic is seen in 25% of cases
• also shows left atrium dilation, which can lead to A fibrillation*
• the combination of the dilation and A fib leads often to mural thrombi

If left untreated, will lead to, first, left sided heart failure and then right sided heart failure

Question 21

What age groups are most common for rheumatic heart disease?

Answer 21

Children (w/ carditis especially)

All age groups get fever and polyarteritis as the first symptoms
- cultures for strep will be negative, but antibody levels will be high against one or mote antigens (usually streptolysin O/ DNAase)

Question 22

Jones criteria for rheumatic valvular disease

Answer 22

Acute rheumatic heart disease is made based on having a previous strep infection and two or more of the following:

1) carditis
2) polyarteritis of large joints
3) subcutaneous nodules
4) annular(butterfly) rash
5) sydenham chorea (neurological disorder w/ involuntary rapid movements)

• can also show fever, arthralgia and elevated acute phase reactants, but these are not diagnostic*

Question 23

Treatment of rheumatic valvular disease

Answer 23

Acute is often treated w/ anti inflammatories and antibiotics if needed

Chronic sometimes requires valvuloplasty

If caught before severe stenosis begins, is usually a good prognosis