Question

Hans Dietz is a 25 year old male patient with a family history of Marfan Syndrome (MFS). He is generally well and enjoys attending regular fitness sessions in his local gymnasium. During a recent gym session, he experienced dizziness followed by a fainting episode. He presented at the emergency department and a new systolic murmur was heard. Mr Dietz subsequently underwent screening for cardiovascular abnormalities associated with his family history of Marfan Syndrome.

Question 1

The fibrous structure of the heart is comprised predominantly of connective tissue proteins.

Describe the microscopic composition of the layers of the mitral valve. Your answer must include a description of the connective tissue element, the cell types found in each layer and how the layers are arranged (i.e. their structure or architecture).

Question 2

Upon further evaluation with an echocardiogram (cardiac ultrasound), Mr Dietz was found to have an enlarged (dilated) proximal ascending aorta, mitral valve prolapse with myxomatous changes and elongated chordae.

The patient was noted as having myxomatous changes in the mitral valve leaflets and associated elongation of the chordae tendineae. Explain what is meant by the term myxomatous changes. Your answer must include a description of the cellular and structural changes that occur within the valve.

Question 3

Where on the body would be the ideal position for the clinician to auscultate for a systolic murmur associated with the mitral valve?

Question 4

Describe the secondary complications (or consequences) that will occur as a result of the changes in the structure of the mitral valve in a patient with Marfan syndrome. Your answer should link to the clinical sign of the new systolic murmur noted in this patient.

Answer 1

1).The mitral valve leaflets are composed of an outer layer of endocardium and a dense connective tissue core, which is continuous with the annulus fibrosus....

Histology of normal mitral valve leaflets

The adult mitral leaflet contains distinct atrialis, spongiosa, fibrosa and ventricularis histological layers. Each layer comprises extracellular components including interstitial fibroblasts and connective tissue fibres. Three types of collagen are present in the leaflet, primarily type I collagen at 74%, with type III collagen consisting of 24% and type V collagen at 2%..The fibrous tissues, along with elastic fibres, are integrated together within a ground substance and are covered by a layer of endothelial cells. The endothelial layer of cells is continuous with the luminal surface of the atrium and the ventricle.

The atrialis is the uppermost layer adjacent to the left atrium. It is composed of mainly aligned elastic and collagen fibres covered with overlying endothelium. Beneath the atrialis is the spongiosa layer which largely consists of an extracellular matrix, or ground substance, of proteoglycans and glycosaminglycans, along with elastic fibres. This layer is the major component of the free edge. The glycosaminglycans and proteoglycans are hydrophilic and attract water molecules. This characteristic causes the ground substance to expand and swell at the free edge, providing a natural physical protective buffer to the leaflet along the point of apposition to offset the effect of leaflet closure at the free edge. Beneath the spongiosa is the fibrosa layer. It is the major load-bearing layer, comprising the central structural collagenous core of the leaflet. The collagen fibres are compact and aligned providing strength and stiffness to the leaflet and are surrounded by glycosaminoglycans and proteoglycans. The fibrosa layer is situated nearest to the ventricular surface of the leaflet that faces the greatest pressure during valve closure. This layer extends from the annulus into two-thirds of the leaflet; it is absent at the free edge. The final layer of the mitral leaflet is the ventricularis, which is covered by a continuous sheet of endothelial cells that overlie elastic fibres and collagen fibres. The thickness of each layer varies from the attachment site at the annulus to the free edge. At the proximal region of the leaflet, near the annulus, the fibrosa is the thickest layer but it becomes thinner towards the free edge of the leaflet and is totally absent at the edge. The spongiosa and atrialis layers increase in thickness distally becoming the main component of the leaflet at the free edge.

Myocardial cells from the atrium do extend a short distance into the base of the mitral leaflet supporting the leaflet. However, there is no myocardial continuity between the atrial and ventricular walls in the normal leaflet. At the atrioventricular junction, fibrofatty tissues interpose around the circumference. A complete cord-like fibrous ring as implied by the term ‘annulus’ seldom exists.... At this fibrous–myocardial junction where the leaflet inserts, there are a number of smooth muscle cells associated with veins and arterioles. These vessels are confined to the base of the leaflet.......

2).Myxomatous degeneration of the cardiac valves (MDMV) stands for the non-inflammatory progressive disarray of the valve structure caused by a defect in the mechanical integrity of the leaflet due to the altered synthesis and/or remodeling by type VI collagen. The gross morphologic features are characterized by voluminous and thickened leaflets, in both longitudinal and transversal axes. This entity involves not only the valve but also the chordae tendineae that has also become thickened, elongated, and sometimes ruptured. Additionally, MDMV mostly involves the posterior leaflet, usually in the absence of commissural fusion and with a normal or enlarged annulus. Histologically, MDMV is characterized by thickening and proliferation of the spongiosa with pooling of glycosaminoglycan that expands to the fibrosa, giving the appearance of cystic spaces and less dense collagen. Common alterations include fragmentation of the collagen of the fibrosa layer, and the presence of disrupted, fragmented, and granular elastic fibers forming an amorphous clump..... The most frequent complication of myxomatous valvular disease is the mitral valve prolapse (MVP), defined as the atrial bulging of the mitral leaflets of more than 2 mm during systole beyond the annular plane, a valvular thickening of ≥3 mm and/or ruptured chordae tendineae.

3).The systolic type of murmur associated with mitral valve is best heard at the apex with radiation to the left axilla. Mitral regurgitation is observed in patients with infective endocarditis, chronic rheumatic heart disease, degenerative valve disease, Ehlers-Danlos syndrome, Marfan syndrome, and systemic lupus erythematosus. ....MVP presents as an early systolic click heard best at the apex. It often is accompanied by a late systolic murmur indicative of mitral regurgitation occurring after mitral valve prolapse

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