Selected Arterial and Venous Diseases
Case 1 -
Congenital Stenosing Arteriopathy with Medial Dysplasia
Alan G. Rose
This 2.5-year-old female presented with convulsions and was investigated for systemic hypertension
(160/100 mm Hg). Physical examination showed retarded milestones, normal height and weight plus a
cardiac systolic murmur and bruit over both carotid arteries. Femoral pulses were equal and there was no
radiofemoral delay. Chest radiography showed clear lung fields with left ventricular enlargement. Renal
function was normal with no elevation of urinary vanillyl mandelic acid. Normal intravenous pyelogram.
An aortogram showed bilateral renal arterial stenosis. The patient collapsed and died less than 10
minutes after the aortogram was completed.
Autopsy revealed concentric hypertrophy of the left ventricle with subendocardial replacement
fibrosis. Fresh infarction was absent. Both coronary ostia had narrow, pinhole orifices (90%
narrowing). Cardiac valves were normal. Luminal narrowing caused by mural thickening of the coronary
arteries affected the proximal 2 cm of the left coronary artery and involved only 0.8 cm of the right
The entire aorta throughout its course was greatly thickened (Figures 1–3) with a much-reduced
internal diameter. At the level of the diaphragm the aortic internal diameter was only 5.0 mm and the
aortic wall was 2.7 mm thick. Diffuse arterial thickening extended from the aorta into both common iliac
arteries as far as their bifurcation points. The diffuse aortic thickening caused severe stenosis of the
origins of all of its branches, e.g. innominate artery, carotid arteries, subclavian arteries, superior
and inferior mesenteric arteries, celiac artery, and both renal arteries. These arteries showed variable
lengths of thickening. An aortogram showed that the superior mesenteric artery gave rise to an abnormal,
large artery, which passed anteriorly to the left kidney to reach the colonic splenic flexure where it
joined a branch of the superior mesenteric artery to form an arterial arcade. Pulmonary artery was also
Histology of the aorta (Figures 4-6) showed a mainly normal intima, apart from a few areas of
intimal sclerosis. Arterial mural thickening was mainly due to hyperplasia of the medial lamellar units
(composed of elastin, smooth muscle cells and collagen) with a mean overall total of 129 lamellar units
compared to a mean of about 60 lamellar units in the normal human aorta.  The lamellar units
appeared to be thicker than normal. The outer one-third of the media also showed a disordered, mosaic
pattern. Pulmonary artery showed similar changes.
Case 1 - Figure 4 - Histology of aorta seen in Figure 3
Case 1 - Figure 5 - Disordered pattern of lamellar units in the outer media as well as an overall excessive number of lamellar units
Case 1 - Figure 6 - Disordered pattern of lamellar units in the outer media as well as an overall excessive number of lamellar units
The unique macroscopic and microscopic features of congenital stenotic arteriopathy (CSA) distinguish
it from other forms of arterial dysplasia. Microscopic features of CSA have been seldom
The present case has been previously reportedby Rose et al. 
Despite the small diameter of the aorta, the number of lamellar units is increased. In the present
patient the lamellar units in the disordered outer media appeared thicker than those in the inner media
and in normal control aortas. This patient's aortic arch branches were narrowed by a similar hyperplasia
of medial lamellar units, but the coronary and renal arteries were narrowed due to changes like those of
the intimal fibroplasia form of fibromuscular dysplasia.  These muscular arteries showed
intimal longitudinal smooth muscle hyperplasia plus elastosis.
Table 1 lists the features of autopsied patients with CSA:
Table 1: Autopsied Patients with Congenital Stenotic Arteriopathy
|Authors || Age ||Sex || Aorta || Arch Brs. ||Pulm ||Coronary || Renal ||Other ||Associated Conditions|
|McDonald  || 10 wk || F || + || + || + || || || Iliac || Supra AS|
|Cagle  || 0 || F || + || + || + || || || || CAVC|
| 5 wk || F || + || + || + || +|| || || |
| 7 wk ||F || + || + || + || +|| || || |
| 11 wk ||F || + || + ||+ || +|| || || |
|Rose  ||2.5 yr || F ||+ || + || + || + || +|| Mesenteric|
As indicated in Table 1, some cases of CSA had associated congenital heart disease. The condition may
produce sudden infant death or stillbirth. A marked female predominance has been noted (all patients
thus far have been females). A familial incidence has also been observed. Because of the diffuse nature
of the arterial disease, the options for surgical correction are limited and no adult cases have thus far
Whereas most aortic diseases are characterized by a loss of medial elastic fibers (e.g. cystic
medionecrosis) or a destruction of many lamellar units (aortitis), CSA is characterized by the reverse
situation i.e. an increase in the number of aortic medial lamellar units.
Morphometry in Cardiovascular Disease
- As we have seen, morphometry of lamellar unit hyperplasia is important in recognition of the underlying abnormality in congenital stenosing arteriopathy.
- It is also important in the accurate assessment of the degree of atherosclerotic narrowing of a coronary artery since during life the residual arterial lumen will be fully distended in the form of a perfect circle in the transverse plane. The circumference of the internal elastic lamina is measured as representing the original lumen of the artery and the circumference of the residual lumen is also measured. Using a simple formula both circumferences are converted into the corresponding perfect circles and the relative areas are compared. The degree of narrowing obtained is usually less severe than the impression formed by pathologic ocular examination only.
- Muscle fiber diameter has also been assessed in a wide variety of conditions and it has been claimed to help in distinguishing various myocardial diseases. 
- The so-called caliber persistent artery is a condition where size and situation of an artery is important in diagnosis. Here one has an artery which is too large for its location due to lack of a normal branching pattern. The condition, which is under- diagnosed, is most often recognized in the gastric mucosa where erosion may lead to fatal hemorrhage (Dieulafoy's erosion).
Review of the Pathology of Fibromuscular Dysplasia (Fmd)
A synonym is fibromuscular hyperplasia. FMD is defined as a developmental vascular anomaly of
medium-sized and small arteries, and rarely veins,  in which the vessel wall is altered by
dysplasia, hypoplasia, and/or hyperplasia of the fibromuscular components usually in the media, rarely in
the intima or adventitia (< 5%), causing stenosis, aneurysm formation, or medial
dissection.  The condition is commonest in females of child-bearing age, but involves all
ages, including children. [6 ]FMD occurs most often in the renal arteries of young women,
followed in frequency of occurrence by the internal carotid arteries, visceral arteries, and rarely, the
coronary arteries. Three main morphologic types are recognized: medial hyperplasia (about 95%), intimal
fibroplasia (2%), and adventitial fibroplasia (about 2%). Medial hyperplasia is sometimes subdivided in
turn into 3 variants: medial fibroplasia, medial hyperplasia and perimedial fibroplasia. Examples of
each of these forms of FMD will be demonstrated.
Grossly or on angiography the appearance of the commonest form of FMD (medial hyperplasia/ medial
fibroplasia) is that of a segmental, irregular, string of beads or corkscrew pattern, which may mimic the
appearance of a vasculitis. Contrary to histologic examination of virtually all other blood vessels, the
artery or vein should be sectioned longitudinally rather than transversely
for microscopy in order to recognize the condition most effectively. This orientation allows for
recognition of the characteristic hill and valley type corrugations of the vessel wall. Elastic van
Gieson or Movat's pentachrome staining is mandatory in this condition.
There is an association between FMD and the development of cerebral berry aneurysms. FMD is a
potentially curable cause of systemic hypertension. Other complications include dissecting aneurysm
(sometimes no intimal tear is present), thromboemboli from the saccular aneurysms in FMD, and sudden
death due to narrowing of the artery to the atrioventricular node.
The etiology of FMD remains uncertain, although hormonal causes are considered important in view of
the sex incidence. Other postulated etiologic factors include arterial mural ischemia, primary
developmental disorder of the multifunctional arterial medial cell and even viral infection. FMD has
been treated by surgery and transluminal angioplasty.
Williams syndrome, which is characterized by hypercalcemia, supravalvular aortic stenosis, elfin
facies, and mental retardation, may also show peripheral vascular disease including renal artery
stenosis, diffuse narrowing of the aorta and aortic coarctation. Coronary arterial stenosis may lead to
myocardial infarction. The possibility of abnormal elastic fibers has been raised. 
Other Conditions Associated with Arterial Dissection or Rupture
Arterial rupture or dissection is usually associated either with systemic hypertension or cystic
medionecrosis of the aortic media. In addition to fibromuscular dysplasia, there are a number of other
conditions that may also predispose to these serious complications. These include segmental mediolytic
arteriopathy, Ehlers-Danlos syndrome and scurvy amongst others.
- Cystic medionecrosis.
Cystic medionecrosis (CMN) is a misnomer since no true cysts and no necrosis is present. The condition is an accompaniment of aging in the aorta and is present in the aorta in young patients with Marfan syndrome and its forme fruste. Deposits of acid mucopolysaccharides replace lost aortic lamellar units. CMN favors the development of dissection or rupture of the aorta. Marfan patients have mutations in FBN1 (fibrillin gene) on chromosome 15q21 and an autosomal dominant transmission occurs. New mutations comprise 25% of patients with Marfan syndrome. Marfan syndrome may produce severe neonatal pulmonary emphysema (see Case 4), as well as floppy mitral valve and aortic root dilatation. The differential diagnosis of Marfan syndrome in the young includes congenital contractual arachnodactyly, homocystinuria, Shprintzen-Goldberg syndrome, and familial aortic aneurysms and dissections.
- Segmental mediolytic arteriopathy.
Segmental mediolytic arteriopathy (SMA), also termed segmental mediolytic arteritis or arterial mediolysis, is defined as a peculiar noninflammatory lesion of arteries, particularly the visceral arteries, and rarely the coronary arteries, that is characterized by focal lytic changes (vacuolation, mucoid degeneration) of the arterial wall that may result in arterial wall hemorrhage or dissection and thrombosis. Gross findings reflect the pattern of arterial involvement and may include ischemic bowel disease, and visceral or myocardial infarction. Microscopy is characterized by focal, segmental, medial lytic changes (vacuolation, mucoid degeneration) of arteries that may lead to mural tearing, rupture or dissection. Although the entity was originally described by Slavin  in 1976, the etiology and pathogenesis of SMA remain unknown. Both (i) an inappropriate vasospastic response to shock or severe hypoxemia, and (ii) a variant of arterial fibromuscular dysplasia  have been suggested as causes. Immune complex disease and a link to systemic lupus erythematosus has also been postulated.  Most reported cases have been in elderly patients, although a histologically similar condition occurs in hypoxic neonates.
- Ehlers-Danlos syndrome (EDS)
The first comprehensive description of a syndrome of laxity and fragility of the skin associated with hypermobile large joints was published by Tschernogobow  in Moscow in 1892. However, the names of a Danish and of a French dermatologist have been used in the eponym for this syndrome. EDS is a heritable disorder of connective tissue having at least 11 subgroups with different clinical manifestations, biochemical defects, and inheritance patterns. Vascular disease is a feature of type IV, the so-called "arterial-ecchymotic" variant, which has a dominant inheritance with about half of the patients being new mutations. The molecular basis for the pathogenesis of Ehlers-Danlos syndrome type IV is believed to be that patients who are heterozygous for mutations in COL3A1 that do not cause premature chain termination produce about equal amounts of normal and abnormal type III procollagen polypeptides.  These interact to form the homotripolymer type III procollagen protein. However, only 1/8 of the proteins will contain three normal polypeptides, whereas the other 7/8 will contain at least one mutant polypeptide and will function abnormally. Type IV EDS results from an abnormality of type III collagen.
Pepin et al.  state that although most affected patients survive the first and second major complications, EDS type IV results in premature death. The diagnosis should be considered in young people who come to medical attention because of uterine rupture during pregnancy or arterial or visceral rupture. In the 419 subjects they studied there were 272 arterial complications of which about half involved the thoracic or abdominal arteries. The most common non-lethal CNS events were fistulae involving the carotid artery, carotid artery dissection, aneurysm and rupture. Twelve women died during the peripartum period (5 of uterine rupture during labor, 2 of vessel rupture at delivery, and 5 of postpartum vessel rupture).
Gross findings of EDS include single or multiple arterial aneurysms, with or without rupture or dissection, affecting aorta, peripheral, visceral and pulmonary arteries. Visceral rupture may also occur repeatedly. Microscopy shows variable degrees of medial degeneration, morphologically indistinguishable from that of Marfan syndrome, cystic medionecrosis and aging. Confirmation of the diagnosis depends on analysis of connective tissue for type III collagen (which is deficient in type IV EDS) and on demonstration of decreased production of type III procollagen by cultured fibroblasts.
Metabolic abnormalities do not always produce morphologically recognizable changes despite greatly decreased structural strength in a blood vessel. We have encountered a scorbutic (vitamin C deficient) ballet dancer whose femoral artery was ruptured by the thumb of her male dancing partner who caught her thighs in his hands. A small sample of the ruptured artery appeared normal histologically.
Vascular Elastosis: A Cause of Intestinal Ischemia in Patients with Ileal Carcinoid Tumors
Carcinoid tumors of the ileum may be associated with gangrene of the small intestine and some such
patients show a unique vascular lesion in the large mesenteric vessels lying close to tumor infiltrated
lymph nodes. The changes, which affect both arteries and veins, comprise pronounced adventitial and
intimal elastification leading to luminal narrowing.  There is no sign of thrombosis or
tumor infiltration. Local release of an elastogenic substance by the tumor is the likely basis of this
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