Revistă de Medicină şi Farmacie - Clujul Medical - Iuliu Haţieganu

Revistă de Medicină şi Farmacie - Clujul Medical - Iuliu Haţieganu Revistă de Medicină şi Farmacie - Clujul Medical - Iuliu Haţieganu

clujulmedical.umfcluj.ro
from clujulmedical.umfcluj.ro More from this publisher
10.11.2014 Views

336 Patologie ginecologică produced within the neighboring endothelial cells. Among these mediators, prostaglandins have been shown to be produced within the umbilical vascular endothelium [11]. Some authors observed similar defective prostacyclin production of umbilical arterial response in cords delivered to cigarette smoking mothers. Another vasodilator that has attracted much attention is nitric-oxide identical with the endothelium-derived relaxing factor, which is produced from the conversion of L-arginine to citrulline by nitric oxide synthase (NOS). This enzyme has been detected immunohistochemically not only in villous syncytiotrophoblast, but also in fetal villous and umbilical endothelium. A reduction in this enzyme’s activity has been correlated with abnormal umbilical artery waveforms [12]. Atrial natriuretic peptide (ANP) is another potent vasodilator that additionally seems to be involved in fetal fluid hemostasis. Its binding sites have been detected in umbilical smooth muscle cells. Immunoreactivity for the peptide itself and its messenger RNA have been found in the umbilical endothelium. Vasoconstrictor substances found in umbilical endothelium comprise angiotensin II, 5-hydroxytryptamine (5-HT) and thromboxane, neuropeptide Y (NPY), as well as endothelin-1. Bindings sites for endothelin-1 have been described in the media of umbilical vessels, the activity of the arteries exceeding that of the vein. The functions of these vasoconstrictors are still under discussion [13]. Immature vessels were more sensitive to angiotensin II, arachidonic acid, and oxytocin; term vessels reacted more to vasopressin, norepinephrine, PGD 2 , and PGE 2 . These findings shed new light on the highly complex mechanisms of autoregulation, not only of the umbilical circulation, but also of the villous circulation, as most of these mediators have been described also in the walls of the larger chorionic and villous vessels. Further studies will have to elucidate the complicated interactions of these substances, as they are very likely to be involved in abnormal conditions, such as intrauterine growth restriction (IUGR) and a high Doppler resistance index. In the media, smooth muscle cells are normally structured, fusiform, with dens cytoplasm and the nucleus positioned in the central area. The muscular coat of the arteries consists of a system of crossing spiraled fibres. Desmin – positive smooth muscle cells are largely concetrated on the outer layer of the media. In contrast the inner media smooth mescle cells are poorly differentiated with few myofilaments. They can contribute actively to postpartal closure of the cord arteries [14]. At the umbilical arteries hyaluronic acid was increased, whereas heparan sulfate and chondroitin 4 and 6 sulfate were reduced in normal umbilical arteries as compared to normal adult systemic arteries. The adventitia, which is a heterogeneous layer, is also predominantly formed by connective tissue with fibrocytes Clujul Medical 2009 Vol. LXXXII - nr. 3 intercalated with smooth muscle cells, nerves and collagen fibers. There are not vasa vasorum, or nerves. Ultrastructural aspects in pregnancy complicated by severe preeclampsia In severe preeclampsia, all the layers of the umbilical arterial wall are affected. The endothelium undergoes alterations that can result in the loss of its cells, with serious consequences on the entire arterial wall. All endothelial cells are columnar, with reduced cytoplasm and many vacuolizations, and the nuclei are elongated along the cell axis (Fig. 9). The number of endothelial cells gradually decreases, both by the loss of nuclei and the complete detachment of cells and their fall into the lumen, which results in the presence of areas without endothelial cells [15,16]. Fig. 9. All endothelial cells are columnar, with reduced cytoplasm and many vacuolizations, and the nuclei are elongated along the cell axis. In parallel to these endothelial alterations, profound structural disorganization changes occur in the media and adventitia of the umbilical artery. Smooth muscle cells undergo shape and structure changes, they are distorted or segmented. Their cytoplasm is altered, reduced, and nuclei become pyknotic. Concomitantly with these alterations, generalized edema occurs, with the formation of large spaces filled with fluid or vesicular formations containing material that is probably of lipoprotein nature [17] (Fig 10, 11). Fig. 10. Interfibrillar spaces are large and contain numerous vacuolar formations.

Articole de orientare At adventitial level, the external elastic lamina seems to lack structure, being clear, non-electron dense (Fig. 13). The connective tissue is scarce, with disorderly collagen fibers and partially altered structure. Fibrocytes are also completely inactive, having a profoundly altered structure. Few macrophages are still active (Fig. 14). Fig. 11. Interfibrillar spaces are large and contain numerous vacuolar formations. Under certain, usually pathological, conditions, the contraction of muscle cells in the media and implicitly, of cells in the system concerned, results in a movement of the muscle cell cytoplasm towards endothelial cells, which are driven to the lumen, so that their apical area undergoes a slight bulbous dilation. As a result, the diameter of the arterial lumen is reduced and implicitly, the blood flow is diminished [18]. In some areas of the media, the material accumulated between the smooth muscle cells (at interfibrillar level) occupies large spaces, and vesicular formations are accompanied by fragments of destroyed muscle cells and even macrophages (Fig. 12). Fig. 13. The external elastic lamina seems to lack structure, being clear, non-electron dense. Fig. 12. Between the smooth muscle cells there are macrophages. In pregnancy complicated by severe preeclampsia the total glycosaminoglycan and colagen content of the umbilical arteries were reduced. These changes were unliked to impair the hemodynamic properties if the cord vessels [19]. The vessels of patients with preeclampsia, growth-retarded fetuses, and diabetes, as well as those of smoking mothers, show reduced prostacyclin production. Degeneration of endothelium from umbilical vessels had earlier been shown to occur in smoking mothers [3]. Although it is attractive to consider that prostaglandins are the principal mediators of umbilical vascular responses, some evidence has been adduced. Clujul Medical 2009 Vol. LXXXII - nr. 3 Fig. 14. At adventitial level, the connective tissue is scarce, with disorderly collagen fibers, inactive fibrocytes and few active macrophages. The pathophysiological changes evidenced in this case of severe preeclampsia suggest a marked vasoconstriction of both maternal and fetal blood circulation, resulting in the reduction of placental blood flow. As a consequence of these phenomena, vascular permeability increases, which will cause edema, both at subendothelial level and especially in the entire tunica media, with alterations including the destruction of smooth muscle cells and fibroblasts in the tunica adventitia, as well as endothelial damage [20]. The increase in arterial wall permeability and the induction of marked edema lead to the decrease of blood flow in the lumen, both by the reduction of the diameter of the lumen and the diffusion of blood plasma to the vascular wall [21]. The increase in arterial wall permeability probably results in an increase in the amniotic fluid volume produced by transudation, which may cause an increased pressure in 337

336<br />

Patologie ginecologică<br />

produced within the neighboring endothelial cells. Among<br />

these mediators, prostaglandins have been shown to be<br />

produced within the umbilical vascular endothelium [11].<br />

Some authors observed similar <strong>de</strong>fective prostacyclin<br />

production of umbilical arterial response in cords <strong>de</strong>livered<br />

to cigarette smoking mothers.<br />

Another vasodilator that has attracted much attention<br />

is nitric-oxi<strong>de</strong> i<strong>de</strong>ntical with the endothelium-<strong>de</strong>rived<br />

relaxing factor, which is produced from the conversion<br />

of L-arginine to citrulline by nitric oxi<strong>de</strong> synthase (NOS).<br />

This enzyme has been <strong>de</strong>tected immunohistochemically not<br />

only in villous syncytiotrophoblast, but also in fetal villous<br />

and umbilical endothelium. A reduction in this enzyme’s<br />

activity has been correlated with abnormal umbilical artery<br />

waveforms [12].<br />

Atrial natriuretic pepti<strong>de</strong> (ANP) is another potent<br />

vasodilator that additionally seems to be involved in fetal<br />

fluid hemostasis. Its binding sites have been <strong>de</strong>tected in<br />

umbilical smooth muscle cells. Immunoreactivity for the<br />

pepti<strong>de</strong> itself and its messenger RNA have been found in<br />

the umbilical endothelium.<br />

Vasoconstrictor substances found in umbilical<br />

endothelium comprise angiotensin II, 5-hydroxytryptamine<br />

(5-HT) and thromboxane, neuropepti<strong>de</strong> Y (NPY), as well<br />

as endothelin-1. Bindings sites for endothelin-1 have been<br />

<strong>de</strong>scribed in the media of umbilical vessels, the activity of<br />

the arteries exceeding that of the vein. The functions of<br />

these vasoconstrictors are still un<strong>de</strong>r discussion [13].<br />

Immature vessels were more sensitive to angiotensin<br />

II, arachidonic acid, and oxytocin; term vessels reacted<br />

more to vasopressin, norepinephrine, PGD 2<br />

, and PGE 2<br />

.<br />

These findings shed new light on the highly<br />

complex mechanisms of autoregulation, not only of the<br />

umbilical circulation, but also of the villous circulation, as<br />

most of these mediators have been <strong>de</strong>scribed also in the<br />

walls of the larger chorionic and villous vessels. Further<br />

studies will have to elucidate the complicated interactions<br />

of these substances, as they are very likely to be involved<br />

in abnormal conditions, such as intrauterine growth restriction<br />

(IUGR) and a high Doppler resistance in<strong>de</strong>x.<br />

In the media, smooth muscle cells are normally<br />

structured, fusiform, with <strong>de</strong>ns cytoplasm and the nucleus<br />

positioned in the central area. The muscular coat of the<br />

arteries consists of a system of crossing spiraled fibres.<br />

Desmin – positive smooth muscle cells are largely<br />

concetrated on the outer layer of the media. In contrast the<br />

inner media smooth mescle cells are poorly differentiated<br />

with few myofilaments. They can contribute actively to<br />

postpartal closure of the cord arteries [14].<br />

At the umbilical arteries hyaluronic acid was<br />

increased, whereas heparan sulfate and chondroitin 4 and<br />

6 sulfate were reduced in normal umbilical arteries as<br />

compared to normal adult systemic arteries.<br />

The adventitia, which is a heterogeneous layer, is also<br />

predominantly formed by connective tissue with fibrocytes<br />

<strong>Clujul</strong> <strong>Medical</strong> 2009 Vol. LXXXII - nr. 3<br />

intercalated with smooth muscle cells, nerves and collagen<br />

fibers. There are not vasa vasorum, or nerves.<br />

Ultrastructural aspects in pregnancy complicated<br />

by severe preeclampsia<br />

In severe preeclampsia, all the layers of the umbilical<br />

arterial wall are affected.<br />

The endothelium un<strong>de</strong>rgoes alterations that can<br />

result in the loss of its cells, with serious consequences on<br />

the entire arterial wall. All endothelial cells are columnar,<br />

with reduced cytoplasm and many vacuolizations, and<br />

the nuclei are elongated along the cell axis (Fig. 9). The<br />

number of endothelial cells gradually <strong>de</strong>creases, both by<br />

the loss of nuclei and the complete <strong>de</strong>tachment of cells and<br />

their fall into the lumen, which results in the presence of<br />

areas without endothelial cells [15,16].<br />

Fig. 9. All endothelial cells are columnar, with reduced cytoplasm<br />

and many vacuolizations, and the nuclei are elongated along the<br />

cell axis.<br />

In parallel to these endothelial alterations, profound<br />

structural disorganization changes occur in the media and<br />

adventitia of the umbilical artery. Smooth muscle cells<br />

un<strong>de</strong>rgo shape and structure changes, they are distorted or<br />

segmented. Their cytoplasm is altered, reduced, and nuclei<br />

become pyknotic. Concomitantly with these alterations,<br />

generalized e<strong>de</strong>ma occurs, with the formation of large<br />

spaces filled with fluid or vesicular formations containing<br />

material that is probably of lipoprotein nature [17] (Fig 10,<br />

11).<br />

Fig. 10. Interfibrillar spaces are large and contain numerous<br />

vacuolar formations.

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!