Histopathology of the spiral arteries in preeclampsia

In the previous paragraphs spiral artery histology near term, as resulting from trophoblast action on the arterial wall, was presented as a black-and-white picture: either a trophoblast had invaded the arteries and these had undergone physiological changes, or a trophoblast had not invaded and the vessels had maintained their ''normal'' vascular architecture, except for the occasional development of atherosis. Such black-and-white schemes do not always represent the reality. To begin with, physiological changes may not involve the whole circumference and may be restricted to only a limited sector of a vessel. Such a situation has been referred to as "partial" change. Sometimes only a few isolated trophoblastic cells can be seen in the arterial wall. In vessels with partial invasion we can obtain a good idea of the local effects of the endovascular trophoblast on vessel wall structure. In such cases the complete removal of media smooth muscle and elastica and its replacement by trophoblast and fibrinoid are immediately obvious, in contrast to the non-invaded sectors of the spiral artery (Figures 1.3a—d). The presence of PAS-positive fibrinoid, which is associated with endovascular invasion from early stages onwards, is thereby very helpful for delineating the extent of physiological change as induced by early endovascular invasion.

Decidual And Myometrial Arteries

Figure 1.3 (a) Myometrial spiral artery near term showing partial physiological change. Trophoblast invasion and vascular incorporation is restricted to the lower side of the vessel. Cytokeratin immunostaining (bar = 100 mm). (b) Same artery, showing fibrinoid deposition at the lower side of the vessel. PAS staining. (c) Same artery, showing a-actin immunostaining. Smooth muscle cells have disappeared from the invaded area of the vessel wall. (d) Same artery, showing elastica (Es) staining. No elastica is present at the lower side of the vessel. Orcein staining.

Figure 1.3 (a) Myometrial spiral artery near term showing partial physiological change. Trophoblast invasion and vascular incorporation is restricted to the lower side of the vessel. Cytokeratin immunostaining (bar = 100 mm). (b) Same artery, showing fibrinoid deposition at the lower side of the vessel. PAS staining. (c) Same artery, showing a-actin immunostaining. Smooth muscle cells have disappeared from the invaded area of the vessel wall. (d) Same artery, showing elastica (Es) staining. No elastica is present at the lower side of the vessel. Orcein staining.

As explained in a previous section, the invaded spiral arteries of the third trimester show restoration of the maternal endothelial layer, which must have been penetrated by a trophoblastic cells previously. In this matter there is confusion in the recent literature, as it is often mentioned that the endovascular trophoblast replaces the endothe-lium, and it is then usually understood that this is the case until the end of pregnancy. Because of the histological features of physiologically changed spiral arteries such ''endothelial replacement' can at the most be a temporary situation, restricted to the first or early second trimester. Another matter of confusion is the claim that the trophoblast may express endothelial cell markers during its endo-vascular invasion (Zhou et al., 1997a), which may thereby be an important factor in the so-called endothelial replacement. Expression of vascular endothelial markers by trophoblast could not be confirmed by other investigators, however (Lyall et al., 2001a; Pijnenborg et al., 1998a), and also a possible defective expression in pre-eclamptic women needs further confirmation (Zhou et al., 1997b).

Spiral Arteries PreeclampsiaSpiral Arteries

Figure 1.4 (a) Physiologically changed spiral artery, showing marked leukocytic infiltration. Cytokeratin immunostaining (bar = 100 mm). (b) Same vessel, showing swelling of infiltrated leukoytes, which are probably being converted into foam cells ("Fc") (bar = 50 mm). (c) Physiologically changed spiral artery near the basal plate. A few foam cells (Fc) are present between intramural trophoblastic cells. Cytokeratin immunostaining (bar = 100 mm). (d) Spiral artery with acute atherosis, containing foam cells (Fc) within a necrotic wall. Remnants of trophoblast (T) are present within the necrotic wall. Cytokeratin immunostaining (bar = 100 mm). (e) Myometrial spiral artery without physiological change, showing muscular hyperplasia. a-Actin immunostaining (bar = 100 mm). (f) Same vessel. Perivascular trophoblastic cells are present, presumably derived from the interstitial pathway of invasion. Cytokeratin immunostaining.

Figure 1.4 (a) Physiologically changed spiral artery, showing marked leukocytic infiltration. Cytokeratin immunostaining (bar = 100 mm). (b) Same vessel, showing swelling of infiltrated leukoytes, which are probably being converted into foam cells ("Fc") (bar = 50 mm). (c) Physiologically changed spiral artery near the basal plate. A few foam cells (Fc) are present between intramural trophoblastic cells. Cytokeratin immunostaining (bar = 100 mm). (d) Spiral artery with acute atherosis, containing foam cells (Fc) within a necrotic wall. Remnants of trophoblast (T) are present within the necrotic wall. Cytokeratin immunostaining (bar = 100 mm). (e) Myometrial spiral artery without physiological change, showing muscular hyperplasia. a-Actin immunostaining (bar = 100 mm). (f) Same vessel. Perivascular trophoblastic cells are present, presumably derived from the interstitial pathway of invasion. Cytokeratin immunostaining.

The process of endothelial repair may be associated with different degrees of intimal thickening, which involves proliferation of fibroblasts and the appearance of myo-intimal cells. Since the latter are immunopositive for a-actin, the occurrence of such cells may confuse inexperienced histologists who expect complete disappearance of smooth muscle in physiologically changed spiral arteries (Figures 1.1a—c). Physiologically changed vessels with thick intimal cushions can be found in decidual and myometrial spiral artery segments in normal pregnancies, but also in decidual invaded arteries in pre-eclamptic women. There is no evidence for a higher incidence of intimal thickening in decidual spiral arteries in pre-eclamptic compared to normal pregnancies, precluding more extensive maternal repair responses in pre-eclampsia (Hanssens et al., 1998). In some situations intimal thickening, comprising the whole circumference of the vessel, may be so intense, even in normal pregnancies, that it leads to a narrowing of the vascular lumen, giving the false impression of a pathological lesion. A consistent observation is that with partial or isolated physiological change, intimal cushions are almost always overlying vascular sectors containing invaded trophoblast and fibrinoid (Figure 1.1d).

In the absence of trophoblast and physiological changes, spiral arteries retain an essentially normal architecture, in the sense that there is an intact medial smooth muscle layer. Nevertheless, as mentioned before, subtle changes have been noted to occur in such vessels (Pijnenborg et al., 1991). One such feature is the occurrence of endothelial vacuolation. Furthermore, the media often shows disorganization, resulting in a loosely structured rather than a tightly packed muscle layer. Occasionally, the media may even become split into two layers, which may be separated by a ''hyaline'' substance, which may reflect alterations in the extracellular matrix. In addition, marked medial hyperplasia may occur, which may lead to extreme narrowing or even a virtual obliteration of the arterial lumen (Figures 1.4e,f). It is not clear at what gestational age these changes take place, which are obviously not associated with the trophoblast-related physiological change. As suggested in the previous section, media disorganization may reflect the early spiral artery remodeling preceding endovascular invasion in the first trimester, which is related to the presence of an interstitial trophoblast (Pijnenborg etal., 1983). It is possible, but hard to prove, that completely unaltered vessels at term are those that did not respond to interstitial trophoblast in the first trimester, but of course early changes may have become reversed later in pregnancy. Media hyper-plasia is usually thought to result from increased blood pressure, and is therefore likely to occur more frequently in chronic hypertensive women. Endothelial vacuolation is a feature not exclusively related to the placental bed, as it also occurs in the decidua vera (Pijnenborg et al., 1983). It has been argued recently that the decidualization process, which forms a necessary prelude to a well-developing pregnancy, should not be viewed exclusively as a feature of the endometrial stroma, but also involves vascular alterations such as endothelial vacuolization or early media disorganization in the inner myometrium. Indeed, there is evidence that the inner myometrium differs structurally and functionally from the outer myome-trium, showing different responsiveness to steroid hormones, and therefore rather forms a functional unit with the decidua (Brosens et al., 2002). It has been speculated that in some women early decid-ual changes of the inner myometrium may be defective from the very beginning, and thus determine pregnancy outcome from the implantation period onwards. The observation that pre-eclamptic women show a higher degree of clustering of separate spiral arteries (Starzyk et al., 1997) may indeed reflect defective decidualization resulting from ineffective extracellular matrix changes and/or disturbed myometrial growth response to steroid hormones. It will not be easy, however, to distinguish systemic steroid effects from the local effects of interstitially invading trophoblast.

A completely different pathological event is the development of acute atherosis. Atherosclerotic-like fibrinoid necrosis with infiltration of lipid-laden foam cells represents the histopathological characteristics of this lesion, which in pregnancy-induced hypertension develops over a shorter time period than the typical hypertension-related vasculopathies in non-pregnant women. Various plasma proteins have been shown to accumulate in atherotic spiral artery walls, suggesting excessive vascular leakage. There is marked deposition of fibrin, showing analogy with the ''plasmatic vasculosis" described by Lendrum (1963) in diseased kidneys. Other plasma protein accumulations such as immunoglobulins, complement components (Kitzmiller and Benirschke, 1973; Labarrere, 1988) and fibronectin (Pijnenborg et al., 1992) have been detected in such vessels. Meekins and colleagues (1994b) pointed out that lipoprotein(A) deposition is an early indicator of atherotic change, but can also be found at low concentrations in normal-looking physiologically changed spiral arteries. The pathogenesis of acute atherosis is still unknown, but an immunological element has often been suspected. Robertson and colleagues (1967) pointed out the histological resemblance of acute atherosis to vascular lesions in rejected kidney allografts, which would suggest some similarity with a delayed maternal hypersensitivity response, possibly directed to fetal antigens. Infiltration of macrophage-derived foam cells sometimes occurs in physiologically changed spiral arteries containing mural trophoblasts (McFadyen etal., 1986; Meekins et al., 1994a) (Figure 1.4c) and, vice versa, cytoker-atin-positive cell remnants, doubtless of tropho-blastic origin, are occasionally found in the wall of atherotic arteries (Hanssens et al., 1998; Meekins etal., 1994a) (Figure 1.4d). On the other hand, acute atherosis also occurs in spiral arteries in the decidua vera, thus in the absence of trophoblasts (Robertson etal., 1986), and this will need further investigation. Atherotic vessels in the placental bed are associated with infarction in the overlying placental regions (Brosens and Renaer, 1972). Extensive placental infarction could seriously interfere with proper placental function. It is, however, important to remember that acute atherosis only occurs in a relatively small number of placental bed spiral arteries (Khong and Robertson, 1992), and that placental infarctions are usually restricted in extent, so that the negative effects can normally be met by the high reserve capacity of the placenta. In our own collection of placental bed biopsies of pre-eclamptic women the incidence of acute atherosis in a biopsy containing at least one spiral artery is on average 30% (Pijnenborg et al., unpublished results). Another aspect of possible importance is the depth of atherosis in the placental bed: in the majority of cases this lesion is found within the spiral arteries of the decidua basalis only, while an extension to the myometrium seems to be indicative for a more severe situation, as shown in the next section.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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