Lamina Elastica Interna Research Articles

Gelsolin amyloid angiopathy causes severe disruption of the arterial wall

Hereditary gelsolin amyloidosis (HGA) is a dominantly inherited systemic disease reported worldwide. HGA is characterized by ophthalmological, neurological, and dermatological manifestations. AGel amyloid accumulates at basal lamina of epithelial and muscle cells, thus amyloid angiopathy is encountered in nearly every organ. HGA patients have cardiovascular, hemorrhagic, and potentially vascularly induced neurological problems. To clarify pathomechanisms of AGel angiopathy, we performed histological, immunohistochemical, and electron microscopic analyses on facial temporal artery branches from 8 HGA patients and 13 control subjects. We demonstrate major pathological changes in arteries: disruption of the tunica media, disorganization of vascular smooth muscle cells, and accumulation of AGel fibrils in arterial walls, where they associate with the lamina elastica interna, which becomes fragmented and diminished. We also provide evidence of abnormal accumulation and localization of collagen types I and III and an increase of collagen type I degradation product in the tunica media. Vascular smooth muscle cells appear to be morphologically and semi-quantitatively normal, only their basal lamina is often thickened. In conclusion, angiopathy in HGA results in severe disruption of arterial walls, characterized by prominent AGel deposition, collagen derangement and severe elastolysis, and it may be responsible for several, particularly hemorrhagic, disease manifestations in HGA.

Does extracellular matrix of the varicose vein wall change according to clinical stage?

The etiology and pathophysiology of chronic venous disease is not fully understood. This study aimed to determine the variation of the extracellular matrix proteins in varicose vein wall according to clinical stage. Forty varicose and 10 control veins were sampled from the saphenofemoral junction. The Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification was used in patients with varicose veins. Samples were stained with hematoxylin-eosin, Masson's trichrome, EVG (Elastica-van Gieson) stain and with laminin, fibronectin, tenascin antibodies. Stained samples were examined immuno-histochemically. Changes in extracellular matrix were determined semi-quantitatively using light microscopy. It was observed that in the early stages (C2-C3) of chronic venous disease, fibrosis is increased in the intima and media layers, with fragmentation in lamina elastica interna, and increased tenascin expression in the intima layer. In advanced stages (C4-C6), the accumulation of tenascin in the intima continued along with fibrosis in the media layer, the thickness of the media layer increased and fibronectin deposition was observed. This study showed that changes first occur in the intima during the early stages of the disease with addition of alterations in the media layer at later stages.

Spontaneous Thrombosis of a DVA with Subsequent Intracranial Hemorrhage

A 24-year-old man was admitted to the emergency room (er) with impaired consciousness and left-sided hemiplegia. He had suffered from progressive headache and emesis since the day before and had been treated with Acetylsalicylic acid (AsA). The previous medical history was otherwise unremarkable. on admission, a computed tomography (CT) scan demonstrated intraparenchymal hemorrhage in the right temporal and parietal lobe with very marked surrounding hypoattenuation and mass effect (Fig. 1). digital subtraction angiography (dsA) revealed the typical caput medusae aspect of the draining vein in the territory affected by hemorrhage with signs of venous outflow obstruction such as prolonged transition, venous stasis, and a missing central venous collector as a sign for thrombosis of the latter (Fig. 2). The patient was transferred to the neurosurgical or and the hematoma was evacuated via a temporoparietal craniotomy. During the operation, an enlarged superficial vein with obvious signs of thrombosis was found. disproportionate perioperative hemorrhage from the subcortical parenchyma was encountered, but could be controlled by means of resecting a subcortical distended vascular structure, reminiscent of an angioma and connected to the thrombosedcollecting vein (Fig. 3). Histopathological examination revealed a vascular malformation with extensively dilated and thin-walled blood vessels consisting of fibrous tissue; however, lacking a lamina elastica interna. A lamina elastica interna as part of the arterial component would be expected in an arteriovenous malformation (AVM). In this case, the malformated vessels showed only venous characteristics. Its vascular nature was confirmed by immunohistochemical expression of smooth muscle actin, Cd31, and Cd34. Blood vessels were located within a hematoma mainly located in the leptomeninges without evidence for previous hemorrhage. In addition, leptomeningeal blood vessels were attached to fragments of neocortex with reactive astrocytes, fibrillary gliosis, and prominent microglial activation. There was no evidence for an associated cavernoma.

Histopathological analysis of cerebral hemorrhage in systemic lupus erythematosus complicated with antiphospholipid syndrome

A 53-year-old woman was admitted due to akinetic mutism and fever. On admission, brain computed tomography (CT) scan revealed a large hemorrhagic lesion in the left anterior lobe that required surgical operation for total removal. Her neuropsychiatric manifestation was not attenuated after the operation, and was gradually ameliorated by high doses of corticosteroid thereafter, suggesting a diagnosis of lupus psychosis. Histopathological examination revealed a necrotizing vasculature, sometimes with a disrupted lamina elastica interna, completely filled with thrombi and infiltrated with inflammatory cells and their debris. It is therefore suggested that the large frontal lobe hematoma in our patient was induced by thrombosis and arteritis in the subarachnoid space.

A Histochemical Approach to the Diagnosis of Visceral Pleural Infiltration by Non-small Cell Lung Cancer

Although invasion of the visceral pleura (VPI) by non-small cell lung cancer (NSCLC) is a TNM-relevant diagnostic criterion and is known to affect the patients' prognoses, until recently there were no standardized or internationally accepted guidelines. This resulted in a diagnostic ambiguity leading to different tumor staging systems and to hardly comparable patient collectives in research studies world wide. The major problem in this issue is to exactly define what constitutes for the diagnosis of VPI with respect to anatomical landmarks. In order to address this problem we investigated the pleural infiltration depth of 173 NSCLC specimens without lymph node metastases and proven tumor-related death using elastic stains and a scoring system referring to prominent pleural elastic layers, the lamina elastica externa and interna, as anatomical landmarks. Performing comparative Kaplan-Meier survival analyses for each patient collective we could not find any significant difference in the patients' survival. This indicates that a differential evaluation of the tumor infiltration depth according to the elastic layers is not practicable. Our findings support the consequent application of the recently proposed, pragmatic approach of the international staging committee for lung cancer (IASLC) to define an internationally accepted and standardized staging system for VPI.

Structural Differences in the Umbilical Vein Wall after Full-Term and Pre-term Delivery

With the exception of its most proximal segment, the human umbilical cord lacks innervation. It might be expected, therefore, that a paracrine effect through the direct contact between the smooth muscle cells and the endothelium may be particularly important in the control of the fetoplacental circulation. In this study, electron microscopy and immunohistochemistry were applied to examine umbilical veins immediately after full-term and pre-term delivery. The smooth muscle cells in the upper layer of the tunica media exhibited long, foot-like processes with c-kit immunoreactivity. In the umbilical vein of full-term neonates more than 50% of these cell processes display a normal ultrastructure and they were closely associated with the lamina elastica interna. Whereas in pre-term infants more than 60% of these cell processes exhibit signs of severe shrinkage and detachedness from the lamina elastica interna. At the same time, the high level of immunoreactivity of the endothelial cells as regards the proapoptotic gene product Bax in pre-term infants is indicative of an enhanced apoptotic process in these cells.

Local elasticity imaging of vascular tissues using a tactile mapping system

This study aimed to map the elasticity of a natural artery at the micron level by using a tactile mapping system (TMS) that was recently developed for characterization of the stiffness of tissue slices. The sample used was a circumferential section (thickness, approximately 1 mm) of a small-caliber porcine artery (diameter, approximately 3 mm). Elasticity was measured with a probe of diameter 1 microm and a spatial resolution of 2 microm at a rate of 0.3 s per point, without significant sample invasion. Topographical measurements were also performed simultaneously. Wavy regions of high elasticity, layered in the circumferential direction, were measured at the tunica media, which was identified as an elastin-rich region. The Young's modulus of the elastin-rich region in the media was 50.8 +/- 13.8 kPa, and that of the elastin-rich region of the lamina elastica interna was 69.0 +/- 12.8 kPa. Both these values were higher than the Young's modulus of the other regions in the media, including smooth muscle cells and collagen fibrils (17.0 +/- 9.0 kPa). TMS is simple and inexpensive to perform and allows observation of the distribution of the surface elastic modulus at the extracellular matrix level in vascular tissue. TMS is expected to be a powerful tool in evaluation of the maturation and degree of reconstruction in the development of tissue-engineered or artificial tissues and organs.

Modeling Plaque Fissuring and Dissection during Balloon Angioplasty Intervention

Balloon angioplasty intervention is traumatic to arterial tissue. Fracture mechanisms such as plaque fissuring and/or dissection occur and constitute major contributions to the lumen enlargement. However, these types of mechanically-based traumatization of arterial tissue are also contributing factors to both acute procedural complications and chronic restenosis of the treatment site. We propose physical and finite element models, which are generally useable to trace fissuring and/or dissection in atherosclerotic plaques during balloon angioplasty interventions. The arterial wall is described as an anisotropic, heterogeneous, highly deformable, nearly incompressible body, whereas tissue failure is captured by a strong discontinuity kinematics and a novel cohesive zone model. The numerical implementation is based on the partition of unity finite element method and the interface element method. The later is used to link together meshes of the different tissue components. The balloon angioplasty-based failure mechanisms are numerically studied in 3D by means of an atherosclerotic-prone human external iliac artery, with a type V lesion. Image-based 3D geometry is generated and tissue-specific material properties are considered. Numerical results show that in a primary phase the plaque fissures at both shoulders of the fibrous cap and stops at the lamina elastica interna. In a secondary phase, local dissections between the intima and the media develop at the fibrous cap location with the smallest thickness. The predicted results indicate that plaque fissuring and dissection cause localized mechanical trauma, but prevent the main portion of the stenosis from high stress, and hence from continuous tissue damage.

Sudden death due to giant cell coronary arteritis

An 89-year-old woman was found dead lying in her bed. Autopsy demonstrated a pronounced thickening of all coronary arteries except for the first 2-4 cm. Death was due to a recent myocardial infarction. Microscopically, the coronary arteries showed a substantial concentric thickening of all three layers with 90% narrowing. There was a dense transmural inflammatory infiltration with lymphocytes, macrophages, and numerous multinucleated giant cells. The CD68 positive giant cells were mostly located at the media-intima border in the vicinity of fragmented fibers of the lamina elastica interna. The aorta and its major branches including the carotid arteries, however, were free of inflammation and thickening. The findings were characteristic for giant cell arteritis, the equivalent of temporal Horton arteritis, but isolated involvement of the coronary arteries is exceptional.

Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL.

A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.

A model of neointima formation in the atherosclerotic carotid artery of mice

To establish a simple, reproducible model of neointima formation in mice with atherosclerotic vessels. Apolipoprotein E/low density lipoprotein receptor double knockout mice were fed an atherogenic diet. Carotid artery injury was induced by separate ligation of the external and internal carotid artery immediately distal to the bifurcation. Mice with normal vessels were used for comparison. Monocytes and macrophages were detected with immunohistochemistry using CD68 antibodies. The transcription factor nuclear factor kappa B was also detected by immunohistochemistry. Expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was evaluated by real time polymerase chain reaction. Neointima and media areas were digitally measured and analyzed. Four weeks later carotid artery ligation had induced neointima formation proximal to the ligation site, apparent as a smooth muscle cell alpha-actin positive layer intimal to the lamina elastica interna. The shape and size of the lesions were reproducible. Nuclear localization of nuclear factor kappa B was found, and the expression of TNF-alpha and IL-1beta increased after injury. CD68 positive cells were detected in the lumen, in the media and in the neointima. We have established in atherosclerotic mice a reproducible model of arterial injury with inflammation and neointima formation.

There is no effect on remodeling of vascular wall 4 weeks after local delivery of antithrombin in a porcine model of coronary overstretching.

Antithrombin III is an effective endogenous inhibitor of thrombin with antiproliferative and anti-inflammatory capabilities. Systematic administration of direct thrombin inhibitors as well as of antithrombin has proven effective at reducing formation of neointima after injury to vessel wall in various animal models. Local delivery of antithrombin attenuates deposition of platelets after balloon injury to porcine coronary vessels. To test our hypothesis that local delivery of antithrombin affects remodeling of vessel wall after balloon injury to the left anterior descending artery (LAD) in pigs. With a balloon:vessel diameter ratio of 1.5 deep vessel-wall injury was performed with conventional balloon angioplasty in the LAD in 16 pigs. After balloon injury the pigs were administered locally two doses of 2.5 ml antithrombin (250 U) or, as a control, two doses of 2.5 ml albumin (10 mg). All pigs were administered 200 U/kg bodyweight heparin before catheterization. The animals were then kept in stalls and fed normal grain. After approximately 4 weeks the animals were killed and lesions were assessed by computer-assisted image analysis. The areas of each vessel-wall layer and the percentage area stenosis were calculated. As a measure of injury, the length of rupture of the lamina elastica interna was measured. The injury was found to be equally profound in pigs of these groups. There was no significant difference between the groups concerning the areas of vessel-wall layers. The percentage area stenosis was similar for pigs in these two groups (36.5 +/- 14.9% for pigs in the antithrombin group versus 35.4 +/- 16.2% for pigs in the control group, NS). Local delivery of 250 U antithrombin to the LAD in pigs did not affect remodeling of the vessel wall 4 weeks after balloon injury.

Localization of vitronectin in the normal and atherosclerotic human vessel wall.

Vitronectin (Vn) regulates proteolytic enzyme systems, as well as cell migration and tissue remodelling. These processes have been implicated in the pathogenesis of atherosclerosis. In this study, the distribution of Vn antigen in apparently normal and atherosclerotic human blood vessels was evaluated. Normal and diseased vessels showed Vn immunostaining in the lamina elastica interna and externa, and in strand-like structures in the adventitia. In most of these instances, the Vn antigen appeared to be located in the proximity of elastin. In pulmonary arteries, Vn staining was additionally detected in the media. The intima was devoid of Vn antigen in all vessels studied. In general, there was increased deposition of Vn antigen in the atherosclerotic arteries. In particular, strong Vn staining was apparent in amorphous material adjacent to cholesterol clefts and in acellular fibrous tissue, in plaques present in the carotic artery and aorta. Collagen layers and fresh fibrin depositions were devoid of Vn antigen. In spite of the abundance of Vn immunostaining throughout the normal and diseased vessel wall, the Vn transcript was not detectably by in situ hybridization. These results indicate that Vn is a constituent of the normal vessel wall and raise the possibility that increased local deposition of Vn may be related to the development of atherosclerotic vascular disease.

Copper-induced inflammatory reactions of rat carotid arteries mimic restenosis/arteriosclerosis-like neointima formation

The pathogenesis of arteriosclerosis and of restenosis after angioplasty is linked with an inflammatory and fibroproliferative response of the arterial tissue. We have induced a non-infectious inflammation by implanting a silicon–copper cuff around rat carotid arteries. The copper ions released from the oxidized copper initiate and mimic all morphological features of post-angioplasty restenotic and arteriosclerotic lesions. The copper-induced lesions were analyzed by electron and light microscopy, immunohistochemical methods and quantified by morphometry. During the first phase of copper-induced tissue reaction (3 days), macrophages and polymorphonuclear leucocytes invaded through the endothelium, accumulated in the subendothelial space and triggered the proliferation of smooth muscle cells which then migrated from the tunica media through the lamina elastica interna into the intima. Within 3 weeks, the accumulated smooth muscle cells, macrophages, leucocytes and newly synthesized extracellular matrix formed a circular mostly eccentric fibrotic thickening that narrows the vessel lumen by 30–40%. The accompanying structural disorganization of the medial layer led to focal rupture and aneurysm-like dilatation of the vessel wall in 3 of 11 animals between day 20 and 43. The neointima progressively increased in thickness over time leading to corresponding reduction of the vessel lumen. The carotid arteries of control animals and animals treated with copper-free silicon cuffs showed no abnormal pathological appearence. Our results show that inflammation-inducing agents can contribute to and simulate restenosis- and arteriosclerosis-like lesions and that the copper-cuff model may be useful in the exploration of new approaches to intervention.

PRENATAL DIAGNOSIS, PATHOLOGY, AND GENETIC STUDY OF FETUS IN FETU

We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in the third trimester showed an anencephalic, acardiac mass with identifiable extremities and spine within an intra-abdominal cystic mass. Pathological examination revealed a fetiform mass weighing 20 g with four extremities, digits, vertebral bodies, an oral cavity with developing teeth, primitive male external genitalia, a urinary bladder, a cloaca with an external opening, large intestines, a membranous capsule, and an umbilical cord with one artery, one vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in the fibrocollagenous tissue below the cuboidal surface epithelium of the membranous capsule, and absence of lamina elastica interna and vasa vasorum in the single artery of the umbilical cord. Both the host infant and the fetus in fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic markers showed no genetic difference between the host infant and the fetiform mass. We report this case as an unusual example of fetus in fetu in co-existence with an amnion-like membrane containing nerve bundles and with a well-formed umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if the fetiform mass has well-developed limbs and spine. We emphasize the necessity for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with calcified solid components is detected prenatally in a fetus by ultrasonography.

Early phase alterations in endothelium dependent vasorelaxation responses due to aneurysm clip application and related manipulations.

Mechanically induced vasoconstriction observed throughout surgery and in the immediate postoperative period was investigated to assess the effects of various microsurgical manipulations. Factors such as the type of aneurysm clip, duration of temporary clipping and peri-adventitial tissue stripping were the variables in this study. Microsurgical clips were applied on guinea pig "cervical carotid arteries" in which peri-adventitia had been removed microsurgically. Arterial rings were removed immediately after surgery. Endothelium dependent relaxations were measured and morphological investigations were performed using light microscopy. It was observed that as the clip application period increased, relaxation responses decreased. Peri-adventitial tissue stripping caused a marked decrease in the relaxation responses in all types of the clips. Microvascular clips, in spite of their lower closing forces, had the greatest deleterious effect on relaxation responses of the vessel, in both normal and peri-adventitial tissue stripped. When the peri-adventitial tissue of the vessel had been stripped, convolutions of the lamina elastica interna were found to be lost in parallel with the decreased tonus of the artery. In the vessels subjected to clipping endothelial denudation and cracking took place. As a conclusion it can be stated that both peri-adventitial tissue stripping and microvascular clip application have deleterious effects in the early postoperative period. While choosing clips from minimal occlusion force tables, care must be taken to choose clips with less width; and while performing microvascular anastomosis, temporary clips with a lesser width must be used in place of microvascular clips. Adventitial stripping must not be unnecessarily generous during microvascular anastomosis.

PRENATAL DIAGNOSIS, PATHOLOGY, AND GENETIC STUDY OF FETUS IN FETU

We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in the third trimester showed an anencephalic, acardiac mass with identifiable extremities and spine within an intra-abdominal cystic mass. Pathological examination revealed a fetiform mass weighing 20 g with four extremities, digits, vertebral bodies, an oral cavity with developing teeth, primitive male external genitalia, a urinary bladder, a cloaca with an external opening, large intestines, a membranous capsule, and an umbilical cord with one artery, one vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in the fibrocollagenous tissue below the cuboidal surface epithelium of the membranous capsule, and absence of lamina elastica interna and vasa vasorum in the single artery of the umbilical cord. Both the host infant and the fetus in fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic markers showed no genetic difference between the host infant and the fetiform mass. We report this case as an unusual example of fetus in fetu in co-existence with an amnion-like membrane containing nerve bundles and with a well-formed umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if the fetiform mass has well-developed limbs and spine. We emphasize the necessity for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with calcified solid components is detected prenatally in a fetus by ultrasonography. © 1997 by John Wiley & Sons, Ltd.

Arterial wall texture after uncomplicated endarterectomy

Recanalisation of the carotid sinus is one of the most frequently performed vascular interventions; endarterectomy of the coronary arteries is an auxiliary measure accompanying aortocoronary bypass. Enucleation of the sclerotic plaque is followed by reconstruction of the intima and by rapid smoothing over of the "steps" along the side of the recanalised segment by proliferation of smooth muscle cells from the remaining media. The thinner the residual media, the thicker grows the neointima. Occasionally elastic lamellae reminiscent of a lamina elastica interna are formed close to the lumen. Moreover, in some cases renewed formation of the characteristic intimal spur (fibrotic ridge) is seen at the carotid sinus inlet, a sign of continued irregularity of blood flow postoperatively. In contrast, no focal lesions are generally observed in recanalised segments in the coronary arteries. New sclerotic pads that occur in the late phase bear a morphological resemblance to those in operated restenoses. The distribution of these pads is largely congruent with that of the sclerotic plaques in non-operated cervical arteries. Thus, even when recanalisation of the carotid sinus is uncomplicated, reparative processes are followed by the reformation of sclerotic pads, largely determined by haemodynamic factors. In the coronary arteries, concentric rather than focal sclerotic lesions predominate.

Arteriosclerotic changes in orbital arteries supplying the human eye

The anatomy of the orbital arteries is well known, and their physiology is under intensive investigation. Their age-related or other pathologic alterations, however, are still largely unknown. The authors obtained at autopsy 22 orbits from 11 persons aged >70 years, and four orbits from two persons between 40 and 50 years. Specimens were taken from 20 locations along the orbital arteries, from the internal carotid to the globe, and studied under light microscopy. They observed the following arteriosclerotic changes: intimal hyperplasia, atherosclerotic fibrous plaques, calcifications of the lamina elastica interna, and medial atrophy. Arteriosclerosis was ubiquitous in persons over 70 years of age. As a rule, its prevalence and severity decreased with narrowing arterial caliber. Degenerative changes in the orbital arteries are likely to play an important role in ophthalmic vascular diseases.

Physiological and Pathological Morphology of the Umbilical and Placental Circulation

Closure mechanisms of fetal vessels are essential after birth. They are physiological. The speedy and characteristic constriction is made possible by the special construction of the fetal vessels. The so-called "folds of Hoboken" in the umbilical artery initially form tapered constrictions which quickly extend to longer sections of the vessel. The contractions continue to include the chorion plate and the villi. Due to a lack of lamina elastica interna, a protrusion of pear shaped, expanded mediamyocytes and myofibroblasts is possible which reduces the cross-sectional area of these vessels. Similar, but lasting reductions in the cross-section of the villous arteries due to a fibrous-muscular media occur in the second half of pregnancy (IVth sign of maturity). Closure of the fetal vessels during intrauterine life leads to placental insufficiency of fetal death in utero. The endarteritis obliterans closes villous vessels by means of a connective tissue plug which starts on one side of the vessel and continues across the whole width of the lumen. The periphery dependent of these villi remains avascular, as the placenta is limited in its resorptive capabilities. In the case of intrauterine asphyxia, intravasal fibrinthrombi form as a sign of subacute insufficiency in the utero-placental circulation. A decompression collapse occurs in the fetal circulation, when fetal death occurs with continuing maternal circulation.