Regional histomorphometry of the hepatic inferior vena cava; a possible sphincteric mechanism / Histomorfometría regional de la vena cava inferior hepática; un posible mecanismo de esfínter

This study was aimed at identifying the changes in diameter and structural composition of the Hepatic Inferior Vena Cava in its infrahepatic, intrahepatic and suprahepatic portions. Eighty adult liver specimens from the Chiromo and Nairobi City mortuaries were used for morphometry, while twenty of them were processed for light microscopy. A constriction was noted in the mid-portion of the HIVC, while structurally; the intrahepatic portion had thicker fibromuscular adventitia. It is plausible that these are sphincteric apparatus to prevent backflow of blood in the Hepatic Inferior Vena Cava.

Este estudio tiene por objetivo identificar los cambios en el diámetro y la composición estructural de la vena cava inferior hepática en sus porciones infrahepática, intrahepática y suprahepática. Ochenta hígados de especímenes adultos de los depósitos de cadáveres de la ciudad de Nairobi y Chiromo fueron usadas para morfometría, mientras que veinte de ellos fueron procesados para microscopía de luz. Se observó una constricción en el medio de la HIVC, mientras que estructuralmente, la porción intrahepática había una gruesa adventicia fibromuscular. Es posible que este sea un aparato esfinteriano para evitar el reflujo de sangre en la vena cava inferior hepática.

The significance of hepatic vein outflow volume in hepatic outflow insufficiency of living right liver graft evaluated by Doppler ultrasound.

The color Doppler ultrasound has been used to evaluate hepatic vein (HV) outflow insufficiency based on flow velocity and waveforms. In our experience, some cases with flat waveforms are clinically asymptomatic. The parameters of HV flow velocity and waveforms are not always correlated with clinical problems. So, we proposed that total HV flow volume (HVFV) may be a more reliable index. From August 2001 to July 2003, 31 cases among 48 adult-to-adult living related transplants of a right liver graft had one HV anastomosis. HV velocity, waveforms, and HVFV were compared both before and after transplantation. We set the minimal HVFV ratio at 80% based on the original HVFV before graft retrieval. There was no significant difference in HVFV before liver graft retrieval between the 2 groups, but there was a significant change after transplantation. There were no cases of HV insufficiency among group A patients (>80%), whose HVFV ranged from 397 to 1181 mL/min with ratios from 75% to 180% (mean 115%). In group B, there were 4 complicated cases with prolonged severe ascites (<80%) with HVFV ratios from 56% to 76% (mean 66%). Fisher exact test showed a great significance (P < .001). Thus the preliminary criteria of 80% minimal HVFV ratio allows detection of HV insufficiency for further interventional management.

Development of the ductus venosus in the SD rat.

We used scanning electron microscopy to observe the development of the ductus venosus in the fetal rat liver. At day 13 of gestation, the vascular system in the liver was already formed and the umbilical vein had branched many capillaries to the parenchyma of the liver and was connected to the posterior vena cava directly by one small ductus venosus. At day 14 of gestation, the umbilical vein bulged at its terminal part and bifurcated into the ductus venosus, which joined the posterior vena cava, and a branch that anastomosed with the vitelline vein. The ductus venosus had no branches and subsequently enlarged and then degenerated just before birth. The bulging part of the umbilical vein and its branches degenerated in the later stages of gestation. The vitelline vein developed to form the capillaries of the liver and the intestinal venous system. In the SD rat liver, the ductus venosus was therefore established by development of the terminal part of the umbilical vein, which anastomosed directly with the posterior vena cava.

Topographical relationships among the portal branchesand the hepatic tributaries in the left lateral division or the liver of brazilian individuals

The left lateral division or left anatomical lobe of the liver is subdivided into posterior lateral or S2 and the anteriorlateral or S3 segments. Because this lobe is widely used in hepatic transplantation, the ramifications of the portal veinand of the hepatic veins have been extensively studied. The aim of this study was to investigate the frequency ofcases in which it is possible to delimit the S2 and S3 hepatic segments. Forty livers from Brazilian subjects ofEuropean and African descent were fixed in neutral formalin solution and dissected. In segment S2, there was alwaysa portal branch located dorsally to the left hepatic tributary. In segment S3, there were three types of interdigitationsdistributed among two portal branches and two hepatic tributaries. In type A (26/40 cases, 65%), the tributariescrossed the dorsal portal branch posteriorly. In subtype A1 (19/26 cases), the tributaries pinched the ventral branch,and in subtype A2 (7/26 cases), they crossed the ventral branch posteriorly. In type B (11/40 cases, 27.5%), the twotributaries pinched the dorsal portal branch, with both pinching the ventral portal branch in subtype B1 (7/11 cases)but only the ventral tributary crossing the latter branch in subtype B2 (4/11 cases). In type C (3/40 cases, 7.5%), theventral and dorsal tributaries crossed the dorsal portal branch anteriorly, with both vessels also crossing the ventralportal branch anteriorly in subtype C1 (2 cases) and only the ventral tributary crossing this branch in C2 (1 case). Inall cases, it was possible to differentiate S2 from S3, even when in type C cases there was no hepatic tributaryseparating them. Moreover, in 23/40 cases (57.5%) there was a fissural umbilical vein greater than 5 mm in diameterand, in 5/23 cases this vein superficially crossed the portal branch destined to segment S3.

Electron microscopy of mast cells in the venous wall of canine liver.

Although many mast cells locate under the endothelial layer along the sublobular veins in canine liver, the cell function remains to be fully defined. To establish the nature of the canine mast cell, the mast cells were examined by electron microscopy. A few monocytes contacted with luminal surface of endothelial cells under which mast cells situated. To confirm the chemotaxis of monocyte by hepatic mast cells, the hepatic venous vessels were treated with a histamine releaser (compound 48/80). The monocytes invaded into the subendothelial layer and extended their pseudopodium to the degranulated mast cells. It presumes that some mediators within the mast cell granules might act as a chemotactic substance to the monocyte. On the contrary, mast cells were migrating from subendothelial layer to venous lumen under normal condition. The migrating mast cell showed strong acid phosphatase reaction in their granules. It suggests that the granules of migrating mast cell became visible to acid phosphatase activity by a physical force such as contact stimulation, and that a part of mast cells remigrate from the venous wall to other places by the blood flow. Furthermore, hepatic mast cells were revealed to contain both endothelin-1 and histamine in their granules by immunocytochemistry. As these substances have an activity of stronger venous constriction, it seems that the mast cells play an important role in the blood flow regulation of the canine liver, mast cell, monocyte.

Ultrastructural study on the venous sphincter in the sublobular vein of the canine liver.

Although the existence of venous sphincters has been demonstrated in the sublobular veins of the canine liver, the role it plays in the regulation of liver blood flow is still uncertain. In the present study, I examined the fine structures of the venous sphincters treated with four kinds of drugs (epinephrine, histamine, isoproterenol, and histamine releaser) by conventional electron microscopy and by scanning electron microscopy using microvascular corrosion casts. Intravenous administration of epinephrine, histamine, and histamine releaser (compound 48/80) resulted in a strong constriction at the small branches (100-400 micron in caliber) of the sublobular veins, while the treatment with isoproterenol showed dilatation in the same branches. When treated with compound 48/80, both the endothelial-specific granules (Weibel-Palade granules) and the mast cell's granules of the sublobular veins showed swelling and became transparent reducing electron density. In contrast, the shape and electron density of the granules did not change when the veins were dilated. The results suggest that the small branches of the sublobular veins have extremely important functions for the regulation of the liver blood flow under normal conditions and that the component parts in the Weibel-Palade granules and/or mast cell's granules may be involved in the constriction of the sphincter muscles.

Sphincters of canine hepatic sublobular veins respond to endothelin-1 and 3.

The dog has been used repeatedly as a model in liver transplantation research. The microcirculation and its regulatory mechanisms play a crucial role during ischemia and reperfusion. Little is known about the role of venous sphincters in regulating blood flow in the dog liver. Hence, we performed this study to elucidate their potential role in regulating local blood flow. In 14 dogs mean systemic (MSP) and mean portal venous pressure (MPP) were measured. Light and electron microscopy (scanning and transmission) of tissue sections and vascular corrosion casts were used to elucidate the microvascular morphology. Immunocytochemistry was applied to identify smooth muscle cells and the innervation of venous sphincters. Endothelins 1 and 3 were injected to find whether the hepatic venous sphincters are sensitive to these vasoactive agents. Tufts of smooth muscle cells were found in the sublobular veins (SLV; 100 to 250 microm in diameter), that reduced the luminal diameters of veins by 34%. Nerve endings were not observed close to these venous sphincters. The MSP and MPP were 75.3+/-2.4 mmHg and 8.9+/-0.95 mmHg, respectively. Treatment with 1.0 microg/kg of endothelin-1 (ET-1) significantly increased the MSP, the MPP and the percentage of focal venous sphincter contraction by 39% (105+/-4.7 mmHg), 43% (12.8+/-1.7 mmHg) and 57% (53.5+/-4.7), respectively (P <0.01). Treatment with ET-3 caused a significant (P <0.01) decrease in the MSP, the MPP and the percentage of sphincter contraction by 19% (61.0+/-2.2 mmHg), 39% (5.8+/-2.9 mmHg) and 38% (20.9%+/-3.15). Sinusoids did not contain sphincters. Hepatic arterioles and central veins were not affected by ET-treatment. The contraction of SLV sphincters correlated with increases in MPP (r=0.81, P <0.01) and was related to the MSP (r=0.67, P <0.01). These data show that the smooth muscle sphincters in SLV of the dog liver are involved in the local regulation of blood flow and that these sphincters are stimulated by non-neurogenic mechanisms. These sphincters contract in response to ET-1 and relax in response to ET-3. Since ET-1 is released during and/or causes inflammation, e.g., during ischemia and reperfusion, its antagonists might be of benefit during transplantation reperfusion of liver.

Spiral structures in the wall of the hepatic venous system in the dog.

Unique spiral structures, located in the wall of the hepatic venous system in the dog, were examined in the central veins and the hepatic venous branches, utilizing microvascular corrosion casting and freeze-fracture technique in scanning electron microscopy and transmission electron microscopy of tissue sections. The whole hepatic venous system was divided into 4 portions: the central, sublobular, collecting and branches of the hepatic veins. The central vein was spindle-shaped with several compressions. Removing the endothelial cells of the central vein, pathways of venous sinusoids were like a labyrinth. In the sublobular veins, spiral structures distinctly appeared as the diameter increased. Beneath the endothelial cells in the constricted portions, smooth muscle bundles were found. The spiral structures gradually became irregular in the collecting veins and discontinuous to form shallow constrictions in cast thicker branches of the intrahepatic veins. A single, fine spindle of the central vein was formed by the arrangement of liver cells. The spiral structures of the sublobular vein were formed by smooth muscle bundles. Irregularity of the spiral structures in the collecting veins was caused by smooth muscle bundles anastomosing with adjacent ones. Disappearance of the spiral structure in cast thicker branches of the intrahepatic veins was due to absence of muscle bundles.

Vascular branching pattern and zonation of gene expression in the mammalian liver. A comparative study in rat, mouse, cynomolgus monkey, and pig.

BACKGROUND: A significant part of the liver volume consists of regions in which hepatocytes are in close contact with large branches of the afferent (portal vein) or efferent (hepatic vein) vessels. As most studies have addressed zonation of gene expression around the parenchymal branches of the portal and hepatic vein only, the patterns of gene expression in hepatocytes surrounding larger vessels are largely unknown. METHODS: For that reason, we studied the patterns of expression of the mRNAs and proteins of the pericentral marker enzymes glutamine synthase, ornithine aminotransferase, and glutamate dehydrogenase and the periportal marker enzymes phosphoenolpyruvate carboxykinase and carbamoylphosphate synthase in the rat liver, in relation to the branching pattern of the afferent and efferent hepatic veins with immuno and hybridocytochemical techniques. These patterns of expression were compared with those seen in mouse, monkey, and pig liver. RESULTS: The distribution patterns of the genes studied appear to reflect the "intensity" of the pericentral and periportal environment, glutamine synthase and phosphoenolypyruvate carboxykinase requiring the most pronounced environment, respectively. The patterns of gene expression around the large branches of the portal and hepatic vein were found to be related to the parenchymal branches in the neighbourhood of these large blood vessels. Only the cells of the limiting plate retain their periportal and pericentral phenotype for those marker enzymes that do not require a pronounced periportal or pericentral environment to be expressed. GS-negative areas in the pericentral limiting plate appear to correlate with a local absence of draining central veins, and become more frequent and extensive around the larger branches of the hepatic vein. CONCLUSIONS: The similarity of the observed patterns of gene expression of the genes studied in mouse, rat, monkey, pig, and man suggests that they reflect a general feature of gene expression in the mammalian liver. A comparison of mouse, rat, pig, and human liver suggests that the presence of glutamine synthase-negative areas reflects the branching order of the efferent hepatic blood vessel.

Incidence of shunt occlusion or stenosis following transjugular intrahepatic portosystemic shunt placement.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) placement has been used for the treatment of recurrent variceal hemorrhage. The 1-year incidence of shunt stenosis or occlusion after TIPS placement was prospectively assessed, and the accuracy of Doppler ultrasonography to predict TIPS stenosis was evaluated. METHODS: Twenty-two patients with recurrent variceal hemorrhage were selected for TIPS placement between April 1991 and May 1992. Preoperative and postoperative evaluation included clinical assessment, upper gastrointestinal endoscopy, portal angiography with pressure measurements, and Doppler ultrasonography. Follow-up was performed at 3 and 12 months post-TIPS and when patients developed recurrent bleeding. RESULTS: Twenty-one of 22 patients (Child-Pugh class A-1, B-11, C-9) had successful TIPS placement. Seventeen of 21 patients have completed follow-up for at least 12 months. Of these 17 patients, 2 of 17 (12%) developed TIPS occlusion, 7 of 17 (41%) developed shunt stenosis, and 8 of 17 (47%) showed no stenosis on follow-up angiography. Doppler ultrasonographic assessment of the TIPS predicted shunt stenosis or occlusion with 100% sensitivity, 98% specificity, and 90% positive predictive value. CONCLUSIONS: Shunt occlusion or stenosis develops frequently within 12 months after TIPS placement, and Doppler ultrasonography is accurate in the noninvasive assessment of shunt stenosis. TIPS placement without careful follow-up and shunt revision cannot be considered a long-term treatment of variceal hemorrhage.

Histological changes of the liver in experimental graft-versus-host disease across minor histocompatibility barriers. IV. A study of lymphocyte-endothelial interaction.

It has been reported in human hepatic graft-versus-host disease (GVHD) that an attachment of lymphocytes to vascular wall, the feature called "endothelialitis", is the most important predictive histologic sign of GVHD. However, its precise nature and significance in GVHD are still unknown. We developed experimental mouse GVHD across minor histocompatibility barriers and examined the lesion during a 14-month period after transplantation. The lesion was transiently found, appearing first at 4 days after transplantation, reaching a maximal level at 2 weeks and disappearing 5 weeks after transplantation. Electron microscopically, an intimate interaction between lymphocyte and endothelial cell was demonstrated. Lymphocytes showed irregular cytoplasmic processes and pseudopods and were in close contact with endothelial cells. Lymphocytes frequently penetrated in between and under the endothelial cells, and migrated into the perivascular spaces. Immunohistochemical analysis revealed that the vast majority of lymphocytes attached to the endothelial cells are helper/inducer T cells, indicating the cardinal role of helper/inducer T cell in lymphocyte-endothelial cell interactions. These results, together with previous evidence of the presence of Ia antigens and an antigen-presenting ability of vascular endothelial cells, suggest that the attachment of lymphocytes to the vascular endothelial cells in the early course of GVHD may represent an in situ morphologic representation of antigen presentation by endothelial cells to helper T cells.

A light and scanning electron microscopic study of hepatic veno-occlusive disease.

Hepatic veno-occlusive disease, which was observed in a patient with hepatic coma, was examined by scanning electron microscopy (SEM), and correlated with its histology. Postmortem examination disclosed microscopic occlusion of the centrilobular and sublobular veins in the liver. These veins were occluded, partially or completely, by intimal and medial thickening of their walls due to proliferation of collagen and reticulin fibers. In addition to venous obliteration, which had not been demonstrated by other techniques, frequent occlusion of the sinusoidal opening into the central veins was observed by SEM. The size and distribution of the openings were irregular in comparison with those in normal controls. There was no evidence of fibrin thrombus formation in the veins. This case exemplified the usefulness of the application of SEM to autopsy material.

Perfusion fixation of hepatic needle biopsies for scanning electron microscopy. A methodological study.

Perfusion fixation is essential for the examination of the hepatic microvasculature by scanning electron microscopy. No detailed study has previously been done on the perfusion of human hepatic needle biopsies. The present paper demonstrates two modifications of a simple technique by which needle biopsies can be perfused. Perfusion was performed either manually (n = 33) or with a constant perfusion pressure of 10-15 mm H2O (n = 54). No significant difference in the ultrastructural preservation was observed in the two groups. Manual perfusion, however, when done gently, was superior in cleaning the sinusoids, and thus larger areas could be investigated by this method. Topographical orientation was possible, allowing the identification of terminal hepatic veins and portal tracts.

Ultrastructure of initial stages of perivenular fibrosis in alcohol-fed baboons.

Perivenular fibrosis was studied in baboons pair-fed with alcohol containing or isocaloric control diets for up to 8.5 years, and biopsies were performed on the animals one to two times a year. The number and types of mesenchymal cells surrounding the terminal hepatic venules were examined at various stages of thickening of the rim of the terminal hepatic venules by light and electron microscopy. The number of mesenchymal cells increased with progression of fibrosis and showed good correlation with the thickness of the rim (r = 0.7435, P less than 0.001, n = 56). myofibroblasts were the most common mesenchymal cells. They were present around the terminal hepatic venules in the control animals and proliferated after alcohol. This was associated with increased deposition of collagen fibers around the terminal hepatic venules. This fibrotic process extended into the perisinusoidal space of the centrolobular areas, sometimes connecting with pericellular fibrosis and/or fat granuloma, which developed in the lobule. Thus, in baboons fed alcohol, perivenular fibrosis is associated with myofibroblast proliferation followed by collagen deposition. Myofibroblast proliferation appears to represent the earliest detectable precursor lesion leading to hepatic fibrosis in alcoholic liver injury.

A scanning electron microscopic study of the liver of the monkey Macaca speciosa. I. Vascular system of the hepatic lobule.

The vasculature of the hepatic lobule of the monkey was investigated by scanning and transmission electron microscopy. The vessel walls of the portal and terminal hepatic (central) veins consist of a closed endothelium, a continuous basement membrane and a connective tissue layer. Sinusoids, however, show endothelia with typical fenestrations, and connective tissue fibres are only sparsely distributed in the space of Disse. Kupffer cells are present in the sinusoids, and occasionally in the terminal hepatic and sublobular veins, but are never present in the portal veins. They are characterized by a ruffled surface and special processes--filopodia and lamellipodia--which anchor them to the endothelial cells and also connect them with adjacent Kupffer cells. Flat branches of perisinusoidal cells, which encircle the endothelia, occur in the space of Disse, and are presumed to have a pericyte-like function.

[Histologic study of the teleost liver. II. The blood vessel system]. / Histologische Untersuchungen an der Teleosteerleber. II. Das Blutgefässsystem.

In the liver of the teleosts investigated in the present study the sinusoidal region shows a space of DISSE, which contains numerous microvilli originating from the hepatocytes. In some species, especially in Tetraodon leiurus, there are also bundles of collagenous fibrils. In the DISSE's space of larger sinusoids (transition sinusoids) sections of filament-rich cells are found. These are sometimes interconnected by desmosomes and can be interpreted as processes of smooth muscle cells from the region of the venae hepaticae. The endothelium of smaller sinusoids is fenestrated and shows micropinocytotic activity. The endothelia of the transition sinusoids and of the venae hepaticae are endowed with structures, which can be interpreted as macrovesicles. In the sinusoidal region true KUPFFER-cells and ITO-cells could not be observed. Nevertheless, the close location of granulocytes to the sinusoidal endothelium suggests that phagocytotic processes cannot be excluded for the sinusoidal region. Exceptionally, in Hemihaplochromis multicolor there were also signs of possible phagocytosis by sinusoidal endothelial cells. The chemomorphology of the sinusoidal region, above all the evidence of alkaline phosphatase, shows great differences between species. The examination of the larger blood-vessels in the liver of Haplochromis burtoni reveals venae portae with very thin walls and venae hepaticae with thick walls, which contain smooth muscle cells. Granulocytes and melanocytes are abundant in the wall of the venae hepaticae. This phenomenon indicates that the defence-functions, which in the liver of higher vertebrates are carried out by the sinusoids (KUPFFER-cells), are undertaken by the region of the venae hepaticae in the liver of Haplochromis burtoni, which is free of KUPFFER-cells. On their extrahepatic course the venae portae are surrounded by a sleeve of exocrine pancreatic tissue, which accompanies the vessels deep into the liver. The pancreatic cells bordering the thin-walled venae portae have sparse microvilli indicating a transfer of substances between venous blood and pancreas similar to the sinusoidal region of the liver. Furthermore, the investigation resulted in a clue to the innervation of the exocrine pancreas.