Lobular Parenchyma Research Articles

Effect of melatonin on the liver histophysiology of adolescent rats exposed to alcohol

The present study evaluated whether melatonin administered during adolescence can prevent the deleterious effects produced by alcohol on the liver. Thirty albino female rats (Rattus norvegicus albinus), 40 days old, virgins, weighing approximately 150±10g, from the Wistar lineage and were divided into the following groups: I – Adolescent rats that did not receive alcohol and euthanized at 60 days of life; II – Adolescent rats subjected to chronic alcohol consumption and euthanized at 60 days of life; III – Adolescent rats subjected to chronic alcohol consumption and simultaneously treated with melatonin, and euthanized at 60 days of life. The collected organs underwent histological processing and to obtain the results, morphometric, histopathological and histochemical analyzes were performed. Alcohol was administered by gavage. intragastric injection at a dosage of 3 g/Kg of ethyl alcohol in the rats of groups II and III for 20 days. Melatonin was administered in daily injections of 0.8 mg/Kg, always at the beginning of the night, intraperitoneally for 20 days. When analyzing the weight of the animals, no significant difference was observed between the groups. The animals in group II presented alterations in the livers such as congestion of the centrilobular vein, hepatocellular ballooning, microgoticular steatosis, leukocyte infiltrate, several pyknotic nuclei in the livers, increase in lobular parenchyma and reduction in non-lobular parenchyma, greater deposition of collagen and reduction of glycogen. Melatonin treatment prevented all these changes. With this, we can conclude that melatonin has great therapeutic potential in the prevention of liver damage in adolescent rats subjected to moderate alcohol consumption, in addition to positive effects on the deposition of collagen and glycogen in the liver.

Melatonin associated with a high-fat diet during pregnancy and lactation prevents liver changes in the offspring

In the present study, we set out to determine whether melatonin combined with a high-fat diet during pregnancy and lactation can prevent liver disorders in offspring. Forty rats were divided into four groups: DC - pregnant rats submitted to the standard diet; DC + Mel - pregnant rats submitted to the standard diet combined with melatonin; HFD - pregnant rats submitted to a high-fat diet; HFD + Mel - pregnant rats submitted to a high-fat diet combined with melatonin. Morphophysiological and biochemical parameters were analyzed. Melatonin (5 mg/kg) was administered intraperitoneally. The HFD group offspring showed an increase in AST, ALT, alkaline phosphatase, cholesterol, triglycerides, LDL and glucose levels, and a reduction in HDL and lipase levels. In the liver obseved steatosis, hepatocellular ballooning, increased lobular parenchyma and reduced non-lobular parenchyma, beside reduced liver glycogen and fibrosis. These changes were not observed in the HFD + Mel group. In conclusion, melatonin combined with a high-fat diet preserves the liver architecture and function in the offspring.

Prominent Pseudoacini in Focal Nodular Hyperplasia: A Potential Diagnostic Pitfall.

Pseudoacini are generally a morphologic feature of hepatocellular carcinoma (HCC), being absent or rare in benign hepatocytic tumors, such as hepatocellular adenoma. However, rarely these can be seen in focal nodular hyperplasia (FNH) and may pose diagnostic challenges, especially when prominent. The study was aimed to evaluate the occurrence of pseudoacini in FNH and their clinicopathologic correlations. A total of 95 FNH cases diagnosed from 2005 to 2020 were included in the study. A pseudoacinus was defined as a circular arrangement of hepatocytes around a central dilated lumen present within the lobular parenchyma of the lesion with or without inspissated bile. Among the 95 FNH cases, 28 (29.5%) showed pseudoacini, which were prominent in 12 (12.6%) cases. Of these 3 occurred in patients above 50 years old. The pseudoacini were numerous in 3 cases, leading to an initial consideration of HCC in the differential diagnosis, and 1 case was diagnosed as well-differentiated hepatocellular neoplasm on initial biopsy. All 12 cases showed map-like staining pattern for glutamine synthetase. The hepatocytes forming the pseudoacini were positive for CK7 and HepPar1, while the inner lumina were highlighted by CD10 and bile salt export pump immunostains similar to adjacent canaliculi. The presence of prominent pseudoacini was not significantly associated with any clinical or pathologic features. The findings suggest that pseudoacini are likely manifestation of hepatocyte biliary transdifferentiation associated with chronic cholestasis in the lesion. This feature may pose a potential diagnostic pitfall especially on needle biopsies and awareness is needed to avoid misdiagnosing this as HCC.

Renal and hepatic changes in the offspring of rats that received biological insecticides during pregnancy and lactation

Bacillus thuringiensis insecticides have been considered safe, being an alternative to the use of synthetic insecticides. However, studies have shown the effects of Bt Cry toxins on various organs, compromising their functions. The objective of this work was to test whether the administration of biological insecticides based on B. thuringiensis in pregnant rats will cause histopathological changes in the liver and kidneys, as well as in the levels of toxicity biomarkers, of their puppies in adulthood. Twenty rats, 90 days old, were used, divided into four groups: GC - Pregnant rats, GX - Pregnant rats that received XenTari®, GDi - Pregnant rats that received Dipel® and GDe - Pregnant rats that received deltamethrin. Insecticides were administered by gavage at a dosage of 1 mg/100 g/day (GX and GDi), and 2 mg/Kg/day (GDe) during pregnancy and lactation. In the animals of the groups whose matrices received the insecticides, there was a reduction in the levels of the biomarkers of toxicity alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, about the control group. The biological insecticides promoted histopathological changes in the liver, with the presence of portal vein, centrilobular and sinusoidal capillaries congestion, and in the kidney, presence of cortical congestion and reduction of the subcapsular space. Histochemical evaluation in the liver demonstrated a significant reduction in glycogen in the groups that received insecticides when compared to the control group, whereas for collagen fibers in both the liver and the kidneys, no differences were observed between the experimental groups. The morphometry of the liver revealed a significant reduction in the lobular parenchyma and an increase in the non-lobular parenchyma, and in the kidney, there was a reduction in the diameter and volume of the glomerulus and Bowman's capsule of the animals whose matrices received both biological and synthetic insecticides. Thus, it is concluded that the biological insecticides XenTari® and Dipel® in sublethal doses in pregnant rats promote changes in the liver and kidney of the offspring similar to the insecticide deltamethrin, which extend into adulthood.

Connective Tissue Framework of the Hepatic Ligaments in the Human Liver

Objectives: To demonstrate the three-dimensional structure of the collagen fiber framework in the human liver ligaments and capsule. Methods: We studied the collagen fiber framework of relatively normal human liver specimens using a cell maceration method and scanning electron microscopy. Results: The collagen fibers of the hepatic falciform ligament subdivided into three types depending on the direction and location. The outer collagen fibers of the hepatic teres ligament formed the longitudinal plate, and the inner fibers had a loop-like structure. The coronary ligament contained two parallel collagen bundles toward the hepatic capsule. The hepatic capsule possesses the outer thicker and inner interlaced layers of the collagen fibers. The hepatic ligaments’ outer layer connected with the hepatic capsule collagen fibers, while the inner layer tended to merge with the hepatic lobular parenchyma’s connective tissue. Conclusions: The hepatic ligaments and liver capsule are layered structures of collagen fibers differing in direction. The hepatic ligaments’ outer layer connected with the liver capsule’s collagen fibers and the inner layer merged with the hepatic lobular parenchyma’s connective tissue.

2228 A Rare Report of Pantoprazole-Induced Acute Hepatocellular and Cholestatic Hepatitis

INTRODUCTION: Pantoprazole is a widely used proton pump inhibitor that is used to treat variety of acid related disorders. It is well tolerated with excellent safety profile. Mild transient elevations in serum aminotransferase can be seen with pantoprazole use that resolves without dose modification. Pantoprazole induced clinically apparent liver injury on the other hand is exceedingly rare. CASE DESCRIPTION/METHODS: A 47-year-old woman with no prior liver disease was referred to the hospital for acute hepatitis. She started pantoprazole 2 months prior to admission for gastritis. Patient had nausea, fatigue, abdominal pain, jaundice and dark urine 2 weeks after starting pantoprazole and stopped it a week prior to hospital admission. She denied alcohol use. Her current medications were levothyroxine, enalapril/hydrochlorothiazide and aspirin and no use of herbal supplements. Physical exam was notable for conjunctival icterus. Baseline liver enzymes were normal. Labs on admission were: AST 681 U/L (< 32 U/L), ALT 2100 U/L (< 36 U/L), total bilirubin 12.3 mg/dL (0.2-1.2 mg/dL), direct bilirubin 8.3 mg/dL (< 0.5 mg/dL), alkaline phosphatase 96 U/L (45-117 U/L) and INR 1.9 (0.8-1.2). Urine drug screen was negative for acetaminophen toxicity. Imaging excluded biliary obstruction and hepatic venous thrombosis. Laboratory investigations for viral and autoimmune hepatitis, wilson’s disease and hemochromatosis were negative. Liver biopsy (Figure 1) reported portal areas with edema and a minimal amount of inflammation composed of mixed lymphocytes, occasional eosinophils and neutrophils. The lobular parenchyma showed cholestasis with lymphocytic and neutrophilic inflammation. Patient noted improvement of symptoms with supportive care (Table 1). Two months after stopping pantoprazole, liver enzymes were normal. DISCUSSION: DILI (drug-induced liver injury) is a significant cause of acute hepatitis. To our knowledge, only 7 case reports of pantoprazole induced liver injury have been published. The timing of starting pantoprazole prior to acute hepatitis, negative serologies, and normalized liver enzymes after stopping suggests pantoprazole as the cause of DILI. Based on its pharmacokinetics, timeline and pattern of insult, an idiosyncratic reaction has been suggested as the mechanism for hepatotoxicity. We have described a rare case of acute mixed (hepatocellular and cholestatic) liver injury from pantoprazole use suggesting its consideration in the differential diagnosis of DILI.

Treatment Dilemma: A Case of Hepatitis C Virus Autoimmune Hepatitis (HCV-AIH) Overlap Syndrome

Hepatitis C virus-autoimmune hepatitis (HCV-AIH) overlap syndrome is a challenging diagnosis that mandates clinical, immunological and histological manifestations of both diseases. Management is controversial and lacks consensus due to the discordant approach to treatment of each separate condition. A 57-year-old woman presented to the Emergency Room with a 2-day history of painless jaundice after her friends noticed her skin and eyes appeared yellow. At presentation her total bilirubin was 12.9 mg/dL and her direct bilirubin was 9.3 mg/dL. Her AST and ALT were 1631 and 1003 U/L, respectively, and her ALP was elevated to 183 U/L. Her Hep C Ab screen came back Grayzone with a reflex RNA PCR of 860,000 IU/mL. CT abdomen showed a normal-appearing liver without focal lesions, and a subsequent MRCP was negative for biliary obstruction. Ultrasound with Doppler was negative for any vascular occlusion. Further workup showed an elevated IgG to 2485 mg/dL, a positive ANA titer of 1:2560 and a positive anti-smooth muscle Ab to 1:320. The patient underwent a liver biopsy that showed lymphoplasmacytic infiltration along the portal ducts and within lobular parenchyma, consistent with autoimmune hepatitis and concomitant acute viral hepatitis vs. drug reaction. The patient denied recent ingestion of any hepatotoxic medications or alcohol. Her aggregate score based on the revised scoring system of the International Autoimmune Hepatitis Group was 17, placing her in the category of definite diagnosis. Prednisone was initiated prior to discharge and follow-up was arranged in clinic. At her follow-up appointment, her transaminitis had largely improved and her hyperbilirubinemia completely resolved. HCV-AIH overlap syndrome requires confirmation of diagnosis of each entity independently with a thorough workup. Management of this syndrome is controversial as treatment of one condition could exacerbate the other. One concept is to determine the predominant insult between the two at presentation and target this insult with initial therapy. This patient's histology lacked bile duct damage and steatohepatitis which is seen in acute HCV infection. Her immunologic markers combined with the biopsy results favored an autoimmune-predominant chronic HCV-AIH overlap syndrome, prompting initiation of immunosuppressive treatment with systemic steroids. The patient's subsequent rapid clinical improvement supports this strategy for initial treatment of HCV-AIH overlap syndrome.

Ductular reaction in alcoholic steatohepatitis, nonalcoholic steatohepatitis and hepatitis C virus infection (immunohistochemical study)

Background and aim. Alcoholic steatohepatitis (ASH), nonalcoholic steatohepatitis (NASH) and hepatitis C virus infection (HCV) are the most frequent causes of liver cirrhosis in the Western world. The course of the disease depends on the balance in fibrogenesis, angiogenesis and regeneration. But if fibrosis was studied intensively during the last decades, mechanisms and signs of reparative regeneration in these diseases remain unknown. Ductular reaction is one of the morphologic signs of regeneration, but it was examined mostly in diseases associated with cholestasis. The aim of our work is to study ductular reaction associated with expression of immunohistochemical marker CK19 in alcoholic steatohepatitis, nonalcoholic steatohepatitis and hepatitis C virus infection.Material and methods. 45 autopsies with diagnosed alcoholic steatohepatitis, nonalcoholic steatohepatitis and viral hepatitis C were enrolled in this study. Diagnosis of ASH was based on the data of alcohol abuse and morphologic signs of alcoholic disease – cardiomyopathy, chronic pancreatitis, alcoholic encephalopathy and typical liver changes. Viral genesis was proved by serological study (RNA HCV) and morphologic signs of HCV (METAVIR criteria). Diagnosis of NASH was verified by the features of metabolic syndrome and hepatic changes (Brunt criteria). The employed measures of reparative regeneration were CK19-positive cells with “biliary phenotype”, evaluated in the liver tissue (area of ductular reaction). Marker quantification was performed by assessing the ratio of stained tissue to the total area of the liver section using image analysis. Histotopographic features of ductular reaction and cellular phenotype were also studied. “STATISTICA FOR WINDOWS6.0” was used to analyze the data. The data were expressed as mean value ± standard deviation (M±s). Differences between groups were analyzed using ANOVA analysis (LSD test). P < 0,05 was considered significant.Results. Evaluation of CK19-positive cells area in the liver section showed the highest degree in HCV group (10,17±0,23). Differences of this marker from the markers revealed in NASH (1,17±0,25) and ASH (1,99±0,4) were statistically significant. In addition to quantitative parameters localization of ductular reaction and cellular phenotype were analyzed. Diffuse spreading of the cells with “biliary phenotype” within the thickness of connective tissue septas was found in NASH and ASH. Most ductules were laid by homogenous cuboidal cells and contained distinct lumens. Probably these findings may be a result of biliary epithelial cell proliferation from the preexisting ductules. In HCV CK19-positive cells were revealed mostly in the site of marginal plate between the lobular parenchyma and connective tissue septa. In histologic examination cellular population with “biliary phenotype” was more heterogenous and some ductules had no lumens. Genesis of such lesions may be associated with activation and proliferation of immature precursors – intermediate hepato-biliary cellsConclusions. Severe ductular reaction associated with marginal localization of CK19-positive cells between the parenchymal and connective tissue compartments is revealed in hepatitis C virus infection. In chronic steatohepatitis (alcoholic and nonalcoholic) diffuse spreading of the cells with “biliary phenotype” within the thickness of connective tissue septas is found. Quantitative and qualitative differences in morphologic signs of ductular reaction revealed in our examination confirm the variable role of new-formed ductules in the pathogenesis of different forms of chronic hepatitis which may be the aim for future researches.

Ovarian Remnant Syndrome at the Trochar Site: A Report of a Rare Complication Following Laparoscopic Ovarian Surgery

drome usually occurs as a result of improper tissue removal or an inappropriate blunt dissection. Endometriosis, pelvic inflam matory disease or previous gynecologic surgeries have been known to increase the risk. Such conditions make removal of ovarian tissue difficult, due to the increased likelihood of dense fibrotic adhesions between an ovary and surrounding structures. Furthermore, with an increase in the number of laparoscopic ovarian surgeries performed, implantation of ovarian tissue also has been recognized as an important cause of ovarian remnant syndrome. 2 Various locations have been identified where residual ovarian tissue was detected after laparoscopic ovarian surgery, including the pelvic wall, cervix, vagina, and bladder. 1 However, reports of residual ovarian tissue detected in an abdominal wall have been rare. This report describes a case of ovarian remnant syndrome caused by residual ovarian tissue at the trochar site after a laparoscopic ovarian cystectomy. that was palpable one week prior to her visit. The mass was not painful and did not show a change in size. Her past medical history was remarkable because she had undergone laparoscopic bilateral ovarian cystectomy due to endometriosis 3 years prior to her visit. Physical examination revealed a surgical scar on her left lower abdomen and an index finger tip-sized mass was pal pable in the abdominal wall under the scar. It was smooth and movable, and was not tender. The laboratory findings were un remarkable. Ultrasonography demonstrated an approximately 1.6×0.9 cmsized hypoechoic mass in the subcutaneous adipose tissue (Fig. 1). An excisional biopsy was performed. The mass was well demarcated from the adjacent soft tissue by a thin fibrous capsule. The cut surface showed a yellow, glistening lobular parenchyma with areas of blood-filled cystic spaces. Histologically, the pa renchyma was composed of luteinized granulosa and theca cell layers, suggesting corpus luteum of the ovary (Fig. 2). There was no evidence of endometriosis. A review of the operation record of the laparoscopic surgery that was performed 3 years prior showed that the patient had 5.4×4.5×4.0 cm- and 3.2×3.0×1.5 cm-sized endometriotic cysts in bilateral ovaries with an associated dense pelvic adhesion. After a cystectomy, the specimens were fragmented and extracted using forceps through the trochar on her left lower abdomen. The patient was discharged after the abdominal wall mass excision and was healthy with no recurrence of the lesion at a follow-up at 32 months.

Sarcoidosis: A Rare Cause of Granulomatous Enterocolitis

Purpose: A 51-year-old Caucasian male who was evaluated for abdominal pain, elevated liver enzymes, leukopenia, thrombocytopenia, severe peripheral arthralgias, and chronic watery diarrhea. He has a history of mediastinal and periaortic lymphadenopathy. Extensive laboratory work-up for liver diseases, infections, malabsorption and a bone marrow biopsy were essentially unremarkable. EGD was unremarkable. Colonoscopy showed scattered right colon ulcerations and erythema. The terminal ileum appeared normal. Biopsies from the duodenum, terminal ileum, and colon showed intramucosal non-caseating granulomas with focal multinucleate giant cell formation in a background of chronic active duodenitis, ileitis, and colitis. Liver biopsy showed moderate non-specific chronic hepatitis with non-caseating granulomas present within portal and lobular parenchyma. Tests for tuberculosis and fungal infections (including histoplasmosis) were negative. Due to the clinical presentation and diffuse multisystem involvement, sarcoidosis was favored and Crohn's disease was less likely. The patient was started on prednisone and had a significant improvement in his symptoms including diarrhea. This multisystem sarcoidosis along with diffuse gastrointestinal involvement is very rare. There are only a few cases of small intestine and colonic sarcoidosis in the literature.Figure: Duodenal biopsy (H&E stain) showing non-caseating granulomatous inflammation (arrowhead).Figure: Terminal ileum biopsy (H&E stain) showing non-caseating granulomatous inflammation (arrowhead).

Liver Fibrosis in Elderly Cadavers: Localization of Collagen Types I, III, and IV, α‐Smooth Muscle Actin, and Elastic Fibers

We have shown a high prevalence of liver fibrosis in elderly cadavers with diverse causes of death by Sirius red stain; however, the various collagen types in these samples have yet to be evaluated. To further characterize the histopathology of the fibrotic lesions in the livers of these elderly cadavers, this study used immunohistochemistry and histochemistry to identify the principal collagens produced in liver fibrosis, fibrogenic cells and elastic fibers. Collagen I and III immunoreactions were found to colocalize in collagen fibers of fibrotic central veins, perisinusoidal fibrotic foci, portal tract stroma, and fibrous septa. α-Smooth muscle actin-expressing perisinusoidal hepatic stellate cells (HSCs), as well as perivenular, portal, and septal myofibroblasts, were closely associated with collagen fibers, reflecting their fibrogenic functions. HSCs and myofibroblasts were also noted to express collagen IV, which may contribute to production of basal lamina-like structures. In fibrotic livers, the sinusoidal lining showed variable immunostaining for collagen IV. Collagen IV immunostaining revealed vascular proliferation and atypical ductular reaction at the portal-septal parenchymal borders, as well as capillary-like vessels in the lobular parenchyma. While elastic fibers were absent in the space of Disse, they were found to codistribute with collagens in portal tracts, fibrous septa and central veins. Our combined assessment of collagen types, HSCs, myofibroblasts, and elastic fibers is significant in understanding the histopathology of fibrosis in the aging liver.

LAM-1/Leu 8 antigen is expressed on portal, but not on lobular intrahepatic mononuclear cells in inflammatory liver disease.

The expression of the selectin receptor LAM-1/Leu 8 was analysed in normal and in inflamed liver tissue, and its expression on mononuclear inflammatory cells was correlated with their topographical distribution in various compartments of the inflamed liver, in order to obtain new insights on possible molecular mechanisms involved in the traffic of mononuclear inflammatory cells throughout the diseased hepatic parenchyma. In normal liver tissue, few scattered mononuclear cells in portal and lobular parenchyma corresponded to both CD4+ and CD8+, as well as to CD45RA+ (2H4+) naive and CD45RO+ (UCHL1+) memory T cells, and were LAM-1/Leu 8+. In acute and chronic inflamed liver biopsies, CD45RO+ (UCHL1+) CD4+ and CD8+ memory T cells largely predominated in both portal and lobular parenchyma. The expression of LAM-1/Leu 8 antigen on these memory T cells varied according to their localization in the liver parenchyma, and it was not correlated with specific aetiological causes. In acute hepatitis, the vast majority of T lymphocytes were LAM-1/Leu 8-. In chronic active hepatitis, memory T cells in portal tracts expressed LAM-1/Leu 8, whereas virtually all intralobular T cells accumulating in areas of periportal and intralobular inflammation were LAM-1/Leu 8-. In chronic persistent hepatitis, the LAM-1/Leu 8+ T cells largely predominated among the numerous mononuclear inflammatory cells within enlarged portal tracts, whereas LAM-1/Leu 8- T cells were restricted to areas of intralobular 'spotty' inflammation. Therefore, two phenotypical populations can be recognized among the memory T cells in inflamed liver tissue, according to their topographical localization: LAM-1/Leu 8+ T cells predominating in portal tracts, and LAM-1/Leu 8- T cells predominating in the lobular parenchyma. These data show that during their migration through the inflamed liver parenchyma, memory T lymphocytes undergo phenotypical changes (LAM-1/Leu 8 shedding) according to their localization in different liver compartments (portal tracts vs. lobular parenchyma), suggesting multiple cellular and molecular mechanisms involved in the regulation of the leucocyte traffic through inflamed liver tissue.

Estudo morfométrico do fígado de ratos submetidos a doses supra-fisiológicas de tiroxina

Tireotoxicose é o estado hipermetabólico causado pelo excesso de hormônios tireoidianos circulantes, que exercem sua ação praticamente em todos os tecidos. No presente estudo avaliou-se, por métodos estereológicos, o fígado de ratos tratados com doses supra fisiológicas de T4 (20µg/100g de peso de corporal) durante 20 dias. Os níveis séricos de T4 desses animais estavam significativamente elevados (p=0,02). Houve tendência a perda de peso corporal dos animais tratados em relação ao grupo controle (p=0,10), enquanto o peso do fígado teve aumento, embora não significativo (p=0,08). A proporção do parênquima lobular foi maior (p=0,05) e a fração volumétrica do parênquima lobular ocupada pelas células de Kupffer foi significantemente menor (p=0,05) nos animais hipertireóideos que nos controles. Houve depleção significativa do glicogênio hepático no parênquima lobular, em relação ao grupo controle (p=0,008). Concluiu-se, então, que a tireotoxicose provoca hiperplasia e/ou hipertrofia dos hepatócitos, com redução das reservas energéticas.

The normal adult human liver biopsy: a quantitative reference standard.

In assessing adult human liver histology, questions remain concerning the normal number of portal tracts and bile ducts in a liver biopsy. We therefore reviewed liver biopsies obtained with use of a percutaneous Menghini cutting needle (14G, internal diameter 1.6 mm), from 16 patients undergoing liver biopsy for screening procedures (age 49 +/- 14 years, +/-SD) and found to be normal by histological examination. The average aggregate length of the liver tissue was 1.8 +/- 0.8 cm (area of 16.4 +/- 10.7 mm2), representing 7 +/- 3 tissue fragments. Portal triads containing at least one profile each of a portal vein, hepatic artery, and interlobular bile duct numbered 11 +/- 6 per biopsy (range 3-23). Portal dyads, which did not contain one of these profiles, usually the portal vein, numbered 8 +/- 5 (range 1-18). On a per-specimen basis, 38% of portal tracts did not contain a portal vein, 7% did not contain a bile duct, and 9% did not contain a hepatic artery. Because of multiplicity of profiles within portal tracts, however, the average number of profiles per portal tract was 6 +/- 5 (range 2-35). Notably, on average there were 2.3 +/- 2.2 interlobular bile ducts per portal tract, compared to 2.6 +/- 2.3 hepatic arteries and 0.7 +/- 0.7 portal veins. The average minimum external diameter of interlobular bile ducts was 13 +/- 4 microm, of hepatic arteries 12 +/- 5 microm, and of portal veins 35 +/- 25 microm. Bile ducts greater than 30 microm in diameter were rare, only one each in two biopsies were observed. In contrast, probable canals of Hering were occasionally evident at the periphery of portal tracts (6 +/- 6 per biopsy) and within the lobular parenchyma as strings of cuboidal cells (5 +/- 5 per biopsy). We conclude that, although multiplicity of profiles is normal, portal dyads are almost as common as portal triads in normal peripheral liver tissue. On average, there are two interlobular bile ducts, two hepatic arteries, and one portal vein per portal tract, with 6 full portal triads per linear cm of tissue obtained by external Menghini biopsy technique with use of a 14G needle, equivalent to 0.8 +/- 0.5 portal triads per mm2. By serving as a reference standard for adult human liver histology, these findings may assist in the histopathological assessment of liver biopsies, particularly those performed for disease conditions featuring loss of intrahepatic bile ducts.

Iron-rich foci in chronic viral hepatitis

Stainable iron in the liver (hemosiderosis) is most commonly seen in individuals with homozygous genetic hemochromatosis, prior transfusion, hemolysis, porphyria cutanea tarda, and chronic alcohol-induced liver disease. In chronic viral hepatitis, however, significant hepatocellular hemosiderosis is uncommon. This report describes unusual foci of hepatocellular hemosiderosis (“iron-rich foci” or IRF) in liver biopsy specimens from three patients with chronic hepatitis with or without cirrhosis (two hepatitis C-related, one hepatitis B-related). IRF present within the lobular parenchyma or cirrhotic nodules contrasted sharply with the immediately adjacent hemosiderinnegative liver tissue. Serum iron indices were abnormal in all three patients, but homozygous hemochromatosis was ruled out based on the hepatic iron concentration and hepatic iron index for each case. These cases highlight the potential for irregular iron storage in chronic viral liver disease and possible confusion with genetic hemochromatosis. The possible pathogenesis of IRF and the relationship of iron storage to the outcome of interferon therapy in chronic viral hepatitis are discussed.

Lobular dissecting hepatitis in juvenile and young adult dogs.

A specific form of chronic hepatitis is described in 21 dogs. The disease appears to develop in the neonatal and juvenile period. Predominant clinical signs include weight loss, ascites, and jaundice. The liver is small, with a smooth surface or a limited number of hyperplastic nodules. A characteristic feature of the hepatitis is disruption of the hepatic architecture by complete fibrotic dissection of the lobular parenchyma into individual and small groups of hepatocytes with subsequent portal hypertension. This lesion may represent a specific pattern of hepatic reaction in the immature animal, and resembles human neonatal hepatitis.

Lymphatic capillaries of the pig lung: TEM and SEM observations

Pulmonary lymphatic vessels extend within the connective tissue sheets surrounding airways and blood vessels. Frequently in this location they also border the lobular parenchyma, but not lymphatic vessels have been found within intralobular compartments between blood capillaries and alveoli. The presence and distribution of lymphatic vessels in pulmonary tissue are consistent with an important role for the lymphatic system in the clearance of interstitial fluids in the lung. Pulmonary lymphatic channels have structural characteristics of initial lymphatics; their walls are formed only by an endothelial layer, and no muscular cells are present. A network of anchoring filaments and collagen and elastic fibers surrounds the vessel walls. Because the lung is a mobile organ the tissue undergoes compression and distension during respiratory phases. These modifications could have a role in the mechanisms for lymph formation and flow.

Standards of morphological evaluation and histological grading in experimental acute pancreatitis.

Acute pancreatitis is characterized morphologically by edema, hemorrhages, parenchymal necrosis and fat necrosis. The inflammation is accompanied by infiltration of polymorphonuclear leukocytes. According to the absence or presence of necrosis the disease can be divided into interstitial (or edematous) pancreatitis and hemorrhagic-necrotizing pancreatitis. The severity of disease can be graded in the histological sections either by giving scores to the different types of morphological alterations or by determining the proportion of necrotic tissue of the total lobular parenchyma. The former method is based on subjective assessment of histological slides and is suitable for the evaluation of both edematous and necrotizing pancreatitis. Histometric measurement of necrotic parenchyma can be used only in the necrotizing forms of experimental pancreatitis, e.g. in those induced by intraductal injection of bile, bile salts or digestive enzymes, and in the dietary ethionine-induced pancreatitis. Grading of the tissue damage is essential when the effects of different therapies are evaluated.

Branchings and course of the larger ducts and accompanying structures within the rat submandibular salivary gland

In the rat submandibular gland, the larger ducts, vessels, and autonomic elements are surrounded by appreciable collagen to form an extensive, ramifying core for the bulk of the parenchyma. This entity is analogous to the armature within a clay sculpture because it provides a framework supporting softer surroundings. Its largest portion, the trunk, begins dorsorostrally at the hilus. Along its caudal course, the trunk emits limbs that, in turn, branch. Rostrally, the trunk and major limbs have their greatest diameters and contain lymphatic vessels and autonomic ganglia that are fewer or absent in the smaller divisions. Four to six orders of branching commonly occur. This architectural device constitutes a physical gradient which peaks at the hilus and is minimal where its components undergo the transition to the lobular parenchyma. The presence of an appreciable amount of connective tissue, nerves, and larger vessels would make this entity firmer than the highly hydrated parenchyma. The major divisions of this grouping are contacted by septa that extend from the organ capsule and demarcate lobules into which smaller divisions penetrate. The parenchyma is consequently ensconced between several strong structures containing abundant connective tissue. The dense collagen encompassing individual components of the biological armature would stabilize duct epithelium and its intercellular channels as well as brace vessels' walls. As a result of this architectural arrangement, the patency of all acinar, duct, and vascular structures is likely to persist despite neck and jaw movements that would otherwise distort them and thus hinder the formation and flow of saliva during feeding. This mechanism may be widespread among organs.

Mouse strain differences in susceptibility to sporidesmin‐induced biliary tract injury

Biliary tract injury was examined in four inbred strains of mice orally dosed with 500 micrograms of the fungal toxin sporidesmin. Semiquantitative histological analysis was used to assess the grade of necroinflammatory changes in the gall bladder, intra- and extrahepatic biliary tree and lobular parenchyma. Injury was greatest in the C57BL/6 and C3H strain mice and was least in SJL/J mice. In these strains injury was greatest at 4 days and had regressed by 10 days. In BALB/c mice the damage, although similar to that in SJL/J mice at 4 days, persisted at the same severity at day 10 and was accompanied by periductal fibrosis and occasionally by obliteration of ducts typical of sclerosing cholangitis. Analysis of the time-course of development of the lesions in C57BL/6 mice showed that the primary target for the toxin is the biliary epithelium. The severity of the lesions within the liver increased centripetally and the worst affected ducts were found at the confluence of the lobar ducts with the common bile duct. The variation in the degree of damage and rate of healing between strains may be due to differences in sporidesmin excretion in bile or interactions with biliary epithelial cells and/or efficacy of protective cellular repair mechanisms.