Abnormal Small Intestinal Mucosa Research Articles

Small intestinal mucosal abnormalities using video capsule endoscopy in intestinal lymphangiectasia

BackgroundIntestinal lymphangiectasia (IL) is a rare protein-losing enteropathy caused by disorders of the intestinal lymphatics. There are only a few case reports and case series concerning the VCE (video capsule endoscopy) findings of IL. This work aimed to evaluate the VCE characteristics of small intestinal mucosal abnormalities in patients with IL, and to investigate the relationship between clinical and VCE characteristics.MethodsConsecutive patients with IL who underwent VCE were enrolled in this retrospective study. The cases were classified into the white villi group and non-white villi group according to mucosal abnormalities detected by VCE. Clinical and endoscopic characteristics were investigated and analyzed.ResultsA total of 98 patients with IL with a median onset age of 26.3 ± 19.2 years were included. VCE revealed the following small intestinal lesions: (i) white villi type (57/98, 58.2%), i.e.: white-tipped or granular villi, white nodular villi or plaques; (ii) non-white villi type (41/98, 41.8%), i.e.: diffused low and round villi; (iii) complications (46/98, 46.9%), i.e.: bleeding, ulcers, protruding or vesicular-shaped lesions, stenosis and lymphatic leakage. A total of 58.2% (57) and 41.8% (41) of the cases were classified into the white villi and non-white villi groups respectively. The percentage of chylothorax in the white villi group was significantly lower than that in the non-white villi group (12/57 vs. 19/41, p = 0.008). In VCE, there were no significant differences in the involved segments and total detected rate of complications between the white villi and non-white villi groups (p > 0.05), while the detected rate of lymphatic leakage in the white villi group was significantly higher than that in the non-white villi group (31.6% vs. 12.2%, p = 0.026).ConclusionsOur study evaluated the entire small intestinal mucosal abnormalities of IL by VCE, especially endoscopic complications. IL has specific VCE abnormalities in addition to classical endoscopic findings.

Incidence of Small Intestinal Lesions in Patients with Iron Deficiency Anemia

A major etiology of iron deficiency anemia (IDA) is chronic blood loss from the gastrointestinal tract or gynecological organs. The impact of small intestinal lesions on IDA is as yet unclear. The aim of the present study was to estimate the incidence of small intestinal lesions in patients with IDA and elucidate the pathogenic nature of small intestinal mucosal abnormalities for IDA. Between January 2007 and October 2008, a total of 30 IDA patients (hemoglobin (Hb) <13.5g/dL for all men and post-menopausal women, Hb <11.0g/dL for pre-menopausal women) without any bleeding sources detected by upper and lower endoscopy were enrolled. All patients underwent CE. The Given Imaging Ltd. database containing 61 healthy volunteers was used as a control. The prevalence of small intestinal lesions was compared. The prevalence of significant lesions including angioectasias, tumors and erosions was higher in patients with IDA than controls (46% vs. 15%, p<0.01). Multivariate analysis showed that IDA was related to significant lesions in the small intestine (OR: 4.7, 95%CI: 1.1-21.3, p=0.04). Subjects with iron deficiency anemia after negative work-up on the bleeding source by conventional upper and lower endoscopies should undergo capsule endoscopy.

SURVEILLANCE OF SMALL INTESTINAL ABNORMALITIES IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: A PROSPECTIVE CAPSULE ENDOSCOPY STUDY

Patients with hepatocellular carcinoma (HCC) sometimes suffer from obscure gastrointestinal bleeding. Portal hypertension (PH), common in cirrhosis, induces esophagogastric varices. Because of the location, PH also may influence mucosal abnormalities in the small intestine. The objective of this study is to estimate the prevalence of small intestinal mucosal abnormalities in HCC patients using capsule endoscopy (CE). We prospectively conducted CE in HCC patients, and analyzed the findings in relation to hepatic function, the number and size of HCC tumor and findings obtained by conventional endoscopy. Thirty-six patients (aged 66.7 ± 7.5 years, 29 men) underwent CE. Abnormal findings in the small bowel were found in 16 patients (44%), angioectasias in eight patients (22%), erosions in five (14%), varices in four (11%), polyps in four (11%), and submucosal tumor in one (3%). The patients with angioectasia had a larger spleen index than the no abnormal lesions group (85.4 ± 15.8 vs 59.0 ± 24.4, P = 0.02). The former group had been more frequently treated for esophageal varices endoscopically (62% vs 15%, P = 0.02). Large HCC nodules seemed more common in the patients with angioectasia than subjects without abnormal lesions (38% vs 5%, P = 0.06). Small intestinal varices also seemed to have a positive association with large HCC. During the follow up after CE, one patient with small intestinal polyps suffered from obscure gastrointestinal bleeding. CE revealed that HCC patients frequently have small intestinal mucosal lesions. In particular, small intestinal angioectasia, which may cause obscure gastrointestinal bleeding, seems to be associated with portal hypertension.

GASTROINTESTINAL ABNORMALITIES AND INVOLVEMENT IN SYSTEMIC MASTOCYTOSIS

Recent studies have shown that involvement of the gastrointestinal tract is much more frequent than originally reported in patients with systemic mastocytosis. Seventy percent to 80% of patients with systemic mastocytosis are found to have gastrointestinal symptoms when a careful history is taken, and abnormalities in the gastrointestinal tract are frequently detected by endoscopic studies, functional studies of absorption, and barium studies. Because of the rarity of the disease, there are few prospective studies of gastrointestinal involvement, so the actual frequency of upper and lower gastrointestinal lesions is unknown. Furthermore, there have been no studies correlating endoscopic abnormalities of the lower gastrointestinal tract with the presence or absence of diarrhea, which is a frequent symptom (mean, 43% [range 14%-100%]). A review of gastric acid studies reveals that a proportion of patients develop gastric acid hypersecretion because of the hyperhistaminemia, which can result in ulcer disease that in turn can cause dyspeptic pain, small intestinal mucosal damage, and malabsorption. In some patients gastric acid hypersecretion in the range seen in Zollinger-Ellison syndrome can develop. A number of studies suggest that the prevalence of peptic ulcer disease has been underestimated in these patients and is certainly higher than the general population. The exact physiologic basis for the diarrhea or nondyspeptic abdominal pain remains largely unknown in these patients. Whereas some studies suggest small intestinal mucosal abnormalities are responsible for most cases of malabsorption not associated with gastric acid hypersecretion, this supposition also remains unproven. Hepatomegaly, portal hypertension, splenomegaly, and ascites occur frequently in patients with systemic mastocytosis, especially those with category II through IV disease. Whereas the histology of the liver and spleen and alterations in hepatic function studies have been well studied, the pathogenesis of each of these abnormalities has not been well studied, and almost all the information comes from a few well-studied case reports.

Radiation effects in the small bowel of the diabetic mouse

Purpose : Irradiation of the small intestine in the mouse induces damaging structural alterations to the architecture of the enteric mucosa. There is growing interest in the possible relevance of underlying additional pathology when appreciating the total response of tissues to irradiation. The possibility that small intestinal mucosal abnormalities in the streptozotocin-induced diabetic mouse may exacerbate radiation-induced injury was tested by examining the combined effects of the two treatments. Materials and methods : Streptozotocin-diabetic and -non-diabetic mice were exposed to 10 Gy abdominal X-radiation. Profiles of mucosal epithelial cell populations were quantified and comparisons with corresponding groups of unirradiated mice made on the third day post-irradiation. Results : The histological appearances of the small intestinal mucosa were similar in both groups of irradiated mice, but the numbers of profiles of crypts and of columnar, goblet, Paneth and entero-endocrine cells were depressed in these groups when compared with values in corresponding groups of unirradiated mice. However, the expression of radiation damage in the diabetic mouse was less severe than in the non-diabetic mouse, particularly in the jejunum where the changes attendant on the onset of diabetes were most marked. Conclusion : These findings suggest that the response of mouse to radiation may be moderated by the presence of this type of pathophysiology. However, there is no evidence that the damage produced by streptozotocin-induced diabetes and radiation is additive.

Further studies of anti-endomysium and anti-gliadin antibodies in patients with suspected celiac disease.

The finding of characteristic small intestinal mucosal abnormalities on histologic examination of a biopsy specimen remains the first requirement for the diagnosis of celiac disease. A reliable and noninvasive test would be ideal for the patient's convenience and for reducing health-care costs. The sensitivity and specificity of anti-gliadin antibodies (AGA-immunoglobulin [Ig] G, AGA-IgA) have been variable; anti-endomysium IgA (EmA-IgA) is more helpful. In an earlier study conducted at the authors' institution, celiac disease was present in 19 patients examined from 1992 to 1995. Anti-endomysium titers were higher than normal in all 19 patients (100%). Total villous atrophy was seen in 14 of 17 biopsy specimens (82%) and subtotal atrophy in 3 (18%). The purpose of the current study was to evaluate further the accuracy of EmA-IgA in diagnosing celiac disease. One hundred seven patients were screened for celiac disease between March 1996 and July 1997. The level of EmA-IgA was measured in all patients, and AGA-IgG and AGA-IgA were measured in 104 patients. Forty-six patients underwent endoscopic biopsy of the small bowel, with measurement of disaccharidase enzymes in 45 patients. Five of 46 patients had celiac disease (three boys and two girls; mean age, 5.3 years; 2-9.5 years); one also had cystic fibrosis and another had insulin-dependent diabetes mellitus. All five had marked to complete villous atrophy with crypt hyperplasia and increased serum EmA-IgA (100% sensitivity). None of the remaining patients had increased EmA-IgA (100% specificity). Serum levels of AGA-IgG and AGA-IgA were increased in all four celiac disease patients (100% sensitivity), but they were also high in patients without celiac disease (38% and 92% specificity, respectively), which compromises their diagnostic value. None of the patients confirmed to have celiac disease had IgA deficiency. Abnormal disaccharidase enzyme activities were documented in all five celiac disease patients: severe generalized deficiency (n = 2), moderately severe generalized deficiency (n = 2), and alactasia with moderate deficiency of the alpha-glucosidases (n = 1). This study confirmed the reliability and accuracy of EmA-IgA in the diagnosis of celiac disease. Small bowel biopsy may be unnecessary in EmA-positive patients in whom celiac disease is suspected.

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

Food sensitive enteropathy: overview and update.

There are two types of food sensitive enteropathy; permanent and temporary. Celiac disease belongs to the former, the temporary food sensitive enteropathies of early childhood to the latter. A food sensitive enteropathy is characterized by an abnormal small intestinal mucosa while having the offending food in the diet; the abnormality is reversed by an elimination diet, only to recur once more on challenge with the relevant food. These disorders are temporary and may follow gastroenteritis. Cow's milk sensitive enteropathy is the most frequent and best known example but soy protein, egg, fish, chicken meat, ground rice and probably gluten may also temporarily damage the small intestinal mucosa in infancy. Treatment is with an elimination diet and protein hydrolysates as a cow's milk substitute. The reason why these enteropathies are temporary has not yet been established.

Current status of digestive intolerance to food protein

Digestive intolerance to food proteins may occur in childhood as a result of a wide range of etiologic and pathophysiologic mechanisms. Cow milk protein intolerance is the most common form of food intolerance in children. Food allergy and food intolerance may be confused because both produce similar symptoms, especially in young children with clinical manifestations of food allergy localized to the gastrointestinal tract. On the other hand, food-sensitive enteropathy may be defined as the clinical food-related syndromes associated with an abnormal small intestinal mucosa. Although several foods have been reported to damage the small intestinal mucosa in infancy (soy, rice, fish, chicken meat, egg), cow milk-sensitive enteropathy is the most common cause. Whatever the mechanisms, digestive intolerance to food proteins with or without enteropathy is primarily a temporary condition of infancy, in contrast to most forms of food allergy. In children with these disorders, symptoms usually resolve by 1 to 3 years of age. The variation in prevalence rates of this disorder in different countries can be explained by different diagnostic criteria. The classic food-sensitive enteropathy syndromes with chronic diarrhea and failure to thrive in infancy have become rarer in some European countries, including Spain. Some risk factors for the development of these conditions appear to be early exposure to cow milk feedings, acute infectious diarrhea, and malnutrition. Breast-feeding appears to be at least partially protective.

Cow milk-sensitive enteropathy: Predisposing factors and treatment

Cow milk-sensitive enteropathy is a temporary disorder of infancy characterized by a variably abnormal small intestinal mucosa while milk is in the diet. This abnormality is reversed by a cow milk-free diet, only to recur on challenge. Important predisposing factors are age (< 3 years), transient IgA immunodeficiency, atopy, and early bottle feeding. The disorder is diagnosed histologically by evidence of mild-to-moderate partial villous atrophy with thin, often patchy mucosa. For an accurate clinical diagnosis, challenge with the offending food after a demonstrated response to cow milk elimination is critical. When available, serial small intestinal bowel biopsies related to elimination and challenge are also important. Treatment is elimination of cow milk and all foods based on cow milk, and substitution of cow milk feedings with commercially available formulas free of cow milk protein. Five types of cow milk substitutes are described; only nutritionally complete formulas are recommended. Later, a milk challenge will determine the timing of safe reintroduction of cow milk to the diet, at a time when the child is gaining weight, thriving, and symptom free. This dietary treatment is always temporary; reintroduction of a normal diet is nearly always possible between 1 and 2 years of age.

Evaluation of a casein and a whey hydrolysate for treatment of cow's-milk-sensitive enteropathy.

A casein and a whey hydrolysate were evaluated in the management of 18 children with cow's-milk-sensitive enteropathy. This diagnosis was based upon clinical features, an abnormal small intestinal mucosa, i.e. an enteropathy, and a clinical response to cow's milk elimination. Two infants refused to take the whey hydrolysate. The median weight gain was higher in children given whey hydrolysate (19.4 g/day) than the casein hydrolysate (9.8 g/day). All children responded to cow's milk elimination and most had a significant improvement in small intestinal morphology after a cow's-milk-free diet. There was some advantage for the whey hydrolysate on morphometric analysis of their small intestinal mucosal response.

Zinc plasma levels after oral zinc tolerance test in nonalcoholic cirrhosis.

Zinc absorption was examined in 25 nonalcoholic cirrhotic patients using the oral zinc tolerance test and comparing results to a healthy control group. With 22.5 mg elementary zinc, the increase in plasma zinc was significantly lower in the cirrhotic patients than in the control group with P less than 0.01 in the first and second hours and P less than 0.05 in the fourth hour. The zinc malabsorption may result from an abnormal small intestinal mucosa. Indeed small intestinal biopsies in all patients showed partial shortening and prominent distension of villi and intense stromal edema with inflammatory cell infiltration of the lamina propria. However, it is not clear whether these intestinal changes are due to zinc deficiency or to portal hypertension. Thus zinc malabsorption appears to contribute to zinc deficiency in nonalcoholic cirrhotics and seems to result, in part, from pathological changes in the mucosa.

Small intestinal mucosal abnormalities in post-perinatal deaths.

Examination of small intestinal mucosa from cases of post-perinatal death in Sheffield between September 1980 and September 1981 showed mucosal changes before death in 18 of 78 cases (20%). There was no significant difference in prevalence between explained and unexplained deaths, nor was there any positive association with viral isolation from the small intestine. The lesion was much more common in males than females and showed a strong association with bottle feeding--no infant wholly breast fed showed an enteropathy. There was a low incidence of symptoms referrable to the gastrointestinal tract among affected infants, and no appreciable evidence of failure to thrive, as reflected by the postmortem body weight, was present. Mucosal changes of the small intestine in cases of sudden infant death syndrome have previously been reported and attributed to heatstroke. Although the finding of similar lesions in infants who died explicably does not appear to support this view, overheating is difficult to exclude as most of the explained deaths with a mucosal lesion occurred at home.

Macromolecular Absorption by Histologically Normal and Abnormal Small Intestinal Mucosa in Childhood

Knowledge of the mechanism of macromolecular absorption in the small intestine is based largely on animal studies. We have attempted to assess qualitatively and quantitatively the amount and the mechanism of uptake of horseradish peroxidase (HRP), a model macromolecule, in human small intestine, employing biopsy material from children undergoing gastrointestinal investigations. The biopsy material was incubated in culture medium containing HRP, and a comparison was made between histologically normal and histologically abnormal biopsies. In the normal specimens HRP was detected in pinocytotic vesicles along the villous epithelium. It was also seen in multivesicular bodies and in the interepithelial cell spaces at the base and tip of the villus. These latter areas corresponded to regions where damaged and extruding enterocytes, diffusely penetrated by HRP, were seen. This demonstrates that intact macromolecules can be taken up by normal small intestine in vitro in childhood and indicates two possible routes of antigen entry: (a) by active absorption through intact enterocytes and (b) through damaged or extruding cells. In the abnormal specimens the distribution of HRP was more varied. Most specimens showed an increased presence of HRP in the interepithelial cell spaces and an increased number of enterocytes diffusely penetrated by HRP, but a decrease in pinocytosis in the most severely abnormal enterocytes. An increase in HRP was also observed in the basement membrane and, in one instance, within capillaries of the lamina propria. It was concluded that when an enteropathy is present, an increase in mucosal permeability to macromolecules may result. This is most likely due to an increase in the passive diffusion of macromolecules into the mucosa.

Macromolecular Absorption by Histologically Normal and Abnormal Small Intestinal Mucosa in Childhood

Macromolecular Absorption by Histologically Normal and Abnormal Small Intestinal Mucosa in Childhood

Macromolecular Absorption by Histologically Normal and Abnormal Small Intestinal Mucosa in Childhood

SummaryKnowledge of the mechanism of macromolecular absorption in the small intestine is based largely on animal studies. We have attempted to assess qualitatively and quantitatively the amount and the mechanism of uptake of horseradish peroxidase (HRP), a model macromolecule, in human small intestine, employing biopsy material from children undergoing gastrointestinal investigations. The biopsy material was incubated in culture medium containing HRP, and a comparison was made between histologically normal and histologically abnormal biopsies. In the normal specimens HRP was detected in pinocytotic vesicles along the villious epithelium. It was also seen in multivesicular bodies and in the interepithelial cell spaces at the base and tip of the villus. These latter areas corresponded to regions where damaged and extruding enterocytes, diffusely penetrated by HRP, were seen. This demonstrates that intact macromolecules can be taken up by normal small intestine in vitro in childhood and indicates two possible routes of antigen entry: (a) by active absorption through intact enterocytes and (b) through damaged or extruding cells. In the abnormal specimens the distribution of HRP was more varied. Most specimens showed an increased presence of HRP in the interepithelial cell spaces and an increased number of enterocytes diffusely penetrated by HRP, but a decrease in pinocytosis in the most severely abnormal enterocytes. An increase in HRP was also observed in the basement membrane and, in one instance, within capillaries of the lamina propria. It was concluded that when an enteropathy is present, an increase in mucosal permeability to macromolecules may result. This is most likely due to an increase in the passive diffusion of macromolecules into the mucosa.

PATHOLOGICAL STUDY ON EARLY CHANGES OF CHOLERA PATIENTS

1) Morphological observations were made on 21 cholera patients who were autopsied soon after death. Since 19 of the cases were those dying within 41 hours after the onset, the changes with time in the early stage of cholera were studied.2) Small intestinal mucosal abnormalities are represented by acute inflammatory reactions and subsequent atrophic alteration of villous architecture. In these changes, the increased reproduction of epithelial cells in crypts by inflammatory stimulus seems to play an important role.3) Increased secretion of excretory glands was seen in goblet cells of the small and large intestines, in Paneth's cells of the intestine, and in goblet cells of the bronchi in cases of aspiration of gastric content. Increased secretion of pancreatic juice and bile was also observed.4) It is speculated that cholera toxin is absorbed by the intestine or some stimulating substance is produced in the intestine. This is suggested by a) reactions of the mesenteric lymphnodes and spleen, b) fatty changes of the liver and kidney, and c) increased secretion of pancreatic exocrine system.5) The death may be attributed to cardiac failure and swelling of the brain resulting from dehydration. Respiratory disturbance due to aspiration of gastric content should also be considered. Renal changes in the early stage of the disease are mild and consequent renal failure could have been prevented by proper transfusion.

Specificity of ultrastructural changes of small intestinal epithelium in early childhood.

Electron microscopical features of the small intestinal mucosa in 30 consecutive biopsies from 14 newly diagnosed coeliac patients, and 16 patients with chronic intermittent diarrhoea due to different causes, were studied. An attempt to define specific changes in each condition was made. An abnormal brush border, increased number of free ribosomes, rich rough endoplasmic reticulum, poorly developed smooth endoplasmic reticulum, large Golgi complexes, and thickened basal lamina were the most frequent findings in the coeliac biopsies. These changes suggest abnormal cellular metabolism, but as they were also observed in children with a variety of clinical conditions, they could not be specifically related to coeliac disease. These observations suggest that in small children different causes leading to different degrees of abnormal small intestinal mucosa, as observed with the light microscope, produce nonspecific changes of the cellular ultrastructure, which cannot be related to the degree of abnormality observed at the light microscope level.

Small intestinal mucosal abnormalities and disaccharidase activity in pernicious anaemia.

Summary. Patients with untreated pernicious anaemia usually show the following morphological and biochemical abnormalities in small‐intestinal biopsy specimens: (1) shortening of villi with diminished surface area; (2) megalocytic changes of the epithelial cells; (3) increased inflammatory infiltrate; (4) generalized depression of disaccharidases. These abnormalities revert to normal following treatment with injections of vitamin B12.

Incidence of small-intestinal mucosal abnormalities and of clinical coeliac disease in the relatives of children with coeliac disease.

Evidence is presented of a higher than normal incidence both of clinical coeliac disease and of small-intestinal mucosal abnormalities in relatives of children with coeliac disease. In such relatives the incidence of mucosal abnormality may differ from the incidence of clinical coeliac disease. The data show an absence of any simple Mendelian pattern of inheritance: in place of the hypothesis that inheritance is through a dominant gene of reduced penetrance, it is argued that the pathogenesis of coeliac disease is multifactorial, the genetic basis of susceptibility being polygenic and interacting with environmental factors. On this hypothesis the relative contributions of inheritance and environment to liability to the clinical condition are estimated, the genetic component being 45% +/- 9. Environmental factors appear more important in the development of mucosal abnormality.