Microvillus inclusion disease: progressive mucosal pathology. A scanning and transmission electron microscopic study, and thoughts about possible pathogenesis.

An infant of African-American descent presented in the immediate newborn period with secretory diarrhea, the cause of which turned out to be microvillus inclusion disease (MID). Small intestinal mucosal biopsies at 6 weeks of age were diagnostic for MID by electron microscopy and repeat biopsies from the small intestine at 15 months demonstrated the seeming relentless progression of this disorder, when a normal structure and organization of small intestinal mucosa was no longer recognizable. Since the child could not tolerate any form of enteral nutrition, a small intestinal transplant was contemplated, but could not be done. The patient did not survive the consequences of an overwhelming sepsis, which resulted in multi-organ failure.

Loss of the glycocalyx of enterocytes in small intestine: a feature detected by scanning electron microscopy in children with gastrointestinal intolerance to dietary protein.

Observations are reported on biopsied small bowel mucosa by scanning and transmission electron microscopy in 10 infants and children with chronic diarrhea and intolerance to dietary protein(s). The most striking and consistent finding was widespread loss of glycocalyx from the surface of enterocytes, exposing the tips of the microvilli. Concomitantly, disaccharidase activities were markedly depressed in nine of the 10 patients, and such enzyme activities showed a tendency to return toward normal after removal of the offending dietary antigen(s) in concert with efforts to rebuild the glycocalyx. By light microscopy, no discernible structural damage was seen in eight of the 10 patients; two showed blunting of villi, but there was also loss of glycocalyx. The pathogenesis of the loss of the glycocalyx is unknown. Its finding is rather unique, because it has not been observed in any other condition characterized by chronic diarrhea in children. It is possible that the loss of the glycocalyx is a sequel to cell damage by a hitherto not defined interaction between host and dietary protein. Immunologic processes may be involved.

Chronic nonspecific diarrhea in children: investigation of the surface morphology of small bowel mucosa utilizing the scanning electron microscope.

Investigations by scanning electron microscopy into changes of surface morphology of small bowel mucosa in children with chronic nonspecific diarrhea are reported. The study population comprised 56 patients, ranging in age from 5 months to 7 years; 65% were between 10 and 28 months old, and 64% of the patients were boys. The major findings were: microorganisms on the mucosal surface; excessive extrusion of cell cytoplasm and of enterocytes (cell shedding); presence of excessive mucus on the mucosal surface; damage to the brush border; and partial villous atrophy. The latter lesion was found in only four patients. All these changes are considered pathologic and, for the most part, are presumed to be due to the presence of antigens, in particular, microorganisms. A depression of disaccharidase activities was encountered in 64% of the patients, but prevalence was without regard to age. Most common was a combined depression of lactase, sucrase, and maltase, as well as an isolated depression of lactase. The possibility has to be considered that enteroadherent microorganisms which are usually not considered pathogenic, and microorganisms such as Mycoplasma, may emerge as intestinal pathogens in susceptible children. It is feasible that genetic traits of the host and environmental factors facilitate adherence and colonization of the small bowel mucosa which, in turn, produces chronic diarrhea. Further studies are needed to confirm the preliminary information contained in this report.

The scanning electron microscope: how valuable in the evaluation of small bowel mucosal pathology in chronic childhood diarrhea?

Data are presented on scanning electron microscopy (SEM) on small intestinal biopsies of children with chronic diarrhea. In particular, there were 230 patients aged 3 months to 13 years with the following diagnoses: chronic nonspecific diarrhea, cow's milk protein intolerance, soy protein intolerance, giardiasis, cystic fibrosis, gluten-sensitive enteropathy, isolated lactase deficiency, isolated sucrase-isomaltase lactase deficiency, microvillus inclusion disease, rotavirus enteritis, protracted diarrhea of infancy, chylomicron retention disease, visceral myopathy and villous asthenia. Examination of biopsied intestinal mucosa by SEM has yielded important new information and insights on structural pathology and ultrastructural topography. Many of the observed changes helped to better understand the pathophysiology of some of the diarrheal disorders. SEM was also able to detect new features such as mycoplasma-like microorganisms and the absence of the glycocalyx. To adequately assess small bowel mucosal pathology at the ultrastructural level, scanning electron microscopy is an indispensable tool.

The small bowel mucosa in disease states characterized by chronic diarrhea: observations by scanning electron microscopy.

This paper summarizes observations by scanning electron microscopy (SEM) of surface ultrastructure of small bowel mucosa in patients (mostly children) with disorders characterized by chronic diarrhea. Included are chronic nonspecific diarrhea; conditions associated with villous damage, such as gluten-, milk protein- and soy protein-intolerance; giardiasis; cystic fibrosis and Crohn's disease. SEM has proven most useful to characterize pathologic processes on the surface of the small bowel mucosa, and thus has helped gain more insight to explain clinical symptoms. This was particularly true for chronic nonspecific diarrhea. It is predicted that SEM will become a valuable tool to aid in the diagnosis of diseases of the intestinal tract, which is considered one of the principal domains for such surface ultrastructure research.

Scanning electron microscopy of soy protein-induced damage of small bowel mucosa in infants.

Observations are reported by scanning electron microscopy (SEM) of soy protein-induced villous atrophy and mucosal recovery in two infants aged 5 weeks and 4 1/2 months. Whereas, by light microscopy, the mucosal lesions appeared similar, i.e., a flat mucosa, their appearance by SEM was different: the damage appeared more severe in the younger infant, although there was a shorter period of exposure to soy protein. The mucosal architecture was restudied 6 weeks after the initial biopsy. The degree of mucosal reconstruction was more advanced in the older infant--the one who showed less severe damage by SEM on the first biopsy. Although these investigations by SEM of damaged small bowel mucosa in soy protein intolerance did not contribute definite information to clarify the pathogenesis of villous atrophy in this condition, the injury was consistent with a lectin-induced toxicity, similar to the one postulated for celiac disease. SEM seems eminently suited to study of the effect of interactions between environment and host at mucosal surfaces; and finer gradations of damage to small bowel mucosa can be determined better by SEM, while this is not possible by light microscopy. Of interest was the rather extensive colonization of the mucosal surface by microorganisms in one of the two patients. However, the contribution of microbial colonization to mucosal damage could not be assessed.

Role of fat maldigestion in pathogenesis of steatorrhea in ileal resection. Fat digestion after two sequential test meals with and without cholestyramine.

To clarify the role of fat maldigestion in the pathogenesis of steatorrhea in patients with ileal resection the total and aqueous phase concentrations of bile acid and fatty acid were characterized in 8 such patients (5 patients with small ileal resection, bile acid diarrhea, and steatorrhea less than 20 g per day; 3 patients with large ileal resection, fatty acid diarrhea, and steatorrhea greater than 20 g per day) as well as 4 healthy control subjects after a morning and an afternoon liquid test meal. The study was then repeated with cholestyramine, 4 g being administered before each meal to induce fat maldigestion. After a conventional test meal, patients with large resections and severe steatorrhea had significantly lower aqueous phase concentrations of bile acids (and fatty acids) than patients with smaller resections or control subjects, explained in part by intraluminal precipitation of about one-half of the bile acids during digestion. When cholestyramine was administered before the meal, aqueous phase bile acid concentrations decreased in all patients, including the normal control subjects; the degree of fat maldigestion induced in the patients with small resections (and the control subjects) became similar to that present after the conventional test meal in the patients with large resections. Because steatorrhea increased little in the patients with small resections when cholestyramine was administered continuously, the data suggest that fat maldigestion per se does not induce severe fat malabsorption in patients with sufficient anatomical reserve, because such patients can absorb fat efficiently by utilizing the distal small intestine. In patients with large ileal resections, severe steatorrhea is explained in part by the combination of fat maldigestion and decreased surface area. It is also speculated that the steatorrhea occurring in patients with small resections and relatively normal fat digestion during two test meals may be explained by impaired fat digestion which occurs during the final meal of the day, which is often the largest meal.

[Diagnostic value of laboratory and scintigraphic investigations in young infants with cholestatic jaundice (author's transl)]. / Möglichkeiten der klinisch-chemischen und nuklearmedizinischen Diagnostik des Cholestase-Syndroms beim jungen Säugling.

The diagnostic value of laboratory and scintigraphic examination techniques in young infants with cholestatic jaundice will be discussed. The correct diagnosis of neonatal hepatitis or extrahepatic biliary atresia cannot be derived from such investigations as determination of bilirubin, enzyme activities, immunologic or serologic parameters or scintigraphy of the liver. Only quantitative changes of serum LP-X before and after administration of cholestyramin and the modified rose-bengal test may help to establish a correct diagnosis in cholestatic jaundice during the first 6 weeks of life.