Impact of Different Exposures, Including Environmental Enteropathies, on Gut Flora and Integrity
Crystal D. Karakochuk, Kyly C. Whitfield, Tim J. Green, Klaus Kraemer in The Biology of the First 1,000 Days, 2017
Environmental enteropathy is defined as a subclinical disorder resulting in structural and functional changes to the small intestine. The morphologic changes are proposed to occur through a T-cell mediated process characterized by a disruption in the balance between the proinflammatory (e.g., tumor necrosis factor alpha and interferon gamma) and regulatory cytokine-producing cells (e.g., transforming growth factor beta) [18]. The alterations include villous shortening and atrophy, crypt hyperplasia, and inflammatory cell infiltrate (e.g., lymphocytes and plasma cells) in the epithelium and lamina propria [16] (Figure 20.1). Gut function is consequently impaired. The damage to epithelial cells results in a loss of essential enzymes, and the decrease in the functional surface area of the intestinal epithelium causes maldigestion and malabsorption. An increase in gut permeability occurs due to the epithelial disruption leading to microbial translocation. This translocation into the systemic circulation consequently causes a state of chronic inflammation [16,19]. and altered intestinal resistance. The resulting in lowered immunity, increased susceptibility to infection, and loss of appetite, propagates the inflammation and malnutrition cycle (Figure 20.2) [20,21]. Continuous exposure to the enteric pathogens results in a state of perpetual hyperstimulation of the mucosal immune system. This is likely why oral vaccines, such as polio and rotavirus vaccines, are less effective in children with EED [22].
Other Complications of Diabetes
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
The esophageal manifestations of diabetic neuropathy result in dysphagia and heartburn, but only in a minority of patients. Gastroparesis causes nausea, vomiting, early satiety, bloating, postprandial fullness, and upper abdominal pain. Delayed gastric emptying is a contributing factor of poor blood glucose control. It may be the first sign of gastroparesis. Intestinal enteropathy can cause constipation, diarrhea, and fecal incontinence. Impaired motility of the small intestine can lead to stasis syndrome, resulting in diarrhea, which can be intensified by hypermotility due to decreased sympathetic inhibition, pancreatic insufficiency, malabsorption of bile salts, and steatorrhea. Fecal incontinence may result from abnormal internal and external anal sphincter function due to neuropathy. Most patients with nonalcoholic fatty liver disease are asymptomatic, but some have malaise or right upper-quadrant fullness. The disease can range from a slight elevation of liver enzymes to severe liver disease with fibrosis and nodular regeneration, but this development is rare.
Gastrointestinal tract lymphomas
Franco Cavalli, Harald Stein, Emanuele Zucca in Extranodal Lymphomas, 2008
Most patients show the HLA DQA1*0501, DQB1*0201 genotypes that characterize celiac disease.101 It occurs most often in the sixth or seventh decades, but there have been sporadic reports of cases in young adults. Abdominal pain and/or exacerbation of enteropathy-associated symptoms (malabsorption, loss of responsiveness to a gluten-restricted diet) are the most common presentation features. Approximately 25% of cases present with an intestinal perforation. The clinical course is often very unfavorable, and most patients die due to multiple perforations of the intestine. A variety of combination chemotherapy regimens have been proposed, but responses to the therapy (which is often poorly tolerated because of the malnourished state of most patients) are in general scarce and brief.97
Duodenal eosinophils as predictors of symptoms in coeliac disease: a comparison of coeliac disease and non-coeliac dyspeptic patients with controls
Published in Scandinavian Journal of Gastroenterology, 2020
Michael D. Potter, James S. Hunt, Marjorie M. Walker, Mike Jones, Cheng Liu, Martin Weltman, Nicholas J. Talley
We were unable to demonstrate an association between the severity of histological changes, specifically villous atrophy, and symptoms. This is consistent with previous studies. A cohort study of 499 adults examining the mode of presentation and the degree of villous atrophy demonstrated no significant correlation between the degree of atrophy and either a classic (diarrhoea/weight loss) or atypical (anaemia/osteoporosis or dermatitis herpetiformis) presentation (p = .25) [26]. A large cohort study of 1408 adult coeliac patients compared the mode of clinical presentation with the severity of enteropathy, and demonstrated no significant differences in regards to any presenting symptom (including dyspepsia, diarrhoea, abdominal pain, nausea, vomiting and constipation) [16]. A positive association was demonstrated in regards to the severity of enteropathy and the presence of anaemia (p < .0001) and low ferritin (p = .01) [16]. Our results support this observation, with more severe enteropathy associated with iron deficiency at presentation in our cohort.
Persistent diarrhoea: current knowledge and novel concepts
Published in Paediatrics and International Child Health, 2019
Robert H. J. Bandsma, Kamran Sadiq, Zulfiqar A. Bhutta
As in high-income settings, PD can be related to underlying immunological causes such as cow milk protein allergy [48]. Monogenic diseases, e.g. prohormone convertase 1/3 deficiency or microvillus inclusion disease, can also lead to persistent and ultimately chronic diarrhoea, often commencing in the neonatal period or early infancy. Monogenic causes of diarrhoea are mostly autosomal recessive, and in countries in which co-sanguinity is more prevalent, children are disproportionally affected. Congenital causes of persistent and chronic diarrhoea related to mutations in genes directly responsible for aspects of intestinal function such as microvillous inclusion disease will probably also be responsible for rare cases of diarrhoea in neonates and infants in low-resource countries but will often go undiagnosed. Congenital causes of enteropathy have been reviewed previously [49]. Very early-onset IBD is a rare group of diseases which are mostly linked to mutations in genes involved in the regulation of immunological function [50]. Symptoms and histological features may overlap with infectious causes of PD and the diagnosis can be challenging.
Gastrointestinal manifestations of primary immune deficiencies in children
Published in International Reviews of Immunology, 2018
Naila Nazi, Fani Ladomenou
Common variable Table 1, Table 2 immune deficiency (CVID) is a primary immune deficiency caused by a defect in antibody production. Inheritance is sporadic for the majority of cases but can be familial in 10 to 20% of patients. Most of the genes causing CVID remain undiscovered and the ones we currently know about include ICOS, TACI, CD19, CD20, CD21, CD81 and BAFF-R. It is thought that mutations in these genes impair B cell activation, function, survival, and co-stimulation.11 The diagnosis of CVID is based on reduced levels of two serum immunoglobulins, IgG and IgA and/or IgM, at least 2 standard deviations below the age-specific mean values, in addition to impaired specific antibody production in response to recent infection or vaccination.12 The estimated prevalence is 1/50,000 to 1/125,000 in the Caucasian population. This condition presents in childhood however it is usually diagnosed in adulthood with the average age at diagnosis being 28–32 years.13 The gastrointestinal tract is the second most commonly affected organ system after the lungs14 and up to 50% of patients with CVID can have gastrointestinal complaints.15 Non-infectious chronic enteropathy can affect up to 10% of patients and can mimic disorders such as inflammatory bowel disease or coeliac disease.
Related Knowledge Centers
- Enteritis
- Gastrointestinal Tract
- Inflammation
- Small Intestine
- Pathology
- Eosinophil
- Enteropathy-Associated T-Cell Lymphoma
- Environmental Enteropathy
- Intestinal Mucosal Barrier
- Eosinophilic Gastroenteritis