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Gastroenterology Feb 2022The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface... (Review)
Review
The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications.
Topics: Animals; Cell Plasticity; Cellular Reprogramming; Gastric Mucosa; Helicobacter Infections; Humans; Hyperplasia; Metaplasia; Parietal Cells, Gastric; Regeneration; Stomach
PubMed: 34728185
DOI: 10.1053/j.gastro.2021.10.036 -
Autopsy & Case Reports 2023
PubMed: 36855561
DOI: 10.4322/acr.2023.421 -
The EMBO Journal Oct 2015The self-renewal and differentiation of tissue stem cells must be tightly controlled. Unrestrained self-renewal leads to over-proliferation of stem cells, which may...
The self-renewal and differentiation of tissue stem cells must be tightly controlled. Unrestrained self-renewal leads to over-proliferation of stem cells, which may cause tumor formation, while uncontrolled differentiation leads to depletion of the stem cell pool. In this issue of , Demitrack (2015) show that the Notch pathway is a key regulator of Lgr5 antral stem cell self-renewal and differentiation. Notch signaling controls the proliferation and differentiation of stem cells as well as gastric tissue growth, while uncontrolled Notch activity in stem cells leads to polyp formation.
Topics: Animals; Homeostasis; Pyloric Antrum; Receptors, G-Protein-Coupled; Receptors, Notch; Signal Transduction; Stem Cells
PubMed: 26358838
DOI: 10.15252/embj.201592859 -
Journal of Anatomy Apr 2022The strengths, directions and coupling of the movements of the stomach depend on the organisation of its musculature. Although the rat has been used as a model species...
The strengths, directions and coupling of the movements of the stomach depend on the organisation of its musculature. Although the rat has been used as a model species to study gastric function, there is no detailed, quantitative study of the arrangement of the gastric muscles in rat. Here we provide a descriptive and quantitative account, and compare it with human gastric anatomy. The rat stomach has three components of the muscularis externa, a longitudinal coat, a circular coat and an internal oblique (sling) muscle in the region of the gastro-oesophageal junction. These layers are similar to human. Unlike human, the rat stomach is also equipped with paired muscular oesophago-pyloric ligaments that lie external to the longitudinal muscle. There is a prominent muscularis mucosae throughout the stomach and strands of smooth muscle occur in the mucosa, between the glands of the corpus and antrum. The striated muscle of the oesophageal wall reaches to the stomach, unlike the human, in which the wall of the distal oesophagus is smooth muscle. Thus, the continuity of gastric and oesophageal smooth muscle bundles, that occurs in human, does not occur in rat. Circular muscle bundles extend around the circumference of the stomach, in the fundus forming a cap of parallel muscle bundles. This arrangement favours co-ordinated circumferential contractions. Small bands of muscle make connections between the circular muscle bundles. This is consistent with a slower conduction of excitation orthogonal to the circular muscle bundles, across the corpus towards the distal antrum. The oblique muscle merged and became continuous with the circular muscle close to the gastro-oesophageal junction at the base of the fundus, and in the corpus, lateral to the lesser curvature. Quantitation of muscle thickness revealed gradients of thickness of both the longitudinal and circular muscle. This anatomical study provides essential data for interpreting gastric movements.
Topics: Animals; Esophagogastric Junction; Esophagus; Muscle Contraction; Muscle, Skeletal; Muscle, Smooth; Rats
PubMed: 34747011
DOI: 10.1111/joa.13587 -
Microorganisms Jan 2021We aimed to provide insight into the actual frequencies of gastric adenoma types and their association with gastritis status and associated mucosal changes with a focus...
BACKGROUND
We aimed to provide insight into the actual frequencies of gastric adenoma types and their association with gastritis status and associated mucosal changes with a focus on Helicobacter infection and the operative link on gastritis assessment (OLGA)/operative link on gastric intestinal metaplasia assessment (OLGIM) staging.
METHODS
From the archive of the Institute of Pathology in Bayreuth, we collected a consecutive series of 1058 gastric adenomas diagnosed between 1987 and 2017. Clinicopathological parameters retrieved from diagnostic reports included adenoma type and localization, associated mucosal changes in antrum and corpus (i.e., type of gastritis, the extent of intestinal metaplasia and atrophy), gender, date of birth, and date of diagnosis.
RESULTS
Intestinal-type adenoma was the most frequent adenoma (89.1%), followed by foveolar-type adenoma (4.3%), pyloric gland adenoma (3.4%), adenomas associated with hereditary tumor syndromes (2.8%), and oxyntic gland adenoma (0.4%). Adenomas were found in the background of () gastritis in 23.9%, Ex- gastritis in 36.0%, autoimmune gastritis in 24.8%, chemical reactive gastritis in 7.4%, and others in 0.1%. More than 70% of patients with gastric adenomas had low-risk stages in OLGA and OLGIM.
CONCLUSIONS
We found a higher frequency of foveolar-type adenoma than anticipated from the literature. It needs to be questioned whether OLGA/OLGIM staging can be applied to all patients.
PubMed: 33466325
DOI: 10.3390/microorganisms9010108 -
Nutrients Jan 2022(1) Background: Acute muscle inflammation leads to increased sonographic echodensity. We developed a technique to characterize the echodensity of the gastric antrum wall...
(1) Background: Acute muscle inflammation leads to increased sonographic echodensity. We developed a technique to characterize the echodensity of the gastric antrum wall and assess its feasibility in evaluating the severity of acute gastrointestinal injury (AGI); (2) Methods: The B-mode images of the gastric antrum of each enrolled patient were obtained daily by point-of-care ultrasound (POCUS). The 50th percentile, 85th percentile, and mean value of the grayscale distribution according to histogram analysis (ED50, ED85, and EDmean, respectively) were used to characterize the gastric antrum echodensity. Consistency and correlation analyses were performed to evaluate the feasibility and reproducibility of gastric antrum echodensity measurement. The association of gastric antrum echodensity with the severity of AGI and its ability to predict feeding intolerance (FI) were analyzed; (3) Results: In total, 206 POCUS images of 43 patients were analyzed. The gastric antrum echodensity measurements had sufficient intra- and inter-investigator reliabilities (intraclass correlation coefficient >0.9 for all parameters). The ED50 showed a significant upward trend as AGI severity increased, as well as ED85 and EDmean (p for trend <0.001, respectively). Patients who experienced FI had a higher ED50 (67.8 vs. 56.1, p = 0.02), ED85 (85.6 vs. 71.2, p = 0.01), and EDmean (70.3 vs. 57.6, p = 0.01) upon enteral feeding initiation; (4) Conclusions: Measurement of gastric antrum echodensity was technically feasible and reproducible in ventilated patients. Increased gastric antrum echodensity was associated with greater severity of AGI. Patients with higher gastric antrum echodensity upon enteral nutrition initiation via a nasogastric tube were more likely to develop FI.
Topics: Critical Illness; Enteral Nutrition; Humans; Infant, Newborn; Pyloric Antrum; Reproducibility of Results; Ultrasonography
PubMed: 35276925
DOI: 10.3390/nu14030566 -
Nature Communications Dec 2023PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are...
PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, and organoid assays identify regional subpopulations and supportive capacities of purified mouse corpus and antral PDGFRA cells. Sub-epithelial PDGFRA myofibroblasts are principal sources of BMP ligands and two molecularly distinct pools distribute asymmetrically along antral glands but together fail to support epithelial growth in vitro. In contrast, PDGFRA CD55 cells strategically positioned beneath gastric glands promote epithelial expansion in the absence of other cells or factors. This population encompasses a small fraction expressing the BMP antagonist Grem1. Although Grem1 cell ablation in vivo impairs intestinal stem cells, gastric stem cells are spared, implying that CD55 cell activity in epithelial self-renewal derives from other subpopulations. Our findings shed light on spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for epithelial support.
Topics: Mice; Animals; Stomach; Gastric Mucosa; Stem Cells; Intestines; Pyloric Antrum; Receptor Protein-Tyrosine Kinases; Epithelial Cells
PubMed: 38042929
DOI: 10.1038/s41467-023-43619-y -
American Journal of Physiology.... Apr 2021Following a classical paper by Dr. Keith A. Kelly published in this journal, and over the past 40 years, there has been increased understanding of the functions of...
Following a classical paper by Dr. Keith A. Kelly published in this journal, and over the past 40 years, there has been increased understanding of the functions of different regions of the stomach, specifically the fundus, antrum, and pylorus. Several of the important physiological principles were based on in vivo animal studies that led to the appreciation of regional function and control mechanisms. These include the roles of the extrinsic parasympathetic vagal innervation, the gastric enteric nervous system and electrical syncytium consisting of pacemaker cells and smooth muscle cells, and duodenogastric reflexes providing feedback regulation following the arrival of food and hydrogen ions stimulating the release of hormones and vagal afferent mechanisms that inhibit gastric motility and stimulate pyloric contractility. Further insights on the role of regional motor functions in gastric emptying were obtained from observations in patients following diverse gastric surgeries or bariatric procedures, including fundoplication, Billroth I and sleeve gastrectomy, and sleeve gastroplasty. Antropyloroduodenal manometry and measurements of pyloric diameter and distensibility index provided important assessments of the role of antral hypomotility and pylorospasm, and these constitute specific targets for individualized treatment of patients with gastroparesis. Moreover, in patients with upper gastrointestinal symptoms suggestive of gastroparesis, the availability of measurements of gastric accommodation and pharmacological agents to reduce gastric sensitivity or enhance gastric accommodation provide additional specific targets for individualized treatment. It is anticipated that, in the future, such physiological measurements will be applied in patients to optimize choice of therapy, possibly including identifying the best candidate for pyloric interventions.
Topics: Animals; Clinical Decision-Making; Enteric Nervous System; Gastric Emptying; Gastroparesis; Humans; Manometry; Muscle Contraction; Muscle, Smooth; Predictive Value of Tests; Pressure; Prognosis; Stomach
PubMed: 33566731
DOI: 10.1152/ajpgi.00006.2021 -
Autonomic Neuroscience : Basic &... May 2023Substance-P (SP) is a commonly used marker of nociceptive afferent axons, and it plays an important role in a variety of physiological functions including the regulation...
Substance-P (SP) is a commonly used marker of nociceptive afferent axons, and it plays an important role in a variety of physiological functions including the regulation of motility, gut secretion, and vascular flow. Previously, we found that SP-immunoreactive (SP-IR) axons densely innervated the pyloric antrum of the flat-mount of the mouse whole stomach muscular layer. However, the regional distribution and morphology of SP-IR axons in the submucosa and mucosa were not well documented. In this study, the mouse antrum-pylorus-duodenum (APD) were transversely and longitudinally sectioned. A Zeiss M2 imager was used to scan the serial sections of each APD (each section montage consisted of 50-100 all-in-focus maximal projection images). To determine the detailed structures of SP-IR axons and terminals, we used the confocal microscope to scan the regions of interest. We found that 1) SP-IR axons innervated the muscular, submucosal, and mucosal layers. 2) In the muscular layer, SP-IR varicose axons densely innervated the muscles and formed varicose terminals which encircled myenteric neurons. 3) In the submucosa, SP-IR axons innervated blood vessels and submucosal ganglia and formed a network in Brunner's glands. 4) In the mucosa, SP-IR axons innervated the muscularis mucosae. Some SP-IR axons entered the lamina propria. 5) The muscular layer of the antrum and duodenum showed a higher SP-IR axon density than the pyloric sphincter. 6) SP-IR axons were from extrinsic and intrinsic origins. This work provided a comprehensive view of the distribution and morphology of SP-IR axons in the APD at single cell/axon/varicosity scale. This data will be used to create a 3D scaffold of the SP-IR axon innervation of the APD.
Topics: Mice; Animals; Pylorus; Substance P; Axons; Duodenum; Neurons
PubMed: 36804650
DOI: 10.1016/j.autneu.2023.103074 -
Anaesthesia Sep 2017We aimed to measure gastric antral cross-sectional area with ultrasound and estimate the gastric volume of 300 patients before unplanned surgery, fasted for at least six...
We aimed to measure gastric antral cross-sectional area with ultrasound and estimate the gastric volume of 300 patients before unplanned surgery, fasted for at least six hours. Measurements were successfully recorded in 263 semi-recumbent patients. The median (IQR [range]) area was 333 (241-472 [28-1803]) mm and the mean (SD) estimated volume was 45.8 (34.0) ml. The area exceeded 410 mm in 92/263 (35%) measurements. Body mass index and morphine administration were associated with larger gastric areas on multivariable linear regression analysis, with beta coefficient (95%CI) 0.02 (0.01-0.04), p = 0.01, 0.23 (0.01-0.46), p = 0.04, respectively. Fasting time was not associated with gastric area and therefore could not substitute for ultrasound measurements in this cohort.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anatomy, Cross-Sectional; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Emergency Medical Services; Fasting; Female; Gastric Emptying; Humans; Male; Middle Aged; Morphine; Pyloric Antrum; Reproducibility of Results; Respiratory Aspiration of Gastric Contents; Stomach; Ultrasonography; Young Adult
PubMed: 28695978
DOI: 10.1111/anae.13963