https://www.ualberta.ca/~loewen/Medicine/GIM%20Residents%20Core%20Reading/DYSPEPSIA%20PLUS%20H.PYLORI/Dyspepsiapathophys.pdf

Pathophysiology and treatment of functional dyspepsia.

Context: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. Main Objective: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. Design: This was a randomized, double-blind, crossover study. Subjects: Subjects included normal human volunteers and patients with GH deficiency. Intervention: Intervention included saline or ghrelin (10 pmol/ kgmin) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. Main Outcome Measures: Measures consisted of gastric emptying parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. Results: The emptying rate was significantly faster for ghrelin (1.26 0.1% per minute), compared with saline (0.83% per minute) (P 0.001). The lag phase (16.2 2.2 and 26.5 3.8 min) and half-emptying time (49.4 3.9 and 75.6 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. Conclusion: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents. (J Clin Endocrinol Metab 91: 3296–3302, 2006)

/pdf/ghrelin-stimulates-gastric-emptying-and-hunger-in-normal-19c30m4nna.pdf

Ghrelin stimulates gastric emptying and hunger in normal-weight humans.

Although delayed gastric emptying is found in some patients with functional dyspepsia, there seems to be little relation between rate of emptying and symptoms. This study examined the hypothesis that food maldistribution rather than gastric stasis may equate to symptoms in such patients and used scintigraphic techniques to quantify the partition of gastric contents between proximal and distal stomach during gastric emptying. Eleven patients with functional dyspepsia characterised by chronic severe postprandial bloating without organic abnormality, and 12 healthy volunteers, ingested a standard meal labelled with technetium-99M (99mTc). Serial images of the gastric area in anterior and posterior projections were taken for 90 minutes, regions of interest for proximal, distal, and total stomach were defined, and activity time curves were derived from the geometric means of anterior and posterior counts. Total emptying in patients (median: 46 minutes; range: 30-76) was not significantly different from controls (45 minutes; 28-58) and only three showed delayed gastric emptying. In controls, food remained predominantly in the proximal half of the stomach after ingestion and then redistributed to the distal half. In the patients, however, initial activity in the proximal half after ingestion (48%; 40-65) was significantly lower (p < 0.05) than in controls (60%; 39-73) and distributed more fully to the distal half of the stomach with a peak distal activity (56%; 34-58), which was consistently higher than in controls (36%; 33-42) (p < 0.05). It is concluded that this subgroup of functional dyspepsia patients show abnormal intragastric distribution of food, independent of gastric emptying rate.

https://gut.bmj.com/content/gutjnl/35/3/327.full.pdf

Abnormal intragastric distribution of food during gastric emptying in functional dyspepsia patients.

In patients with functional dyspepsia, scanning by a novel ultrasonographic method was carried out to investigate postprandial accommodation of the proximal stomach. Twenty patients with functional dyspepsia and 20 controls were scanned fasting in a sitting position after drinking 500 ml meat soup. Images were recorded up to 25 min after the ingestion period using an ultrasound sector scanner with a 3.25-MHz transducer. The area in a sagittal section and the maximal diameter in an oblique frontal section were chosen as the main variables for calculating the emptying fraction of the proximal stomach, defined as: (aV2.5min-aVactual/aV2.5min. All subjects were asked to score total symptoms (1–9) provoked by the meal. From 7.5 to 25 min after the ingestion period the patients exhibited both smaller area in the sagittal section (P<0.018) and shorter diameter in the frontal section (P<0.046) compared with healthy controls, and they suffered more symptoms in response to the meal (P=0.002). Dyspeptic patients revealed higher emptying fractions (P=0.0005, ANOVA), andH. pylori status did not influence the emptying fractions. Diagnostic sensitivity of the method at 20 min postprandially was 70% and the specificity was 65%. Patients with functional dyspepsia have impaired accommodation of the proximal stomach to a meal, temporarily related to symptom induction.

Impaired accommodation of proximal stomach to a meal in functional dyspepsia

The physiology and pathophysiology of small bowel motility are reviewed with particular focus on the motility patterns and periods that are detected by intraluminal manometry. Motility patterns are groups of phasic pressure waves resulting from contractions of the circular muscle layer of the small bowel that are organized by the enteric nervous system. Phase III of the migrating motor complex, the hallmark of the fasting motility period, thus reflects enteric neuromuscular function. Response to meal challenge also involves the CNS, reflexes beyond the gut and endocrine responses. Although specific disease diagnosis cannot be made by motility studies of the small bowel, the functional integrity is revealed. The normal occurrence of the essential patterns and periods of motility and the absence of distinctly abnormal patterns evidence preserved function, whereas the opposite indicates clinically significant dysmotility. Certain motility patterns are occasionally seen both in health and disease, and increased prevalence indicates a moderate dysfunction of yet unclear significance. Bacterial overgrowth with Gram-negative bacilli is the consequence of severe small bowel dysmotility, and a diagnosis that can be predicted by a motility study. Testing can be useful in the clinical management of paediatric and adult patients also by predicting the prognosis and response to enteral nutrition and medical therapy. Further studies are, however, needed to take full advantage of motility testing in clinical practise.

The patterns of small bowel motility: physiology and implications in organic disease and functional disorders.

Gastric emptying, mouth-to-cecum transit (MCT), and whole-gut transit of a solid-liquid meal was measured in 30 control subjects and in 43 patients with essential dyspepsia, in whom organic digestive diseases and secondary disorders of gastric emptying had been excluded. The rate of gastric emptying was determined by an anterior gamma camera technique, MCT by the hydrogen breath test, and whole-gut transit by the first appearance of stool markers. Approximately 30% of patients with essential dyspepsia, predominantly women, in whom statistical analysis failed to reveal any specific pattern of symptoms, had significantly delayed gastric emptying suggesting idiopathic gastric stasis. Concerning MCT and whole-gut transit, significant differences between the control and study group could not be detected.

Friedhelm Leverkus

Papers

Frequency of idiopathic gastric stasis and intestinal transit disorders in essential dyspepsia.