The stomach in health and disease

Abstract

The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.

Keywords: GASTRIC DISEASES; GASTRIC MOTILITY; GASTRIC PHYSIOLOGY; IMMUNOLOGY; OBESITY.

Figure 1

Schematic outline of neural pathways and receptors involved in the control of the accommodation reflex in man. The identity of the nutrient sensors that trigger activation of the accommodation reflex and of other potentially involved neurotransmitters and receptors requires additional studies. CNS, central nervous system; cGMP, cyclic guanosine monophosphine; NO, nitric oxide; VIP, vasoactive intestinal peptide.

Figure 2

(A) Example of intragastric pressure response and satiation score evolution during intragastric nutrient infusion. Nutrient infusion induces an initial drop in pressure, followed by gradual recovery associated with rising satiation scores. (B) Schematic conceptual model of gastric mechanoreceptors, relative to the muscular compartment. The four panels represent the modelled differential behaviour of `in series' tension receptors and `in parallel' elongation receptors during distension or contraction.

Figure 3

Schematic outline of gastric events and their relationships in response to nutrient ingestion. TLESR, transient lower oesophageal sphincter relaxation.

Figure 4

Caloric intake at maximum satiation by gender and body mass index. There was higher caloric intake at maximum satiation in male subjects compared with women (left). Reproduced from ref. 82.

Figure 5

Immunological interactions in response to H. pylori infection. APC, antigen-presenting cells; IFN, interferon; IL, interleukin; TNF, tumour necrosis factor.

Figure 6

(A) Non-atrophic H. pylori-associated gastritis: The number of the native antral glands is within the normal limits; inflammatory cells are detectable in the lamina propria (H&E; original magnification ×25). (B) Atrophic gastritis with extensive gastric glands intestinalisation (intestinal metaplasia of the native mucus secreting antral glands) (H&E; original magnification ×25). (C) Atrophic gastritis. The population of the resident glands is decreased (`mucosa desertification'); the glandular units are replaced by extensive fibrosis of the lamina propria (H&E; original magnification ×25). (D) Intraepithelial neoplasia ((IEN), ie, dysplasia) in intestinalised glands. The glandular structures are crowded (back to back appearance), and the dysplastic glandular units show columnar atypical epithelia (H&E; original magnification ×40).

Figure 7

Birth cohort patterns of common digestive diseases in mortality data from England and Wales. GCA, gastric cancer; GU, gastric ulcer; DU, duodenal ulcer; Rectum, rectum cancer; Colon, colon cancer

Figure 8

Classification of gastric cancer based on gene expression patterns. Adapted from ref. 189. CIMP, CpG Island Methylator Phenotype; EBV, Epstein–Barr virus.

Figure 9

(A and B) A small gastric cancer detected by magnification endoscopy equipped with image-enhanced modalities. A small flat lesion with abnormal surface mucosal patters that is sharply demarcated by normal mucosa showing regular pit pattern. Inside the lesion, irregular, tortuous cork-screw like vessels can be identified. Alteration of mucosal surface pattern together with the presence of irregular vessels suggests early gastric cancer. Histology of the endoscopically resected specimen verified the diagnosis of gastric cancer. NBI, narrow band imaging; FICE, flexible spectral imaging colour enhancement.

Figure 10

Key functions of the stomach and common harmful and noxious agents that affect gastric mucosal, secretory and motor functions.