The stomach is a key part of the gastrointestinal (GI) tract, sitting between the esophagus and duodenum. Its functions are to mix food with stomach acid and break food down into smaller particles using chemical and mechanical digestion.
The stomach can perform these roles due to the layers of the stomach wall. These are the gastric mucosa, submucosa, muscularis externa and serosa. All parts of the GI tract tend to follow this same pattern of tissue layer arrangement, which means that the stomach is essentially just a widening of the GI tube. These layers are best observed when you’re looking at the microanatomy, or histology, of the stomach.
Surface mucous cells: simple columnar epithelium
Gastric pits: surface mucous cells
Gastric glands: parietal, chief, enteroendocrine cells
Lamina propria: connective tissue
Muscularis mucosa: two smooth muscle layers
|Submucosa||Connective tissue, submucosal (Meissner’s) plexus|
|Muscularis externa||Smooth muscle layers (longitudinal, circular, oblique), myenteric (Auerbach’s) plexus|
|Serosa||Connective tissue, mesoderm|
Histology may not be the easiest to digest, but we will help you sink your gnashers right into this topic and break it down into small logical sections. No hydrochloric acid needed! If you still find it daunting, why not brush up on your histology basics first?
- Stomach wall
- Muscularis externa
The stomach wall consists of 4 layers of tissue. From deep (external) to superficial (internal) these are the serosa, muscularis externa, submucosa and mucosa. This layered arrangement follows the same general structure in all regions of the stomach, and throughout the entire gastrointestinal tract. The outer layer of the stomach wall is smooth, continuous with the parietal peritoneum. The inner wall (mucosa and submucosa layers) is thrown into folds known as rugae, or gastric folds, which allow the stomach to distend upon the entry of the food. A bolus of food enters the stomach from the esophagus. The various tissue layers of the stomach wall then combine their functions to digest the bolus into a viscous, pulpy fluid called chyme. Chyme is directed into the duodenum of the small intestine for further digestion and absorption.
You can easily remember the four layers of the stomach wall using the mnemonic 'M.S.M.S'. It stands for: Mucosa, Submucosa, Muscularis externa & Serosa.
Although the stomach is anatomically divided into four regions, histologically we identify only three; cardia, fundus and pylorus. This is because the fundus and body are histologically identical. Let’s now take a closer look at the 4 layers of the stomach, as well as their regional variations.
The innermost layer of the stomach wall is the gastric mucosa. It is formed by a layer of surface epithelium and an underlying lamina propria and muscularis mucosae. The surface epithelium is a simple columnar epithelium. It lines the inside of the stomach as surface mucous cells and forms numerous tiny invaginations, or gastric pits, which appear as millions of holes all throughout the stomach lining. These gastric pits are important as they are connected to the various glands of the stomach.
There are 3 types of glands found in the stomach; cardiac, gastric and pyloric, named after the region in which they are found. These glands produce the digestive enzymes and mucous secretions of the stomach. The gastric glands of the fundus/body have the important role of producing digestive gastric juice while the cardiac and pyloric glands predominantly produce mucous secretions which protect the stomach from the harsh effects of the digestive acid and prevent stomach self-digestion.
Surface mucous cells
The surface mucous cells, also known as foveolar epithelium, are the simple columnar epithelium lining the lumen of the stomach. They secrete alkaline, highly viscous mucus, which closely adheres to the cellular surface.
The mucus protects the stomach lining by minimising the abrasion from food particles and forming a physical barrier from the hydrochloric acid, in which the mucous cells are constantly bathed. Without these mucous secretions the stomach acid would literally burn holes through the stomach wall! They stain fairly lightly in H&E sections due to the mucin they contain, because it doesn’t pick up either of the stains particularly well.
Gastric pits are formed by invaginations of the surface epithelium. Gastric pits connect to gastric glands and thus allow the glandular products to be delivered into the stomach lumen. The pits are lined with the same mucus secreting surface epithelium that faces the stomach lumen. In a histological section these will often be cut transversely rather than longitudinally, so will appear as small circular openings, rather than tubular invaginations.
Gastric glands open into the base of gastric pits. They are found throughout the entire inner surface of the stomach and are divided into 3 types depending on the region in which they are found. Gastric glands proper (principal glands) are found in the fundus/body of the stomach. The cells of these glands produce around two litres of gastric juice a day. The mucus secreting pyloric glands are only associated with the pyloric antrum and cardiac glands are located only within the cardia of the stomach.
Gastric pits and gastric glands are made up of the same 5 cell types: mucous neck cells, stem cells, parietal (oxyntic) cells, chief (zymogenic) cells and enteroendocrine cells. You can see these cells, as well as the substances they secrete, summarised in the table below.
|Mucous neck cells||
Mucus secretion (less alkaline than that of the surface epithelial mucous cells)
Round nuclei and apical secretory granules
Shorter than surface mucous cells
|Stem cells||Replace damaged cells|
|Parietal (oxyntic) cells||Intrinsic factor production
Hydrochloric acid (HCl) secretion
Large round or pyramidal cells
Highly acidophilic (stain pink)
Central rounded nuclei
|Chief (zymogenic) cells||Pepsinogen and gastric lipase secretion
Found in lower regions of gastric glands
Basophilic (stain blue)
|Enteroendocrine cells||Gastrin (released into blood)
Single cells (don’t form clusters)
All 3 types of glands are long, branched, tubular structures, extending through the whole thickness of the lamina propria. However, their cellular composition differs based on their location and associated function. Gastric glands proper are very rich in digestive enzyme producing parietal and chief cells, as the majority of digestion takes place in the body and fundus of the stomach. Pyloric and cardiac glands largely lack parietal and chief cells, but have abundant mucous neck cells. This makes sense, as these segments are areas of transition between the stomach and other parts of the GI tract. Therefore, the mucous secretions they produce protect the esophagus and the duodenum from the corrosive effects of the gastric juices. Enteroendocrine cells are scattered throughout all types of gastric glands.
Stem cells are concentrated in the region of the gland known as the isthmus or neck. It is a transitional area between the gastric glands and the gastric pits. That allows stem cells to migrate both up the gastric pit and down to the gastric glands to replace damaged cells. The surface and gastric pit cells are constantly surrounded by a very harsh environment and so have a high cell turnover of only 4 to 7 days, while the turnover of the cells in the gastric glands is slower. The isthmus also contains mucous neck cells and some surface mucous cells.
Lamina propria and muscularis mucosae
The muscularis mucosae layer consists of two thin layers of smooth muscle. It separates the lamina propria from the underlying submucosa. The inner layer of muscularis mucosae consists of circular fibres while the outer layer fibres are arranged longitudinally. Its function is to help expel the secretions of the gastric glands into the stomach lumen.
Test yourself on the histology of the upper GI tract with this custom quiz.
Deep to the mucosa is a thick layer of connective tissue known as the gastric submucosa. Its arrangement means that it is durable, yet flexible and mobile. Aside from rich vasculature and lymphatics, this layer also holds the submucosal (Meissner’s) plexus. The nerve fibres of this plexus carry parasympathetic innervation to the blood vessels and smooth muscle of the stomach wall. Parasympathetic stimulation is associated with ‘rest and digest’ functions and therefore, stimulates digestion.
The gastric muscularis externa, also known as tunica muscularis, is the smooth muscle located deep to the submucosa. It is made up of 3 layers: inner oblique, middle circular and outer longitudinal. The muscularis externa layer produces churning movements required for mechanical digestion. When these layers contract, they throw the mucosa and submucosa into rugae.
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The arrangement of the muscularis externa varies between different stomach regions. In the cardia the layers are well-developed, creating a sphincter to prevent acid reflux from the stomach into the esophagus. In the fundus, the muscle is poorly developed as a lot less churning takes place in this region. The body is composed of all three muscle layers, except in the anterior and posterior parts of the stomach where the longitudinal muscle layer is largely absent. In the pyloric region the muscularis externa is well developed in order to propel chyme into the duodenum, while its thickened circular layer forms the pyloric sphincter.
Housed within the muscularis externa is the myenteric (Auerbach's) plexus, carrying both sympathetic and parasympathetic fibres to the smooth muscle layers. The neurons of this plexus are linked to smooth muscle cells through interstitial cells of Cajal (ICCs). As well as mediating neural signals, these cells act as intrinsic pacemakers of the gut controlling the slow contractions of the stomach wall required for churning of the food. The activity of ICCs is controlled by the autonomic nervous system.
As we mentioned previously, in addition to the myenteric (Auerbach's) plexus in the muscularis externa, we have a submucosal (Meissner’s) plexus in the submucosa. If you struggle remembering the difference between the two a mnemonic can help! Use SMP & MAPS, which stand for:
You can learn more about the musculature of the stomach by diving into the following learning materials!
Gastric serosa is the outermost layer of the stomach wall. It consists of a layer of simple squamous epithelium, known as mesothelium, and a thin layer of underlying connective tissue. The mesothelium produces serous fluid, which lubricates the outer wall of the stomach and ensures its smooth movement in the abdominal cavity. The serosa is continuous with the parietal peritoneum. It is absent at the attachment sites of the greater and lesser omenta to the stomach, as well as over a small superoposterior area near the cardiac orifice where the stomach is attached to the diaphragm via gastrophrenic and gastropancreatic folds.