2/4 - Digestion



This is a four-part series covering gastrointestinal physiology.

  • Part I - Overview of the gastrointestinal system & the oral cavity.
  • Part II - Digestion: stomach & control of digestion.
  • Part III - Secretion: pancreas & hepatobiliary system.
  • Part IV - Absorption: small intestines.

The stomach is crucial for digestion of nutrients ingested from our diet. The stomach is well suited for this process because its specialised epithelium secretes hydrochloric acid and digestive enzymes.

Anatomy of the stomach

The stomach is located at the distal end of the oesophagus beyond the gastroesophageal sphincter. 

The predominant functions of the stomach are storage of ingested food, secretion of digestive juices (enzymes and hydrochloric acid) and mixing of gastric content. The combination of these functions leads to the production of a thick, acidic liquid termed chyme.

The stomach is divided into five distinct areas; fundus, cardia, body, antrum and pylorus.

The fundus is the uppermost part of the stomach. It connects to the cardia, which is the superior inlet to the stomach located inferior to the gastro-oesophageal sphincter. The body is the main portion of the stomach and is important in the storage of ingested food.

The muscular antrum comprises the lower section of the stomach, which is vital for mixing gastric contents. The pylorus forms the distal aspect of the stomach, it ends at the pyloric sphincter. This is important for the control of gastric emptying.

Gastric mucosa

The mucosa of the stomach is important for the secretion of enzymes and digestive juices.

It is composed of simple columnar epithelium. This mucosa contains numerous deep pockets due to infolding. They are termed gastric pits and they contain some of the exocrine and endocrine glands that help the stomach carry out its function. The mucosa of the stomach is divided into two key areas, the oxyntic area and pyloric gland area.

Oxyntic area

The oxyntic area is found in the body and fundus of the stomach. It primarily contains important exocrine cells including; mucous cells, chief cells and parietal cells. 

Mucous cells secrete an alkaline rich fluid that helps protect the gastric mucosa. This mucus layer helps to lubricate the gastric lining reducing the risk of mechanical injury. It also serves as protection from the highly acidic environment and a barrier to the digestive enzyme pepsin, which could otherwise lead to self-digestion. 

Chief cells secrete the proenzyme pepsinogen. Pepsinogen is activated by hydrochloric acid into the active enzyme pepsin. Pepsin breaks polypeptides into peptide fragments.

Parietal cells (oxyntic cells) are important for the secretion of hydrochloric acid (HCl) and intrinsic factor (see below). HCL acid is responsible for the stomach having a pH 2. HCl is involved in pepsinogen activation, the breakdown of connective tissue, denaturing proteins and has antimicrobial activity.

The oxyntic area also contains enterochromaffin-like cells (ECL). These cells secrete histamine in response to stimulation by gastrin or acetylcholine (ACh). Histamine increases the secretion of hydrochloric acid.

Pyloric gland area

The pyloric gland area is situated in the antrum and pylorus. It contains two important endocrine cells that help to regulate gastric secretions: G cells and D cells

G cells are involved in the secretion of gastrin, which stimulates parietal cells to secrete hydrochloric acid. D cells secrete somatostatin which has an inhibitory action on gastric secretions.

Intrinsic factor

Intrinsic factor, a glycoprotein produced by gastric parietal cells, is key in the absorption of vitamin B12.

Intrinsic factor binds to vitamin B12 and allows it to be transported through the intestines. This complex is then absorbed from the terminal ileum. Vitamin B12 deficiency may result from:

  • Impaired intrinsic factor function (pernicious anaemia) 
  • Terminal ileitis (malabsorption)

Control of digestion

Gastric secretions are coordinated by a series of neurohormonal mechanisms.

Approximately 2 litres of gastric secretions are produced each day. Gastric secretions are crucial for digestion and absorption of nutrients from our diet. The control of digestion is divided into three stages: cephalic, gastric and intestinal.


The cephalic stage of digestion occurs prior to the entry of food into the stomach. During the cephalic stage, there is an increase in hydrochloric acid and pepsinogen. 

Higher cortical functions, senses (e.g. taste, smell), chewing and swallowing all drive the increases in gastric secretions. These processes lead to vagal stimulation which increases ACh release. ACh acts directly on parietal and chief cells triggering them to secrete HCl and pepsinogen respectively. It can also act indirectly via endocrine cells (e.g. G cells and enterochromaffin-like cells). 


The gastric stage features a significant increase in gastric secretions and follows food entering the stomach. Food entering the stomach leads to stimulation of the enteric nervous system and endocrine cells. Protein is the most powerful stimulus during the gastric stage of digestion.

Ultimately, there are many overlapping pathways that occur during the gastric phase of digestion, this culminates in increased secretion of two key products: pepsinogen and hydrochloric acid.

Hydrochloric acid (HCl), a strong acid, has numerous important functions within the stomach. It helps denature proteins and its low pH is key to the innate immune defence. It is also critical for the activation of the proenzyme pepsinogen into the active enzyme pepsin.

Pepsin is important in the breakdown of polypeptide chains into small peptide fragments. Pepsin is able to autocatalyse itself, this mean pepsin can activate pepsinogen. This leads to a significant increase in the availability of the active enzyme. 


The intestinal stage of digestion is the final phase, which is chiefly inhibitory of gastric secretions.

Gastric emptying of chyme into the duodenum stimulates the release of hormones from endocrine cells and activates local neurones. Activation of D cells leads to the release of the inhibitory hormone somatostatin. This leads to a decrease in gastric secretions. Additionally, the loss of food from the stomach reduces the stimulus for further gastric secretions.

Gastric emptying

Gastric emptying is the process of moving acidic gastric chyme into the duodenum.

It may be regulated by factors arising from the stomach, duodenum or cortex (pain/emotion). Factors arising from the duodenum are the main regulatory mechanisms. These include fat, acidity, tonicity and distension.

Enterogastrone: this is any hormone that inhibits the forward movement of chyme.

These four factors trigger both neural and hormonal responses. The neural response is mediated by both the autonomic nervous system and enteric nervous system. They trigger an enterogastrone reflex that slows gastric emptying. The hormonal response leads to the secretion of enterogastrones (CCK, secretin) which delay gastric emptying and initiate hepatobiliary secretions.

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