S2: Gastric Acid Secretion: Regulation Flashcards
Describe anatomy of stomach and what each area secretes
Fundus and Body have glands that secrete pepsinogen (cheif cells), mucus and hydrochloric acid - exocrine secretions
Body of stomach also had parietal cells that secrete intrinsic factor which is necessary for vitamin B12 absorption
Cardiac and pyloric area have mucus secreted cell (goblet)
Antrum is thick with muscle and secretes mucus, pepsinogen and gastrin
What does gastric juice in fasting state contain?
- Cations: Na+, K+, Mg2+, H+ (has a pH of around 3)
- Anions: Cl-, HPO42-, SO42-
- Pepsins
- Lipase
- Mucus
- Intrinsic factor
What do parietal cells release?
Wall of the glands is lined with parietal cells that release HCl and intrinsic factor.
What does gastrin do?
Increases acid secretion by binding to its receptor
What do enterochromaffin-like cells (ECL) secrete?
Paracrine agents e.g. histamine
How is gastric acid made in the stomach lumen?
- CO2 diffuses in cell and reacts with water to produce carbonic acid, which then dissociates into a bicarbonate and proton. Bicarbonate exchanged for a Cl- in the blood, which decreases the acidity of venous blood from the stomach.
- Excess Cl- diffuses into the stomach through chloride channels as the H+ is pumped into the stomach lumen (via K+/H+ ATPase, this pumps H+ out into the lumen of the stomach).
The net effect is a net flow of H+ and Cl- out of the parietal cell and into the lumen of the stomach.
Gastrin, Ach and other mediators drive this
What factors drive HCl formation in gut lumen?
Gastrin
Ach
Other mediators
Describe the contents of gastric secretions
The resting juice (when not fasting or eating) is similar to plasma but a little bit more alkaline due to higher HCO3-.
There is also mucus present which is thick and sticky and important in protecting the epithelial cells that line the stomach from H+
Lipaes breaks down TAGs to fatty acids and glycerol.
Intrinsic factor prevents perinicious anemia through absorption of vitamin B12.
HCl kills bacteria and it is involved in the acid denaturation of digested food and activates pepsinogen to pepsin which is important in protein digestion
What are the three phases in HCl secretion?
- Cephalic
- Gastric
- Intestinal
What regulates HCl secretion?
How?
HCl secretion is regulated by neuronal pathways and duodenal hormones (enterogasterones)
They do this by:
- Directly - acting on parietal cells to increase acid secretion
- Indirectly - influencing the secretion of gastrin and histamine which increases acid secretion
Some of the enterogastrins inhibit HCl secretion (duodenal hormones are important in this, because we need to modulate release, so we don’t damage our gut)
Describe cephalic phase in HCl secretion
Higher centres respond to senses and stimulate enteric neurones to release Ach which act on parietal cells to secrete HCl
This stimulation of the parasympathetic nervous system also stimulates ECL to release histamine which act on parietal cells to secrete HCl
G-cells can be activated to release gastrin which act on ECl cells.
Acid can be damaging so there needs to be an inhibitory factor. HCl stimulates D cells which release somatostatin.
Somatostatin inhibits ECl and G cells to prevent hypersecretion of acid.
Describe gastric phase in HCl secretion
This is where food has been ingested and there is distention of stomach that stimulates neurones.
If peptide concentration goes up (protein), this stimulates acid release (through gastrin release from G cells) and acidity will increase lowering pH.
Distension of the stomach stimulates enteric nervous system to release more Ach and stimulate HCl release from parietal cells (also it acts on ECL cells and on G-cells). So distension has a big role to play in terms of the effects we get.
Importantly, peptides in our food act as a buffer of acid (decrease [H+]) to prevent stimulation of the somatostatin releasing cells (D-cells) and hence trying to prevent somatostatin release. (acid secretion decreases as acidity of lumen increases)
Somatostatin is trying to decrease HCl secretion, so if we shut off this mechanism by buffering acid, then we are allowing more acid secretion to occur.
What in our food can acts as a buffer of acid?
Peptides of food can act as a buffer
This helps prevent stimulation of D cells
Describe intestinal phase in HCl secretion
This is a stage where balance of secretory activity of the stomach and the digestive and absorptive capacities of the small intestines.
The high acidity of duodenal contents as a reflex inhibits acid secretion. This is because increased acidity would inhibit the activity of digestive enzymes, bicarbonate and bile salts.
The enterogastrones are important in this control.
Distension of the duodenum, hypertonic solution, amino acids, fatty acids and monosaccharides all inhibit acid secretion. Enteric neural reflex is also inhibited so less Ach released.
Explain how acid secretion is inhibited (what factors)
Inhibition of acid secretion also depends on the composition of chyme (containing AA etc.) and volume of chyme (can cause further distension).
Short (within enteric system) and long neuronal (vagal) reflexes and hormones (enterogastrones e.g. secretin and CCK) inhibit acid secretion by the parietal cells, ECL cells or gastrin secretion by G cells which is inhibited by somatostatin.
There is increased sympathetic discharge which has an inhibitory effect and we turn down parasympathetic discharge.
