Gastric Physilogy Flashcards
What are the functions of the stomach?
Store (before chyme enters the duodenum) and mix food
Digestion of proteins (activate pepsin) and production of chyme
Kill microbes
Secrete intrinsic factor
What are the key cell types of the stomach and a brief overview of their function:
Mucous cells - secrete an alkaline mucus that protects the stomach
Parietal cells - secrete intrinsic factor which binds to vitamin B12 which allows the terminal ileum absorption of it. Also responsible for the production of HCl
Chief cells - release pepsinogen
Enteroendocrine cells
What is chyme?
The semifluid mass of partly digested food expelled by the stomach into the duodenum.
How many litres of HCl are produced a day?
2 L
This process is energy dependent
How is gastric acid produced?
The parietal cell has a proton pump that pumps H+ into the stomach. This process requires ATP and the H+ is derived from ionised water.
K+ are pumped into the parietal cell and Cl- ions are pumped out this is to keep the charge constant.
The Cl- are replaced from the capillary with the exchange of HCO3-
The HCO3- in the cell can come from carbonic acid
How is gastric acid secretion switched on in the cephalic phase?
This is via the sympathetic nervous system (vagus nerve)
It is switched on with the sight, taste and chewing of food
Acetylcholine (ACh) is released which acts on parietal cells, causing the release of gastrin and histamine and therefore an increased acid production.
Gastrin and histamine both cause an increase in acid production by the parietal cells.
How is gastric acid secretion increased (gastric phase)?
Gastric distension and the presence of peptides causes the release of gastrin.
Gastrin directly acts on parietal cells and also causes the release of histamine, which also acts on parietal cells.
Hence there is an increase in secretion of HCl by parietal cells.
One final way how gastric secretion are increased?
Proteins in the stomach act as a buffer and mop up H+ causing pH to rise.
This leads to decreased somatostatin (inhibits parietal cell activity) and hence there is more parietal cell activity and more HCl produced.
How is gastric acid secretion turned off? (Gastric phase)
Low luminal pH (high H+)
Directly inhibits gastrin secretion
Decreased gastrin also means decreased histamine
Also stimulates somatostatin release
All of this inhibits/decrease parietal cell secretions
How is gastric acid secretions turned off? (Intestinal phase)
Duodenal distension
Low pH
Presence of a.a and fatty acids
Trigger the release of enterogastrones
Secretin — inhibits gastrin release and promotes somatostatin
Hence decrease gastric acid secretions
Secretin Gastrin Somatostatin Histamine ACh
Enterogastrone
Enterogastrone - which inhibits the release of gastrin and promotes somatostatin and hence decrease gastric acid secretions
Gastrin - hormone that is secreted by G cells. It stimulates the secretion of gastric acid in parietal cells, also stimulates histamine secretion
Histamine - stimulates the production of gastric acid
ACh - acetylcholine - stimulates release of gastrin and histamine
Enterogastrone = An enterogastrone is any hormone secreted by the mucosa of the duodenum in response to dietary lipids
Overview of gastric acid secretion:
Controlled by = brain, stomach and duodenum
1 parasympathetic neurotransmitter ACh = + (gastrin and histamine)
1 hormone (gastrin +)
2 paracrine factors (histamine+ and somatostatin -)
2 key entergastrones (secretin - and CCK -)
Is in a peptic ulcer?
An ulcer is a breach in the mucosal surface
What are the causes of a stomach ulcer?
Helicobacter pylori
NSAIDs
Bile salts
How does the gastric mucosa protect itself from ulcers?
Mucous cells secrete alkaline mucous
Tight junctions between epithelial cells - no gastric acid into the tissues
Replacement of damaged cells
How does helicobacter pylori cause peptic ulcers?
It is a bacteria that lives in the gastric mucus and secretes urease that splits urea into CO2 and ammonia.
NH3 + H+ — NH4+
The ammonium produced as well as the proteases and vacuolating cytotoxin A damage the gastric epithelium
There is also an inflammatory response which may cause further damage.
More easy for an ulcer to form - breach the mucosa layer!
How do NSAIDs cause peptic ulcers?
Non-steroidal antiinflammatory drugs
Mucus secretion is stimulated by prostaglandins cyclo-oxygenase 1 is needed for prostaglandin synthesis
NSAIDs inhibit it and hence music can not be secreted = increase change of ulcer formation
How do bile salts cause peptic ulcers?
Duodeno -gastric reflux
The regurgitated bile strips away the mucus layer
Leading to reduced mucosal defence
How to treat helicobacter pylori?
Proton pump inhibitor - increase pH, hostile to bacteria
Then use 2 antibiotics e.g
Amoxicillin and clarithromycin
How to treat NSAIDs ulcers?
Use prostaglandin analogues - misoprostol
+ Reduce gastric acid secretion with proton pump inhibitors
What cells produce pepsinogen and then how is pepsin produced?
Chief cells produce pepsinogen - due to ACh.
Pepsinogen is then converted to pepsin by HCl (pH dependent most efficient at a pH of 2) and then pepsin also catalyses this conversion (positive feedback loop)
Pepsin then acts on proteins producing smaller peptides
Is pepsin functional in the duodenum?
No it is only active at a low pH - inactivated in small intestine by HCO3-
What is the role of pepsin in digestion?
Not essential stomach can be removed and protein digestion can still occur.
Normally accounts for 20% of total protein digestion
Volume of stomach when empty vs volume of stomach when full?
Empty = 50ml
Full 1.5L with little increase in luminal pressure
How does receptive relaxation of the stomach take place?
It is mediated by the parasympathetic nervous system acting on enteric nerves plexuses
Afferent via the vagus nerve
NO and serotonin released by enteric nerves mediate relaxation…
Enteric nerves (intrinsic nerve system of the GI tract)
After the stomach is filled then it starts chaining of the food.
What is this process?
Peristaltic waves begin in gastric body these are weak.
More powerful contractions in the gastric antrum take place and the pylorus closes as a peristaltic wave reaches it.
A little chyme will enter the duodenum but most forced backwards which causes it to mix/churn and hence produces chyme.
What cause the gastric motility?
The interstitial cells of Cajal are responsible for the basic electrical rhythm they are found in the muscualris propria and 3 waves will take place per minute.
These pacemaker cells undergo slow depolarisation - repolarisation cycles
ACH and hormones depolarise the membranes and an action potential is produced when the threshold is reached.
The depolarisation waves transmit through the gap junctions to adjacent smooth muscle cells
What increases the strength of the peristaltic contractions?
Gastrin
Gastric distension (food in stomach)
What decreases gastric motility?
Duodenal luminal fat
Duodenal distension
Decrease in duodenal pH
Sympathetic nervous system - blood away from stomach - fight or flight
What happens if you overfill the duodenum from the stomach?
Known as dumping syndrome - vomiting, bloating, cramps, dizziness
What is gastroparesis?
How is it caused?
Delayed gastric emptying
May be caused by drugs
Parkinson’s, multiple sclerosis etc
What drugs cause gastroparesis?
Gastrointestinal agents:
Aluminium hydroxide antacids
Proton pump inhibitors
Anticholinergic medication:
Benadryl
Tricyclic antidepressants
Miscellaneous:
Beta adrenergic receptor agonists
Calcium channel blockers
Symptoms fo gastroparesis?
Nausea - writing food in stomach
Vomiting
Anorexia
Bloating
