gastric physiology 1 Flashcards
functions of the stomach (9)
store and mix food
dissolve and continue digestion
regulate emptying into duodeum
kill microbes
secrete proteases
secrete intrinsic factor
activate proteases
lubricatiin
mucosal protection
what are the key cell types of the stomach (6)
mucous cells
parietal cells
chief cells
enterochromaffin-like (ECL) cells
G cells
D cells
what do mucous cells secrete
mucous, at entrance to gland
what does mucous do (2)
- lubrication
- protection of mucosa
what do parietal cells do
produce gastric acid (HCL) and intrinsic factor
function of gastric acid / HCL (3)
- digestion
- activates pepsinogen
- kills pathogens
function of intrinsic factor
absorption of Vitamin B12
– in terminal ileum
what do chief cells do
produce pepsinogen
function of pepsinogen
converted to pepsin – protease enzyme for digestion
what do enterochromaffin-like (ECL) cells do
release histamine
what does histamine do
stimulates HCl secretion
what do G cells do
release gastrin
what does gastrin do (2)
- stimulates HCl secretion
- stimulates histamine secretion
what do D cells do
release somatostatin
what does somatostatin do
inhibits HCl secretion
how much HCL does stomach produce
about 2 litres a day
[H+] > 150 mm
pH of HCL
2
very strong
how is HCL/gastric acid secretion regulated
by neurohumoral regulation
which cells secrete gastric/hcl acid
parietal cells
it is energy dependent
what are the 4 stages of gastric acid secretion
- cephalic stage ON
- gastric stage ON
- gastric stage OFF
- intestinal phase OFF
when does the cephalic stage occur
during a meal
when does the gastric stage occur
once food has reached the stomach
what initiates the gastric phase of turning on parietal cells for gastric acid secretion
by gastric distension from the volume of ingested material, presence of peptides and amino acids (released by the digestion of luminal proteins)
describe gastric phase of turning on parietal cells for gastric acid secretion
gastrin release
gastrin acts directly on parietal cells
gastrin triggers release of histamine
histamine also acts directly on parietal cells
both gastrin & histamine increase the number of H+/K+-ATPase pumps on the
plasma membrane of the parietal cell
net effect = increased acid production
why is histamine really important
it acts directly but also mediates the effect of gastrin and acetylcholine
amplifies the signal from the vagus nerve
thus can be a good therapeutic target for e.g. acid overproduction etc.
what initiates the cephalic phase of turning on parietal cells for gastric acid secretion
sight, smell, taste of food and chewing
describe the cephalic phase of turning on parietal cells for gastric acid secretion
parasympathetic nervous system
acetylcholine release
ACh acts directly on parietal cells
ACh triggers release of gastrin (from G
cells in the pyloric antrum of stomach) and histamine (from ECL cells)
both gastrin & histamine increase the number of H+/K+-ATPase pumps on the
plasma membrane of the parietal cell
net effect = increased acid production
how do proteins in the stomach turn on parietal cells for gastric acid secretion
proteins in the stomach are a direct stimulus for gastrin release
proteins in the lumen act as a buffer, reducing amount of H+ causing pH to rise :
results in:
- decreased secretion of somatostatin
- more parietal cell activity (lack of inhibition )
- more acid secretion
describe gastric phase of turning off parietal cells for gastric acid secretion
low luminal pH (high [H+])
- directly inhibits gastrin secretion so
indirectly inhibits histamine release (via gastrin) - also stimulates somatostatin release which inhibits parietal cell activity
what initiates the intestinal phase of turning off parietal cells for gastric acid secretion
- duodenal distension
- low luminal pH
- hypertonic luminal contents
- presence of amino acids and fatty acids
describe the intestinal phase of turning off parietal cells for gastric acid secretion
in the duodenum
- trigger release of enterogastrones ;
- secretin (inhibits gastrin release, promotors somatostatin release )
- cholecystokinin (CCK)
- also trigger short and long neural pathways, reducing ACh release
net effect = reduced acid secretion
how is gastric acid secretion regulated
controlled by brain, stomach, duodenum
1 (parasympathetic) neurotransmitter (ACh+)
1 hormone (gastrin +)
2 paracrine factors (produced in stomach) (histamine + , somatostatin-)
2 key enterogastrones (secretin -, CCK-)
define ulcer
an ulcer is a breach in a mucosal surface
most common cause of peptic ulcers
helicobacter pylori infection
lives in gastric mucus
causes of peptic ulcers
- helicobacter pylori infection
- drugs - NSAIDS
- chemical irritants. - alcohol, bile salts, diary factors
- gastrinoma
describe normal stomach defences
they are suffiencent to resist attack so no ulcers
how do peptic ulcers occur
either increased mucosal attack
or
reduced mucosal defence
how does the gastric mucosa defend itself (4)
alkaline mucus on luminal surface
tight junctions between epithelial cells
replacement of damaged cells - stem cells at the base of pits to produce new cells
feedback loops
what does helicobacter pylori do
lives in the gastric mucus
secretes urease, splitting urea into carbon dioxide and ammonia
ammonia + H+ = ammonium
Ammonium is toxic to gastric mucosa resulting in less mucous produced
secreted proteases, phospholipase & vacuolating cytotoxin A can then begin
attacking the gastric epithelium further reducing mucous production
results in an inflammatory response and less mucosal defence
what are NSAIDs
non-steroidal anti-inflammatory drugs
how do NSAIDs cause peptic ulcers
non steroidal anti inflammatory drugs
mucus secretion is stimulated by prostaglandins
(in inflamed tissue, prostaglandin
triggers inflammatory response thus inhibition = less inflammation)
cyclo- oxygenase 1 needed for prostaglandin synthesis
NSAIDs inhibit cyclo-oxygenase 1
reduced mucosal defence
how do bile salts cause peptic ulcers
duodeno- gastric reflux
regurgitated bile strips away mucus layer
reduced mucosal defence
how to treat peptic ulcer disease caused by helicobacter pylori
kill the organism
use triple therapy
1 proton pump inhibitor - (inhibits
pump pumping H+ ions into stomach lumen thereby increasing gastric pH making conditions inhospitable for helicobacter pylori)
2 antibiotics
- clarithromycin
- amoxicillin
- tetracycline
- metronidazole
describe the epithelium of the stomach
the epithelial layer lining the stomach invaginates into the mucosa,
forming many tubular glands
simple columnar
describe the upper portion of the stomach
it is thin
contains glands that :
contain mucous cells
- secrete mucuous
contains parietal cells
- secrete HCL
contains chief cells
- secrete the enzyme precursor pepsinogen
describe the lower portion of the stomach
has a much thicker layer of smooth
muscle
is called the antrum
is responsible for mixing the stomach contents -
the glands in this region of the stomach secrete little acid but contain the endocrine cells that secrete the hormone gastrin (G cells)
describe the process of gastric acid secretion
- H2O in the parietal cell breaks down into OH- and H+
- The origin of the H+ ions is CO2
- CO2 & H2O from respiration are converted into bicarbonate (H2CO3) via the enzyme carbonic anhydrase
- H2CO3 rapidly disassociates into HCO3- and H+
- The H+ ions produced can then react with the OH- ions from the breakdown of H2O to regenerate H2O
- The H+ ions from the break down of H2O are then pumped into the stomach lumen via H+/K+ ATPase pumps in the luminal membrane of parietal cells
- they pump 1 K+ ion into the parietal cell for every 1 H+ ion they pump out into the stomach (so as to ensure there is no change in polarity of the cell) - these pumps require ATP to function
- the K+ ions pumped in can then diffuse back out into the stomach via K+ channels on the plasma membrane of parietal cells
- the HCO3- from the breakdown of H2CO3 is secreted into the capillary for the exchange of Cl- ions
10.Cl- ions can then enter the stomach by diffusing through Cl- channels in the plasma membrane of the parietal cell
- then in the stomach, the H+ ions and Cl- ions can react to form HCl
- removal of the end products of this reaction enhance the forward rate of reaction - in this way production and secretion of H+ are coupled
- increased acid secretion stimulated by the factors mentioned below, results from the migration of H+/K+ - ATPase protein in the membranes membranes of intracellular vesicles in the parietal cell to the plasma membrane by fusion of these vesicles with the membrane thereby increasing the number of pump protein in the plasma membrane meaning more H+ can be pumped in = more acid
how to treat peptic ulcers caused by NSAIDs
use prostaglandin analogues (mimic effect of prostaglandins)
e.g. misoprostol and reduce acid secretion
how do chemical irritants cause peptic ulcers
alcohol, bile salts
secreted into duodenum but can reflux into stomach and wash way protective mucous lining
duodenal-gastric reflux causes bile to enter stomach, alkaline bile strips away
gastric mucous layer of stomach resulting in reduced mucosal defence
what is gastrinoma
rare tumours of parietal cells = excessive gastrin release =
increase in gastric acid =
increased attack on gastric mucosa = ulcer
what are the synthetic ways to reduce gastric acid secretion
- proton pump inhibitors
- H2 receptor agonists
what do proton pump inhibitors do
inhibit pumps pumping H+ into stomach lumen,
they only block pumps NOT the activators
e.g. gastrin, examples include; omeprazole, lansoprazole & esomeprazole (all have varied side effects)
what do H2 receptor agonists do
block receptors for histamine thereby reducing acid secretion,
examples include; cimetidine & ranitidine
