Gastric secretion Flashcards
What does the stomach secrete (5) ?
H+ Pepsinogen Mucus HCO3- Intrinsic factor (IF)
What part of the stomach secretes the most acid, pepsinogen and IF?
Body
What does antrum do?
Secrete somatostain, gastrin and holds food
What is the structure of the gastric gland?
Gastric pits which open into necks and leads to base, deep invaginations in the epithelial layer
What 6 cells make up gastric pits?
Parietal (oxyntic) cells in the base and neck: secrete HCl and intrinsic factor (for vitamin B12 absorption in the ileum)
Chief (peptic) cells in the base and neck: secrete pepsinogen
Endocrine cells in the base: secrete regulators such as gastrin, somatostatin via the bloodstream
Mucous neck cells: secrete mucus
Superficial epithelial cells in the pit and on the surface lining: secrete mucus along with HCO3- ions
Basal regenerative cells
What cells secrete IF?
Parietal
What secretions are there in an unstimulated stomach, what cells from?
Non-parietal surface epithelial cells
Juice is rich in Na+, Cl-, and is isotonic.
What secretions are there in a stimulated stomach, what cells from?
Secreted by parietal cells
Concentrated HCl.
What factor determines which juice is secreted by the stomach, how does it vary in a stimulated vs unstimulated stomach?
Secretory rate
When stimulates the secretory rate is much faster
What do parietal tubovesicles contain?
H+/K+ATPase.
What does stimulation of parietal cell trigger tubovesicles to do?
Merge into the apical membrane
How does the shape of the parietal cell membrane change when stimulated?
Stimulated parietal cells posses deep invaginations of apical membrane called secretory canaliculus.
How does the surface area of the parietal cell change?
When stimulated H+/K+ATPase containing tubovesicles merge with the membrane and the number of canaliculi ride
Why does the H+/K+ATPase have no effect on cytoplasm pH when in vesicles?
Vesicle is arranged so that ATPase is ‘inside out’ (H+ pumped in K+ pumped out)
K+ cannot recycle by entering the vesicle (vesicle impermeable to K+)
[K+] in the vesicle falls, low K+ availability within the vesicle ‘brakes’ the activity of the ATPase.
Describe the mechanism and transporters behind secretion of H+ and Cl-
Intracellular CA catalyses hydration of CO2 to yield H+ and HCO3-
H+/K+ATPase pumps H+ ions into the lumen in exchange for K+
K+ recycles out of the cell through apical K+ channels
HCO3- exits across basolateral on Cl-/HCO3- exchanger
Cl- ions diffuse through apical channels to join H+ ions in the lumen.
Water follows by osmosis
What are 3 ways of regulating gastric acid secretion?
Neurocrine: ACh from vagus binds M3 and stimulate GRP (gastrin releasing peptide) and histamine release
Endocrine: gastrin (in response to GRP from vagus nerve or AA in lumen) binds CCKB receptors, triggers IP3 cascade
Paracrine: histamine from ECL cells, binds H2 receptors (adenylyl cyclase cascade)
What underpins all the mechanisms behind activating parietal cells?
Kinase activation leads to cytoskeletal rearrangement via phosphorylation which leads to tubulovesicle insertion
What is the common mediator hypothesis?
ACh and gastrin bind M3 and CCKB receptors on ECL (enterochromaffin-like cells) cells to induce histamine release, as well are their role on parietal cells.
Why is histamine action arguably the most important factor for affecting parietal cell secretions?
It is unregulated by ACh and gastrin
What are 3 phases of gastric acid secretion?
Cephalic: ACh and GRP release after vagal stimulation
Gastric: distension initiates vagovagal reflex (triggers acid & histamine secretion) and protein digestion products trigger gastrin release
Intestinal: protein digestion products stimulate duodenal G cells
What do endocrine D cells do?
Release somatostatin which reduces gastric acid secretion
What do endocrine D cells do?
Release somatostatin which reduces gastric acid secretion
What hormones does secretin stimulate and inhibit?
Stimulates somatostatin
Inhibits gastrin
What do chief cells secrete?
Pepsinogens
How are pepsinogens activated?
Activated by N-terminal truncation, spontaneous activation occurs in acidic lumen.
Low pH is also required for optimal activity of pepsin.
What % of ingested protein do pepsins digest?
20%
What is pepsin release stimulated by (&pathway)?
ACh, via M3 receptors, Ca2+ signalling
Gastrin and CCK, via CCKB receptor, Ca2+signalling
Secretin, via adenylyl cyclase-coupled receptors, cAMP signalling
What is mucin?
Large glycoprotein with high viscosity
Why is it essential to have a protective mucous layer?
Gel is a barrier to H+ ion diffusion from the acidic bulk solution in the lumen
Protects the gastric mucosa
What cells secrete HCO3-?
Surface cells
How does mucous move out of the pits?
Secretion of gel raises the hydrostatic pressure inside the gastric pits, this forces the secretions upwards in the pit.
How does pressure in pit act as a protective mechanism?
Encourages the acid to bore through the mucous without lateral spread
What is the stream of H+ exiting the pit termed as?
Viscous finger
What induces mucous secretions?
ACh induced Ca2+ signalling
What prevents autodigestion of stomach mucosa from acidic contents?
Mucous cells produce mucus which is barrier to H+ diffusion
Surface epithelial cells secrete HCO3- to neutralise H+ which penetrates mucous lining
What are the causes of peptic ulcers?
Diet e.g. spicy food, alcohol
H pylori
Excess acid from hypo/hyperglycaemia or Zollinger Ellison
NSAID drugs directly damage mucosa
What is the secondary messenger for histamine induced acid release?
cAMP
What action does CCK have on gastric acid secretion?
Inhibits it
What does ranitidine inhibit?
H2 receptors - acid secretion by histamine action
What does omeprazole inhibit?
H+/K+ATPase - acid secretion
What is the common mediator for stimulation of gastric acid secretion?
Histamine
What is the main inhibitor of gastric acid secretion?
Somatostatin (secretin also does by upregulating it)
CCK? (if only option)
What drug most completely suppresses gastric acid secretion?
Omeprazole
