Physiology and drugs of Gastric Secretions Flashcards
what causes the stomach to relax
relaxes receptively- driven by vagus
what is the role of the stomach
starting point for digestion of proteins, continues carb digestion, mixes food with gastric secretions to produce chyme, stores food, secrete gastric juice
how absorptive is the stomach
limited-except for alcohol
when does the stomach relax
in anticipation of food
what works to digest protein in the stomach
pepsin and HCL
name three different parts of the stomach
fundus, body, antrum
describe the fundus
Next to oesophagus
Thin smooth muscle layer
Receives food but little mixing
Little food stored there – usually a pocket of gas
describe the body of the stomach
storage aspect of gastric function
Middle section
Thin smooth muscle layer
Little mixing
describe the antrum
breaks food down into smaller and smaller particles
Next to duodenum
Thicker smooth muscle layer
Highly contractile
Much mixing of c 30mL at a time with gastric secretions
how is food mixed in the stomach
retropulsion- the churning action of gastric smooth muscle against a closed pyloric sphincter
what are the peristaltic contractions driven by
supra-threshold gastric slow waves
what determines the escape of chyme through pyloric sphincter
strength of antral wave: governed by gastric and duodenal factors
what are the gastric factors that govern the strength of the antral wave
volume of chyme in stomach (distension increases motility)
consistency of chyme
how does distention increase motility
stretch of smooth muscle- myogenic action
stimulation of intrinsic nerve plexuses (mechano receptors)
increased vagus nerve activity and gastrin release
what is the vagovagal reflex
gastrointestinal tract reflex circuits where afferent and efferent fibers of the vagus nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain. mediated by ANS
how does the duodenum delay emptying
Neuronal response: the enterogastric reflex – decreases antral activity by signals from intrinsic nerve plexuses and the ANS
Hormonal response – release of enterogastrones [e.g. secretin and cholecystokinin CCK)] from duodenum inhibits stomach contraction
what stimuli within the duodenum drive the neuronal and hormonal response
fat, acid, hypertonicity, distention
what types of cells excrete what in the pyloric gland area (antrum)
d cells- somatostatin
G cells- gastrin
what types of cells excrete what in the oxyntic mucosa (fundus and body)
Enterochromaffin-
like cell,
Histamine
Parietal cell,
Hydrochloric acid
Intrinsic factor
Gastroferrin
Chief cell
pepsinogen
what is the function of HCL
Activates pepsinogen to pepsin
Denatures protein
Kills most (not all) micro-organisms ingested with food
what is the function of pepsinogen
Inactive precursor of the peptidase, pepsin. Note: pepsin once formed activates pepsinogen (autocatalytic)
what is the role of the intrinsic factor and gastroferrin
Bind vitamin B12 and Fe2+ respectively, facilitating subsequent absorption
what is the role of histamine
stimulates HCL secretion
what is the role of mucus
protective
what is the role of gastrin
stimulates HCL secretion
what is the role of somatostatin
inhibits HCL secretion
how is HCL made
Carbonic acid unstable, dissociates into proton and bicarbonate ions. The process requires potassium which enters the cell
Bicarbonate exits cells in exchange for chloride via AE2, which joins with H+ to make HCL in the lumen
what induces the secretion of acid from the gastric parietal cell
ACh, gastrin and histamine - work by indirect and direct mechanisms
what signalling pathways does gastrin and ACh act on
PLC - IP3
what signalling pathway does histamine work on
cAMP- PKA
what causes the inhibition of secretion of acid (H+)
somatostatin and prostaglandins work via cAMP- PKA signalling pathways
describe the stimulated state of the parietal cell
H+/K+ATPase traffics to the apical membrane taking residence in extended microvilli
what is the rare of gastric secretion controlled by
stimulatory and inhibitory mechanisms that occur in three overlapping phases (cephalic, gastric and intestinal)
what is the cephalic stage
before food reaches the stomach preparing it to receive food - driven directly and indirectly by the CNS and vagus nerves
what is the gastric phase
when the food is in the stomach, involves both physical (distention) and chemical (amino acids stimulate G cells, food buffers (decrease ss inhibition)) mechanisms
what is the intestinal phase
after food has left the stomach - chyme entering the upper small intestine causes weak stimulation of gastric section via neuronal and hormonal mechanisms
what are the three phases of gastric acid secretion
cephalic phase, gastric phase, intestinal phase
how does the vagus nerve drive the cephalic stage
stimulates enteric neurones that release ACh, increase secretion of histamine and GRp (Causes release of gastrin) and inhibits D cells
what inhibits gastric secretion in the cephalic stage
when vagal nerve activity decreases upon cessation of eating/ emptying of the stomach
what inhibits gastric secretion in the gastric stage
pH falls when food exits stomach (due to decreased buffering of gastric HCl) – release of somatostatin from D cells recommences, decreasing gastrin secretion
prostaglandin E2 (PGE2) continually secreted by the gastric mucosa acts locally to reduce histamine- and gastrin-mediated HCl secretion
what works to inhibit gastric acid secretion in the intestinal phase
factors that reduce gastric motility also reduce gastric secretion (neuronal reflexes, enterogastrones)
what else can cause a reduction in vagal activity and an increase in symp activity that reduce gastric secretion
pain, nausea and negative emotions
what drug classes decrease acid secretion
muscarinic recptor antagonists (block competitively)
H2 histamine receptor antagonists (blck competitively)
proton- pump inhibitors (block by covalent modification)
what drugs increase acid secretion
NSAIDs (block irreversibly)
how is the mucosa protected from HCL and pepsin
locally produced prostaglandins (reduce acid secretion, increase mucous and bicarbonate secretion, increase mucosal blood flow)
how does the treatment of peptic ulcers aim to promote healing
reducing acid secretion,
increasing mucosal resistance,
eradicating the bacterium H. pyloric (secretes agents that weaken the mucosal barrier)
what is a peptic ulcer
any ulcer in an area where the mucosa is exposed to HCL and pepsin
why do NSAIDs cause peptic ulcers
as they reduce prostaglandin formation (COX 1 inhibition) and may:
trigger gastic ulceration and cause bleeding
give an example of a NSAID
aspirin
what can gastric damage due to long term NSAIDs be prevented by
with a stable PGE1 analogue (misoprostol)
what are the adverse effects of a stable PGE1 anaglogue
inhibits basal and and food-stimulated gastric acid formation
maintains (or increases) secretion of mucus and bicarbonate
what are drugs that reduce acid secretion used to treat
peptic ulcer, gastro-oesophageal reflux disease, acis hypersecretion (zollinger ellison syndrome/ cushing’s ulcers)
what is gastro oesophageal reflux disease
inappropriate relaxation of lower oesophageal sphincter allowing reflux of acid gastric contents into the oesophagus and subsequent tissue damage – oesophagitis
what are the mechanisms used to reduce acid secretion by drugs
irreversible inhibition of the proton-pump (H+/K+ ATPase)
competitive antagonism of histamine H2 receptors
competitive antagonism of muscarinic M1 and M3 ACh receptors (mostly obsolete)
antagonism of gastrin (CCK2) receptors (not utilized clinically)
give an example of a proton pump inhibitor
omeprazole
what do proton pump inhibitors do
inhibit the active H+/K+ -dependant ATPase (proton pump)
what activates proton pump inhibitors within the body
a strongly acidic pH, inactive at neutral pH
how are PPIs delivered to the stomach
absorved from the GI tract and delivered via the systemic circulation to the stomach
why is timing of a PPI dose important
inhibition of acid secretion (typically 10-14 hr duration after a single dose before breakfast) greatly exceeds plasma half-life
drug must be present in plasma at an effective concentration whilst proton pumps are active
how do histamine H2 receptor antagonists work to reduce gastric acid secretion
act as competitive (reversible) antagonists of H2 receptors
completely block the histamine-mediated component of acid secretion and reduce secretion evoked by gastrin and ACh
how are PPIs administered
effective orally once daily
how are HH2RA administered
once/twice daily orally
what are HH2RA used to treat
peptic ulcers and reflux oesophagitis
give two examples of a HH2RA
ranitidine and cimetidine
give two examples of mucosal strengtheners
sucralfate and bismuth chealate
how does sucralfate work and how is it administered
requires an acid environment for activation – releases aluminium to acquire a strong negative charge
binds to the ulcer base (positively charged proteins) and forms complex gels with mucus – provides a mucosal barrier against acid and pepsin
increases mucosal blood flow, mucus, bicarbonate and prostaglandin production
administered orally
how does bismuth chealate work and how is it administered
has mucosal strengthening actions similar to sucralfate
is toxic towards H. pylori - used in combination with antibiotics and histamine H2 antagonists (ranitidine) to promote eradication of the bacterium and ulcer healing
administered orally (in combination with ranitidine)
what turns off the secretion of succus entericus
fasting
where are the digestive enzymes in the small intestine
not secreted in succus entericus
sits instead on the apical membrane (brush border)
why do CF patients also have problems with both mucous and electrolytes in the small intestines
as mucous and chloride are secreted in to the lumen, chlorine secreted by the cystic fibrosis transmembrane conductance regulator channel
do alpha amalyses produce glucose
no
what must glucose be broken down into to be absorbed
monomer- monosaccarides
