B5.006 - LES and Stomach Flashcards
what is the LES made up of
smooth muscle
describe the LES innervation
receives direct inhibitory innervation no dilator muscles open the LES
how does the LES open
opening is due to the movement of the bolus through the relaxed sphincter
describe how the LES relaxes during a swallow
the result of excitation of receptors in the pharynx
the afferent stimulus travels to the sensory nucleus, the nucleus solitarius.
A programmed set of events from teh dorsal vagal nucleus and the nucleus ambiguus mediats eh esophageal peristalsia nd th sphincter relaxation. The vagal efferent fibers communicate with the myenteric neurons that mediate LES relaxation.
how is contraction of the crural diaphragm controlled
by the inspiratory center in the brainstem and the nucleus of the prenic nerve. The crural diaphragm is innervated by the right and left phrenic nerves through nicotinic cholinergic receptor Ach + excitatory effects
mechanisms involved in the regulation of basal LES tone
excitatory cholinergic nerves ACh and the toni cmyogenic property of the LES favor contraction, wheras the inhibitory nitrergic (NO) pathway favors inhibitions.
describe the LES in advanced achalasia
the LES remains contracted owing to its myogenic property when completely de innervation
what does transient relaxation of the LES do and when does this happen
allows for gas venting
suppressed in horizontal position
blocked by sleep
lasts about 15s
what is hypotensive LES and what are the causes
reduced basal tone of the LES
can result in reflux into the esophagus
may have contractons
most often caused by reduced myogenic tone of LES but can be due to cholinergic suppression or drugs that cause smooth muscle relaxation
what can hypotensive LES lead to
GERD, erosive esophagitis, peptic stricture, barretts esophagus
what are 3 mechanisms of LES incompetence in GERD
LES may be hypotensive
LES barrier may be overwhelmed by increased intragastric pressure (pregnancy)
LES may exhibit frequent reflex transient LES relaxation (single most important precipitant for reflux)
what is different about the stomach and the esophagus as far as how it handles contact with acid
in gastric and duodenual epithelia, hydrogen ions must cross the mucus unstirred water layer-bicarbonate layer before ocntact can be made with surface of the epithelum. The esophagus does not have this layer.
what are structural barriers to H+ ions in epithelial defence against acid injury
apical cell membrane and intercellular junctional complex.
what are functional components of the epithelial defense against acid
intracellular buffering by negatively charged proteins and bicarb ions, and H+ extrusion
diffusion or refluxed gastric acid into intercellular space can cause what
sustained esophageal contraction
describe how sustained esophageal contraction can result from GERD
When H+ enters the intercellular space it encounters and activates the chemosensitive nociceptors whose signals are transmitted via the spinal cord to the brain for symptoms receptions (heartburn), activation of the same nociceptors is also capable of initiating a short relfex arc to esophageal smooth muscle (longitudinal)
what do longitudinal muscles of the esophagus do
cause shortening of esophagus which may facilitate esophageal transit and help with relaxation of the lower esophageal spincter
activity does not affect manometry readings
sustained contractions of longitudinal muscle of esophagus may be associated with what
chest pain
gastric acid can cause longitudinal muscle of esophagus contraction which can cause what
sliding hiatal hernia
what is a hiatal hernia
displacement of the stomach into the thoracic cavity via diaphragmatic esophageal hiatus
often associated with disruption of the LES
how does displacement of the LES relative to the diaphragm cause hiatal hernia
crural diaphragma normally encircles the LES and is thought to help with the sphincter function, thus displacemtn fo the LES eliminates this contribution
what symptoms are associated with hiatal hernia
GERD
impaired esophageal emptying
what is schatzkis ring
ring forms at the junction which may limit entry of poorly chewed food into the stomach
the mucosal ring is Schatzkis ring or B ring
what is achalasia
failure of LES to relax, failure to generate peristalsis due to nerve damage to inhibitory nerves or both inhibitory and excitatory
what are symptoms of achalasia
chest pain, regurgitation, difficulty swallowing, heartburn, cough, weight loss
what is a dilated esophagus and birds beak deformity of distal esophagus associated with
achalasia
achalasia
no peristalsis and LES not opening
what does an achalasia monometry reading look like
absent peristalsis, only low amplitude spontaneous activity is present. Intraesophageal pessure is higher than intragastric pressure and esophageal transit time is very slow
what types of cells are in the stomach
superficial epithelial cells
mucous neck cells
stem/regenerative cells
parietal cell - acid
cheif cell - pepsinogen
endocrine cell
what are the sections of the stomach
fundus
body
antrum
pylorus
what are the hormones involved in regulated gastric acid production
gastrin releasing peptide
BLI
gastrin
histamine
somatostatin
GIP
epiderman growth factor
where is gastrin releasing peptide found
muscle, mucosa, plexuses
gastrin releasing peptide location and major action
GI nerves
gastrin release and acid secretion
gastrin location and major action
gastric antrum, duodenum
gastric acid and pepsinogen secretion
histamine location and major action
ECL cells
stimulus of gastric acid secretion
somatostatin location and major action
gastric D cells
paracrine regulator of acid and gastrin
GRP releases NTs where and what does that do
mucosa
acts on G cell that produce gastrin
gastrin producing G cells
responsive to GRP
what family does gastrin belong to
cholecystokinin
why can gastrin bind to CCK receptors better than many cholecystokinins?
it shares a stretch of amino acids in common
what induces gastrin release
antrum distension
gastrin releasing peptide
fat, proteins, amino acids
beta 2 adrenergic agonists
lumen neutralization
suppressors of gastrin release
somatostatin
starvation
lumen acid <3
what does gastrin do
stimulates acid secretion and histamine release
increases tone of LES
regulates antral muscle activity
induces somatostatin relase
induces mucosal growth
where are D and G cells found
antrum
describe how G cells are stimulated to make gastrin
the GRP nerve from the mucosa is stimulated by ACh and then sends a signal to the GRP receptor which stimulates the creation and release of gastrin into a nearby capillary bed
what happens with gastrin in the oxyntic mucosa (more cranial)
gastrin comes from the capillaries and acts on the colocystokinin receptor on the parietal cell inducing acid release and also on Histamine producing cells (ECL cells) stimulating histamine production
what are ECL cells
histamine producing cells
what does histamine do in the oxyntic mucosa
activates the histamine receptor 2 on pairetal cells
acts in a paracrine way
what is a D cell
somatostatin cell
function of D cells
reduce the production of HCl, Pepsin, histamine and gastrin and affects gastric motility
in the antrum what does somatostatin do
acts on G cell to shut down gastrin production and release
what does the somatostatin produced in the oxyntic mucosa do
reduces histamine release
reduces HCl secretion
reduces pepsin secretion
what other than hormones can induce the gastrin/somatostatin pathway
stretch receptors in stomach
what are the inhibitors of gastric acid secretion from the pancreas and small intestine
CCK
Secretin
VIP
GIP
Neurotensin
Peptide YY
Somatostatin
Prostaglandin E2
Urogastrone
describe how parietal oxyntic cells stimulate secretion
ACh muscarinic receptors, histamine receptors and gastrin CCK-B receptors are activated and cause canuliculi to form to tubulovesicles open to the lumen leading to H+/K+ ATPase pump to be activated
what is the primary pump for H
H/K ATPase
how does the HK ATPase pump get activated
adenylate cyclase (histamine) and PLC (gastrin, ACh) activate kinases that in turn activate pump
what happens when H+ exits the apical side of the parietal cell
HCO3- flows down the electrochemical gradient out the basolateral membraen which draws Cl- into the cell
how does Cl get into the lumen
Cl- diffuses into thelumen via anion channel
how is B12 prevented from being degraded in the stomach
R protein made by salivary gland
what is IF
helps protect B12 in the lower part of the intestine
how does B12 get into the blood
transcobalamin 2 moves vitamine B12 into the blood
what is a cheif cell
contain zymogen granules that contain pepsinogen –>acid–> pepsin that breaks down proteins
how does pepsinogen production get stimulated
somatostatin at the level of the cheif cell
what is the main patwhay
that cheif cells are stimulated
through ACh reflex activated by acid production in stomach
acid produced by the parietal cell stimulates production of what
secretin
what does secretin do
acts back on cheif cell to stimulate pepsinogen production
what are parts A and B of stomach
A - storage
B - grinding of solids
how does gastric emptying occur generally
restoration of fundic tone and volume from ACh dependent tonic contraction
what are 3 kinds of relaxation of the gastric reservoir
receptive
adaptive
feedback relaxation
what do NO, VIP and ACh do in gastric emptying
ACh stimulates tonicity
VIP and NO stimulate relaxation
what cranial nerve is key in stomach relaxation/contraction
vagus nerve
what are the muscle laters of the stomach
oblique
circular
longitudinal
what is the corpus pacemaker
that is in the body of the stomach that initiates the contraction moving across the stomach and then sweeping down
how does a slow propagating wave in the stomach begin
interstitial cells have a natrual fluxuation fo membrane potentials
linked to eachother via gap junctions with eachother and smooth muscle cells
the enteric motor neuron has varicosities that releases NTs to the smooth muscle cells and interstital cells
what component of the production of a slow propagating wave in the stomach is requrired for the fluxuating membrane potential to be stimulated to the point that it creates a contraction
neurotransmitters released from varicosities
stretch
ACh
parasympathetic
what are the 3 phases of the gastric pump
phase of propulsion
phase of emptying
phase of retropulsion
what happens in the phase of propulsion in the antrum
contraction of proximal antrum
propulsion of chyme into relaxing terminal antrum + duodenal contraction
what happens in the emptying phase of the antrum
contraction of the middle antrum
transpyloric and tretrograde flow + duodenal relaxation
what happens in the retropulsion phase of the antrum
contraction of the terminal antrum
jet like back flow with grinding + duodenal contraction
what phase is the pylorus open and why
the mid antrum is contracting, emptying phase
the peristaltic contractions in the duodenum are stopped as well because if they didnt the contraction would block the entry of those contents into the small intestine
what is the function of retropulsion
grinding of solid particles is caused by the forceful get like retropulsion through the small orifice of the terminal antral contraction
what is sieving function
liquids and small particles leave the stomach more rapidly than large particles because the bulge of the terminal antrum retains the larger particles
what is emptied faster liquids or solids and why
liquieds
large solid particles only begins after sufficient grinding, afterwards viscous chyme is mainly emptied in a linear fashion
what is the lag phase
the grinding of solid particles that delays it from being emptied
what is rapid emptying
caused by tonic contraction of the resivoir, deep peristaltic waves along the gastric body, deep constrictions of the antral waes, a wide opening of hte pylorus, a duodenal resceptive relaxation and peristaltic dodenal contractions
what is delayed emptying
due to feedback inhibition caused by a prolonged relaxation fo the reservoir , shallow peristaltic waves along the gastric body, shallow antral waves, a small pyloric opening, a lacking duodenal relaxation and segmenting duodenal contractions
what mechanisms help slow the gastric emptying
I cell - in duodenum CCK comes out and activates receptors to send singals to slow emptying
L cells - in ileum, secrete GLP, CPR to stimulate the delay of gastric emptying
what stimulates I cells and L cells
free fatty acid
is a phase 3 contraction
a very strong contraction with pylorus being open to get residual things out of your stomach
