Gastric motility and secretion Flashcards
Stores ingested food until it can be emptied into the small intestine.
Located between the esophagus and duodenum
Stomach
The 1st area of stomach is covered by the regis called ___
Ruga
The stomach is divided into 3 major parts
fundus, stomach body, antrum
Between stomach and duodenum, we have the ___ sphincter, which guards the antrum from the stomach into the duodenum
pyloric
The stomach stores ___ in the duodenum at a rate that does not exceed in the small intestine functional capacity.
The stomach cells also secrete __ and ___, the enzyme necessary for protein digestion.
chyme
HCL
pepsinogen
the stomach contains: ___ __ muscle and ___ smooth muscle layer
Circular smooth
longitudinal
oblique smooth muscle cells
serves in the complex grinding of the food
Two functional zones of the stomach
the proximal stomach and distal stomach
primarily serves as a reservoir and it stores the food before it can move to the distal stomach
proximal stomach
has thick muscle layer and is able to perform powerful muscle contraction. Serves to grind, titurate the meal and regulate rate at which partially digested food is emptied into the duodenum
distal stomach
During fasting, the entire content of the digestive tube catches undigested materials or ingested foreign substance moves them along the entire length of the digestive tract starting in the stomach. This can be considered a ___ ___ function of the digestive tract
house keeping
The house keeping function is accomplished with the help of __, which causes growling
migrating myoelectric complex MMC
migrating myoelectric complex MMC occurs in 3 phases
the quiescent,
irregular electric motor activity
most powerful contraction
in the absence of MMC – migrating motor complexes, undigested materials or ingested foreign particles can accumulate and form aggregate known as ___, which can obstruct the digestive lumen in particularly in the stomach and lead to ulcers
BEZOARS
The migrating myoelectric complexes are induced by peptide gastro-intestinal hormone called ___.
MOTILIN
levels of endogenous motilin correlate with the phases of migrating motor complex contractions, and if we inject the exogenous motilin, we can induce phase ___ of the MMC contraction ( the phase with stronger contraction)
Another peptide hormone is ___, which is suspected to regulate this activity
3
GHRELIN
___ and several erythromycin analogs known as __ can mimic the effects of motilin and significantly increase the gastrointestinal motility
Erythromycin
motilides
lower doses the erythromycin can promote the release the __ from the neurons of myenteric plexus and induce increase motility.
at higher doses erythromycin can directly stimulate the ___ receptors in the smooth muscles cells and induce very strong contraction and increase gastrointestinal motility
Ach
motilin
the increase in gastrointestinal motility by erythromycin can be used as a prokinetic agent and can actually be useful in patients that have impaired gastro-motility, like patients with ___ ___
DIABETIC GASTROPARESIS
As the stomach receives the food, it relaxes to accommodate the incoming meal known as ___ ___
receptive relaxation
triggered when the mechanoreceptor are stimulated in the stomach wall by the incoming food. Its
Mediated by intrinsic and vago-vagal reflexes
Its Mediated by ___ and __ reflexes
receptive relaxation response
intrinsic
vago-vagal
when food is going to the stomach, the wall of the stomach stretches and stimulates the mechanoreceptors, this cause the vagal nerve endings to release ___. ___ then acts pre-synpatically to promote the release of additional neurotransmitters, Nitric oxide and vasoactive intestinal peptide VIP
acetylcholine
Ach
__ and __ induce the relaxation in proximal stomach, as a result the stomach is able to accommodate the incoming food.
NO
VIP
When food moves from the proximal stomach to the distal stomach it is mixed and triturated by the strong contractions of the enteron
Pacemaker cells, the ___ ___ __ ___, which initiate the slow wave potentials and electrical activity of smooth muscle cells.
when slow wave potential reaches threshold, the peristatic wave is initiated and moves from stomach fundus to body, towards the enteron—small portion of chyme is emptied into the duodenum, through partial open pyloric sphincter
interstitial cells of cajal
when the perisitic wave of contractions reaches the pyloric sphincter and empties small amounts of chyme, the pyloric sphincter contracts and it seals the exit and chyme goes back into the ___ until the next contraction.
enteron
refers to the collection of disorders of different etiology in which gastric emptying is impaired or delayed
Gastroparesis
Causes of impaired gastric motility
SURGERY
MEDICATIONS
DIABETES
gastro paresis and the delayed gastric emptying can aggravate the symptoms of __, making the symptoms worse
diabetes
MEDICATIONS such as ___ or __ drug decrease gastro motility and cause gastro paresis.
anticholinergic
opioids
With a delayed gastric emptying, the delivery of nutrients to the duodenum is unpredictable and may influence the ability of the subject to maintain ___ control.
glycemic
MOST CLINICALLY CHALLENGING OF GASTRO PERISIS is patients with long standing
___ affects the cellular metabolism and membrane functions thickening of the capillary basement membrane
diabetes mellitus
Hyperglycemia
When capillary basement membrane is too thick, it might result is __, destroying the normal neuronal functions and result in neuronal death and disruption of the neuronal pathways which regulate the stomach motility resulting in gastro paresis.
hypoxia
causes of gastro paresis
damages to the nerve fibers,
loss of the pace maker cells
loss of enzymes Nitric Oxide Synthase
the loss of NO can result in __ spasm, constant contraction of the pyloric sphincter.
pyloric
what kind of diet would you recommend to a patient with impaired gastric emptying
low fat meals
Overall the function of smooth muscle cells of the stomach is regulated by 3 major types of factors:
Gastric factors
Duodenal factors
The factors that are coming from the outside of the duodenum system
factors that originate in the duodenum
Duodenal factors
factors that originate in the stomach
Gastric factors
The major gastric factors regulates the gastric motility is the presence of large amounts of chyme in the stomach.
when there’s a lot of chyme in the stomach, the gastric motility is stimulated by the action of vagus nerve ending and myenteric plexus. In addition, there’s a hormone release by the enteron endocrine cells of the stomach, and this hormone is called __.
GASTRIN
the central hormone produced by the stomach. has a stimulatory effect on both gastric motility and gastric secretion.
Gastrin
the __ has the power to inhibit the motility until it is ready to process more nutrients
duodenum
The major factors that inhibit the stomach motility in the duodenum are
fatty, hypertonic, acidic chyme
the presence of fatty, hypertonic, acidic chyme in the duodenum initiate two types of response:
hormonal response
neural response.
Occurs Outside the digestive system
emotion, intense pain
The 3 major enterogastrons include
SECRETIN, CCK, GIP
The hormonal response of fatty, hypertonic, acidic chyme in the duodenum are collectively known as ___ and inhibit gastric motility
ENTERO-GASTRONS
involves the reflexes that are integrated entirely within the enteric nervous system
SHORT REFLEXES
reflexes that involve autonomic nervous system
LONG REFLEXES
With the presences of fatty, hypertonic, acidic chyme, we decrease the ___ fibers and increase the activity of the ___ fibers (activity). As a result, the gastric motility is inhibited
parasympathetic
sympathetic
___ in the duodenum inhibit gastric motility
fats
NO is produced by NO synthase. how does the loss of NO synthase affect gastric motility
results in impaired gastric emptying
NO is a major inhibitory neurotransmitter, and induces the ___ of smooth muscle cells. Without, we have constant contractions of the pyloric sphincter
relaxation
the MMC migrating motor complex accomplishes the ___ functions of the digestive tract.
house keeping
segmentation id observed in the ___ intestine
small
during vomiting, the stomach, esophagus and corresponding sphincters are ___
relaxed
The main force of expulsion during vomiting comes from the respiratory muscles:
diaphragm
major aspiration muscle
abdominal muscle
Vomiting is regulated by the vomiting center which is in the ___ of the brain stem
medulla
the stomach is squeezed by diaphragm from ___ and the abdominal muscles from __ which causes the forceful expulsion of the stomach content into the esophagus and into the oral cavity
above
below
during vomiting the content of the stomach does not enter the respiratory airways bc the __ is closed
glottis
Vomiting is proceeded by:
profuse salivation
sweating
rapid heart rate
sensation of nausea due to discharge of the ANS
phayngeal stimulation is delivered to the vomiting center with the help of the ___ NERVE.
GLOSSOPHARYNEAL
The irritation of gastric mucosa by various drug, cytotoxic drugs, and the presence of pathogenic bacteria or viruses is transmitted and relayed to the vomiting center and the information is relayed from the gastric mucosa with the help of the ___ NERVE
VAGUS
the vestibual nuclei and the cerebellum signals mediates the vomiting associated with __ sickness and vertigo
motion
In this zone we have a specific chemoreptor cells which constantly monitor the blood and the cerebral spinal fluid for the presence of the potentially toxic or harmful compound; lacks a blood brain barrier
“chemoreceptor trigger zone”
The chemoreceptor trigger zone has a high concentration of
serotonin
dopamine receptors
muscarinic receptors
cannabinoid receptors
What is the ligand for the neurokinin-1 receptor?
Substance P
the solitary tract nucleus relays information to the vomiting center from the __, small intestine and pharynx. Contains high concentration of :
stomach cannabinoid receptors. serotonin dopaminergic receptors mucarinic receptors histamine receptors neurokinin-1 receptors
Information from the vestibular nuclei and cerebellum is transmitted to the vomiting center with the help of histamine receptors H1 and __ receptors.
muscarinic
anti-emetic class are classified according to their receptors:
serotonin antagonists dopamine antagonists histamine H1 antagonists muscarinic antagonists neurokinin antagonists cannabinoid agonist
Serotonin receptor antagonist inhibit the function serotonin receptors in the ___ and the ___ mucosa. They interfere with the serotonin receptor function in the chemoreceptors trigger zone and the vomiting center
gastric
intestinal
are widely used drugs that treat emesis associated with cancer chemotherapy – cytotoxic drugs
serotonin receptor antagonist
most widely used anti-emetic
considered to be the general purpose anti-emetics, and are also effective against the vomiting associated with cancer chemotherapy
dopamine receptor antagonist
Anti-emetic drugs are considered ___ drugs
Neuroleptic
Two adverse effects that occur if we inhibit the dopaminergic receptors on the brain/CNS:
Parkinsons disease- parkinsonism symptoms can develop
Lethargy dyskinisia – involuntary movement of various parts of the body
used to manage the vomiting associated with motion sickness, so they inhibit the transmission of information from the vestibular nuclei to the vomiting center.
Histamine H1 antagonist and muscarinic receptors
stimulated by substance P, this antagonist is used as the additional therapy for patients experiencing multiple cycles of chemotherapy, and is effective against delayed vomiting
neurokinin1 receptor
interferes with the vomiting reflex by stimulation that the cannabinoid receptors in the vomiting center
Dronabinol
The surface of the stomach is covered by the invagination shown above. The upper part of the invagination is called gastric __ and the bottom gastric __.
pit
gland
Deep below the gastric gland we have chief cells. The chief cells produced ___
pepsinogen
The pepsinogen is an inactive precursor of the digestive enzyme __, so it is converted into its active form pepsin with the help of __ and the pepsin is a protolytic enzyme, it digest proteins
pepsin
HCL (hydrochloric acid)
In the middle of the gastric gland we have parietal cells, which secrete __ and intrinsic factors. The intrinsic factor is necessary for successful absorption of ____ in the intestine.
HCL
vitamin B12
Enteroendocrine cells
gastrin
Parietal cells
HCl and intrinsic factor (B12)
Mucous neck cells
thin watery mucus
Surface epithelial cells
thick, viscous, alkaline mucus = protective barrier
Aids in the breakdown of muscle and connective tissue, reducing large food particles into smaller particles
HCl
Kills microorganisms ingested with food
Uncoils and denatures the proteins exposing more peptide bonds for digestion
HCL
Why not produce the pepsin right away?
The main building block of the cells is protein. If activated right away it’ll destroy its own proteins.
The 3 level barrier of the gastric defense are:
Pre-epithelial
epithelial
sub-epithelial
this level barrier secretes mucus. its primarily composed of water, phospholipids and glycoproteins. This mucus prevents the diffusion of hydrogen ions and pepsin .
pre-epithelial
in the pre-epithelial, the mucus gel functions as a non-stirred water layer blocking diffusion of__ and __. __ secreted by surface epithelial cells forms a pH gradient (pH 1-2 in the gastric lumen, and pH 6-7 along the epithelial cell surface).
H+
pepsin
Bicarbonate
In the gastric mucosa we have a very high level of ___, which can increase the secretion of mucus, and bicarbonate. They can also inhibit the parietal cells, the acid secretion
prostaglandins
___ are necessary to maintain the normal mucosal blood flow. Overall they are considered one of the most significant factors in the maintenance of the gastro mucosal defense.
Prostaglandins
____drugs which inhibit the synthesis of prostaglandins in the gastric mucosa are associated with a variety of effects in the gastrointestinal system. Most dangerous of course is gastro intestinal bleeding and hemorrhage
non-steroidal inflammatory
prostaglandins - functions
regulare release of bicarb and mucus
inhibit parietal cell secretion
maintains mucosal blood flow
within the gastric submucosal layer supplies micronutrients and oxygen while removing toxic metabolites.
Microvascular system
The three main stimulants of H+ ion secretion are
acetylcholine, gastrin, and histamine
Characteristic features of the inactive parietal cell:
tubulovesicular network contains inactive proton pumps. When stmulated by HISTAMINE, ACETYLCHOLINE, or GASTRIN, which bind to receptors on the vasolateral membrane, tubulovesicular network is going to fuse with apical membrane of the parietal cells, and as a result the surface area of the membrane can increase up to 100 folds and we have insertion of active proton pumps into the membrane and the acid secretion
The main player of of acid secretion is ___
____ ___ is present at high concentrations in the parietal cells
H/K ATPase
Carbonic anhydrase
Parietal cells contain receptors for acetylcholine, gastrin, and histamine on their basolateral membrane. Stimulation of these receptors promotes ___ ___
acid secretion
Histamine stimulate ___ receptor
acetylcholine acts on ___ receptor
gastrin stimulates the ___ _ receptor
Activation of these receptors/pathway, is insertion of H/K ATPase into the membrane and secretion of acid
The effect of these 3 pathways are synergistic
H2 histamine
cholecystokinin 2
M3 muscarinic
The most potent acid suppressor drugs are the ___, which suppress the final step of acid production, the proton pump itself
proton pump inhibitor ppi
the inhibition of proton pump means that the proton pump inhibitor is going to reduce the __ production independently from pathway stimulating the acid secretion. Except the H2 histamine receptor antagonist bc there effect can be overcome by the __ or __
acid
Ach
gastrin
All __ are pro-drugs, to become active they need to be activated in the acidic environment of the stomach
PPI
Acid secretion resumes only after __ pump molecules are synthesized and inserted into the luminal membrane, providing a prolonged (up to 24- to 48-hour) suppression of acid secretion.
new
There may be rebound acid ___ (acid secretion above pretreatment levels) upon discontinuing the PPI therapy
Prolonged treament can significantly increase gastric ph which is a well established stimuli for the G cells, entero-endocrine cells, which secrete hormone ___, which stimulate the enterochromaffin-like cells to produce histamine
hypersecretion
gastrin
Histamine stimulates the H2 histamine receptors on the parietal to increase the acid production.
which is what leads to hypersecretion after the discontinuation of __ therapy
PPI
The most common side effects of PPI:
nausea, abdominal pain, constipation, flatulence, diarrhea
PPIs are linked with 2-3-fold increased risk of _____ among elderly patients with chronic comorbidity and on broad-spectrum antibiotic
Clostridium difficile-associated diarrhea (CDAD)
. The acidity in the the stomach is not only an important sterilizer but also the absorption of ____
calcium
acid in the stomach helps to free the ca ions from the insoluble calcium salt in our food. This will decrease calcium plasma concentration and is a stimulus to release ___ hormones which is aimed to restore the normal ca concentration in the blood circulation
parathyroid
the acid in the stomach is not only important for absorption of Ca but also
vitamin B12, iron, and magnesium.
potential risks of PPIi
infections enteric infection community acquired pneumonia bone fractures nutritional deficiency: vit b12, iron, Mg2+
There are 3 major phases of gastric secretion
Cephalic phase
Gastric phase
Intestinal phase
its initiated before the food actually enters the stomach. Its initiated by the food anticipation, think, or smelling the food
Cephalic phase
phase where food enters the stomach itself
Gastric
this phase starts when 1st portion of chyme enter the duodenum
intestinal
the neurons in the myenteric plexuses they stimulate the __ of the smooth muscles in the stomach while the submucosal plexuses neurons they promote the secretion of __ and ___
contraction
pepsinogen
HCL
What occurs in the stomach when the ph drops below 2?
it serves as a inhibitory signal and temporarily inhibits the gastric motility and secretion until the ph is elevated again
The ___ ___ is the main site for ingestion and absorption of food
small intestine
Two repsonse occur when the chyme enters the duodenum:
So the information of these receptors act to inhibit the neurons in the myenteric plexuses and submucosal plexuses and we have the inhibition of gastric secretion and gastric motility.
1st the chymes stretch the duodenum wall and we have the activation of mechanoreceptors and the partially digested nutrients in the duodenum active various chemoreceptors which are present in the duodenum wall
2nd is the endocrine response
So the presence of acidic, hypertonic chyme in the duodenum activates the specialized entero-endocrine cells in the duodenum wall which secrete the hormones collectively known as _____
entero-gastron
that the major entero-gastron are gastric inhibitory peptide:
GIP, secretin, and CCK Cholecystokinin
These hormones are released into the blood and they reach the gastric cells through circulation, and they again inhibit gastric motility and secretion
GIP, secretin, and CCK Cholecystokinin
in an experiment, rabbits are administered a cholinergic agonist, pentagastrin or histamine via iv and the acid secretion is measured. which drug when co-administered with each of these agents would be expected to block gastric acid secretion produced by any of the stimuli?
PPI
3 pathways that can stimulate the insertion of the proton pump into the membrane and stimulate acid secretion
histamine H2 receptor antagonist activated by binding of histamine, the muscarinic M3 receptor activated by Ach, and Cholinestikinin 2 receptors activated by gastrin
histamine H2 receptor antagonist activated by binding of histamine, the muscarinic M3 receptor activated by Ach, and Cholinestikinin 2 receptors activated by gastrin are inhibited by the ___
proton pump inhibitor PPI
disruption of the mucosal integrity of the stomach and/or duodenum, leading to local defector excavation due to active inflammation.
a breakage in the intestinal mucosa or duodenum mucosal
Ulcer
___ deaths per year occur as a consequence of complicated PUD. (peptic ulver disease)
15,000
Acid ___ disorders are common in the US, with ~4 million individuals (new cases and recurrences) affected per year.
peptic
The pain in the stomach is aggravated by the ___ while the pain in the duodenum ulcer is relieved by the ___.
meals
meals
the integrity of the gastro intestinal mucosa depends on the balance between the ___ factors and the ___ factors
hostile
protective
Hostile factors included:
H. pylori infections, gastric acid, pepsin, NSAIDs
Protective factors include
Bicarbonate, prostaglandins, mucus production, blood flow to mucosa
Three major causes of peptic ulcer are
chronic helicobacter pylori infection, NSAIDs, and Acid hypersecretory states (such as zollinger-Ellison syndrome)
a short, spiral-shaped, microaerophilic gram-negative bacillus, is the leading cause of peptic ulcer disease. It is associated with up to 70%- 80% of duodenal ulcers.
H. pylori
colonize the deep layers of the gel that coats the mucosa and disrupt its protective properties causing release of certain enzymes and toxins. It makes the underlying tissues more vulnerable to damage by digestive juices causing injury to the stomach and duodenum cells.
-H. pylori
H pylori penetrate the ___ layer which cover the gastric epithelial cells. At this level the ph is neutral compared to the lumen which is about 2.
mucin
pylori can further increase ph in its micro environment through the production of the enzyme ___. Urease produces ammonia, which helps to further increase ph
UREASE
The two major toxins secrete by H. pylori are
Vac A
Cag toxin
collapse the endocytic compartment of the cells which causes the appears of large non-functional vacuole
VacA
disrupts the normal function of the cytoskeleton
Cag
In fact the chronic infection with ___ is the strongest known risk factor for gastric cancer development. Gastric cancer is the __ leading of cancer related worldwide
h pylori
2nd
H pylori increase risks or another type of cancerous tumor called
MALT LYMPHOMA (mucosal associated lymphoid tissue)
The current gold standard for h pylori eradication is a triple combination of drug:
first line
second line
third line therapy
In 1st line therapy: we have admin of the proton pump inhibitor, with two antibiotics __ and __ or sometimes the PPI with ___ and ___
clarithromycin amoxicillin or clarithromycin metronidazole
2nd line of defense we have admin of PPI with :
or PPI and
or PPI
bismuth
metronidazole
tetracycline
or metronidazole
tetracycline
or metronidazole and amoxicillin
third line results in ___ rescue therapy or treatment tailored to individual _____ sensitivity
emperic
antibiotic
H. pylori oscillates between a replicating state (pH ___,antibiotic sensitivity) and nonreplicating state (____, antibiotic insensitivity) according to the pH in the microenvironments
So the administration of proton pump inhibitors only helps to increase the ½ life of antibiotics but it also helps to switch the h pylori into the ___ cycle where its sensitive to antibiotics.
6-8
pH 4-6
replication
In ___ syndrome, the endocrine tumor develops in the pancreas and secretes very high levels of hormone gastrin. This increase of gastrin stimulates stomach cells to produce the excessive amounts of acid and pepsin which are deposited in the duodenum overwhelming the protective properties of the duodenum mucosa and lead to the development of duodenal ulcers
Gastrinoma (Zollinger-Ellison syndrome
in Gastrinoma (Zollinger-Ellison syndrome) If the tumor cannot be removed it is managed with ___.
proton pump inhibitor
PPI can also be used to prevent and treat gastro intestinal ulcerations associated with ___ administration.
NSAIDs
Since NSAID inhibit the ___ synthesis and this is the major reason of increase risk of gastric intestinal ulceration and peptic ulcer disease, so the introduction of the synthetic ____ analogs together with NSAIDs seem to be a logical approach to prevent the adverse effects in the gastrointestinal tract associated with NSAIDs
prostaglandin
prostaglandin
the synthetic prostaglandin E2 (PGE2) analog and it has been shown to reduce the risk of peptic ulcers in patients who high doses of NSAIDs
it’s associated with a number of adverse effects and its not used very often. Usually the proton pump inhibitor is preferred in those patients
MISOPROSTOL
