Flashcards in Smith Deck (91)
What is dysbiosis?
microbial imbalances on or inside the body
Is there dysbiosis in a healthy status? What is there?
Normal behavior, emotion, nociception
Normal levels of inflammatory cells & mediators
Normal gut microbiota
Is there dysbiosis in a stressed state?
Changes in behavior, cognition, emotion, nociception
Altered levels of inflammatory cells & mediators
What is the effect of sympathetic stimulation on the gut?
decrease in secretions & peristalsis
blood redirected away from the gut & to other places like the brain
What is the effect of parasympathetic stimulation on the gut?
increase in secretions & peristalsis
What are some of the things that can affect the gut?
What percentage of the vagus nerve is sensory?
Self-contained inside the gut are what neurons?
IPANs: intrinsic primary afferent neuron
What portions of the GI does the vagus innervate?
1/3 of colon
What are some afferent nerves that supply the GI that go thru the paravertebral/prevertebral ganglia to get there? Where are their cell bodies located?
Greater splanchnic nerve
Lumbar colonic nerve
Where are the cell bodies of the afferent vagal fibers?
Where are the cell bodies of the pelvic nerves found?
in the DRG of the sacral region of the spinal cord
What are the 3 pathways that connect the gut to the CNS?
1. Vagal afferents-->upper GI
2. Pelvic afferents-->colorectal (colon, rectum, internal anal sphincter)
3. splanchnic afferents-->throughout GI tract, nociceptive
What percentage of the splanchnic nerve fibers are afferent? Where are their cell bodies found?
Cell bodies in the DRG
Some of the extrinsic afferent nerves are chemosensitive & some are not. What are these chemical agents that some are sensitive to?
What are the differences b/w a generator potential & an action potential?
graded; larger stimulus-->larger potential-->large frequency of AP firing; but if doesn't meet threshold-->no AP
**dependent on coupled transmitters
doesn't propagate-->local phenomenon
no refractory period
all or none
What is the process of a spinal reflex?
Visceral Afferent Neuron
Interneuron (in spinal cord)
What counts as mechanical stimuli in the gut?
What counts as signaling molecules released from Peyer's patches in the gut?
What types of luminal contents would signal enteroendocrine cells to release gut peptides?
What types of gut peptides would enteroendocrine cells release?
What areas of the brain are activated by the gut peptides released by enteroendocrine cells?
dostral vagal complex
What is the function of endocrine cells in the GI tract?
They are detectors that analyze luminal contents, survey mucosal status, & activate afferent neurons.
What are 5 examples of endocrine cells in the GI tract?
I cells in duodenum
S cells in stomach & intestine
EE cells in gut
What do the I cells in the duodenum release? When do they release it? What happens next?
released in response to fat & protein digestion
CCK causes satiation; increases gastric blood flow & mucous protection
CCK inhibits gastric motility & emptying
What do the S cells in the stomach & intestine release? When does it release it? What is the response?
in response to duodenal acidification
It enhances pancreatic exocrine secretion & bile flow.
What do the enteroendocrine cells in the gut do?
Release up to 20 different kinds of neuropeptides that can stimulate the vagal afferents in a paracrine fashion or the brain in an endocrine fashion
Where is most of the serotonin in the body stored?
90% of 5-HT stored in EC cells
What stimulates EC cells to release their stores? What do they store? What is the effect?
mechanical & chemical stimulation
Activates peristalsis (intrinsic)
Activates relaxation of the stomach (extrinsic afferent neurons)
Where is the lymphoid tissue found in the gut? What cell types are found here?
antigen-sampling M cells
Of the gut nerves we have been talking about...which are sympathetic? Parasympathetic?
Sympathetic: Splanchnic nerves, Hypogastric nerves
Parasympathetic: Vagus, Pelvic nerves
What percentage of sympathetic nerves are afferent fibers?
What percentage of the vagus nerve?
Sympathetic: 20% afferent
Vagus: 80% afferent
Pelvic: 50% afferent
What do the vagal neurons sense?
pH & distention of the stomach
What do the pelvic neurons sense?
distention of the rectum & colon
Which set of visceral afferent nerve fibers senses pain in the gut?
Sympathetic nerves--splanchnic nerves
What does splanchnic stimulation elicit? Vagal stimulation?
Which set of afferent nerve fibers regulate visceral tone, distention, motility & secretion?
Parasympathetic: vagal & pelvic
What conditions include chronic visceral pain? How is this treated?
severe peripheral vascular disease
Surgically sectioning sympathetic nerve trunks, but not parasympathetic nerve trunks
What are there more of:
visceral sensory neurons
What is the result of this?
10X as many mechanosensory neurons
Result: visceral sensations are diffuse & difficult to localize
Describe the neuron type of vagal & spinal afferents.
Describe the neuron type of IPANs.
Where are IPANs found? What do they sense?
found only in the intestine & gut
sense mucosal stimulation & stretch
The vagus returns info to the brainstem via what? What type of info?
nucleus tractus solitarius
What is another name for tonic mechanoreceptors? What's the deal with them?
Wide Dynamic Range
tonic activity @ rest
responds to contraction/distention
**it signals filling of: stomach, colon, rectum
**discomfort/pain in: organ inflammation
What is another name for high threshold mechanoreceptors? What's the deal with them?
low activity @ rest
responds to high levels of organ distention
**chemosensitive to inflammatory mediators
**receptive fields in serosa & mesentery
What are some inflammatory mediators?
BK, eicanosoids, free radicals
What are silent nociceptors sometimes considered? What's the deal with them?
sometimes considered chemonociceptors
silent @ rest
mechanosensitive during inflammation via inflammatory mediators
In colon mucosa: sensitive to luminal chemicals & fine tactile stimulation
What are IMAs?
individual branch of a vagal afferent fiber
vagal mechanoreceptors that innervate GI smooth muscle
What are IGLEs?
intraganglionic laminar endings
vagal afferent fiber terminating in several intraganglionic laminar endings
mechanotransduction sites of vagal tension receptors in stomach
What are IVAs?
mucosa intravillous arbors
chemical receptors in mucosal units
How can the 5-HT released by enterochromaffin cells in the gut end up in general circulation?
if it is taken up into portal blood & taken up into platelets via SERT. Then it won't be degraded by MAO. It can go into the liver & then into general circulation.
What type of a reflex is emesis?
a somato-autonomic reflex
integrated in the medulla oblongata
What 2 drugs target 5-HT3 receptors to stop emesis? Which part of the pathway is this? What is one situation that they don't work particularly well in?
**this is where the serotonin released by EC cells in the SI activates the vagal afferent neurons
What is often taken in Parkinson's disease treatment that increases vomiting?
At which points in the pathway of emesis is dopamine involved?
There are dopamine receptors in the CTZ, NTS, & stomach vagus neurons.
How do the drugs metoclopramide & domperidone inhibit emesis?
They are both dopamine receptor antagonists. They work on dopamine receptors in the stomach & upper SI.
What is haloperidol & where does it work?
It is a dopamine antagonist & it works in the CTZ.
What is cyclizine & where does it work to stop emesis?
antihistamine & antimuscarinic drug.
works in the brainstem.
What are 2 kinda broad drugs that inhibit emesis?
levomepromazine & prochlorperazine
What are the 2 diseases under the umbrella of inflammatory bowel disorders?
What portion of the GI tract is affected in Crohn's disease? What are the common symptoms?
SI & LI
blood in stool
What does the bowel of a Crohn's patient look like when it is affected? What are the extreme things that can happen to the bowel?
cobblestone appearance of the mucosa (from linear ulcerations)
patchy inflammation that extends into all the tissue layers
Extreme Results: fistulas, absecesses, strictures
WIth IBD what's the deal?
the immune system is overreacting to normal bacteria and causing a ton of inflammation
What portion of the GI tract is mainly affected w/ ulcerative colitis? What are the symptoms?
urgent need for bowel movement
What are 2 common types of ulcers?
What causes gastric ulcers?
H. Pylori that is usu fine in the stomach sometimes causes inflammation. When this happens tissue is damaged & ulcers form & pain results.
Irritable Bowel Syndrome is considered a functional gastrointestinal disorder. What happens w/ this? What is thought to cause it?
strong contractile activity of the gut
visceral afferent nerve hypersensitivity is thought to be the cause...
Aside from visceral afferent hypersensitivity what are other possible causes?
altered bowel motility
What are the symptoms of IBS?
abdominal pain with changes in frequency of bowel movements.
Diarrhea or constipation or both
whitish mucus in stool
T/F Inflammation is involved in IBS as well as IBD.
FALSE. only IBD.
NOT IBS. Thus, IBS is less serious in terms of long term consequences.
Gastric ulcers & gastritis both cause inflammation in the stomach. What does this do to visceral sensitivity?
This causes visceral hypersensitivity to gastric distention.
Describes what happens in an injury to cause an increased sensitization of nociceptive fibers.
inflammatory soup (from injured cells & other cells)
Sensitization of nociceptive fibers
What types of substances, present in the inflammatory soup, cause pain?
If after an injury the firing gets really intense...what 2 substances might be released from afferent neurons?
Calcitonin Gene Related Peptide (CGRP)
What are TRP receptors?
they are transient receptive potential receptors
**found on afferent neurons
**responsive to temp
**responsive to certain substances, like capsaicin
**when these things activate the TRP there is a transient depolarization of the terminal membrane
What is hyperalgesia?
exaggerated pain in response to a painful stimulus
What is allodynia?
pain in response to an innocuous stimulus
What is secondary hyperalgesia?
a receptive field expansion that enables input from non-injured tissue to cause pain
What causes all these things: hyperalgesia, allodynia?
an increase in synaptic efficacy & a decrease in inhibition; central amplification
Basically, you're injured & now you have a low threshold for sensory inputs to effect a pain circuit.
What is the convergence theory of referred pain?
This theory recognized that somatic sensory fibers & visceral sensory fibers both have cell bodies in the same DRG in the spinal cord & synapse w/ the same interneurons.
Sometimes the brain just can't discriminate.
Explain the basic idea behind visceral organ cross-sensitization.
2 inputs converge on the same second order spinal neuron in the spinal cord...one is insulted & the other is also amplified
This often happens b/w the colon & bladder...people w/ IBS also have bladder hypersensitivity b/c of cross-sensitization.
What is congenital analgesia?
rare genetic disorder in which you can't feel pain
life-threatening b/c you have no warning mechanism!!
Describe the Gate Control Theory of Pain.
It involves a gating mechanism located in the dorsal horn of the spinal cord.
Inhibitory neuron in spinal cord acts as the gate.
projection cells go to the brain & signal pain.
Large nerve fibers stimulate both inhibitory & projection & therefore no pain is felt. This means that there was a normal stimulus.
Small nerve fibers (nociceptive) inactivates the inhibitor & activates the projection. Gate open.
Descending pathways from the brain can stop some of this pain.
Describe when opiods can & cannot be good options for treatment of gut pain.
Opiods suppress pain.
Good: if you have painful diarrhea b/c a side effect is constipation.
Bad: if elderly or have other complications b/c constipation is a major side effect along with a number of others.
What are the 3 opiod-derivatives that are approved by the FDA?
What are 3 sources of cannabinoids? What is the ligand that makes it up?
What are the 2 beneficial receptors that anandamide activates? What are the effects?
CB1: antiulcer, reduction in gastric & intestinal motility, reduction in intestinal secretions
CB2: reduction in cytokines, visceral pain & contractility
**can be useful to treat the inflammation of IBD
What receptor that is bad can be activated if you smoke too much marijuana? What are the results?
This increases inflammation, contractility, & hypersecretion.
Can cause vomiting, polydipsia, desire to take repeated hot showers.
What is SSRI? Lidocaine?
SSRI: selective serotonin reuptake inhibitor
Lidocaine: local anesthetic
What is dysbiosis?
a condition w/ microbial imbalances inside or on the body; prominent in GI & on skin