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1

What is dysbiosis?

microbial imbalances on or inside the body

2

Is there dysbiosis in a healthy status? What is there?

Healthy Status
Normal behavior, emotion, nociception
Normal levels of inflammatory cells & mediators
Normal gut microbiota

3

Is there dysbiosis in a stressed state?

Stress/Disease
Changes in behavior, cognition, emotion, nociception
Altered levels of inflammatory cells & mediators
Intestinal dysbiosis

4

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
NE released

5

What is the effect of parasympathetic stimulation on the gut?

increase in secretions & peristalsis
ACh released

6

What are some of the things that can affect the gut?

bacteria
toxins/chemicals
parasites
hormones
nutrients

7

What percentage of the vagus nerve is sensory?

80-90%

8

Self-contained inside the gut are what neurons?

IPANs: intrinsic primary afferent neuron

9

What portions of the GI does the vagus innervate?

stomach
SI
1/3 of colon

10

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
Hypogastric nerve
DRG

11

Where are the cell bodies of the afferent vagal fibers?

nodose ganglia

12

Where are the cell bodies of the pelvic nerves found?

in the DRG of the sacral region of the spinal cord

13

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
**pudendal nerves

14

What percentage of the splanchnic nerve fibers are afferent? Where are their cell bodies found?

7%
Cell bodies in the DRG

15

Some of the extrinsic afferent nerves are chemosensitive & some are not. What are these chemical agents that some are sensitive to?

ATP
bradykinin
capsaicin
5-HT
histamine

16

What are the differences b/w a generator potential & an action potential?

Generator 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
AP:
all or none
refractory period
propagation

17

What is the process of a spinal reflex?

Visceral Afferent Neuron
Interneuron (in spinal cord)
Pregang efferent
Postgang efferent
Effector

18

What counts as mechanical stimuli in the gut?

stretch
pressure
distortion
shearing forces

19

What counts as signaling molecules released from Peyer's patches in the gut?

Proteases
histamine
serotonin
cytokines

20

What types of luminal contents would signal enteroendocrine cells to release gut peptides?

nutrients
toxins
antigens

21

What types of gut peptides would enteroendocrine cells release?

hormones
neuropeptides

22

What areas of the brain are activated by the gut peptides released by enteroendocrine cells?

area prostrema
dostral vagal complex
hypothalamus

23

What is the function of endocrine cells in the GI tract?

They are detectors that analyze luminal contents, survey mucosal status, & activate afferent neurons.

24

What are 5 examples of endocrine cells in the GI tract?

I cells in duodenum
S cells in stomach & intestine
EE cells in gut
EC cells
lymphoid tissue

25

What do the I cells in the duodenum release? When do they release it? What happens next?

CCK
released in response to fat & protein digestion
CCK causes satiation; increases gastric blood flow & mucous protection
CCK inhibits gastric motility & emptying

26

What do the S cells in the stomach & intestine release? When does it release it? What is the response?

Release Secretin
in response to duodenal acidification
It enhances pancreatic exocrine secretion & bile flow.

27

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

28

Where is most of the serotonin in the body stored?

90% of 5-HT stored in EC cells

29

What stimulates EC cells to release their stores? What do they store? What is the effect?

mechanical & chemical stimulation
5-HT/serotonin
Activates peristalsis (intrinsic)
Activates relaxation of the stomach (extrinsic afferent neurons)

30

Where is the lymphoid tissue found in the gut? What cell types are found here?

Peyer's patches
antigen-sampling M cells
macrophages
eosinophils
neutrophils
mast cells

31

Of the gut nerves we have been talking about...which are sympathetic? Parasympathetic?

Sympathetic: Splanchnic nerves, Hypogastric nerves
Parasympathetic: Vagus, Pelvic nerves

32

What percentage of sympathetic nerves are afferent fibers?
What percentage of the vagus nerve?
Pelvic nerves?

Sympathetic: 20% afferent
Vagus: 80% afferent
Pelvic: 50% afferent

33

What do the vagal neurons sense?

pH & distention of the stomach

34

What do the pelvic neurons sense?

distention of the rectum & colon

35

Which set of visceral afferent nerve fibers senses pain in the gut?

Sympathetic nerves--splanchnic nerves
nociception

36

What does splanchnic stimulation elicit? Vagal stimulation?

Splanchnic: pain!!
Vagal: nothing.

37

Which set of afferent nerve fibers regulate visceral tone, distention, motility & secretion?

Parasympathetic: vagal & pelvic

38

What conditions include chronic visceral pain? How is this treated?

cancer
severe peripheral vascular disease
Surgically sectioning sympathetic nerve trunks, but not parasympathetic nerve trunks

39

What are there more of:
visceral sensory neurons
mechanosensory neurons?
What is the result of this?

10X as many mechanosensory neurons
Result: visceral sensations are diffuse & difficult to localize

40

Describe the neuron type of vagal & spinal afferents.

pseudounipolar

41

Describe the neuron type of IPANs.

multipolar

42

Where are IPANs found? What do they sense?

found only in the intestine & gut
sense mucosal stimulation & stretch

43

The vagus returns info to the brainstem via what? What type of info?

nucleus tractus solitarius
BP
CO2
Gut distention

44

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

45

What is another name for high threshold mechanoreceptors? What's the deal with them?

Phasic
low activity @ rest
responds to high levels of organ distention
**chemosensitive to inflammatory mediators
**receptive fields in serosa & mesentery

46

What are some inflammatory mediators?

BK, eicanosoids, free radicals

47

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

48

What are IMAs?

Intramuscular arrays
individual branch of a vagal afferent fiber
vagal mechanoreceptors that innervate GI smooth muscle

49

What are IGLEs?

intraganglionic laminar endings
vagal afferent fiber terminating in several intraganglionic laminar endings
mechanotransduction sites of vagal tension receptors in stomach

50

What are IVAs?

mucosa intravillous arbors
chemical receptors in mucosal units

51

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.

52

What type of a reflex is emesis?

a somato-autonomic reflex
integrated in the medulla oblongata

53

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?

Ondansetron
Granisetron
**this is where the serotonin released by EC cells in the SI activates the vagal afferent neurons
**palliative care

54

What is often taken in Parkinson's disease treatment that increases vomiting?

dopamine agonist

55

At which points in the pathway of emesis is dopamine involved?

There are dopamine receptors in the CTZ, NTS, & stomach vagus neurons.

56

How do the drugs metoclopramide & domperidone inhibit emesis?

They are both dopamine receptor antagonists. They work on dopamine receptors in the stomach & upper SI.

57

What is haloperidol & where does it work?

It is a dopamine antagonist & it works in the CTZ.

58

What is cyclizine & where does it work to stop emesis?

antihistamine & antimuscarinic drug.
works in the brainstem.

59

What are 2 kinda broad drugs that inhibit emesis?

levomepromazine & prochlorperazine

60

What are the 2 diseases under the umbrella of inflammatory bowel disorders?

Crohn's disease
Ulcerative Colitis

61

What portion of the GI tract is affected in Crohn's disease? What are the common symptoms?

SI & LI
abdominal pain
vomiting
diarrhea
blood in stool
fatigue
weight loss
growth problems

62

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

63

WIth IBD what's the deal?

the immune system is overreacting to normal bacteria and causing a ton of inflammation

64

What portion of the GI tract is mainly affected w/ ulcerative colitis? What are the symptoms?

LI
bloody diarrhea
abdominal cramping
urgent need for bowel movement

65

What are 2 common types of ulcers?

gastric ulcers--stomach
duodenal ulcers--SI

66

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.

67

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...

68

Aside from visceral afferent hypersensitivity what are other possible causes?

Neurotransmitter imbalance
infection
psychosocial factors
altered bowel motility

69

What are the symptoms of IBS?

abdominal pain with changes in frequency of bowel movements.
Diarrhea or constipation or both
whitish mucus in stool
bloated abdomen

70

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.

71

Gastric ulcers & gastritis both cause inflammation in the stomach. What does this do to visceral sensitivity?

This causes visceral hypersensitivity to gastric distention.

72

Describes what happens in an injury to cause an increased sensitization of nociceptive fibers.

injury
inflammatory soup (from injured cells & other cells)
Sensitization of nociceptive fibers

73

What types of substances, present in the inflammatory soup, cause pain?

K+
H+
ATP
Bradykinin
Histamine
Prostaglandins

74

If after an injury the firing gets really intense...what 2 substances might be released from afferent neurons?

Calcitonin Gene Related Peptide (CGRP)
Substance P

75

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

76

What is hyperalgesia?

exaggerated pain in response to a painful stimulus

77

What is allodynia?

pain in response to an innocuous stimulus

78

What is secondary hyperalgesia?

a receptive field expansion that enables input from non-injured tissue to cause pain

79

What causes all these things: hyperalgesia, allodynia?

Central sensitization
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.

80

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.

81

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.

82

What is congenital analgesia?

rare genetic disorder in which you can't feel pain
life-threatening b/c you have no warning mechanism!!

83

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.

84

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.

85

What are the 3 opiod-derivatives that are approved by the FDA?

loperamide
diphenoxylate
difenoxin

86

What are 3 sources of cannabinoids? What is the ligand that makes it up?

Endogenous
Synthetic
Plant-derived
*anandamide

87

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

88

What receptor that is bad can be activated if you smoke too much marijuana? What are the results?

TRPV 1
This increases inflammation, contractility, & hypersecretion.
Can cause vomiting, polydipsia, desire to take repeated hot showers.

89

What is SSRI? Lidocaine?

SSRI: selective serotonin reuptake inhibitor
Lidocaine: local anesthetic

90

What is dysbiosis?

a condition w/ microbial imbalances inside or on the body; prominent in GI & on skin

91

T/F Sensitization of sensory pathways during acute episodes of gastroenteritis contributes to the development of postinfectious functional GI disorders.

True.