Visceral Afferents T. Smith Flashcards
1
Q
(blank) refers to a condition with microbial imbalances on or inside the body. It is most prominent in the digestive tract or on the skin, but can also occur on any exposed surface or mucous membrane such as the vagina, lungs, mouth, nose, sinuses, ears, nails, or eyes. It has been associated with different illnesses, such as inflammatory bowel disease, as imbalances in the intestinal microbiome may be associated with bowel inflammation and chronic fatigue syndrome.
A
Dysbiosis (also called dysbacteriosis)
2
Q
What do parasympathetics do for the gut?
What do symapthetics do for the gut?
A
stimulates peristalsis and secretion
inhibits peristalsis and secretion
3
Q
Where are the ganglion for the cell bodies of vagal afferents?
A
nodose ganglion
4
Q
Inside the gut wall in the submucous plexus we have (blank) neuron that sense what is happening in the mucosa.
A
intrinisic primary afferent neurosn (IPANs)
5
Q
Visceral afferents will have cell bodies in the (blank) and will travel through the prevertebral and paravertebral ganglia to the spinal cord.
A
dorsal root ganglion
6
Q
What percentage of the vagus is made up of sensory nerve fibers?
A
80%
7
Q
The distal colon is represented in thoracolumbar and lumbosacral spinal segments by (blank and blank)
A
least splanchnic and pelvic nerve inputs.
8
Q
Gastric input to the CNS is represented in the brainstem and thoracic spinal cord by (blank and blank)
A
vagal and splanchnic inputs.
9
Q
Extrinisic afferents reach the gut via (blank, blank, blank, and blank)
A
vagal, splachnic, pelvic, and pudendal
10
Q
What are the three pathways that connect the gut to the CNS?
A
vagal afferents-> upper GI regions
Pelvic afferents-> Colorectal region
Splachnic afferents-> throughout GI, thought to be nociceptive
11
Q
What do pelvic afferents regulate?
A
regulate colon, rectum and internal anal sphincter
12
Q
What are the splachnic afferents thought to be?
A
nociceptive
13
Q
Afferent neurons or their nerve terminals may be sensitized or inhibited by (blank) released from several cell types.
A
chemical mediators
14
Q
Are all the afferents chemosensitive?
A
no some are and some arent
15
Q
A bolus of food in the pharynx stimulates (blank) in the wall of the pharynx
A
tension receptors
16
Q
Pharyngeal contraction coincides with relaxation of the (Blank)
A
upper esophageal sphincter (UES)
17
Q
What follows pharyngeal contraction and UES relaxation?
A
sequential (peristaltic) phasic contraction along the esophageal body, which propels the swallowed bolus toward the stomach.
18
Q
What follows the peristaltic/phasic contractions along esophageal body?
A
LES relaxes and remains relaxes until the peristaltic wave arrives
19
Q
Is a generator potential different than an action potential? How?
A
Yes
Generator potentials do not propagate and are local
Action potentials propagate
20
Q
A generator potential is (blank); it is small when few transmitters are coupled to their receptors and become larger when a lot of transmitters are attached. (so not all or none)
A
graded
21
Q
If you have a weak stimulus what will happen to your generator potental?
Strong stimulus?
A
weak stimulus-> small generator potential-> low frequency action potential
Strong stimulus-> large generator potential-> high frequency action potentials
22
Q
The basic spinal reflex arc that changes activity in an effector consists of what five things?
A
1) visceral afferent neuron plus sensory receptor
2) interneuron
3) preganglionic neuron
4) postganglionic neuron
5) effector
23
Q
Which is faster, reflexes in ANS or reflexes in skeletal muscle?
A
Reflexes in skeletal muscle
24
Q
What will microbial signals and antigens stimulate?
A
immune and tissue defense signals; local, systemic and neural
25
Information about luminal factors and conditions of the gut are signalled through (blank and blank) to the brain stem and spinal cord, respectively.
extrinsic vagal and spinal afferents
26
Mechanical stimuli (stretch, pressure, distortion and shearing forces) can activate spinal, vagal and intrinsic primary afferents (IPANs) directly, without (blank) such as the enteroendocrine (EE) cells.
intermediary cells
27
Signalling molecules (including proteases, histamine, serotonin and cytokines) that are produced by immune cells in Peyer's patches and within the gut epithelium can activate their respective receptors on (blank and blank).
vagal and spinal afferents
28
Enterochromaffin (EC) cells signal to both (blank and blank).
IPANs and vagal afferents
29
Different classes of EE cells are interspersed between (blank) throughout the gastrointestinal tract.
gut epithelial cells
30
EE cells, Upon luminal stimulation (or upon activation by postganglionic sympathetic or vagal nerves), these cells can release up to 20 different gut peptides from their basolateralsurface.
EE cells
31
Released peptides can activate closely adjacent vagal afferent nerve terminal, in a (blank) fashion, or when released into the circulation they can exert an (blank) effect, signalling to various sites in the brain and other parts of the gastrointestinal tract.
paracrine
| endocrine
32
(blank) function as detectors that analyze luminal contents, survey the mucosal status and activate afferent neurons.
Endocrine cells in the GI tract
33
(blank) release CCK in response to fat and protein digestion.
I cells in the duodenum
34
(blank) is involved in satiation, reflex inhibition of gastric motility and emptying, reflex increase in gastric blood flow and mucosal protection.
CCK
35
(blank) cells, in response to duodenal acidification, release secretin from endocrine cells in the proximal small intestine to enhance pancreatic exocrine secretion and bile flow.
S cells in stomach and intestine
36
(blank) release ~20 different neuropeptides that can stimulate vagal afferents in a paracrine fashion, or when released into the circulation they can exert an endocrine effect signaling to various sites in the brain and other parts of the GI tract.
EE cells throughout the gut
37
(blank) cells via mechanical and chemical stimulation, releases 5HT to activate both intrinsic (peristalsis) and extrinsic afferent neurons to cause receptive relaxation of the stomach.
Enterochromaffin cells (EC)
38
(blank) includes antigen-sampling M cells, macrophages, eosinophils, neutrophils and mast cells (mainly aggregated in Peyer's patches)
Lymphoid tissue
39
The enteric nervous system and central nervous system communicate with each other via (blank)
epithelial cells
enteroendocrine cells
immune cells
intrinsic and extrinsic sensory neurons
40
The enteric nervous system and central nervous system communicate with each other via (blank)
epithelial cells
enteroendocrine cells
immune cells
intrinsic and extrinsic sensory neurons
41
Most visceral afferent nerve fibers mediating sensation and nociception (pain) accompany the (blank)
sympathetic nerves (splachnic nerves)
42
(blank) stimulation elicits severe pain in conscious humans, whereas vagal nerve stimulation doesn't produce pain.
splachnic nerve stimulation
43
Chronic visceral pain (e.g. cancer, severe peripheral vascular disease) relieved by surgically sectioning (blank).
sympathic nerve trunk by not parasympathetic nerve trunks
44
Chronic visceral pain (e.g. cancer, severe peripheral vascular disease) relieved by surgically sectioning (blank).
sympathic nerve trunk by not parasympathetic nerve trunks
45
About (blank)% of the total nerve fibers running with sympathetic nerves are afferent. In contrast, (blank)% of all fibers in the vagus nerve and (blank)% of all fibers in the pelvic nerves are afferent.
20%
80%
50
46
Because of the relative lack of visceral sensory neurons compared to mechanosensory neurons (x10),visceral sensations are (blank)
diffuse and difficult to localize.
47
Vagal and spinal primary afferent neurons are (blank) and have collaterals that run to enteric ganglia.
pseudounipolar
48
The cell bodies of spinal primary afferent neurons are in dorsal root ganglia, their central processes end in the (blank) of the spinal cord and their peripheral axons pass via sympathetic ganglia to the intestine.
dorsal horns
49
The (blank) receives information about blood pressure, carbon dioxide levels, gut distention.
nucleus tractus solitarius (NTS)
50
(blank) are multipolar and their terminals are confined within the wall of the intestine.
Intrinsic primary afferent neurons
51
Entirely peripheral primary afferent neurons have been found in other organs. T or F?
False it has not been found in other organs
52
(blank) are considered to convey to the CNS the sensations of discomfort and pain and contribute to a variety of reflexes. .
Spinal afferents
53
(blank) have tonic levels of resting activity; they respond to contractions and distension with a linear relationship to wall tension. It is most likely that these receptors signal filling of the stomach, colon and rectum to give rise to sensations of fullness. Because they encode distending stimuli well into the noxious, non-physiological range, it is considered that they can also contribute to discomfort and pain, particularly in the presence of organ inflammation.
Tonic mechanoreceptors
54
(blank) have low resting activity and respond only to noxious intensities of organ distension.
Accordingly, they are considered mechanonociceptors. They are also chemosensitive, responding directly to inflammatory mediators, including BK, eicosanoids and free radicals. Their receptive fields have sometimes been identified in the serosa and mesentery.
High threshold (or phasic) mechanoreceptors
55
(blank) are silent at rest.
They develop activity and mechanosensitivity during and after inflammation through action of inflammatory mediators (BK and eicosanoids demonstrated so far) and nerve growth factor. Silent nociceptors have been most extensively studied in somatic tissues, where some have been characterised as chemonociceptors.
Mucosal receptors have similar properties to vagal mucosal afferents in their sensitivity to luminal chemicals and selective responses to fine tactile stimulation. So far they have been found only in in vitro preparations of colon
Silent nociceptors (or mechanically insensitive afferents)
56
What are the three types of vagal afferent endings?
intramuscular array
intraganglionic laminar endings (IGLEs)
Mucosal Intravillous Arbors (IVAs)
57
(blank) consist of plates of terminal puncta apposed to myenteric neurons; these plates are located at the interface between the myenteric ganglia and the smooth muscle layers they lie between.
IGLEs
58
The mucosal eptihelium contains which cells?
Enterocytes and EE cells
59
What will we find in the submucosal plexus??
cell bodies of secretomotor, vasodilator, and intrinsic sensory neurons
60
What will we find in the submucosal plexus??
cell bodies of secretomotor, vasodilator, and intrinsic sensory neurons
61
What will we find in the myenteric plexus?
cell bodies of motor neurons, interneurons, and a pop. of intrinisic sensory neurons
62
Explain the cycle of 5HT released for EC cells
It can escape into feces, it can be taken up by epithelial cells via SERT, it can go to LP and interact with nerve terminals, it can enter the blood
63
What degrades 5Ht in the blood?
MAO or glucuronidases (5ht w/ platelets is protected from degredatioN so these are the only ones that enter circulation)
64
Under normal conditions, where will we find 5HT in the general circulation?
in platelets
65
(blank) are located within the submucosal and myenteric plexuses. They activate enteric reflexes that regulate motility, secretion and blood flow.
Intrinisic primary afferent neurons (IPANs)
66
(blank) are activated by mechanical (low-intensity), thermal and chemical stimuli. This have their cell bodies in nodose ganglion and central terminals in brainstem nucleus tractus solitarius.
Vagal afferents
67
(blank) contribute to chemonociception and autonomic and emotional responses to painful stimuli.
vagal afferents
68
Are vagal afferents generally perceived?
no
69
(blank) are activated by low and high intensity mechanical stimli. These have their cell bodies in dorsal root ganglia and central terminals in superficial dorsal horn of spinal cord.
Spinal afferents
70
(blank) are generally polymodal (respond also to chemical and thermal stimuli). and convey information about painful stimuli.
spinal afferents
71
What is emesis?
vomiting
72
What do we do to reduce emesis and help alleviate nausea?
5-HT3 antagonists
| slide 18 for more info
73
Explain what causes emesis?
an instinctive defense reaction caused by somato-autonomic nerve reflex which is integrated into medulla oblongata. This causes EC cells release too much 5HT->activated 5HT3 receptors on vagal afferents, makes you vomit
74
What don't you want in your body if you are trying not to vomit?
cisplatin, copper sulfate, domain agonists, seritonin
75
hat does vagus-reverse peristalsis do?
make you vomit
76
What are the most common GI problems?
Duodenal and gastric ulcer
77
What has a cobblestone appearance in the mucosal surface of the bowel? This disease results in a bowel with a narrow lumen and a thickened wall
crohn's disease
78
Inflammatory bowel disease can refer to 2 different diseases, what are they?
crohn's disease and ulcerative colitis
79
What causes IBD?
the body's immune system is overreacting to the normal bacteria living in our intestines causing inflammation and damage
80
(blank) is a type of chronic inflammatory bowel disease. It involves the formation of areas of patchy inflammation, primarily in the small intestine (terminal ileus) but sometimes in other parts of the digestive tract, including the mouth, esophagus, stomach, and colon. Where inflammation exists, it extends into all the tissue layers of the intestinal wall (mucosa). Since patients may have different areas of their intestine affected, the symptoms of vary but can include abdominal pain, vomiting, diarrhea, blood in the stool, fatigue, weight loss, and growth failure. In some patients, the inflammation in this disease can be quite severe and lead to complications such as fistulas (inflammatory tunnels from the bowel to the skin or other organs), abscesses, or strictures (scarring and narrowing of the intestine). An estimated 450,000 people in the United States live with this disease; 27,000 of whom are children.
Crohn's disease (CD)
81
(blank) is a form of IBD in which the inflammation is limited to the large intestine. In some patients, the inflammation only affects the last portion of the colon, close to the anus, and this is called "ulcerative proctitis." In other patients, the inflammation affects the entire colon, which is sometimes called "pancolitis." Most patients with ulcerative colitis have bloody diarrhea, abdominal cramping, and a feeling of urgency, or little warning, when they need to have a bowel movement. Some patients loose a substantial amount of blood from ongoing intestinal bleeding. An estimated 520,000 people in the United States live with this; 18,000 of whom are children.
Ulcerative colitis
82
(blank) is associated with strong contractile activity of the gut. While this can be painful, it doesn't lead to other health problems or damage the GI tract. It is likely that this increased awareness of gut movements is due to visceral afferent nerve hyper-sensitivity
IBS
83
Is IBS a disorder that affects motility or a disorder of inflammation of intestine?
motility
| Only IBD is inflammation
84
5-HT3 antagonists such as (blank and blank) block the 5-HT activation, which is released from enterochromaffin cells, of vagal afferents.
(alosetron, ondansetron)
85
(balnk) sensitizes responses to gastric distension.
inflammation
86
What happens when you have an injury?
| What is this called?
Damaged cell releases potassium, hydrogen, ATP. These then trigger surrounding tissue to release bradykinin, histamine and prostaglandins.
Hyperalgic phenomena
87
What do the 6 mammalian thermo-TRP channels do?
Mediate thermal thresholds from very hot to cold.
| i.e tell you chili peppers are hot
88
(blank) exaggerated pain in response to a painful stimulus.
hyperalgesia
89
(blank) is pain in response to an innocuous stimulus.
allodynia
90
What is central sensitization?
you will have increase in synaptic efficacy, and reduction in synaptic inhibition.
91
What are the 2 ways you can get central sensitization?
hyperalgesia and allodynia
92
Sensitization of peripheral visceral sensory neurons is defined by....?
1) increase in number of AP triggered by stimulus
2) decrease in stimulus intensity required for AP generation
3) lowering of the threshold for action potential generation
93
Sensization of peripheral visceral sensory neurons may be associated with .....?
- increase in transmitter release at central synapse
- change in transmitters released at central synapses
- enhanced response (increased excitability) of postsynaptic neurons.
94
Sensitization of central visceral sensory neurons is associated with....?
- increase in response magnitude of central neurons
- increase in size of area of referred sensation
- increase excitability of spinal and supraspinal neurons
95
your (blank) pain is can be a sign of something insidious happening in your liver, gall bladder, stomach, spleen, lungs, or pericardial sac
shoulder
96
Explain how referred pain can work to confuse us about where our pain is stemming from?
somatic and visceral sensory fibers can travel through the same ganglion and synapse on the same neurons in the spinal cord
97
(blank) among pelvic structures may contribute to chronic pelvic pain of unknown etiology and involves convergent neural pathways of noxious stimulus transmission from two or more organs.
Cross-sensitization
98
(blank) between the lower gut and pelvic urinary or gynecological organs is recognized to be relatively common and clinically troublesome with respect to management of symptoms. For example, patients with irritable bowel syndrome often exhibit signs of urinary bladder hypersensitivity: nocturia, frequency and micturition urgency, incomplete bladder emptying, back pain, and in women, dyspareunia.
Cross-organ sensitization
99
HOw do we get cross-organ sensitization?
convergence of inputs onto the same second order spinal nerve
100
What is the gate control theory of pain?
Emotions influence pain;
this is due small fiber (nociceptor fiber) stimulation which inactivates inhibitory neurons which allows projection neurons to send signals to the brain informing it of pain.
101
Stuff you find in the lumen like, nutrients, toxins and antigens in the gut are sensed by (blank)
EPANS
102
Stuff you feel (stretch, pressure, distentions, sheering etc.) in the gut is sensed by (blank)
IPANs
103
The gate control theory of pain explains why when you hurt your finger, you can shake your hand around and it makes it feel slighter better, explain this mechanically?
When you shake your hand, you shut off the small fiber pathway and turn on the normal somatosensory pathwy which allows for large fiber stimulation which will turn on the inhibitory neuron and therefore shut down the projection neuron and not tell your brain about the pain.
104
(blank) is a rare genetic disorder where the individual is unable to feel pain. You might think this sounds like a good thing, but it's actually a life-threatening condition. Pain serves as a warning against injury, so people who don't feel it can be severly injured hurt by things that most of us would react quickly to. For example, Ronald Melzack and Patrick Wall describe a girl who got third-degree burns on her knees by climbing on a hot radiator. There was no signal for her to stop. Researchers are trying to reproduce this condition by genetically altering mice so that they can study the genetic contributions to pain perception.
Congenital analgesia
105
How do you treat diarrea/gut pain?
opiods-> for diarrea
| Such as loperamide, diphenoxylate and difenoxin
106
What will opoids do in the LES?
inhibition of relaxation
107
What will opoids do in the gallbladder?
Increase contraction and reduce secretion
108
What will opoids do in the stomach?
it will cause delayed gastric emptying, increased pyloric zonal contraction and acid release
109
What will opoids do in the small intestine?
It will increase tonic and segmental contraction, and increase transit time, and decrease secreion
110
What will opoids do in the colon?
increase segmentation, decreased frequency of contraction and secretion
111
What will opoids do in the rectum?
decrease rectal sensitivity, increase internal sphincter tone
112
Endogenous, synthetic and plant-derived cannabinoid agonists act on (blank) receptors located on enteric nerves of the digestive tract.
CB1
113
What are the pharmacological effects of cannabinoid agonists on the GI tract?
gastroprotection
reduction of gastric and intestinal motility
reduction of intestinal secretion
114
Afferents regulating visceral tone, distention, motility and secretion accompany the parasympathetic (blank) nerves.
parasympathetic (vagus and pelvic)
115
People with increased sensitivity to visceral stimulation should use what 3 drugs?
SSRIs
5-HT4 receptor antagonists (tegaserod)
5-HT3 receptor antagonis (alocetron)
116
What are these:
Blockers of
TRPV1 and P2X channels as well as peripherally acting κ opioid receptor agonists are under development.
therapies for visceral pain for gut pain
117
patients with functional gastrointestinal diseases exhibit increased (blank) to visceral stimulation.
sensitivity
118
What explains the poor discriminatory ability of sensory input?
low innervation density and polymodal character of visceral sensory neurons
119
(blank) is responsible for pain referral to somatic areas and may contribute to coexistence of different functional disorders.
Convergence!
120
(blank) of sensory pathways during acute episodes of gastroenteritis contributes to the development of postinfectious functional gastrointestinal disorders.
sensitization
