Term
| ____ is the state of absent motility |
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Definition
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Term
How does the sympathetic action work?
1) increase motility by presynaptic agonism
2) presynaptic inhibition to prevent enteric neural output
3) postsynaptic inhibition to prevent enteric neural output
4) presynaptic inhibition to inactivate smooth muscle contraction |
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Definition
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Term
| T/F: Neural communication with the gut has no impact on the gut flora |
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Definition
S system impacts the make up of the gut biome…there is BIDIRECTIONAL communication.
Every time you tx px w/ ABX you influence this…
1. Bidirectional communication between sympathetic neurons and inflammatory processes in the gut.
2. Sympathetic transmitters may have significant influences on gut flora. |
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Term
| Vagal/Pelvic innervation of small and large intestinal is causes both contraction or relaxation of digestive musculature |
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Definition
| True: PS innervation is EXCITATORY but vagus stim gut smooth muscle by RELAXING the sphincters… |
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Term
| What are the nerve supplies of the enteric NS? |
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Definition
| It has its own nerve supply….key is myenteric plexus (deeper below the circular muscle) and Submucous plexus (most superficial below mucosa) – neural reg of secretion/absorption |
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Term
| T/F: The gut has pacemakers that depend on action potentials |
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Definition
| F: in the SI, electrical slow waves without APs are present => contraction |
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Term
| T/F: Frequency of electrical activity determines frequency of contractions |
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Definition
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Term
ICCs form networks that contact GI musculature. Which of the following is true?
•Pacemakers for electrical slow waves
•Neural cells of mesenchymal origin
• Serve as relays for transmission from sympathetic neurons to GI musculature |
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Definition
Only the first is true
• Pacemakers for electrical slow waves
• Non-neural cells of mesenchymal origin
• Serve as relays for transmission from enteric motor neurons (extrinsic nervous system) to GI musculature
o Excitatory and inhibitory neurotransmitters spread diffusely from axonal varicosities to the ICC networks |
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Term
| What's the purpose of the submucous plexus? |
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Definition
| o Submucous plexus is important for secretomotor functions |
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Term
| what is the mech of disease in esophageal dysphagia? |
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Definition
| achalsia: loss of inhibitory neurons to LES and/or dysfunctional/weak peristalsis |
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Term
| What are causes of oropharyngeal dysphagia? |
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Definition
o Difficult initiating a swallow
o Only one manifestation of the primary disease (e.g. stroke, MG causing weak pharyngeal contraction) |
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Term
| Describe the vago-vagal reflex |
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Definition
| Stomach wall senses stretch – sends signal up thru vagus – brain medulla processes it and you have motor nuclei sending signals down Eff to the Enteric NS…the ICCs activate the inhibitory motor neurons => MUSCLE RELAXATION BULK of vagus is sensory (85%)… |
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Term
| Name some factors affecting gastric emptying (many receptors and feedback mechanisms): |
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Definition
| vaso-vagal, propulsive motility of antral pump, compliance in gastric reservoir, composition of gastric contents, feedback signals from duodenum, ileal brake phenomenon, physical/emotional stress |
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Term
| What controls the motor behavior of the antral pump? |
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Definition
| • Motor behavior of antral pump is initiated by a dominant pacemaker in the mid-corpus of stomach. |
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Term
| T/F: The pacemaker potential determines all of the following: maximal frequency, propagation velocity, propagation direction |
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Definition
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Term
| What determines rate of gastric emptying? |
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Definition
• Gastric empyting onset and rate determined by composition of meal
o Liquids are faster, solids are slower
o Gastric empyting can be measured in laboratory test
o Lag phase between liquid and solid reflects time required for reduction of particles to sufficient size for emptying
o Helps diagnose gastroparesis |
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Term
| If you have a vagotomy how does that affect the gastric reservoir? |
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Definition
• Adaptive relaxation in gastric reservoir is lost after vagotomy
o Loss of adaptive relaxation is associated with a lowered threshold for sensations of fullness and pain |
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Term
| Name some causes of gastroparesis: |
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Definition
| o Causes: mechanical (e.g. obstruction), endocrine and metabolic (e.g. hypothyroidism), gastric smooth muscle abnormalities (e.g. scleroderma), neuropathies (e.g. diabetes), medications, CNS and psychiatric disorders, miscellaneous (e.g. post-viral) |
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Term
| How are interneurons in the walls of the bowel (myenteric plexus) stimulated? |
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Definition
o Mechanical stretch and mucosal distortion by chyme stimulate interneurons
Interneurons are in the walls of the bowel (myenteric plexus)
Circular muscle is the real player in peristalsis |
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Term
| What two signals released from inhibitory motor neurons result in relaxation of muscle? |
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Definition
| inhibitory junction potentials on the muscle cells are mediated by nitric oxide (NO) or vasoactive intestinal pepetide (VIP) released from the motor neuron => relaxation of muscle |
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Term
| What signals released from excitatory motor neurons => contraction of muscle in the SI? |
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Definition
| excitatory junction potentials are mediated by Substance P or ACh release from motor neurons => contraction of muscle |
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Term
| What is the MMC and when is it active (i.e. how often, what triggers it)? What key functions does it have? |
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Definition
• Migrating motor complex (MMC) is the small intestinal motility pattern of the interdigestive state
o Sweeping peristaltic wave keeps nutrients going in right direction and also prevents bacterial overgrowth
Diabetes can affect the MMC
Occurs every 90mins – 2 hrs
o Motilin produced by epithelial cells triggers the MMC (levels peak during the MMC, prior to “Phase III”)
Pacemaker cells in stomach most sensitive to motilin |
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Term
| What does the MMC shift to? |
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Definition
• Feeding shifts neural programming from the interdigestive motility pattern (MMC) to the digestive pattern (segmentation)
o Net effect of segmentation is downstream, but there is a “to-and-fro” motion to mix contents |
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Term
| What are three causes of myopathic hypoactive musculature leading to pseudoobstruction? |
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Definition
(These patients have weak and poorly propagating MMCs/contractions)
Familial (Types I, II, III)
• E.g. familial visceral myopathy is a degenerative disease of the smooth muscle that leads to pseudoobstruction. Vacuolar histological appearance of smooth muscle.
Collagen diseases (e.g. scleroderma)
Amyloidosis |
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Term
| What are four causes of neuropathic hyperactive active musculature and what exactly does it do? |
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Definition
(since natural tone is in contracted state, loss of inhibitory motor neurons leads to uncontrolled and uncoordinated myogenic contractions - chaotic and not segmental!)
Hirschprung’s Disease: children fail to develop distal myenteric plexus (no enteric neurons!) megacolon
• In development, mutations in genes encoding GDNR and Et-3 are linked to Hirschbrung’s
• GDNR signals through Ret (receptor tyrosine kinase) and Et-3 signals through endothelin receptor B
Chagas Disease
Paraneoplastic syndrome (e.g. bind to Ca channels)
Idiopathic forms |
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Term
| What mutations result in Hirschprung's and what do they signal through? What is the clinical result of this disease? |
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Definition
| GNDR and Et-3. GNDR signals through Ret and Et-3 signals through Endothelin receptor B |
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Term
| What kind of disease does enteric neuropathy result in? |
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Definition
Disinhibitory Motor Disease: inhibitory motor neurons (NO, VIP) are preferentially affected.
Failure of disinhibition affects: sphincters (failure to relax LES, Oddi, and internal anal sphincter);
Pylorus: hypertrophic pyloric stenosis;
Small and large intestine (pseudoobstruction): Chagas, Paraneoplastic, Hirschsprung’s, idiopathic
Paraneoplastic syndrome: autoimmune antibodies attack enteric neurons leading to pseudoobstruction |
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Term
| A patient presents with bacterial enteritis and reports extreme urgency to go to the bathroom, and if he doesn't he soils his pants. What's the mechanism here? |
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Definition
• Power propulsion: intestinal motor pattern specialized for rapid propulsion over long distances
o Reaction to an insult on GI system to try and get rid of it
o Occurs in pathologic states with diarrhea, abdominal pain and nausea
o Causes: enteritis (bacterial, viral, parasitic, radiation), toxin (enterotoxins, food toxins), food allergy (shellfish, tree nuts, eggs, milk, peanuts), mucosal irritation (senna, ricinoleic acid) |
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Term
An elderly patient presents with constipation. He has had diabetes for a long time and you suspect that he has a dysfunctional _________.
What are other causes of constipation? |
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Definition
anal sphincter
o Hypotonic (colonic inertia): slow movement through colon (can detect with markers)
o Outlet delay: problem with seniors, problem with actually going to bathroom (e.g. coordination of muscles etc.)
o Anal sphincter dysfunction (e.g. diabetics with neuropathy)
o Spastic constipation (e.g. constipation prone IBS) |
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Term
| You suspect that a patient has gastroparesis due to sclerodermal smooth muscle abnormalities. What medications can you give him and how do they act? |
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Definition
o Metoclopramide (Reglan) – dopamine receptor antagonist (block an inhibitory pathway promote motility). Effects mostly in upper GI tract (e.g. gastroparesis). CNS side-effects. Also an anti-emitic.
o Domperidone – dopamine receptor antagonist. Fewer side-effects than Reglan. Not FDA approved (available elsewhere in the world). Also effective for gastroparesis |
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Term
| You believe a patient has defective enteroendocrine cell function causing hypomotility of the MMC which normally should peak with plasma motilin levels so you prescribe him _____ |
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Definition
| o Erythromycin – motilin receptor agonist (happens to bind to motilin receptor). Prone to tachyphylaxis (rapid decrease in drug response over time) |
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Term
| Why aren't we prescribing 5HT for gut problems...? |
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Definition
| o Serotonin (5-HT) receptor subtypes (e.g. 5-HT3 and 5-HT4) are popular targets for drug development. Subtypes are good targets because somewhat specific to the gut. Some unacceptable side-effects in first gen. of FDA approved meds |
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Term
When the propulsive segment is active what are the actions of the circular/longitudinal muscles?
How do we get circular muscle to relax? |
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Definition
circ - contracted, long - relaxed
By providing circ muscle with excitatory motor neuron input, but the stimulus to the interneuron is INHIBITORY. In order to get circ muscle to contract, the opposite is true. |
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Term
| Which drug has its action closest to vibrio cholerae? |
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Definition
| Lubiprostone (ammitiza) - it's a Cl channel activator to put more water into the gut! |
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