Smooth Muscle and Motility Flashcards
what are the types of muscles in the GIT?
Smooth (involuntary) muscle:
* most regions
* Skeletal (voluntary) muscle:
* in pharynx, top third of oesophagus, external
anal sphincter
what are the 2 ways that the smooth muscle can behave in?
Two types:
Phasic, rapid contraction and relaxation
- Allows for peristalsis and segmentation to take place
- body of oesophagus, stomach antrum,
small and large intestines
Tonic, sustained contractions
- sphincters (lower oesophageal, ileocaecal,
internal anal), orad (upper) stomach
what is the mechanism of smooth muscle contraction?
Calcium enters the cell through:
Via voltage gated calcium ion channels
via an intracellular signalling pathway (ACh -mAChR) –> release from sarcoplasmic reticulum that result in IP3
The Ca2+ binds to calmodulin –> this activates myosin light chain kinase.
MLCK then phosphorylates myosin to myosin phosphate using ATP
Myosin phosphate can then interact with actin and cause contraction of the smooth muscle.
what is the mechanism of smooth muscle relaxation?
You must restore intracellular [Ca2+] to its low resting value:
The cell may extrude Ca2+ using either a Na-Ca exchanger or a Ca2+ pump at the plasma membrane.
However, this would eventually deplete the cell of Ca2+.
Instead, Ca2+ re-uptake into the sarcoplasmic reticulum (mediated by SERCA-type Ca2+ pump) is the most important mechanism by which the cell returns intracellular Ca2+ to resting levels
However merely restoring intracellular [Ca2+]i to its resting value is not enough
In order to allow for relaxation of smooth you also need to dephosphorylate the phosphorylated myosin. This is catalysed by myosin light chain phosphatase.
This means myosin can no longer interact with actin which then causes relaxation.
You can also cause relaxation through a cAMP/pKa mediated pathway (induced by VIP):
This is where you phosphorylate myosin light chain kinase
This stops it from interacting with calmodulin –> no longer phosphorylating myosin –> contraction cannot occur
describe the innervation of the GIT
The GIT is innervated intrinsically by the ENS and extrinsically by the ANS
Intrinsic innervation: ENS
ENS made up of:
Submucosal plexus
Between submucosa and circular muscle
Myenteric plexus
Between longitudinal and circular muscle
Extrinsic innervation: ANS
Parasympathetic NS - Contraction of Smooth Muscle
Sympathetic NS - Relaxation of smooth muscle
what occurs during intrinsic innervation (ENS)?
Activation of myenteric plexus results in:
↑ tonic contraction
↑ intensity/rate of phasic contractions
↑ velocity of conduction
Activation of submucosal plexus:
↑ secretory activity
Modulates intestinal absorption
what occurs during extrinsic innervation (ANS)?
Stimulating Sympathetic NS –> inhibit motility (by hyperpolarising)
Stimulating Parasympathetic NS –> ↑ motility (by depolarising)
Parasympathetic Innervation supply:
Vagus nerve: provide parasympathetic innervation from oesophagus to transverse colon
Pelvic nerves: provide parasympathetic innervation from descending colon to the rectum
how is the ENS organised?
Sensory Neurones:
- Mechanoreceptors sense distension (e.g. distention is stomach after you have eaten)
- Chemoreceptors sense luminal pH and fat content (short chain fatty acids)
Motor neurones (interneurones)
Inhibitory: Inhibit effects in previous flashcard
Excitatory: Stimulate effects in previous flashcard
I.e. information from sensory neurones is transmitted to motor neurones (via interneurons) which will then innervate smooth muscle/secretory cells resulting in muscle contraction/relaxation or secretion/no secretion.
define the two types of reflexes
Excitatory: Stimulation of sensory neurone results in activation of excitatory motor neurone
Inhibitory: Stimulation of sensory neurone results in activation of inhibitory motor neurone
what is an example of an excitatory reflex?
Examples of excitatory reflex:
Gastro-colic Reflex
Have a big meal causes distension of the stomach
This distention is detected by mechano receptors.
This causes reflex by sending signals to colon via excitatory motor neurones which causes ↑ motility of colon.
This is to make room for the chyme that will enter the colon from the stomach.
other examples:
- Gastro-enteric Reflex
- Gastro-ileal Reflex
- Duodeno-colic Reflex
what is an example of an inhibitory reflex?
Examples of inhibitory reflex:
Ileo-gastric reflex
Distention of Ileum (due to presence of chyme) results in activation of mechanoreceptors.
However, the Chyme that is present in ileum has not yet been digested and absorbed.
Therefore, an Inhibitory signal is sent to stomach, via inhibitory motor neurones, to stop contraction (emptying) of the stomach which would otherwise cause movement of more chyme into the ileum.
what is Hirschsprung Disease?
treatment?
congenital lack of neuronal ganglionic cells in the ENS plexi.
This results in the affected part of the Gut becoming aganglionic and so aperistaltic (no motility).
This may cause megacolon above the point where the nerves are missing.
The aganglionic, aperistaltic bowel segment effectively prevents the propulsion of the fecal stream, resulting in in megacolon) above the point where the nerves are missing and hypertrophy of the normal proximal colon.
Treatment: Removal of aganglionic segment and then joining of two healthy ends.
what is Chagas disease?
infectious disease of a parasitic nature, resulting in the significant reduction in the number of neuronal ganglionic cells in the ENS
Primarily involves the oesophagus
Can also cause a megacolon
Chagas disease in humans is due to the infection with the protozoan parasite, Trypanosoma cruzi
what has previously been studied on chagasic colonic involvement?
– degeneration and decreased number of intrinsic myenteric neurons
– deficiency of interstitial cells of Cajal (ICC) (smooth muscle cells!!!!)
– ganglion cell damage by T lymphocytes
what is Achalasia?
dramatic reduction in the number of neuronal cells in the lower oesophageal segment.
This results in the gastroesophageal sphincter failing to relax
Etymology: from a- (=without) + Greek chalasis
(=slackening, relaxation)
- Disease of the esophagus
- Due to a lack of inhibitory motor neurones in the lower part of the esophagus, and in the LES (lower esophageal sphincter)
- characteristic “bird’s beak” image
clinical presentation and diagnoses of Achalasia?
clinical presentation:
– Predominantly solid dysphagia 90-100% (75% also with dysphagia to liquids)
diagnosis:
– plain film x-ray (air-fluid level, wide mediastinum, absent gastric bubble, pulmonary infiltrates)
– barium esophagram (dilated esophagus with taper at LES)
* good screening test (95% accurate)
– endoscopy (rule out GE junction tumors, esp. age>60)
– esophageal manometry (absent peristalsis, LES relaxation, & resting LES >45 mmHg)
treatment of Achalasia?
Treatment - reduce LES pressure and increase emptying
– nitrates and calcium channel blockers
– botulinum toxin (prevents ACH release at NM junction)
– pneumatic dilation (disrupt circular muscle)
– surgical myotomy (open or minimally-invasive)
describe the storage function of stomach?
Empty stomach volume ~50ml
When empty, the stomach is highly folded.
Upon filling, these folds flatten out –> increased stomach volume –> therefore wall tension and intraluminal pressure change only very slightly
This process continues to around 700ml.
At this point all the fold are fully open.
Therefore, as you consume more food the intraluminal pressure increases dramatically.
what is relaxation of the fundus regulated by?
Relaxation in the fundus of the stomach is regulated by the vago-vagal reflex (receptive relaxation)
Vagal innervation allows the folds to slowly open out when you consume food to increase the volume of the stomach.
If vagal innervation is interrupted (e.g. vagotomy) then you don’t get receptive relaxation.
The folds do not automatically open up to increase volume –> intra-gastric pressure increases even at low volumes.
what are the 3 phases of gastric motility?
- Phase of propulsion:
The solid particles of the stomach are propelled down towards the pylorus.
This is done through propulsive gastric contractions
The pylorus is partially closed through contraction of the pyloric musculature - Phase of grinding:
Once a bolus of material is trapped near the antrum it is churned to help reduce the size of the particles.
Then only a small portion of gastric material (particles smaller than 2 mm) is propelled through the pylorus to the duodenum. - Phase of retropulsion:
The rest of the gastric contents are returned to the body of the stomach for pulverization and shearing of solid particles.
These processes of propulsion, grinding, and retropulsion repeat multiple times until the gastric contents are emptied.
what is the structure of the SI and what is its function?
9ft long, 1.5 inches in diameter
Extends from the stomach to the colon
Functions:
Digestion and Absorption:
Mixing chyme from the stomach with secretion of pancreas, liver and intestines => Digestion.
Propulsion of food to correct sites for absorption
Release of chyme into colon
what happens during segmentation?
Segmentation:
Rings of circular muscle at intervals contract and then relax.
Then adjacent rings contract and relax
Overall result: Matter is being broken down and mixed with various secretions.
It produces segmental contractions
They result in increased mixing (or churning) which enhances digestion and absorption of dietary nutrients.
what happens during peristalsis?
Peristalsis:
The outer longitudinal layer of smooth muscle contracts in front of the bolus - this shortens the area of the GIT immediately in front of the bolus.
The inner circular layer of smooth muscle behind the bolus contracts and thus pushes it forwards.
You therefore get a wave of muscle contraction with the overall result - propels chyme along gut
It produces peristaltic contractions
Which cause propulsion of food and its digestive products in a caudal direction which result is elimination of nondigested, non-absorbed material.
what happens in the GIT during the fasted state?
In the fasted state the Small bowel is relatively quiescent (inactive)
But is does exhibit the migrating motor complex
what is the Migrating Motor Complex?
describe the stages
MMC: Synchronised, rhythmic changes in both electrical and motor activity
MMCs in humans occur at intervals of 90-120 minutes and consist of 4 distinct phases:
1. A prolonged quiescent period
2. Period of ↑ action-potential frequency and contractility
3. Period of peak electrical and mechanical activity that lasts a few minutes
4. Period of declining activity that merges into the next quiescent period
Role of the MMC: propel particles greater than 2 mm in diameter from the stomach into the duodenum.
NB: MMC becomes weaker more distally in the gut (i.e. contractile activity ↓ as you go down gut).
On the graph you can see phasic pattern of activity - quiescence and active (multiple peaks)
Feeding terminates MMCs and initiates the appearance of the “fed motor pattern” - segmentation and peristalsis
what is the Ileocecal sphincter?
2 mechanisms by which it works?
Ileocecal sphincter: A sphincter that separates the ileum from the colon
Mechanism (2 parts)
1. Stimuli (pressure) proximal to the sphincter cause sphincteric relaxation (opens)
Stimuli (pressure) distal to the sphincter causes sphincteric contraction (closed)
2. Distension of the ileum results in relaxation of the sphincter
Distension of the proximal colon causes contraction
Therefore, ileal flow into the colon is regulated by luminal contents and pressure, both proximal and distal to the sphincter
Sphincter is under control of the ANS and ENS
Gastrin causes the relaxation of the sphincter and contraction of the distal ileum - moves from from ileum to cecum
what is the structure of the colon?
2.5 inches in diameter, last 4 foot of GIT
SA is only 1/30th of that of small intestine
No villi, but still has crypts
Longitudinal muscle layers thickened to form 3 muscular bands which run the length of the colon - taeniae coli
Contractions of these muscles gather up the colon forming haustra
what controls the motility in the colon?
ANS
Sympathetic NS - inhibits motility
Parasympathetic NS - increase motility
Specifics:
Parasympathetic innervation of the proximal colon (cecum, ascending and transverse colon) is via branches of vagus nerve
Vagal stimulation causes RPCs of the proximal part of the colon
Parasympathetic innervation of distal colon (descending and sigmoid colon, rectum and anal canal) is via Pelvic nerves.
Stimulation of the pelvic nerves brings about expulsive movements (GMCs) of distal colon and sustained contraction of some segments
what are the 2 anal sphincters called?
what are they each made up of?
Internal anal sphincter:
- Superior sphincter
- Circular involuntary smooth muscle
External anal sphincter:
- Inferior sphincter
- Striated voluntary muscle
describe the defamation reflex
- When we are not passing stool there is sympathetic innervation (L1,L2) to the rectum and internal anal sphincter
- Sympathetic innervation inhibits contraction of wall of rectum and stimulates contraction of internal anal sphincter.
- Faeces enter and fill the rectum (via mass movement) and causes distension of rectal wall
- This results in stimulation of stretch receptors (mechanoreceptors)
- The Intrinsic defaecation reflex is then initiated by the myenteric plexus
- Peristalsis however is currently weak - requires reinforcement
- Reinforcement in the form of a parasympathetic (S2,S3,S4) defaecation reflex
- This results in amplification of peristaltic waves throughout large intestine and relaxation of the internal anal sphincter
- Then with relaxation of the external anal sphincter, defecation takes place.
- Defaecation can be inhibited by contraction of the external anal sphincter
