Smooth Muscle and Motility

Question 1

what are the types of muscles in the GIT?

Answer 1

Smooth (involuntary) muscle:
* most regions
* Skeletal (voluntary) muscle:
* in pharynx, top third of oesophagus, external
anal sphincter

Question 2

what are the 2 ways that the smooth muscle can behave in?

Answer 2

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

Question 3

what is the mechanism of smooth muscle contraction?

Answer 3

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.

Question 4

what is the mechanism of smooth muscle relaxation?

Answer 4

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

Question 5

describe the innervation of the GIT

Answer 5

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

Question 6

what occurs during intrinsic innervation (ENS)?

Answer 6

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

Question 7

what occurs during extrinsic innervation (ANS)?

Answer 7

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

Question 8

how is the ENS organised?

Answer 8

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.

Question 9

define the two types of reflexes

Answer 9

Excitatory: Stimulation of sensory neurone results in activation of excitatory motor neurone
Inhibitory: Stimulation of sensory neurone results in activation of inhibitory motor neurone

Question 10

what is an example of an excitatory reflex?

Answer 10

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

Question 11

what is an example of an inhibitory reflex?

Answer 11

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.

Question 12

what is Hirschsprung Disease?
treatment?

Answer 12

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.

Question 13

what is Chagas disease?

Answer 13

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

Question 14

what has previously been studied on chagasic colonic involvement?

Answer 14

– degeneration and decreased number of intrinsic myenteric neurons
– deficiency of interstitial cells of Cajal (ICC) (smooth muscle cells!!!!)
– ganglion cell damage by T lymphocytes

Question 15

what is Achalasia?

Answer 15

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

Question 16

clinical presentation and diagnoses of Achalasia?

Answer 16

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)

Question 17

treatment of Achalasia?

Answer 17

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)

Question 18

describe the storage function of stomach?

Answer 18

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.

Question 19

what is relaxation of the fundus regulated by?

Answer 19

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.

Question 20

what is the “sieving function“?

Answer 20

Liquids and small particles leave the stomach more rapidly than
large particles. This discrimination is called Sieving function

Question 21

what are the 3 phases of gastric motility?

Answer 21

1. 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
2. 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.
3. 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.

Question 22

how does gastric emptying occur?

Answer 22

The pylorus allows for carefully regulated emptying of gastric contents into duodenum.
It is innervated by
Vagus nerve - relaxation
Sympathetic NS - constriction
This is done:
So, you do not overwhelm the duodenum.
Duodenal mucosa is resistant to bile, but may be damaged by acid if emptying is rapid
To prevents regurgitation of duodenal contents into stomach
Gastric mucosa is highly resistant to acid but can be damaged by bile regurgitated from duodenum

Question 23

what are the 3 phases that control gastric emptying?

Answer 23

Cephalic Phase
Gastric Phase
Intestinal Phase

Question 24

describe the cephalic phase

Answer 24

approach of food or food in mouth
Food is sensed via:
Sight or smell (conditioned reflex)
Taste, chewing (unconditioned reflex)
This is an Inhibitory phase - Controlled by inhibitory nerve fibres in the vagus nerve
Results in receptive relaxation of stomach enabling it to store large volumes

Question 25

describe the gastric phase

Answer 25

food in stomach The stomach empties at rate proportional to the volume in it (more food means greater rate of emptying). This is an Excitatory phase: Occurs due to: Myogenic reflex: stretching activate mechanoreceptors which causes smooth muscle reflex contraction Gastrin released in response to peptides etc. Activation of pressure receptors: this sends impulses in local nerve plexi and in the vagus nerve

Question 26

describe the intestinal phase

Answer 26

food in duodenum, ileum or colon This is (mainly) an inhibitory phase This phase is mainly controlled through hormonal and paracrine mechanisms, activated by duodenal chemoreception General scheme: Low pH -> activates secretion of Secretin High fats/lipids -> increase secretion of CCK High levels of amino acids -> increase secretion of Gastrin High levels of carbohydrates -> increased secretion of GIP (stimulates insulin secretion) Ileogastric reflex: Chyme entering the ileum activates pressure receptors which delays gastric emptying (via nerves in plexi). This allows more time for digestion to take place.

Question 27

what is the structure of the SI and what is its function?

Answer 27

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

Question 28

what are the 2 types of motility in the small intestine when in the fed state?

Answer 28

When in the fed state you get Rhythmic phasic contractions (RPCs). RPC include: - Segmentation - Peristalsis

Question 29

what happens during segmentation?

Answer 29

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.

Question 30

what happens during peristalsis?

Answer 30

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.

Question 31

what happens in the GIT during the fasted state?

Answer 31

In the fasted state the Small bowel is relatively quiescent (inactive) But is does exhibit the migrating motor complex

Question 32

what is the Migrating Motor Complex? describe the stages

Answer 32

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

Question 33

what controls the MMC?

Answer 33

The ENS, humoral factors and extrinsic innervations all impact to regulate both MMCs and transition to the fed state. A major determinant of the MMC pattern is the hormone motilin, a 22-amino-acid peptide that is synthesized in the duodenal mucosa and released just before the initiation of phase 3 of the MMC cycle.

Question 34

what is the function of the MMC?

Answer 34

It cleanses the bowel: MMCs clears the small intestine of its residual content, including undigested food, desquamated cells, and intestinal, pancreatic, biliary secretions. It prevents bacterial overgrowth in SI: Stops colonic bacteria from migrating into the terminal ileum.

Question 35

what is the motility in the ileum like?

Answer 35

Ileogastric reflex – inhibitory 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. Gastroileal reflex: ↑ in gastric activity causes ↑ in ileal motility and ↑ movement of chyme through the ileocecal valve These reflexes are mediated through ENS

Question 36

what is the Ileocecal sphincter? 2 mechanisms by which it works?

Answer 36

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

Question 37

what is the structure of the colon?

Answer 37

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

Question 38

function of colon?

Answer 38

Proximal colon - site of absorption, secretion and bacterial fermentation: Absorb large quantities of fluid and electrolytes which converts liquid content of ileocecal material to solid. Absorbs short chain fatty acids (product of carbohydrate fermentation) Secretes mucus and ions (K+, Cl-, HCO3-) Provides environment for beneficial bacteria which synthesise vitamins (K, B complex) Distal colon: Storage/reservoir function Regulated release of faecal material

Question 39

what are the 2 phases of colonic motility?

Answer 39

Colonic Rhythmic Phasic Contractions Colonic Giant Migrating Contractions

Question 40

describe Colonic Rhythmic Phasic Contractions

Answer 40

The fluid contents of the ascending colon gradually become semi-solid to solid in the sigmoid colon as water is absorbed. To meet his challenge the colon generates 2 types of RPCs: Short-duration RPCs (2-3 seconds in duration) - no propagation Long-duration RPCs (15-20 seconds) - may propagate over short distances. Longer durations enable them to turn over/propel contents more effectively Colonic RPCs are highly disorganised in space and vary widely in amplitude and duration Function: They are therefore effective in turning over faecal material with a very slow rate of propulsion

Question 41

describe Colonic Giant Migrating Contractions

Answer 41

GMCs: large-amplitude lumen-occluding contractions. They propagate very rapidly (about 1 cm/sec) in the distal direction, over appreciable distances to produce mass movements. Function: Allows faecal matter to move down to rectum. Spontaneous GMCs occur randomly about 2-10/day in the proximal, middle, or descending segments of the colon Colonic GMCs occur in both the fasting and fed state

Question 42

what adds bulk to the stool? what does this do?

Answer 42

Eating indigestible material (dietary fibres e.g. cellulose, lignins, pectins, gums, bran, vegetables) adds bulk to the stool. Bulkier stool creates luminal distention which then activates pressure receptors which elicits motility. This allows the stool to pass through quickly. This is mediated via the myenteric plexus

Question 43

what controls the motility in the colon?

Answer 43

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

Question 44

what are the 2 anal sphincters called? what are they each made up of?

Answer 44

Internal anal sphincter: - Superior sphincter - Circular involuntary smooth muscle External anal sphincter: - Inferior sphincter - Striated voluntary muscle

Question 45

describe the defamation reflex

Answer 45

1. When we are not passing stool there is sympathetic innervation (L1,L2) to the rectum and internal anal sphincter 2. Sympathetic innervation inhibits contraction of wall of rectum and stimulates contraction of internal anal sphincter. 3. Faeces enter and fill the rectum (via mass movement) and causes distension of rectal wall 4. This results in stimulation of stretch receptors (mechanoreceptors) 5. The Intrinsic defaecation reflex is then initiated by the myenteric plexus 6. Peristalsis however is currently weak - requires reinforcement 7. Reinforcement in the form of a parasympathetic (S2,S3,S4) defaecation reflex 8. This results in amplification of peristaltic waves throughout large intestine and relaxation of the internal anal sphincter 9. Then with relaxation of the external anal sphincter, defecation takes place. 10. Defaecation can be inhibited by contraction of the external anal sphincter