Motility and Gastric Reflux Disease

Question 1

Answer 1

Question 2

Answer 2

Question 3

Patterns of alimentary canal motility can be delineated into two distinct periods: […] and[…].

Answer 3

Patterns of alimentary canal motility can be delineated into two distinct periods: Digestive and Inter-digestive.

Question 4

Interdigestive Period

Answer 4

The inter-digestive period is when no digestion products (referred to as chyme) are resident proximal to the large intestine. This period normally exists during sleep and is ended when cephalic signals (smell or sight of appetizing foods) initiate a completely different pattern of motility that is associated with the digestive and absorptive functions of the canal.

Question 5

Digestive Period

Answer 5

• The events of digestion involve both mechanical and chemical breakdown of ingested material.
• For these processes to be carried out optimally, the alimentary organs must balance two opposing functions.
• On one hand, contents must be held long enough for mixing breakdown and absorption to occur.
• Conversely, gastrointestinal contents must be moved analward (aboral) to make room for more food and to remove wastes.
• The neural-hormonal-muscular apparatus of the alimentary tract coordinates motility to accomplish these important aspects of digestion.
• The longitudinal muscle layer is used to rhythmically shorten and lengthen the canal thereby propelling digestate (chyme) along the tract.
• Rhythmic contraction of the circular layer is used to mix contents, restrict movements at specific sites (sphincters), but also propel chyme more slowly than the longitudinal contractions.

Question 6

The underlying patterns of muscle contraction are either […] or […].

Answer 6

The underlying patterns of muscle contraction are either tonic or phasic (rhythmic).

Question 7

Phasic Contractions

Answer 7

• Phasic contractions occur in both longitudinal and circular layer
• Rhythmic cycling between contracted and relaxed states (rhythmic segmentation) is required for mixing and propulsion of chyme.
• Local mixing within the canal is driven by short reflexes within the submucosal plexus. Coordination of contractility over a significant length of canal or between segments is dependent on central reflex arcs, and is used to propel chyme long distances. This coordinated activity, referred to as peristalsis, depends on smooth muscle contraction proximal to the chime with coordinated relaxation distal to the chyme.

Question 8

Tonic Contractions

Answer 8

• Tonic contractions are primarily observed in circular muscle, especially for functioning of the sphincters.
• Tonic contraction refers to sustained changes in the tone of the muscle that either occludes or holds open the lumen diameter.

Question 9

Answer 9

Question 10

Esophageal Motility

Answer 10

• Esophageal peristalsis begins with a voluntary swallow; the progression of the contractile wave through the esophagus is involuntary.
• The esophageal body is “guarded” at the upper end by the upper esophageal sphincter and the gastroesophageal junction by the lower esophageal sphincter (LES). The initial 1/3 of the esophagus is lined with skeletal muscle.
• Initiation of a swallowing event elicits a programmed reflex providing relaxation below the bolus with subsequent contraction as the chyme moves past; i.e., peristalsis. The lower 2/3 of the esophagus is lined with smooth muscle.

Question 11

Primary Peristalsis

Answer 11

•The initial programmed event (swallowing) is referred to as Primary Peristalsis

Question 12

Secondary Peristalsis

Answer 12

• Secondary Peristalsis refers to the distension-mediated events in the smooth muscle required for full esophageal clearing.
• Smooth muscle re-activated in case the bolus doesn’t make itto the stomach - In general, the majority of a bolus is removed from the esophagus during the initial swallow. Any food remaining in the esophagus causes distension of the lumen. This distension is sensed by pressure receptors in the lumen wall, which induces a local reflex to initiate secondary contractile waves limited to the smooth muscle region.

Question 13

Achalasia

Answer 13

•Achalasia means “failure to relax” and refers to the inability of the lower esophagus and esophageal sphincter to open and let food pass into the stomach. Early in the development of achalasia, inflammation is observed around the enteric nerves eventually leading to degeneration and inability of the lower esophageal body to support peristaltic waves. With time, the body of the esophagus stretches and becomes dilated and dysfunctional.

Question 14

Gastric Motility

Answer 14

• The stomach serves as a temporary storage organ (“proximal” stomach), and as a “grinding mill” which mechanically and chemically breaks down food (“distal” stomach).
• Emptying of chyme from the stomach into the small intestine is highly regulated with both the physical and chemical composition of the meal itself regulating the rate of emptying.

Question 15

Two factors that Regulate Rate of Emptying

Answer 15

• bulk of the meal (physical composition)
• nutrient content (chemical composition)

Question 16

Accomodation

Answer 16

• Pressure transducers follow changes in muscle tone and lumen diameter. The upward deflection in the top figure is the pressure caused by the bolus arriving in the distal esophagus. However, upon swallowing, prior to the bolus reaching the lower esophagus, the LES opens to prepare for movement into the stomach. As the LES opens, the circular muscle of the proximal 1/3 of the stomach also relaxes in proportion to bolus size. Thus, the stomach accommodates the bolus such that “intragastric” pressure changes are minimal.
• This increase in diameter to accommodate the incoming bolus is referred to as receptive relaxation.
• If the vagus nerve is cut, receptive relaxation does not occur, or is significantly reduced causing stomach pressure to increase upon ingestion.
• The reservoir function of the proximal stomach depends on its ability to accommodate food without change in pressure. Therefore, after vagotomy, the resulting high pressure in the proximal stomach causes reflux of stomach contents into the esophagus, and often premature gastric emptying leading to damage to the esophagus and lining of the intestine, respectively.

Question 17

Factors Affecting LES Tone

Answer 17

•Pregnancy

• progesterone
• PGE₁

•Drugs

• isoproterenol (decrease)
• opiods (increase –> constipation)

Question 18

GERD Causes

Answer 18

• increased gastric pressure
• decreased LES function/relaxation
• drug/hormone dependent
• hiatal hernia

Question 19

Gastric Emptying

Answer 19

• After a meal, the ingested food remains in the stomach for 1 to 3 hours.
• The driving force for emptying the stomach contents into the small intestine is provided by wall motion of the distal (2/3) stomach.
• Chyme is forced towards the closed pyloric sphincter at high pressure. As the contractile wave passes, the chyme rushes back away from the pylorus (retropulsion).

Question 20

Factors that Regulate Movement Through Pyloric Sphincter

Answer 20

•Physical and Chemical properties of the chyme determine movement through the sphincter; i.e., the rate of gastric emptying.

-For example, liquids empty faster than solids (i.e.; fiber slows emptying).

• In addition, chemical characteristics, such as the osmotic pressure, pH and fat content of the chyme, as it reaches the duodenum, feedback onto the pyloric sphincter to inhibit emptying.
• The mechanism by which these factors feedback to regulate emptying is not completely clear.

Question 21

Solids vs. Liquids Effects on Pyloric Sphincter

Answer 21

Question 22

pH Effect on Pyloric Sphincter

Answer 22

Question 23

Effects of What Goes in on Pyloric Sphincter

Answer 23

•nothing solid leaves during digestion

-movement during the inter-digestive period moves solid objects out

Question 24

Types of Intestinal Motility

Answer 24

• Peristalsis
• Rhythmic Segmentation
• As chyme moves from the stomach to the intestine, “digestive period” like functions are activated and maintained in the intestine for 3-5 hours. Mixing of intestinal juices with the chyme requires wall motion. Distension is the primary stimulus for increasing contractility eliciting its response through enteric nerves. A decrease in inhibitory output to the smooth muscle cells leads to generation of action potentials initiating contractility. The underlying slow wave activity sets the frequency of the contractile response. Local reflexes assure that regions filled with nutrients are activated not only mechanically, but also have increased blood flow, secretory and absorptive activity.

Question 25

Rhythmic Segmentation

Answer 25

• A series of rhythmic contractions localized to a specific region is referred to as Rhythmic Segmentation. What is usually observed are tonic constrictions (segmentation) at either end of a rhythmically contracting canal segment assuring adequate mixing of the contents therein.
• Slow waves set the frequency of contractions within the muscle layers. A gradient of rhythmic segmental contractions in the small intestine exists with the highest frequency in the most proximal regions. This gradient promotes aboral propulsion of the intestinal chyme because the pressure buildup is slightly greater in the proximal intestine where contractile frequency is highest.
• Rhythmic segmental contractions required for mixing are driven primarily by local signals (distension) and are capable of slowly moving chyme throughout the intestine

Question 26

Peristalsis

Answer 26

• Peristaltic contractions are used for movement of chyme over longer distances rapidly.
• Peristalsis requires the release of tonic contractions below the bolus to open the lumen coupled to a wave of contractile activity initiated behind (proximal to) the bolus of chyme moving analward. Therefore, long distance peristalsis often requires long reflex arcs mediated through central afferents.
• For this reason, loss of central reflexes (vagotomy) may cause interference with reflexes such as the emetic response (vomiting). However, chyme can still be digested and moved along the intestine, and nutrients absorbed without central control due to propulsion based on the gradient of slow wave mediated rhythmic segmentation.

Question 27

Answer 27

Question 28

Ileocecal Sphincter

Answer 28

• The ileocecal sphincter is critically important for maintaining normal function of the small intestine. As discussed later, large numbers of bacteria in the colon are capable of digesting nutrients and in the process producing acids.
• A competent ileocecal sphincter allows the digestate to move into the colon but quickly closes to retard retrograde movement from the colon.
• Bacterial infiltration into the ileum alters absorption of many compounds, but most importantly bile acids and vitamins leading to some profound deficiencies.

Question 29

Motility of the Large Intestine

Answer 29

• Haustrations
• Mass Movements
• Rectosphincteric Reflex
• Once the final digestate leaves the intestine, it will remain within the colon normally for a period of 1 to 3 days, though this varies. Thus, the colon acts as a reservoir for chyme for extended periods and must mix and move the feces aborally.
• The primary function of the colon is to extract the remaining nutrients and in particular water and electrolytes from the chyme. In the process, the chyme is compacted for transit from the body. The permeability of colon epithelium to water is low, so relatively long periods are required for efficient water extraction.

Question 30

Haustrations

Answer 30

• Chyme within the proximal colon (cecum and ascending colon) is rhythmically mixed as in the small intestine but at a much slower rate.
• The normal appearance of the proximal colon is that of a link of sausages with repeating constrictions referred to as haustrations. Between the constrictions, the circular muscle is undergoing very slow rhythmic mixing contractions.
• The haustral appearance is dynamic with constrictions moving back and forth; i.e., no net aboral movement.

Question 31

Mass Movement

Answer 31

•Infrequent but regular (several/day) peristaltic events called Mass Movements sweep the contents towards the distal colon.

-Propulsive peristaltic contractions

• Again as in the small intestine the rhythmic segmentation ceases (haustrations disappear), and coordinated contractions of longitudinal muscle shorten the colon moving the contents distally.
• Central afferents appear to be involved in coordinating this reflexive activity.

Question 32

Rectosphincteric Reflex

Answer 32

• In the distal colon (descending and sigmoid), the chyme becomes semisolid. This region holds and compacts the subsequent feces, and is characterized by frequent slow segmental contractions, with more limited mass movements. The rectum itself is usually void of feces.
• During mass movements in the distal colon, some feces can reach the rectum causing distension. The distension of the rectum elicits a reflex, which initiates relaxation of the internal anal sphincter (smooth muscle), and elicits afferent impulses, which signal the urge for defecation (rectosphincteric reflex). If conditions are not conducive for defecation, the external anal sphincter (skeletal muscle) will not relax, since these muscles are under somatic control (pudendal nerves). In this case, the smooth muscle of the rectum will begin to relax, and in doing so accommodates the feces. Passage of more feces into the rectum initiates another reflex. The process of defecation normally involves a sequence of voluntary acts including relaxation of the external sphincter, and contractions of the diaphragm and muscles of the abdominal wall to raise intra-abdominal pressure.

Question 33

Answer 33

Question 34

Answer 34

Question 35

Inter-Digestive Motility

Answer 35

•The Interdigestive Period (“Housekeeping”) can be delineated into three distinct phases, which migrate temporally along the alimentary canal.

• Periods of quiescence predominate (Phase I)
• followed by a phase of intermittent and irregular activity (Phase II).
• A relatively short period (5-10 min) of intense activity is then observed (Phase III) prior to resumption of quiescence.
• When viewed at different regions, this pattern of activity is seen to migrate aborally starting in the distal stomach and finishing in the ileum.
• This activity underlies a sweeping of the canal and is referred to as the Migrating Motor Complex (MMC).
• A MMC is initiated in the distal stomach every 90 to 120 mins.
• The hormone motilin reaches its peak blood levels immediately prior to activation of contractility in the duodenum; that is, near the initiation of the MMC.
• The function of this migrating wave of contractile activity is to sweep the contents of the canal analward. In the simplest case, this function is important for moving non-digestible solids (coins) from the stomach to colon, but is of equal importance in maintaining the bacterial count low in the small intestine by moving infiltrating bacteria back into the colon.

Question 36

Disorders of Motility

Answer 36

•opiates

• enhance sphincter tone
• decrease central relfex activity

•anesthetic effect

• depression of GI motility
• cholinergic treatment to activate contractility but lots of side effects - motilin used now

•IBD

• enteric or central: very complex and very individual
• basal motility not altered
• hypersensitivity to activation, alters coordinated flow
• CNS component: anxiety
• inflammatory/immune component

Question 37

Prokinetics

Answer 37

• Substances which enhance transit of materials through the GI tract;
• Cholinomimetics are sometimes included but generally the increase in force of contractions produced by these agents has little effect on intestinal transit.

Question 38

Prokinetic Drugs Improve Gastrointestinal Propulsion by Increasing:

Answer 38

• Esophageal clearance
• Gastric emptying (useful for GERD);
• Rate of transit in proximal intestine;
• Rate of transit in distal sm. intestine;
• Rate of transit in colon.

Question 39

Prokinetic Drugs are Often Used for:

Answer 39

• Gastroesophageal reflux disease (GERD)
• Gastroparesis (Gastric Emptying Disorders)
• Severe refractory constipation (sometimes caused by irritable bowel syndrome (IBS)

Question 40

Metoclopramide

Answer 40

• Several drugs are available to increase gastrointestinal motility associated with diabetic gastroparesis (inadequate gastric emptying) and small bowel failure of propulsion.
• The prototype drug is metoclopramide (Reglan®) stimulates gastric contractions and promotes gastric emptying. Metoclopramide also exhibits antiemetic activity and is often considered an antiemetic of choice in patients receiving antineoplastic drugs.
• Metoclopramide is a Dopamine antagonist acting against 5-hydroxytryptamine (5-HT3) receptors with agonist activity at 5-HT4 receptors.
• The mechanism by which metoclopramide and related prokinetic drugs increase gastro-intestinal contractions is likely related to increased release of acetylcholine at the terminals of enteric cholinergic neurons innervating gastrointestinal smooth muscle, and/or release of acetylcholine at interneurons in the myenteric plexus.
• Since Metaclopramide crosses the blood brain barrier, it also has significant CNS effects.

Question 41

Domperidone

Answer 41

• Domperidone acts on the same peripheral receptors as metaclopromide, but does not cross the BBB.
• For this reason, Domperidone is preferred as a prokinetic drug, however Domperidone does not demonstrate anti-emetic effects

Question 42

Erythromycin

Answer 42

• The antibiotic, Erythromycin, acts as an agonist at smooth muscle Motilin receptors resulting in significant prokinetic effects, and also has no antiemetic effects.
• The advantage of treatment with Motilin/Erythromycin is that their effect of activating coordination in antro-duodenal contractions predominate providing an approach to for the most part effect gastric emptying. Derivatives are currently being studied for use as general prokinetic agents as well.

Question 43

Baclofen

Answer 43

• treatment for GERD
• Baclofen is a GABAB agonist that has been used as a muscle-relaxing agent, but at lower dosages also has been shown to reduce transient lower esophageal sphincter relaxation.
• Since Baclofen has centrally mediated effects including drowsiness and dizziness, several new derivatives are being developed that only act peripherally.

Question 44

Loperamide

Answer 44

• anti-diarrheal
• Loperamine (Imodium) is an opioid-receptor agonist acting on the μ-opioid receptors in the myenteric plexus, and potentially directly on circular sphincteric smooth muscle.
• The resulting increase in sphincter tone increases the amount of time chyme stays within the intestine, allowing for more water to be absorbed from fecal matter.
• Loperamide at higher dosages also has been shown to decrease colonic mass movements in response to ganglionic reflexes such as the gastro-colic reflex, suggesting some effects proximal (mesenteric and hypogastric plexi) to the enteric plexi.