GUT Chapter 5

Deglutition (Swallow) Reflex in Animals
• Mastication precedes transfer of material to oropharynx
• Contraction of oropharynx coincident with relaxation of UES
• Material enters esophagus coincident with contraction of UES & relaxation of LES
• Peristalsis propels material through the esophagus and relaxed LES into the fundus of relaxed proximal stomach (Receptive relaxation reflex of proximal stomach)
• LES and fundus of proximal stomach relaxed throughout the esophageal phase
• Primary peristalsis is migrating ring of contraction that propels material from pharynx to LES with each swallow
• Secondary peristalsis initiated if primary peristalsis fails to clear esophageal body of swallowed material
• Secondary peristalsis is reflex response initiated by esophageal sensory neurones and does not involve swallowing reflex
Gravity provides some assistance in transport of swallowed material from pharynx to stomach
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Deglutition (Swallow) Reflex in Animals
• Mastication precedes transfer of material to oropharynx
• Contraction of oropharynx coincident with relaxation of UES
• Material enters esophagus coincident with contraction of UES & relaxation of LES
• Peristalsis propels material through the esophagus and relaxed LES into the fundus of relaxed proximal stomach (Receptive relaxation reflex of proximal stomach)
• LES and fundus of proximal stomach relaxed throughout the esophageal phase
• Primary peristalsis is migrating ring of contraction that propels material from pharynx to LES with each swallow
• Secondary peristalsis initiated if primary peristalsis fails to clear esophageal body of swallowed material
• Secondary peristalsis is reflex response initiated by esophageal sensory neurones and does not involve swallowing reflex
Gravity provides some assistance in transport of swallowed material from pharynx to stomach
Image: Deglutition (Swallow) Reflex in Animals • Mastication precedes transfer of material to oropharynx • Contraction of oropharynx coincident with relaxation of UES • Material enters esophagus coincident with contraction of UES & relaxation of LES • Peristalsis propels material through the esophagus and relaxed LES into the fundus of relaxed proximal stomach (Receptive relaxation reflex of proximal stomach) • LES and fundus of proximal stomach relaxed throughout the esophageal phase • Primary peristalsis is migrating ring of contraction that propels material from pharynx to LES with each swallow • Secondary peristalsis initiated if primary peristalsis fails to clear esophageal body of swallowed material • Secondary peristalsis is reflex response initiated by esophageal sensory neurones and does not involve swallowing reflex Gravity provides some assistance in transport of swallowed material from pharynx to stomach
THREE PHASES OF SWALLOW REFLEX
Oral (Voluntary) --> Pharyngeal (Involuntary) --> Oesaphageal (Involuntary)
Image: THREE PHASES OF SWALLOW REFLEX Oral (Voluntary) --> Pharyngeal (Involuntary) --> Oesaphageal (Involuntary)
DEGLUTITION REFLEX IN ANIMALS
● Cricopharyngeal muscle functions as the UES and maintains tonic contractile tone of UES except during swallowing
● UES contains inner longitudinal & outer circular slow (type 1) twitch striated muscle
● UES innervated by vagus (CNX), with input from CNIX & RLN in some species
● Oesophagus transports material through cervical, thoracic & abdominal regions of the body.
UES, upper oesaphageal sphincter; LES, lower esophageal sphincter.
CNIX, _______________________________________;
RLN, _________________________________________________ a branch of the _________________________ nerve.
Upper esophageal sphincter (UES) is a high-pressure zone between pharynx & cervical esophagus. Sphincter protects against reflux (aspiration) of food into airways & prevent entry of air to the gut. Esophagus is a musculomembranous tube that transports ingesta, fluids & saliva from pharynx to the stomach. Swallowing is one of the most complex stereotyped patterns of motor behaviour involving over 30 pairs of muscles in the mouth, pharynx, larynx and oesophagus.]
Image: DEGLUTITION REFLEX IN ANIMALS ● Cricopharyngeal muscle functions as the UES and maintains tonic contractile tone of UES except during swallowing ● UES contains inner longitudinal & outer circular slow (type 1) twitch striated muscle ● UES innervated by vagus (CNX), with input from CNIX & RLN in some species ● Oesophagus transports material through cervical, thoracic & abdominal regions of the body. UES, upper oesaphageal sphincter; LES, lower esophageal sphincter. CNIX, _______________________________________; RLN, _________________________________________________ a branch of the _________________________ nerve. Upper esophageal sphincter (UES) is a high-pressure zone between pharynx & cervical esophagus. Sphincter protects against reflux (aspiration) of food into airways & prevent entry of air to the gut. Esophagus is a musculomembranous tube that transports ingesta, fluids & saliva from pharynx to the stomach. Swallowing is one of the most complex stereotyped patterns of motor behaviour involving over 30 pairs of muscles in the mouth, pharynx, larynx and oesophagus.]
NEURAL CONTROL SWALLOWING (DEGLUTITION)
Esophageal Muscle Type
Smooth: Birds, amphibians, reptiles
Striated: Rums, dog, rodents
Striated & distal SM: Cat, horse, pig
Striated-mixed-SM: Human
Rum drunk rodent struts at the smooth BAR
Image: NEURAL CONTROL SWALLOWING (DEGLUTITION) Esophageal Muscle Type Smooth: Birds, amphibians, reptiles Striated: Rums, dog, rodents Striated & distal SM: Cat, horse, pig Striated-mixed-SM: Human Rum drunk rodent struts at the smooth BAR
EFFERENT INNERVATION OF OESAPHAGEAL BODY
•Special vagal somatic motor fibres directly innervate the striated muscle fibres of the circular and longitudinal muscle.
•Cell bodies of these lower motor neurones lie in a central pattern generator in the nucleus ambiguus (NA).
•Dorsal motor nucleus (DMN) projects VEF & VIF to SM of esophagus & LES
•Myenteric plexus and ICC throughout esophagus regardless of muscle type

[NOTE: All voluntary movement relies on spinal lower motor neurones, which innervate skeletal muscle fibers and act as a link between upper motor neurones and muscles.
Cranial nerve lower motor neurones control movements of the eyes and tongue, and contribute to chewing, swallowing and vocalization.
Upper motor neurones are motor neurones that originate either in the motor region of the cerebral cortex (motor cortex) or brain stem and transmit motor information to lower motor neurones
Image: EFFERENT INNERVATION OF OESAPHAGEAL BODY •Special vagal somatic motor fibres directly innervate the striated muscle fibres of the circular and longitudinal muscle. •Cell bodies of these lower motor neurones lie in a central pattern generator in the nucleus ambiguus (NA). •Dorsal motor nucleus (DMN) projects VEF & VIF to SM of esophagus & LES •Myenteric plexus and ICC throughout esophagus regardless of muscle type [NOTE: All voluntary movement relies on spinal lower motor neurones, which innervate skeletal muscle fibers and act as a link between upper motor neurones and muscles. Cranial nerve lower motor neurones control movements of the eyes and tongue, and contribute to chewing, swallowing and vocalization. Upper motor neurones are motor neurones that originate either in the motor region of the cerebral cortex (motor cortex) or brain stem and transmit motor information to lower motor neurones
Oesaphageal Striated MuscleVagal Somatic Motor Neurones
● Deglutition reflex initiated by activation of pharyngeal mechanoreceptor afferent fibres of the glossopharyngeal (CNIX) & vagal (CNX) nerves that project to the nucleus tractus solitarius (NTS), which relays information to NA & respiratory centre
● Deglutition reflex initiates deglutitive inhibition via central control by NA
● Swallow induced primary peristalsis in striated muscle via central pattern generator (CPG) in NA, results in sequential activation of vagal somatic lower motor neurones
● Swallow-pattern generator located in the deglutition (swallow) center coordinates sequence of sequential firing of neurone groups 1, 2 & 3.
● Secondary peristalsis of striated muscle is a vagovagal reflex involving esophageal vagal afferents to the NTS and then via interneurones to the nucleus ambiguus (NA).
Deglutitive inhibition describes the reflex relaxation of the esophageal musculature coincident with onset of swallow reflex. Esophageal muscle returns to normal tone with passing of the peristaltic wave. Facilitates peristaltic propulsion of material through the esophageal body by minimizing aboral resistance to the swallow pressure wave. Deglutitive inhibition essential for multiple rapid swallowing (MRS) of fluids (beer!).
Neural control of secondary peristalsis differs between striated and smooth muscle. Secondary peristalsis of striated or smooth muscle occurs without swallow reflex and relaxation of UES
Image: Oesaphageal Striated MuscleVagal Somatic Motor Neurones ● Deglutition reflex initiated by activation of pharyngeal mechanoreceptor afferent fibres of the glossopharyngeal (CNIX) & vagal (CNX) nerves that project to the nucleus tractus solitarius (NTS), which relays information to NA & respiratory centre ● Deglutition reflex initiates deglutitive inhibition via central control by NA ● Swallow induced primary peristalsis in striated muscle via central pattern generator (CPG) in NA, results in sequential activation of vagal somatic lower motor neurones ● Swallow-pattern generator located in the deglutition (swallow) center coordinates sequence of sequential firing of neurone groups 1, 2 & 3. ● Secondary peristalsis of striated muscle is a vagovagal reflex involving esophageal vagal afferents to the NTS and then via interneurones to the nucleus ambiguus (NA). Deglutitive inhibition describes the reflex relaxation of the esophageal musculature coincident with onset of swallow reflex. Esophageal muscle returns to normal tone with passing of the peristaltic wave. Facilitates peristaltic propulsion of material through the esophageal body by minimizing aboral resistance to the swallow pressure wave. Deglutitive inhibition essential for multiple rapid swallowing (MRS) of fluids (beer!). Neural control of secondary peristalsis differs between striated and smooth muscle. Secondary peristalsis of striated or smooth muscle occurs without swallow reflex and relaxation of UES
Vagal Somatic Motor Neurones Control Contractility Striated Muscle in Pharynx & Oesaphagus
Swallow (stimulus)-induced peristalsis in striated muscle is due to sequential activation of lower motor neurones of vagal somatic nerves in the nucleus ambiguus in the brainstem medulla.
The swallow-pattern generator located in the deglutition (swallow) center coordinates sequence of sequential firing of group 1 neurones, then group 2 neurones etc.
Primary peristalsis is defined as a reflex oesophageal peristaltic contraction wave associated with swallowing. The primary wave of peristalsis begins in the pharynx (oropharynx) and progresses aborally. A marker of the start of the swallowing activity is contraction of the mylohyoid muscle, which is called the lead muscle of swallowing reflex. A bolus of food initiates the swallow reflex when it is pushed into the pharynx and stimulates proprioceptive afferent fibres of cranial IX (glossopharyngeal) in the pharynx.
Peristaltic contractions are lumen-occluding contractions that begin in the pharynx and move down the oesophagus at a velocity of about 4 cm/sec. A primary peristaltic activity requires about 5 - 15 seconds to complete depending on species/size of animal.
Secondary peristalsis does not involve a full swallowing reflex. It occurs without pharyngeal contraction, actual swallow or UES relaxation. The amplitude and propagation speed of these contractions resemble those of primary peristalsis.
Secondary peristalsis in striated muscle has identical neuronal circuitry to that of primary peristalsis except for the circuitry dealing with pharyngeal phase of swallowing. Secondary peristalsis in oesaphageal striated muscle is a vagovagal reflex involving vagal afferents to the NTS and then via interneurones to the nucleus ambiguus. Both primary and secondary peristalsis of oesaphageal striated muscle are dependent on central vagal pathways and classic vagovagal reflex.
Secondary peristalsis in oesaphageal smooth muscle of the esophagus is a local reflex elicited by local (intrinsic) sensory nerves and integrated by the myenteric plexus of the enteric nervous system. Distention of the esophageal smooth muscle causes activation of local sensory nerves that elicit contraction above the distention and relaxation below it. The contraction wave (secondary peristalsis) then progresses distally, moving the food bolus ahead of it.
ICC & myenteric ganglia (MG) striated muscle: Recent work shows that ICC and enteric myenteric ganglia exist within striated muscle of the oesaphagus, and possibly pharyngeal striated muscle. Enteric neurones and vagal somatic excitatory fibres from the nucleus ambiguus co-innervate endplates of esophageal striated muscle.
https://link.springer.com/article/10.1007/s00418-016-1500-1; https://link.springer.com/content/pdf/10.1007%2Fs00418-016-1500-1.pdf
Image: Vagal Somatic Motor Neurones Control Contractility Striated Muscle in Pharynx & Oesaphagus Swallow (stimulus)-induced peristalsis in striated muscle is due to sequential activation of lower motor neurones of vagal somatic nerves in the nucleus ambiguus in the brainstem medulla. The swallow-pattern generator located in the deglutition (swallow) center coordinates sequence of sequential firing of group 1 neurones, then group 2 neurones etc. Primary peristalsis is defined as a reflex oesophageal peristaltic contraction wave associated with swallowing. The primary wave of peristalsis begins in the pharynx (oropharynx) and progresses aborally. A marker of the start of the swallowing activity is contraction of the mylohyoid muscle, which is called the lead muscle of swallowing reflex. A bolus of food initiates the swallow reflex when it is pushed into the pharynx and stimulates proprioceptive afferent fibres of cranial IX (glossopharyngeal) in the pharynx. Peristaltic contractions are lumen-occluding contractions that begin in the pharynx and move down the oesophagus at a velocity of about 4 cm/sec. A primary peristaltic activity requires about 5 - 15 seconds to complete depending on species/size of animal. Secondary peristalsis does not involve a full swallowing reflex. It occurs without pharyngeal contraction, actual swallow or UES relaxation. The amplitude and propagation speed of these contractions resemble those of primary peristalsis. Secondary peristalsis in striated muscle has identical neuronal circuitry to that of primary peristalsis except for the circuitry dealing with pharyngeal phase of swallowing. Secondary peristalsis in oesaphageal striated muscle is a vagovagal reflex involving vagal afferents to the NTS and then via interneurones to the nucleus ambiguus. Both primary and secondary peristalsis of oesaphageal striated muscle are dependent on central vagal pathways and classic vagovagal reflex. Secondary peristalsis in oesaphageal smooth muscle of the esophagus is a local reflex elicited by local (intrinsic) sensory nerves and integrated by the myenteric plexus of the enteric nervous system. Distention of the esophageal smooth muscle causes activation of local sensory nerves that elicit contraction above the distention and relaxation below it. The contraction wave (secondary peristalsis) then progresses distally, moving the food bolus ahead of it. ICC & myenteric ganglia (MG) striated muscle: Recent work shows that ICC and enteric myenteric ganglia exist within striated muscle of the oesaphagus, and possibly pharyngeal striated muscle. Enteric neurones and vagal somatic excitatory fibres from the nucleus ambiguus co-innervate endplates of esophageal striated muscle. https://link.springer.com/article/10.1007/s00418-016-1500-1; https://link.springer.com/content/pdf/10.1007%2Fs00418-016-1500-1.pdf
OESOPHAGEAL SMOOTH MUSCLE PARALLEL INHIBITORY & EXCITATORY VAGAL INNERVATION
• Preganglionic excitatory (VEF) and inhibitory (VIF) innervate esophageal SM
• Anatomical 'top-to-bottom' arrangement of soma of VEF and VIF in DMN are matched with craniocaudal distribution of their synapses in the esophagus
• Preganglionic cholinergic VEF & VIF connect synaptically with postganglionic enteric excitatory or inhibitory motor neurones, respectively
• Deglutitive inhibition: swallowing induces a wave of hyperpolarization & relaxation of esophageal striated/smooth muscle and the LES
• Activation of VIF induces hyperpolarization & relaxation of esophageal smooth muscle (deglutitive inhibition) before onset of primary peristalsis
• Sequential, stepwise activation of VEF concordant with inactivation of VIF results in peristaltic contractions that migrate to the LES
• Deglutitive inhibition essential for rapid multiple swallows (RMS) in man & animals
Image: OESOPHAGEAL SMOOTH MUSCLE PARALLEL INHIBITORY & EXCITATORY VAGAL INNERVATION • Preganglionic excitatory (VEF) and inhibitory (VIF) innervate esophageal SM • Anatomical 'top-to-bottom' arrangement of soma of VEF and VIF in DMN are matched with craniocaudal distribution of their synapses in the esophagus • Preganglionic cholinergic VEF & VIF connect synaptically with postganglionic enteric excitatory or inhibitory motor neurones, respectively • Deglutitive inhibition: swallowing induces a wave of hyperpolarization & relaxation of esophageal striated/smooth muscle and the LES • Activation of VIF induces hyperpolarization & relaxation of esophageal smooth muscle (deglutitive inhibition) before onset of primary peristalsis • Sequential, stepwise activation of VEF concordant with inactivation of VIF results in peristaltic contractions that migrate to the LES • Deglutitive inhibition essential for rapid multiple swallows (RMS) in man & animals
Control Peristalsis in Oesaphageal Smooth Muscle
● Activation of pharyngeal mechanoreceptors during swallowing reflexly activates preganglionic VIF with resultant hyperpolarization (deglutitive inhibition) of all esophageal smooth muscle until passing of primary wave of peristalsis
● Vagal excitatory fibres (VEF) fire in a descending order to direct esophageal peristalsis in smooth muscle.
● VIF become inactive at onset of VEF-induced contraction.
● Inactivation of VIF is prerequisite for active VEF to incite contraction
● Esophageal smooth muscle resumes normal resting tone after passage of the peristaltic wave.
● Secondary peristalsis in esophageal smooth muscle is local intrinsic reflex involving mucosal mechanoreceptors & ENS and occurs without swallow or relaxation of UES
● Secondary peristalsis in striated muscle governed by vagovagal reflex
cDMN, caudal dorsal motor nucleus; rDMN, rostral dorsal motor nucleus
Image: Control Peristalsis in Oesaphageal Smooth Muscle ● Activation of pharyngeal mechanoreceptors during swallowing reflexly activates preganglionic VIF with resultant hyperpolarization (deglutitive inhibition) of all esophageal smooth muscle until passing of primary wave of peristalsis ● Vagal excitatory fibres (VEF) fire in a descending order to direct esophageal peristalsis in smooth muscle. ● VIF become inactive at onset of VEF-induced contraction. ● Inactivation of VIF is prerequisite for active VEF to incite contraction ● Esophageal smooth muscle resumes normal resting tone after passage of the peristaltic wave. ● Secondary peristalsis in esophageal smooth muscle is local intrinsic reflex involving mucosal mechanoreceptors & ENS and occurs without swallow or relaxation of UES ● Secondary peristalsis in striated muscle governed by vagovagal reflex
CONTROL OF PERISTALSIS IN OESAPHAGEAL SMOOTH MUSCLE
Upon swallowing, the inhibitory pathway neurones (VIF) in the caudal DMN (cDMN) are activated first, which results in simultaneous inhibition of all parts of the esophagus. This inhibition lasts longer in the lower than in the upper parts. This effect is known as deglutitive inhibition of the oesaphagus.
Swallow reflex then incites sequential activation of excitatory cholinergic neurones (VEF) in the rostral DMN (rDMN) which elicits a contraction wave that is peristaltic in nature. Majority, if not all, VIF fibres must be inactive when VEF are active and exciting smooth muscle cells and/or intramuscular ICC (IM-ICC) in oesaphageal smooth muscle.
Primary peristalsis in oesophageal smooth muscle is due to distally increasing duration of deglutitive inhibition followed by deglutitive excitation.
Secondary peristalsis activated by local distention of tube and involves intrinsic reflex via intrinsic mechanosensitive primary afferent neurones (IPANs) and ENS.
Nitric oxide (NO) is produced from neural nitric oxide synthase (nNOS) in nerve terminals of enteric inhibitory motor neurones in the oesophagus. Nitric oxide is a major inhibitory neurotransmitter secreted at the smooth muscle neuromuscular junction by enteric inhibitory motor neurones. Nitric oxide causes inhibition of contraction by a cyclic guanosine monophosphate (cGMP)-dependent mechanism. Vasoactive intestinal peptide (VIP) plays a supportive role.
During prolonged or rapid drinking of fluid, the deglutitive inhibition persists as long as the animal is drinking. Lack of oxygen usually curtails excessive intakes of fluid at any given moment.
Acetylcholine and substance P are the major excitatory neurotransmitters. In the circular smooth muscle, acetylcholine causes influx of calcium. Influx of calcium causes activation of the calmodulin-myosin light chain kinase pathway to cause contraction of smooth muscle.
Image: CONTROL OF PERISTALSIS IN OESAPHAGEAL SMOOTH MUSCLE Upon swallowing, the inhibitory pathway neurones (VIF) in the caudal DMN (cDMN) are activated first, which results in simultaneous inhibition of all parts of the esophagus. This inhibition lasts longer in the lower than in the upper parts. This effect is known as deglutitive inhibition of the oesaphagus. Swallow reflex then incites sequential activation of excitatory cholinergic neurones (VEF) in the rostral DMN (rDMN) which elicits a contraction wave that is peristaltic in nature. Majority, if not all, VIF fibres must be inactive when VEF are active and exciting smooth muscle cells and/or intramuscular ICC (IM-ICC) in oesaphageal smooth muscle. Primary peristalsis in oesophageal smooth muscle is due to distally increasing duration of deglutitive inhibition followed by deglutitive excitation. Secondary peristalsis activated by local distention of tube and involves intrinsic reflex via intrinsic mechanosensitive primary afferent neurones (IPANs) and ENS. Nitric oxide (NO) is produced from neural nitric oxide synthase (nNOS) in nerve terminals of enteric inhibitory motor neurones in the oesophagus. Nitric oxide is a major inhibitory neurotransmitter secreted at the smooth muscle neuromuscular junction by enteric inhibitory motor neurones. Nitric oxide causes inhibition of contraction by a cyclic guanosine monophosphate (cGMP)-dependent mechanism. Vasoactive intestinal peptide (VIP) plays a supportive role. During prolonged or rapid drinking of fluid, the deglutitive inhibition persists as long as the animal is drinking. Lack of oxygen usually curtails excessive intakes of fluid at any given moment. Acetylcholine and substance P are the major excitatory neurotransmitters. In the circular smooth muscle, acetylcholine causes influx of calcium. Influx of calcium causes activation of the calmodulin-myosin light chain kinase pathway to cause contraction of smooth muscle.
Muscle Groups of Oesaphageal-Gastric Sphincter • Crural and costal are separate muscles of the diaphragm • Costal diaphragm is primarily a ventilator muscle innervated by phrenic nerve. • Crural has two functions, ventilator and sphincter-like action at the esophageal-gastric junction. • Vagal excitatory (VEF) & sensory neurones and phrenic motor nerves innervate the crural diaphragm • Crural diaphragm provides tonic or sustained increase in pressure of the LES during inspiration, recumbency, abdominal compression and exercise.MUSCLE COMPONENTS OF THE ESOPHAGEAL-GASTRIC JUNCTION (LES) The LES is an unusual sphincter. The LES refers to the junction of the esophagus with the stomach (esophageal-gastric junction). Sphincter properties require complimentary roles of oesaphageal clasp fibres, gastric sling fibres and striated muscle of the Crural diaphragm. The sphincter-like properties that regulate the relaxation, opening and closing (contraction) of the LES are determined by neural circuitry & the physiological properties of the semicircular arrangement of the clasp fibres that blend with the oblique layer of the sling fibres. Crural and costal are separate muscles of the diaphragm. Costal diaphragm is primarily a ventilator muscle innervated by motor and sensory fibres of the left and right phrenic nerves. Crural diaphragm has two functions, ventilator and sphincter-like action at the esophageal-gastric junction. Phrenic and vagal sensory and motor fibres innervate the crural but not the costal (phrenic only) muscle. Crural diaphragm provides tonic or sustained increase in pressure of the LES during inspiration phase of breathing, recumbency, abdominal compression and exercise. Bottom left: This schematic shows a three-dimensional representation of the arrangement of the lower esophageal sphincter in animals and humans. Anatomical positioning and myogenic properties esophageal clasp & sling muscle groups serve the function of a sphincter that separates the esophagus from the gastric lumen contents. Crura striated muscle plays important supporting role during inspiration and exercise. Equine emesis: Horse can condition their gastric musculature to perform strong orad-directed propulsive contractions of the emetic reflex. However, the shallow angle of the oesaphagus at their LES makes it very difficult to accomplish reflex relaxation of the sling and clasp fibres during strong contractions of a usually distended stomach. In some cases, stomach may rupture.Transient Lower Esophageal Sphincter Relaxation (TLESR) • In transient LES relaxation, a temporary reduction in vagal excitatory drive to smooth muscle of the LES (esophageal clasp fibres, gastric sling fibres) and excitatory drive to striated muscle of the crura (vagus & phrenic). This results in transient relaxation of LES and decrease in constrictive tone in the crura • TLESR necessary for emesis and belching in nonruminants & ruminants • Belching in ruminants caused by exposure of cardia chemoreceptors to CO2 • TLESR dysfunction responsible for gastric reflux that can damages smooth muscle of caudal esophagus • Transient lower esophageal sphincter (LES) relaxation is major cause of gastroesophageal reflux in humans, dogs, and ferrets • Gastric distention triggers transient LES relaxations • Acid reflux into caudal esophagus incites inflammation & erosion of mucosaSUMMARY: PHASES OF DEGLUTITION (SWALLOW) REFLEX Oral or Voluntary Phase of Deglutition ● Prehension, moistening (saliva), mastication, bolus formation ● Action of tongue moves digesta into oropharynx where it stimulates stretch (mechanosensitive) receptors that connect to the deglutition centre in the medulla ● Deglutition centre coordinates breathing and contractility of striated muscle of the UES, esophageal striated/smooth muscle and smooth muscle of the LES ● Activation of mechanoreceptors in oropharynx incites deglutition reflex ● CN V, VII, IX, X and XII necessary for oral & pharyngeal phases of deglutition Involuntary Pharyngeal Phase ● Pharyngeal phase has early voluntary and late involuntary component ● Closure of the nasopharynx & larynx with contraction of muscular wall of pharynx ● Reflex inhibition of breathing (deglutition apnea) ● Primary wave of peristalsis in the oropharynx pushes material through relaxed UES ● Swallowing occurs during expiration & is associated with deglutition apnea Involuntary Esophageal Phase (Vagal & enteric neurone dependent) ● Deglutition centre (medulla) controls primary peristalsis in striated & smooth muscle ● Deglutition induces an inhibitory relaxation of entire esophageal body ● Primary wave of peristalsis pushes material through the relaxed esophagus & LES ● LMN in NA control primary & secondary peristalsis in striated muscle ● Vagal excitatory & inhibitory neurones control primary peristalsis in smooth muscle ● Secondary peristalsis occurs if primary peristalsis fails to clear esophageal tube ● Secondary peristalsis in striated muscle is centrally mediated vago-vagal reflex ● Secondary peristalsis in smooth muscle is a local enteric reflex LMN, vagal lower motor neuron; NA, nucleus ambiguus CN V: ____________________________________________ CN VII: __________________________________________ CN IX: ___________________________________________ CN X: ___________________________________________ CN XII: ___________________________________________In esophageal striated muscle, primary & secondary peristalsis is centrally generated via nucleus tractus solitarius (NTS) and nucleus ambiguous (NA) that projects vagal somatic lower motor neurones to the neuromuscular junction in plasma membrane (sarcolemma) of esophageal striated muscle. ICC are present in esophageal striated muscle and may play role in modulating responses to neural input by somatic vagal neurones. Secondary peristalsis in striated muscle is classic vago-vagal reflex involving esophageal vagal afferents to NTS & then via interneurones to NA Esophageal smooth muscle is innervated by vagal preganglionic neurones whose soma reside in the DMN of the vagus. Soma of vagal excitatory neurones (VEF) reside in rostral DMN, whereas soma of vagal inhibitory fibres (VIF) reside in caudal DMN. In smooth muscle, preganglionic excitatory and inhibitory vagal cholinergic fibres connect synaptically with EEMN and EIMN, respectively, via interneurones in the myenteric plexus. Enteric excitatory and inhibitory fibres form terminal varicosities adjacent to intramuscular ICC in myenteric plexus. Primary peristalsis of smooth muscle initiated by deglutition (swallowing) reflex, whereas secondary peristalsis in response to dilatation of esophagus or presence of digesta/gastric reflux in esophagus is a local, intrinsic myenteric reflex. Three muscle groups contribute to function of the LES. DMN projects vagal excitatory motor neurones to striated muscle of the crural diaphragm, and VEF and VIF to esophageal clasp fibres and gastric sling fibres of the LES. Vagal afferents transmit sensory information from each of the three muscle groups to the NTS. The LES relaxes transiently (TLESR) in absence of swallowing in humans and animals to allow burping, belching or emesis. Dysfunction in one or more of the three muscle groups of the LES results in gastric reflux and subsequent development of esophagitis. VEF: vagal excitatory fibre; VIF: vagal inhibitory fibre; ACh: acetylcholine; NO: nitric oxide; VIP: vasoactive intestinal polypeptide; UES: upper esophageal esophagus; LES: lower esophageal esophagus; LMN lower motor neurones.CLINICAL ASPECTS OF DEGLUTITION • Oesaphageal ectasia (dilatation) commonly referred to as megaesophagus • Failure of primary/secondary peristalsis to move digesta along oesaphagus to LES and thence stomach • Accumulation of digesta in dilated region(s) is refluxed to mouth and expelled or remains in esophagus where it putrefies leading to esophagitis • Aspiration pneumonia a common problem •Animals present with signs of malnutrition, emaciation, dehydration, osteopenia and/or aspiration pneumonia resulting from regurgitation • Congenital idiopathic megaesophagus in dog, cat and horse • Adult idiopathic (acquired) megaesophagus in adult animals in dog, cat horse • Pathology often not determined, but some cases coexist with or caused by: ⟡ Localized/systemic myasthenia gravis ⟡Immune-mediated polymyositis ⟡ Esophageal obstruction- tumors, ⟡ Addison's disease (primary hypoadrenocorticism) or hypothyroidism ⟡ IdiopathicClinical Lexicon Esophageal Diseases • Esophagitis: Inflammation of the esophagus (esophagitis) is usually caused by certain drugs (such as doxycycline), foreign objects, or acid reflux. Esophagitis may also be result of swallowing of an irritating or caustic substance, cancer or as result of respiratory disease. Signs of esophagitis include regurgitation, drooling, difficulty or repeated swallowing, pain, depression, loss of appetite, and extension of the head and neck. Esophagitis should be determined by use of an endoscope. • Esophageal Dysmotility describes any insult that causes abnormal motility of the oesaphagus. • Esophageal Diverticula are pouch-like expansions (dilations) of the oesophageal wall. Two types of acquired diverticula include: (1) pulsion diverticula caused by increased esophageal pressure that promotes rupture (hernia) of the inner lining and (2) traction diverticula caused by presence of fibrous tissue that contracts and pulls the oesophageal wall outward. Large diverticula require surgery involving removal of the pouch and rebuilding of the esophageal wall. • Esophageal Stricture is a narrowing of the esophagus associated with ingestion of a foreign object, caustic substance, inflammation of the esophagus or gastroesophageal reflux (GER). In patients with GER, dysfunction of one or more of the three groups of muscle that function as the lower oesaphageal sphincter result in gastric acid refluxes into the caudal (distal) oesaphagus.Clinical Lexicon Esophageal Diseases • Achalasia the failure of a ring of muscle fibers, such as a sphincter of the esophagus, to relax. • Oesaphageal Achalasia (failure of oesaphagus to relax) Pathophysiologically, achalasia cardia (LES) is caused by progressive loss of myenteric ganglia concerned with activation of enteric inhibitory motor neurones. In initial stages, degeneration of inhibitory nerves in the esophagus results in unopposed action of EEMN which secrete excitatory acetylcholine causing high amplitude non-peristaltic contractions (vigorous achalasia). Progressive loss of cholinergic neurons over time results in dilation and non-progressive low amplitude simultaneous contractions in the esophageal body (classic achalasia). In general, achalasia is failure of normal relaxation of the lower esophageal sphincter associated with uncoordinated contractions of the thoracic esophagus, resulting in functional obstruction and difficulty swallowing. • Cricopharyngeal Achalasia indicates failure of the vagal-controlled striated fibres of the cricopharyngeal muscle to relax during swallowing. The cause is unknown (idiopathic) but may be result of genetic defects in juvenile animals or neuromuscular disorder in adults. Surgical cutting or dissection of the abnormal muscle has been successful in animals with congenital defect in neural control of cricopharyngeal muscle. • Esophageal Ectasia (megaesophagus) refers to a dilatation, expansion of a hollow or tubular organ such as the esophagusClinical Lexicon Esophageal Diseases • Esophageal Obstruction (Choke) HORSE: commonly encountered in equine practice. Esophageal obstruction in horse can be primary or secondary. Primary obstruction common result of esophageal intraluminal impaction with feedstuffs. Dental problems predispose animal to obstruction because of inadequate mastication before swallowing. Clinical signs associated with esophageal obstruction include nasal discharge of feed material or saliva, dysphagia, coughing, or ptyalism. Affected horses may continue to eat or drink, worsening the clinical signs. CATTLE: clinical signs of esophageal obstruction include free-gas bloat, ptyalism, or nasal discharge of food and water. Ruminants may be bloated and in distress or recumbent. Protrusion of the tongue and/or extension of the head observed. Acute and complete esophageal obstruction is an emergency because it prohibits eructation of ruminal gases, and free-gas bloat develops. Severe free-gas bloat may result in asphyxia, because the expanding rumen puts pressure on the diaphragm and reduces venous return of blood to the heart. Esophageal Obstruction in Large Animals - Digestive System - Veterinary Manual (msdvetmanual.com)1. Explain the timing and coordination of mechanical pressure changes of the oropharynx, upper and lower esophageal sphincters, and esophageal body during pharyngeal and esophageal phases of the deglutition reflex.(1) What are the three phases of deglutition, and which are voluntary or involuntary?(2) Do UES and LES maintain a zone of high pressure within each sphincter at rest (i.e., not participating in a swallow reflex)? (3) What is the major purpose of maintaining a high-pressure zone in contracted UES and LES when not swallowing?(4) Is the first committed step of the reflex associated with contraction of pharynx (oropharynx) coincident with relaxation of the upper esophageal sphincter (UES)?(5) When does the LES relax during a swallow and does it relax briefly, as occurs for UES, and when does it constrict?(7) In some species (e.g., human, grazing cow), does gravity assist or contribute little or no assistance to migrating pressure wave that moves swallowed bolus through esophageal body?(6) Define primary and secondary peristalsis.(8) Define deglutition apnea and why it is necessary. [Deglutition apnea is an essential part of the deglutition reflex. Deglutition apnea is a brief pause in breathing that starts immediately before and remains during the entire involuntary pharyngeal phase. Coincident with pause in the respiratory cycle, the epiglottis closes off the entrance to trachea to prevent passage of digesta into the airways during the pharyngeal phase of deglutition. Typically, deglutition occurs during later stages of expiration when it stops to allow passage of material through open UES into esophagus (swallow) at which point respiration continues with completion of the expiratory phase of the respiratory cycle. The expiration-swallow-expiration (E-S-E) pattern prevents the pharyngeal contents from insulting the bronchioles and bronchiole.]2. Identify name(s) and muscle type(s) that comprise the UES and LES.(1) What is/are muscle type(s) and name(s) of the major muscle(s) of UES?(2) What is/are muscle type(s) and name(s) of the muscle(s) of the LES?3. Describe and explain the neural motor and sensory control during the three phases of deglutition reflex, including deglutitive inhibition, in animals whose oesophagus includes striated muscle alone, striated, and smooth muscle or smooth muscle only.(1) Do cranial nerves V, VII, IX, X and XII participate in small or extensive ways in deglutition reflex [Yes.](2) What nerves (two) participate in major way in providing afferent information during the pharyngeal and esophageal phases of deglutition?(3) Which cranial nerve responsible for practically all efferent outflow to smooth and straited muscle of oesophageal body and LES?(4) Summarize the neural circuitry controlling primary peristalsis in straited muscle of the oesophagus.(4) Briefly define/describe deglutitive inhibition of esophageal muscle regardless of muscle type, either as striated or smooth muscle.(5) In esophageal striated muscle, does the nucleus ambiguus supply special somatic vagal lower motor neurones whose terminals form neuromuscular junctions with striated muscle? [Deglutitive inhibition of striated muscle caused by decrease in somatic vagal neurone input to striated muscle.](7) What is the role of vagal soma residing in the rostral and caudal regions of the DMN as regards control of peristalsis in esophageal smooth muscle?(6) Does a central pattern generator control sequential firing of vagal somatic lower motor neurones in the nucleus ______________________ that are arranged in an array of descending input that corresponds to a cranial-caudal order of innervation of striated muscle? [Yes.](8) Do VEF originating in the caudal DMN control deglutitive inhibition in esophageal smooth muscle?(9) Is there a descending order of soma of preganglionic VEF in rostral DMN that corresponds to a cranial-caudal order of innervation of esophageal smooth muscle?4. Identify the major differences between primary and secondary peristalsis in striated and smooth muscle of the esophagus.(1) What elicits (causes) secondary peristalsis?(2) Is secondary peristalsis a vagovagal reflex in striated muscle or smooth muscle regions of the esophagus(4) What is the neural circuitry of secondary peristalsis in esophageal smooth muscle?(3) Define a vagovagal reflex. [Vagal afferents sense distortion of esophageal body, information transmitted via nodose ganglion to NTS that forwards integrated information to DMN containing efferent vagal neurones that act to adjust/correct the initial problem at site of sensing or elsewhere with intent to correct/mitigate the problem.](5) Does secondary peristalsis in smooth muscle of esophagus occur with or without central (brain) input?5. Describe and explain functions of the three muscle groups that interact to form the lower oesaphageal sphincter at the oesophageal-gastric junction.(1) Identify names, locations, type of muscle and their respective functions to a patent (functioning) LES(2) Explain role of crura and its innervation as pertaining to function of LES(3) What is role of LES in TLESR [Describe the general mechanism for transient lower oesaphageal sphincter relaxation (TLESR) and how it relates to belching and gastroesophageal reflux disease (GERD).]6. Describe the differential diagnoses and consequences of megaesophagus (esophageal dilatation orectasia) in animals.