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Universidad Autónoma de Guadalajara 1 The gastrointestinal The gastrointestinal tract tract Regulation and Regulation and motility part 1 motility part 1 Dra. Ma. Elena Torres Dra. Ma. Elena Torres Zazueta Zazueta

1 GI MOTILITY PART 1 regulation, swallow, esophagus 0902

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Universidad Autónoma de Guadalajara1

The gastrointestinal tractThe gastrointestinal tract

Regulation and motility Regulation and motility part 1part 1

Dra. Ma. Elena Torres ZazuetaDra. Ma. Elena Torres Zazueta

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Universidad Autónoma de Guadalajara2

Objectives

• Describe the overall role of the gastrointestinal system with respect to the whole body balance of water, electrolytes, carbohydrates, fats, and proteins. Include the processes of digestion, absorption, metabolic production, metabolic consumption, secretion, and excretion.

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INTEGRATED RESPONSE TO A MEAL

From: Silverthorn. Human Physiology. 2nd Edition

Prentice Hall

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Objectives• Describe the histoanatomical characteristics of the

enteric nervous system. Given either a cross section or a longitudinal section of the intestine, name and locate the myenteric and submucosal plexus.

• Contrast the sympathetic and parasympathetic modulation of the enteric nervous system and the effector organs of the GI tract.

• Classify the following enteric nervous system neurotransmitters as excitatory or inhibitory: norepinephrine, acetylcholine, CCK, VIP, histamine, and somatostatin.

• Describe the similarities and differences in regulating gastrointestinal function by nerves, hormones, and paracrine regulators. Include receptors, proximity, and local vs. global specificity.

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NEURONS OF THE ENTERIC NEURONS OF THE ENTERIC NERVOUS SYSTEMNERVOUS SYSTEM

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NEURONS OF THE ENTERIC NEURONS OF THE ENTERIC NERVOUS SYSTEMNERVOUS SYSTEM

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The Enteric The Enteric Nervous Nervous

System and it System and it relationship relationship

with the ANS with the ANS

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•Form hollow structures, do not contract against skeleton•Electrically coupled, gap junctions, contracts as syncitium•Actin:myosin ratio 15:1 (skeletal muscle 2:1)•Not striated, neurotransmitter released from varicosities•Have slow wave activity

From: Silverthorn. Human Physiology

Prentice Hall

Intestinal smooth muscleIntestinal smooth muscle

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From: Silverthorn. Human Physiology Prentice Hall

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Ca++Ca++

Ca++Ca++CalmodulinCalmodulin

Ca++ -Ca++ - CalmodulinCalmodulin

Inactive myosin Inactive myosin light chain kinaselight chain kinase

Active myosin Active myosin light chain kinaselight chain kinase

Muscle Muscle contractioncontraction

Phosphorilated myosin light chain

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FUNCTIONS OF MOTILITY

• PROPULSION -propagated contractions-

• MIXING

- Mechanical dispersion

- Contact with digestive secretions

- Increasing contact with absorbing cells

• RESERVOIR FUNCTION

- Stomach

- Gallbladder

- Colon

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Objectives

• State the stimulus that initiates the swallowing sequence. Identify the point at which the swallowing sequence becomes automatic (independent of voluntary control).

• Identify the normal resting esophageal pressure and explain why this pressure varies with the respiratory cycle.

• Contrast primary and secondary peristalsis based on initiating event, voluntary control, reflex propagation, and regions of the pharynx and esophagus involved.

• Describe the origin and consequence of the high basal tone found in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES).

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Objectives• Contrast the patterns of external and internal

innervations of the upper, middle, and lower esophagus. • Describe the pressure changes that occur in the

esophagus as a bolus of food moves from the pharynx to the stomach, including the pressures immediately oral and aboral to the bolus, and the pressures in the upper and lower esophageal sphincters.

• Contrast the lower espohageal tone, innervation, and motility defects that lead to heartburn with those leading to achalasia.

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Swallowing sequence

1. Oral phase: [voluntary]

2. Pharyngeal phase: less than one second

3. Esophageal phase:

Primary peristalsis

Secondary peristalsis

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1. Oral phase

Oral phase: [voluntary]. Bolus of food moved up and back, forced into pharynx, initiates reflex.

From: Silverthorn. Human Physiology Prentice Hall

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2. Pharingeal phase.2. Pharingeal phase.Pharyngeal phase: less than one second:

1. Palatopharyngeal folds move in to close off nasopharynx.

2. Vocal cords come together and larynx is raised up and forward against epiglottis.

3. UES relaxes and superior constrinctor muscles of pharynx contract.

4. Peristaltic wave begins with superior constrictor muscles and moves toward the esophagus, forcing food through UES. From: Silverthorn. Human

Physiology Prentice Hall

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• UES reflexly constricts after bolus passes.

• Primary peristalsis: Peristaltic wave travels length of esophagus in 5 to 10 sec.

•Secondary peristalsis:If food remains, it elicits secondary peristalsis, which is more locally controlled.

• Reflex relaxation of LES and stomach to receive food, followed by constriction of LES are part of normal swallowing reflex.

3. Esophageal phase:

From: Silverthorn. Human Physiology Prentice Hall

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Swallowing initiates pharyngeal and esophageal peristalsis and sphincter relaxation

Manometry

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NOVIP

ACh

VEF = vagal excitatory fiber

VIF = vagal inhibitory fiber

NEUROTRANSMITTERS MEDIATE LES RELAXATION

Action potentialsAction potentials

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COMMON FACTORS CHANGING LES PRESSURE

INCREASE

• PROTEIN

• INTRA-ABDOMINAL

PRESSURE

• GASTRIC pH

DECREASE

• FAT

• CHOCOLATE

• PEPPERMINT

• ALCOHOL

• SMOKING

• GASTRIC DISTENSION (aerophagia)

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EFFECT OF PEPTIDES AND HORMONES ON LES PRESSURE

INCREASE

• GASTRIN

• MOTILIN

• SUBSTANCE P

• PANCREATIC POLYPEPTIDE (PP)

• VASOPRESSIN

• ANGIOTENSIN II

DECREASE

• SECRETIN

• CHOLECYSTOKININ (CCK)

• GASTRIC INHIBITORY PEPTIDE (GIP)

• VASOACTIVE INTESTINAL PEPTIDE (VIP)

• PROGESTERONE

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ACHALASIAACHALASIA

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ACHALASIAACHALASIA

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Copyright © 2004 by Karl Loren

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ACHALASIAACHALASIA

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Case-Based Learning in Gastroenterology and Hepatology: Esophageal DisordersA Classic Achalasia in a Young Woman

Klaus Bielefeldt, M.D., Ph.D. http://www.vh.org/adult/provider/internalmedicine/GICases/Esophageal/Achalasia/Achalasia.htmlhttp://www.vh.org/adult/provider/internalmedicine/GICases/Esophageal/Achalasia/Achalasia.html

A 19-year-old Caucasian woman presented with "problems swallowing." Ten months ago, she noted pressure and fullness in the retrosternal area immediately after swallowing. This initially subsided within a few minutes but progressively worsened.For several months, she had been unable to complete a meal, as she became very uncomfortable with significant pain triggered by food intake. The consistency of food did not significantly affect her symptoms. She frequently regurgitated undigested food, which alleviated the pressure and chest discomfort. She had lost about 25 kg during this time period.

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She frequently awoke at night due to coughing spells. She did not have prior medical problems. On physical examination she was thin, but not anorectic. No other significant physical findings were noted.

Her symptoms are typical for esophageal dysphagia. The combination of dysphagia for liquids and solids suggests a motility disorder.

A barium swallow was performed as the initial evaluation.

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It demonstrated a distended esophagus with pooling of contrast and a "bird beak" appearance of the lower esophageal sphincter Over time, some barium passed into the stomach. However, the lower esophageal sphincter never fully opened

Copyright © 2004 by Karl Loren

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Retention of saliva in the distal esophagus was noted. The distal esophagus was macroscopically normal.

The lower esophageal sphincter area had a "pin hole" appearance      . However, the endoscope could easily be passed into the stomach, which was unremarkable.

Endoscopy examinationEndoscopy examination

Copyright © 2004 by Karl Loren

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A manometric study demonstrated no appreciable motility in the tubular esophagus.

The lower esophageal sphincter had a normal resting pressure but did not relax upon swallowing

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Discussion to the clinical case Achalasia:

The diagnostic studies confirmed the initial impression that the patient has an esophageal motility disorder, demonstrating classical findings of achalasia. Achalasia is an idiopathic disorder of the esophagus.

Anatomically, the NO-containing neurons are absent from the myenteric plexus of the distal esophagus. The loss of these neurons results in an inability of the lower esophageal sphincter to relax. Concomitantly, the tubular esophagus typically demonstrates simultaneous, non-propagating contractions.

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The diagnostic method of choice is the barium swallow, which shows a smooth narrowing of the distal esophagus ("bird beak"), often associated with distension of the tubular esophagus and food retention.

Mucosal irregularities or a long narrowing of the GE junction should raise the suspicion of "pseudo-achalasia" due to an infiltrating lesion. Not present in this patient.

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Manometrically, the lower esophageal sphincter has a normal or high resting pressure that does not appropriately relax upon swallowing.

In the early stages, simultaneous contractions with normal or even high amplitudes can be recorded in the tubular esophagus ("vigorous achalasia").

With progression of the disease, the esophagus becomes distended and swallows trigger weak contractions that are similarly registered at several points due to a common cavity phenomenon

The main role of endoscopy is to rule out infiltrative processes in the GE junction.

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The treatment: The goal is a reduction in the resting pressure to allow passage of the food bolus into the stomach.

Medical therapy with smooth muscle relaxants, primarily organic nitrates and calcium channel blockers, has only limited effectiveness.

More definitive treatment options include pneumatic dilation, injection of botulinum toxin and surgical myotomy.

Balloon dilation leads to improvement in about 60 to 80 % of the patients (risk of perforation between 2 - 6 %), more than half of the individuals will require a repeat dilation within less than 5 years.

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• Continue with motility part 2: Continue with motility part 2: gastric and duodenal motilitygastric and duodenal motility