Esophageal and Gastric Physiology Richmond Sy, MD FRCPC Division of Gastroenterology The Ottawa...
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Transcript of Esophageal and Gastric Physiology Richmond Sy, MD FRCPC Division of Gastroenterology The Ottawa...
Esophageal and Gastric Physiology
Richmond Sy, MD FRCPCDivision of GastroenterologyThe Ottawa HospitalSept. 8, 2015
Objectives Describe the mucosal protective mechanisms of the
esophagus and stomach.
Illustrate the role of the stomach in the digestion of food.
Explain the processes making up normal gastric secretion.
Summarize the regulatory mechanisms controlling gastric digestion, secretion and emptying.
Summarize the process of normal gastric contractility and emptying.
Gastric Anatomy
Functions of the Stomach Motor
Reservoir Mixing and grinding Controlled emptying
Secretory HCl secretion Mucosal barrier Pepsinogen secretion Intrinsic factor
Main function of Gastric Motility
Accommodate meal (receive food via receptive relaxation)
Grind down solids (triturate) to chyme Regulated emptying of stomach contents into the
duodenum The 3 major neuromuscular activities of the
stomach Receptive relaxation of the fundus Recurrent peristaltic waves of the corpus and
antrum Antral peristaltic waves coordinated with
antropyloroduodenal coordination
Gastric Electrophysiology Gastric pacemaker is located along the
greater curve at the proximal or mid corpus Gastric slow waves originate at the
interstitial cells of Cajal Slow waves propagate in longitudinal and
circumferential direction Migrate towards the pylorus at
14mm/second Coordinated propulsive peristaltic activity Do not go pass the pylorus
Fasting Stomach In fasted state, the motor activity of the stomach is
known as the migratory motor complex (MMC) MMC made of three sequences
Phase 1 – quiescence phase Phase 2 – random and irregular contraction phase Phase 3 – burst of uninterrupted phasic contractions
that last 5 – 10 minutes (activity front) Individual cycles last 1-2 hours Activity front can migrate from the antrum to ileum Stimulated by vagus nerve and motilin
Motor Response to a Meal On initiation of swallowing, the gastric
fundus relaxes to accommodate incoming food – mediated by the vagus nerve
Tone and phasic contractions are inhibited as meal enters the proximal stomach
Abolishes the cyclical MMC Accommodation results in 2-3 fold increase
in gastric volume Leads to retention of food in stomach until
it is distributed to the antrum
Liquid Meal Trituration of the meal is accomplished with
the propulsive force generated by the tonic contractions of the proximal stomach and the resistance of the antrum, pylorus and the duodenum
Liquids rapidly disperse through the stomach without a lag phase
Rate depends on volume, nutrient content and osmolarity Empty nutrient liquids empty quickly Rich nutrient liquids empty slower
Liquid Meal
Total stomach emptying time
Proximal stomach emptying time
Distal stomach emptying time
Solid Meals Solid meal emptying occurs in two phases
Initial lag phase Linear emptying phase
Solid component initially held in proximal stomach
As liquid empties, the solid components move to antrum for trituration
Lag phase causes redistribution of solids Restrict emptying of solid particles > 1mm
Solid Meals The antrum and pylorus grinds down
larger particles into smaller particles Then empties in linear fashion with
liquids The lag phase depends on size and
consistency of meal For typical western diet, the lag phase
is 60 minutes
Solid Meals
Total stomach emptying time
Proximal stomach emptying time
Distal stomach emptying time
Antropyloric motility Trituration is the function of coordinated
contractions High amplitude waves originate in proximal
antrum Propagate to pylorus At the midantrum point, the pylorus is open
permitting flow of liquids and liquefied solid particles
At the distal antrum, the terminal antral contraction closes the pylorus, promoting retropulsion of particles too large to exit the pylorus
Solid particles continue to move in and out of the antrum until it is broken down
Grinding and Emptying
Regulation of Gastric Emptying
Controlled by central and local neurohormonal control
Neuronal control includes: Intrinsic myenteric plexus Extrinsic postganglionic sympathetic fibers of the celiac plexus Preganglionic parasympathetic fibers of the vagus nerve
Vagus afferents can be relaxatory and excitatory
Hormonal control via CCK Relaxes fundic tone, decreases antral contraction and increase pyloric tone Also other hormones (glucagon like polypeptide, peptide YY) can control gastric emptying
Enterogastric Reflexes
Distension
Distension
RELAXATION
Gastric SecretionCell populations
Gastric epithelial cells Mucus and HCO3
Cells of the gastric glands Cells of the lamina propria
Mast cells: histamine Plasma cells: immunoglobulins
Neurocrine secretion E.g. ACh, VIP, somatostatin
Functional Gastric Anatomy
Cells of the Gastric GlandsGland type Cell type Secretory products
Cardiac Mucous Mucus, pepsinogen II
Endocrine e.g. D cells: somatostatin
Oxyntic Mucous Mucus, pepsinogens I and II
Parietal HCl, intrinsic factor
Chief Pepsinogen and Leptin
Enterochromaffin-like cells Histamine
D cells Somatostatin
Enterochromaffin ANP, serotonin, adrenomedullin
Pyloric Mucous Mucus, pepsinogens II
G cells Gastrin
enterochromaffin ANP, Serotonin
D cells Somatostatin
The Oxyntic and Pyloric Gland
HCl SecretionFunctions of gastric acid
1. Facilitate peptic hydrolysis of dietary proteins
2. Inactivate ingested microorganisms3. Facilitate intestinal absorption of
calcium, Vitamin B12 and iron
The Parietal Cell
Activation of the Parietal Cell
3 pathways:1. Neurocrine: Acetylcholine, released
from vagal efferences2. Endocrine: Gastrin, released from
antral G cells3. Paracrine: histamine, released from
mast cells and ECL cells
The Parietal Cell
Pathways of Activation of H+ Secretion
Mucosal nerves Mediate cephalic phase and response
to gastric distension ACh:
Stimulates parietal cell Stimulates gastrin release inhibits somatostatin release
Pathways of Activation of H+ Secretion
Gastrin Stimulated by:
Raised gastric pH Amino acids Gastric distension ACh
Stimulates histamine release via ECL cells and mast cells
Stimulates parietal cell directly
Pathways of Inactivation of H+ Secretion
Luminal H+ Gastrin release is inhibited once
gastric pH < 2.5 - 3 Somatostatin
Secretion is stimulated by gastric acid, gastrin and VIP
Inhibits histamine and gastrin release Inhibits histamine-mediated
activation of parietal cell
Pathways of Inactivation of H+ Secretion
Prostaglandins Autocrine secretion from macrophages
and endothelial cells of lamina propria Inhibit histamine-related parietal cell
activation Inhibit gastrin-related histamine release
TGF-alpha Vasoactive Intestinal Peptide (VIP)
Phases of Gastric Secretion
3 phases:1. Cephalic2. Gastric3. Intestinal
Cephalic Phase Vagally mediated stimulation of
the parietal cell Triggers:
Thought of food Sight Smell Taste and mastication
Gastric Phase
Distension Vaso-vagal and local reflexes
Parietal cell activation
High pH
Peptides
Caffeine
Gastrin
Mast cells
ECL cells
Histamine
Intestinal Phase
Distension
Hypertonicity
Carbohydrates
Fat
Low pH
Vago-vagal and local reflexes
Somatostatin
CCK
(-)
Pancreas
HCO3- SECRETIN
Patterns of Acid Secretion
Gastric Mucosa
Gastric Mucosal Barrier Mucous layer* HCO3*t
Epithelial tight junctions Mucosal blood flow*
* Modulated by prostaglandinst Stimulated by ACh
Mucoprotective Mechanisms
Esophageal Protective Mechanisms
Why is esophagus not damaged by reflux of fluid from the acid environment of the stomach?
Esophageal Peristalsis Contraction wave propagated down to the esophagus in
response to swallowing and distention clear acid bolus Saliva
pH of saliva is 6.4-7.8 which neutralizes acid Esophageal submucosal glands
In response to acid reflux from the stomach submucosal glands secrete bicarbonate rich fluid that neutralizes acid
Tissue Factors Esophageal epithelium with relatively “tight” limiting ionic
movement Esophageal stratified squamous epithelium is 25-30 cell layers
thick Na2+/H+ as well as Cl-/HCO3- transmembrane ion exchangers
remove hydrogen from the cell allow bicarbonate to enter cell In response to acid, blood flow increased to esophagus to clear
H+ and deliver HCO3-
Pepsinogens
Pepsinogen Pepsin
Proteins Peptides
Amino acids
H+
Stimulate acid secretion
Gastrin
Ach
Histamine
Secretin
Pepsin
Inactivated at pH>4
Somatostatin
Prostaglandins
CCK
_
+
Intrinsic FactorB12 – dietary protein
B12Dietary proteinR-binder
B12 - R
RB12 IF
B12 - IF
H+, pepsin
Pancreatic enzymes
Intrinsic Factor
Drugs Used in Acid-peptic Disorders
Acid-suppressive therapy Proton pump inhibitors (PPI’s) H2 receptor antagonists (H2RA’s) Antacids
Prostaglandin analogs Misoprostol
Prokinetics Domperidone Metoclopramide
Sucralfate and bismuth compounds
Acid-suppressive Therapy
H2 RA’s
4 types Cimetidine, ranitidine, nizatidine, famotidine Achieve ~70% acid suppression, especially
nocturnal Exceptional safety record Side effects
Antiandrogenic effect, hematopoietic, CNS, hepatic, prolonged QT if rapid infusion, ?immunomodulator
PPI’s 6 types
Omeprazole, esomeprazole, lanzoprazole, dexlanzoprazole, pantoprazole, rabeprazole
Mechanism of action1. Accumulation in the parietal cell2. Activation of the PPI by protonation3. Irreversible binding and inactivation of the H+/K+
ATPase
Side-effects: diarrhea, headaches Drug interactions
Secondary to P450 metabolism Secondary to achlorhydria
PPI’s – Practical Aspects PPI’s cannot be activated outside the
parietal cell Importance of parietal cell activation
Timing of PPI intake Timing of onset of action Impact of concomitant inhibitors of parietal cell
activity Bond to H+/K+ ATPase is irreversible Effects of chronic achlorhydria
Hypergastrinemia Bacterial overgrowth
Parietal Cell and PPI Interaction
H2RAPPI
Placebo
Objectives Describe the mucosal protective mechanisms of the
esophagus and stomach.
Illustrate the role of the stomach in the digestion of food.
Explain the processes making up normal gastric secretion.
Summarize the regulatory mechanisms controlling gastric digestion, secretion and emptying.
Summarize the process of normal gastric contractility and emptying.